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Lantus Solostar (A-S Medication Solutions): FDA Package Insert, Page 6
Page 6: A-S Medication Solutions: LANTUS is indicated to improve glycemic control in adult and pediatric patients with diabetes mellitus. LANTUS is a...
Lantus Solostar (Page 6 of 8)
14.4 Additional Clinical Studies in Adults with Diabetes Type 1 and Type 2
Different Timing of LANTUS Administration in Diabetes Type 1 and Diabetes Type 2
The safety and efficacy of once daily LANTUS administered either at pre-breakfast, pre-dinner, or at bedtime were evaluated in a randomized, controlled clinical study in adult patients with type 1 diabetes (Study H, n=378). Patients were also treated with insulin lispro at mealtime. The average age was 41 years. All patients were White (100%) and 54% were male. The mean BMI was approximately 25.3 kg/m 2. The mean duration of diabetes was 17 years.
LANTUS administered at pre-breakfast or at pre-dinner (both once daily) resulted in similar reductions in HbA1c compared to that with bedtime administration (see Table 12). In these patients, data are available from 8-point home glucose monitoring. The maximum mean blood glucose was observed just prior to LANTUS injection regardless of time of administration. In this study, 5% of patients in the LANTUS-breakfast group discontinued treatment because of lack of efficacy. No patients in the other two groups (pre-dinner, bedtime) discontinued for this reason.
The safety and efficacy of once daily LANTUS administered pre-breakfast or at bedtime were also evaluated in a randomized, active-controlled clinical study (Study I, n=697) in patients with type 2 diabetes not adequately controlled on oral antidiabetic therapy. All patients in this study also received glimepiride 3 mg daily. The average age was 61 years. The majority of patients were White (97%) and 54% were male. The mean BMI was approximately 28.7 kg/m 2. The mean duration of diabetes was 10 years. LANTUS given before breakfast was at least as effective in lowering HbA1c as LANTUS given at bedtime or NPH insulin given at bedtime (see Table 12).
Table 12: Study of Different Times of Once Daily LANTUS Dosing in Type 1 (Study H) and Type 2 (Study I) Diabetes Mellitus Treatment durationTreatment in combination with Study H24 weeksInsulin lispro Study I24 weeksGlimepiride LANTUSBefore Breakfast LANTUSBefore Dinner LANTUSBedtime LANTUSBefore Breakfast LANTUSBedtime NPHBedtime * Intent-to-treat † Not applicable Number of subjects treated * 112 124 128 234 226 227 HbA1c Baseline mean 7.6 7.5 7.6 9.1 9.1 9.1 Mean change from baseline -0.2 -0.1 0.0 -1.3 -1.0 -0.8 Basal insulin dose (Units) Baseline mean 22 23 21 19 20 19 Mean change from baseline 5 2 2 11 18 18 Total insulin dose (Units) – – – NA † NA † NA † Baseline mean 52 52 49 – – – Mean change from baseline 2 3 2 – – – Body weight (kg) Baseline mean 77.1 77.8 74.5 80.7 82 81 Mean change from baseline 0.7 0.1 0.4 3.9 3.7 2.9
Progression of Retinopathy Evaluation in Adults with Diabetes Type 1 and Diabetes Type 2
LANTUS was compared to NPH insulin in a 5-year randomized clinical study that evaluated the progression of retinopathy as assessed with fundus photography using a grading protocol derived from the Early Treatment Diabetic Retinopathy Scale (ETDRS). Patients had type 2 diabetes (mean age 55 years) with no (86%) or mild (14%) retinopathy at baseline. Mean baseline HbA1c was 8.4%. The primary outcome was progression by 3 or more steps on the ETDRS scale at study endpoint. Patients with prespecified postbaseline eye procedures (pan-retinal photocoagulation for proliferative or severe nonproliferative diabetic retinopathy, local photocoagulation for new vessels, and vitrectomy for diabetic retinopathy) were also considered as 3-step progressors regardless of actual change in ETDRS score from baseline. Retinopathy graders were blinded to treatment group assignment.
The results for the primary endpoint are shown in Table 13 for both the per-protocol and intent-to-treat populations, and indicate similarity of LANTUS to NPH in the progression of diabetic retinopathy as assessed by this outcome. In this study, the numbers of retinal adverse events reported for LANTUS and NPH insulin treatment groups were similar for adult patients with type 1 and type 2 diabetes.
Table 13: Number (%) of Patients with 3 or More Step Progression on ETDRS Scale at Endpoint LANTUS (%) NPH (%) Difference * , † (SE) 95% CI for difference * Difference = LANTUS – NPH † Using a generalized linear model (SAS GENMOD) with treatment and baseline HbA1c strata (cutoff 9.0%) as the classified independent variables, and with binomial distribution and identity link function Per-protocol 53/374 (14.2%) 57/363 (15.7%) -2.0% (2.6%) -7.0% to +3.1% Intent-to-Treat 63/502 (12.5%) 71/487 (14.6%) -2.1% (2.1%) -6.3% to +2.1%
The ORIGIN Study of Major Cardiovascular Outcomes in Patients with Established CV Disease or CV Risk Factors
The Outcome Reduction with Initial Glargine Intervention study (i.e., ORIGIN) was an open-label, randomized, 2-by-2, factorial design study. One intervention in ORIGIN compared the effect of LANTUS to standard care on major adverse cardiovascular (CV) outcomes in 12,537 adults ≥ 50 years of age with:
Abnormal glucose levels (i.e., impaired fasting glucose [IFG] and/or impaired glucose tolerance [IGT]) or early type 2 diabetes mellitus and
Established CV disease or CV risk factors at baseline.
The first coprimary endpoint was the time to first occurrence of a major adverse CV event defined as the composite of CV death, nonfatal myocardial infarction, and nonfatal stroke.
The second coprimary endpoint was the time to the first occurrence of CV death or nonfatal myocardial infarction or nonfatal stroke or revascularization procedure or hospitalization for heart failure.
Patients were randomized to either LANTUS (N=6,264) titrated to a goal fasting plasma glucose of ≤95 mg/dL or to standard care (N=6,273). Anthropometric and disease characteristics were balanced at baseline. The mean age was 64 years and 8% of patients were 75 years of age or older. The majority of patients were male (65%). Fifty nine percent were Caucasian, 25% were Latin, 10% were Asian and 3% were Black. The median baseline BMI was 29 kg/m 2. Approximately 12% of patients had abnormal glucose levels (IGT and/or IFG) at baseline and 88% had type 2 diabetes. For patients with type 2 diabetes, 59% were treated with a single oral antidiabetic drug, 23% had known diabetes but were on no antidiabetic drug and 6% were newly diagnosed during the screening procedure. The mean HbA1c (SD) at baseline was 6.5% (1.0). Fifty-nine percent of the patients had had a prior CV event and 39% had documented coronary artery disease or other CV risk factors.
Vital status was available for 99.9% and 99.8% of patients randomized to LANTUS and standard care respectively at end of study. The median duration of follow-up was 6.2 years (range: 8 days to 7.9 years). The mean HbA1c (SD) at the end of the study was 6.5% (1.1) and 6.8% (1.2) in the LANTUS and standard care group respectively. The median dose of LANTUS at end of study was 0.45 U/kg. Eighty-one percent of patients randomized to LANTUS were using LANTUS at end of the study. The mean change in body weight from baseline to the last treatment visit was 2.2 kg greater in the LANTUS group than in the standard care group.
Overall, the incidence of major adverse CV outcomes was similar between groups (seeTable 14). All-cause mortality was also similar between groups.
Table 14: Cardiovascular Outcomes in ORIGIN in Patients with Established CV Disease or CV Risk Factors – Time to First Event Analyses LANTUSN=6,264 Standard CareN=6,273 LANTUS vs Standard Care n(Events per 100 PY) n(Events per 100 PY) Hazard Ratio (95% CI) Coprimary endpoints CV death, nonfatal myocardial infarction, or nonfatal stroke 1041(2.9) 1013(2.9) 1.02 (0.94, 1.11) CV death, nonfatal myocardial infarction, nonfatal stroke, hospitalization for heart failure or revascularization procedure 1792(5.5) 1727(5.3) 1.04 (0.97, 1.11) Components of coprimary endpoints CV death 580 576 1.00 (0.89, 1.13) Myocardial Infarction (fatal or nonfatal) 336 326 1.03 (0.88, 1.19) Stroke (fatal or nonfatal) 331 319 1.03 (0.89, 1.21) Revascularizations 908 860 1.06 (0.96, 1.16) Hospitalization for heart failure 310 343 0.90 (0.77, 1.05)
In the ORIGIN study, the overall incidence of cancer (all types combined) or death from cancer (Table 15) was similar between treatment groups.
Table 15: Cancer Outcomes in ORIGIN – Time to First Event Analyses LANTUSN=6,264 Standard CareN=6.273 LANTUS vs Standard Care n(Events per 100 PY) n(Events per 100 PY) Hazard Ratio (95% CI) Cancer endpoints Any cancer event (new or recurrent) 559(1.56) 561(1.56) 0.99 (0.88, 1.11) New cancer events 524(1.46) 535(1.49) 0.96 (0.85, 1.09) Death due to Cancer 189(0.51) 201(0.54) 0.94 (0.77, 1.15)
| https://medlibrary.org/lib/rx/meds/lantus-solostar-1/page/6/ |
(PDF) Nutritional status of children in India: Household socio-economic condition as the contextual determinant
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Nutritional status of children in India: Household socio-economic condition as the contextual determinant
August 2010
International Journal for Equity in Health 9(1):19
DOI: 10.1186/1475-9276-9-19
License
CC BY 2.0
Authors:
Md. Hafizur Rahman
Abstract and Figures
Despite recent achievement in economic progress in India, the fruit of development has failed to secure a better nutritional status among all children of the country. Growing evidence suggest there exists a socio-economic gradient of childhood malnutrition in India. The present paper is an attempt to measure the extent of socio-economic inequality in chronic childhood malnutrition across major states of India and to realize the role of household socio-economic status (SES) as the contextual determinant of nutritional status of children.
Using National Family Health Survey-3 data, an attempt is made to estimate socio-economic inequality in childhood stunting at the state level through Concentration Index (CI). Multi-level models; random-coefficient and random-slope are employed to study the impact of SES on long-term nutritional status among children, keeping in view the hierarchical nature of data.
Across the states, a disproportionate burden of stunting is observed among the children from poor SES, more so in urban areas. The state having lower prevalence of chronic childhood malnutrition shows much higher burden among the poor. Though a negative correlation (r = -0.603, p < .001) is established between Net State Domestic Product (NSDP) and CI values for stunting; the development indicator is not always linearly correlated with intra-state inequality in malnutrition prevalence. Results from multi-level models however show children from highest SES quintile posses 50 percent better nutritional status than those from the poorest quintile.
In spite of the declining trend of chronic childhood malnutrition in India, the concerns remain for its disproportionate burden on the poor. The socio-economic gradient of long-term nutritional status among children needs special focus, more so in the states where chronic malnutrition among children apparently demonstrates a lower prevalence. The paper calls for state specific policies which are designed and implemented on a priority basis, keeping in view the nature of inequality in childhood malnutrition in the country and its differential characteristics across the states.
Prevalence of Malnutrition among children (0-59 months) across fifteen major states of India (NFHS-3) …
Trend in Malnutrition in India among Children (0-35 months) …
Scatter plot showing relationship between NSDP and CI for Stunting, across the states. …
Conceptual Framework …
Trend in Malnutrition in India among Children (0-35 months) …
Figures - uploaded by
Nutritional status of children in India: household
socio-economic condition as the contextual
determinant
Barun Kanjilal
1
, Papiya Guha Mazumdar
2*
, Moumita Mukherjee
2
, M Hafizur Rahman
3
Abstract
Background: Despite recent achievement in economic progress in India, the fruit of development has failed to
secure a better nutritional status among all children of the country. Growing evidence suggest there exis ts a socio-
economic gradient of childhood malnutrition in India. The present paper is an attempt to measure the extent of
socio-economic inequality in chronic childhood malnutrition across major states of India and to realize the role of
household socio-economic status (SES) as the contextual determinant of nutritional status of children.
Methods: Using National Family Health Survey-3 dat a, an attempt is made to estimate socio-economic inequality
in childhood stunting at the state level throug h Concentration Index (CI). Multi-level models; random-coefficient
and random-slope are employed to study the impact of SES on long-term nutrit ional status among children,
keeping in view the hierarchical nature of data.
Main findings: Across the states, a disproportionate burden of stunting is observed among the children from poor
SES, more so in urban areas. The state having lower prevalence of chronic childhoo d malnutrition shows much
higher burden among the poor. Though a negative correlation (r = -0.603, p < .001) is establ ished between Net
State Domestic Product (NSDP) and CI values for stunting; the development indicator is no t always linearly
correlated with intra-state inequality in malnutrition prevale nce. Results from multi-level models however show
children from highest SES quintile posses 50 percent better nutritional status than those from the poorest quintile.
Conclusion: In spite of the declining trend of chronic childhood malnutrition in India, the concerns remain for its
disproportionate burden on the poor. The socio-economic gradi ent of long-term nutritional status among children
needs special focus, more so in the states where chronic malnutrition among children apparently demons trates a
lower prevalence. The paper calls for state specific policies which are designed and implemented on a priority
basis, keeping in view the nature of inequality in childhood malnutrition in the country and its differential
characteristics across the states.
Introduction
Despite recent achievement in economic progress in
India [1], the frui t of development has failed to secu re a
better nutritional stat us of children in the country [2-5].
India presents a typical scen ario of South-Asia, fitting
the adage of ‘ Asian Enigma ’ [6]; where progress in child-
hood malnutrit ion seems to have sunken into an appa r-
ent undernutrition trap, lagging far behind the other
Asian countries characterized by similar levels of eco-
nomic development [7-10].
Exhibiting a sluggish declining trend over the past
decade and a half, the recent estimate from the National
Family Health Survey -3 (NFHS-3)- the unique source
for tracking the status of ch ild malnutrition in India
[11]- indicates about 46 percent of the children under
5 years of age are moderately to severely underweight
(thin for age), 38 percent ar e moderately to severely
stunted (short for age), and approximately 19 percent
are moderatel y to severely wasted (th in for height) [12].
The decline in prevalence however becomes unimpres-
sive with the average levels marked by wide inequality
* Correspondence: [email protected]
2
Future Health Systems India, Institue of Health Management Research,
Kolkata, India
Full list of author information is available at the end of the article
Kanjilal et al . International Journal for Equity in Health 2010, 9 :19
http://www.equityhealthj.com/content/9/1/19
© 2010 Kanjila l et al; licensee BioMed Ce ntral Ltd. This is an Open Ac cess article distribu ted under the terms of the Cr eative Commons
Attribution L icense (http://creati vecommons.org/lice nses/by/2.0), which perm its unrestricted use, di stribution, and repro duction in
any medium, p rovided the original wor k is properly cited.
in childhood malnutrition across the states and various
socio-economic groups [2,3,13,14]. Growing evidence
suggests [13] that in India the gap in prevalence of
underweight children among the rich and the poor
households is inc reasing over the years with wide re gio-
nal differentials. From this specific context, the paper is
an attempt to study the specific interplay between
household socio-economic conditions and the nutri-
tional status for In dian children (particular in respe ct to
stunting, whi ch is an indicator for long-t erm nutritional
status), considering controls for various other estab-
lished predi ctors of the chronic child m alnutrition lying
at individual, maternal, household and community
characteristics.
Socio-economic inequality in childhood malnutrition:
Contextualizing the extent in India
Socio-economic differences in morbidity and mortality
rates across the wo rld have received its due attent ion in
the recent years [15-17 ]. Such differentials in health sta-
tus in-fact ar e found pervasive across na tions cross-cut-
ting stages of development [18-29]. Studies have
identified poverty as the chief determinant of malnutri-
tion in develop ing countries that perpet uates into inter-
generational transfer of poor nutritional status among
children and prevents social improvement and equity
[30,31]. Nut ritional status of und er-five children in par -
ticular is often co nsidered as one of the most important
indicator of a household ’ s living standard and also an
important determi nant of child survival [32]. The deter-
ministic studies in India while exploring the impact of
covariates o n the degree of childhood ma lnutrition sug-
gests an important nexus shared with household socio-
economic status [2,25,33-41]. The two-way causality of
poverty and under nutrition seems to pose a ver y signif-
icant pretext for malnutrition in India like other devel-
oping nations, where poverty and economic insecurity,
coupled by constrained access to economic resources
permeate malnourishment am ong the children [42-46].
Thus, economi c inequality constitutes t he focal point of
discussion while studying malnut rition and deserves sui-
table analytical treatment to examine its interplay with
other dimensions of malnutrition and to prioritize
appropriate programme intervention. Such attempt to
the best of our knowledge is still awaited, using recent
nationwide survey data in India.
In this backdrop, the p aper attempts to shed lights on
two specific objectives: 1) to find out the extent of
socio-economic inequality in chronic childhood malnu-
trition, across the major states of India, separated for
urban and rural locations, and 2) to understand the con-
ditional impact of househol d socio-economic condition
on nutritional status of children per se, controlling for
various other important cov ariates. The conceptual
framework (F igure 1) of the study is based o n review of
existing literature on the topic and adapts from various
existing framework on determinants of childhood mal-
nutrition in general [47], adding a special emphasis on
household soci o-economic status as the key exp lanatory
variable.
Methodology
Data
The paper uses the National Family Health Survey
(NFHS) 3rd round data (2005-06) for study and analysis.
Similar to NFHS-1 and NFHS-2, NFHS-3 was designed
to provide estimates of important maternal and child
health indicators including nutritional status for young
children (under five years for NFHS-3), following stan-
dard anthropometric components. The survey was con-
ducted following stratified s ampling technique, details
on the sampling procedure can be found at IIPS, 2007
[12]. Of the total 43,737 children for whom NFHS-3
provides height-for-age z-score (HAZ ), a subset of
24,896 child ren was considered; th ose were alive, hailed
from fifteen major states and had the HAZ score within
the range of -5 to +5 standard deviation from the
WHO-NCHS reference population.
We have also used secondary data from Handbook of
Indian Economy 2004-05 [48], for the statistics on per
capita Net State Domestic Product (NSDP), for the fif-
teen major states.
Methods used
The study uses two analytical methods for studying the
objectives. The first objective is catered through the
measurement of co ncentration index and underst anding
its linkage with the state level indicator of economic
development. While for study ing the second objective,
multi-level regression model have been employed.
Further details on methodology are presented below.
Concentration Index
The widely used standard tool that examines the magni-
tude of socio-economic inequality in any health out-
come, i.e. Concentration Index (CI) [49] is employed to
study the extent of inequity in chronic child malnutri-
tion across the states of India. The tool has been univer-
s a l l yu s e db yt h ee c o n o m i s t st om e a s u r et h ed e g r e eo f
inequality in various health system indicators, such as
health outcome, health care utilization and financing.
The value of CI ranges between -1 to +1, hence, if there
is no socio-ec onomic differential th e value returns zero.
A negative value implies that the relevant health variable
is concentrated among the poor or disadvantaged people
while the opposite is true for its positive values, when
poorest are assigned the lowest value of the wealth-
index. A zero CI implies a s tate of horizontal equity
Kanjilal et al . International Journal for Equity in Health 2010, 9 :19
http://www.equityhealthj.com/content/9/1/19
Page 2 of 13
which is defined as equal treatm ent for equal needs (For
further readings on application of CI in malnutrition
refer to Wagstaff & Watanab e 2000) [50]. CI values cal-
culated for stunting help us fi nd the possible concentra-
tion among rich and poor children below five years of
age during NFHS-3.
Multi-level regression
Due to the stratified nature of data in NFHS [12], the
children are naturally nested into mothers, mothers are
nested into households, hou seholds are into Primary
Sampling Units (PSUs) and PSUs into states. Hence
keeping in view this hierarchically clustered nature, the
paper uses multi-level regr ession model to estimate
parameter for nutritional status among children to avoid
the likely under-estimatio n of parameters from a single
level model [51]. Since here siblings are expected to
share certain common char acteristics of the mother and
the household (mother ’ s education and household eco-
nomic status for e.g.) and children from a particular
community or village have in common community level
factors such as availability of health facilities and out-
comes, it can be reasonably asserted that unobserved
heterogeneity in the outcome variable is also correlated
at the cluster levels [52-54]. This amounts to an estima-
tion problem employing conve ntional OLS estimators,
which gives efficient estimates only when the commu-
nity level covariates and the household level covariates
are uncorrelated with the individual and maternal effects
covariates.
Researchers have ad opted fixed effects models to esti-
mate nutrition models and control for unobservable
variables at the cluster level, which leads to the diffi-
culty that if the fixed effect is differenced away, then
the effect of those variables that do not vary in a cluster
will be lost in the estimation process [54]. Allowing the
contextual effects in our analysis of the impact of
household socio-economic status on child undernutri-
tion, we adopt an al ternative approach of using multi le-
vel models.
Individual Characteristics of Child
• Age
• Sex
• Birth Order
• Size at birth
• Child feeding practice
Mother Specific
• Education
• Occupation
• Nutritional Status
(BMI)
• Anemia status
• Healthcare related
autonomy
Household Characteristics
Household Specific
• Ethnicity
• Socio-economic status
Health Service Uptake
• Status of
Institutional
Delivery
• Status of
immunization
Place of Residence
• Urban
• Rural
State
Distant
Intermediate
Proximate
Chronic Malnutrition among Children
Figure 1 Conceptual Framework
Kanjilal et al . International Journal for Equity in Health 2010, 9 :19
Broadly, we test the two types of multilevel models
following the practice in co ntemporary literature; the
variance comp onents (or random interce pt) models and
the random coefficients (or random slopes) models. As
in above, STATA routines for hie rarchical linear models
using maximum likelihood estimators for linear mixed
models were used for both model forms.
The variance-components model correct for the
problem of correlated observations in a cluster, by
introducing a random effect at each cluster. In other
words, subjects within the same cluster are allowed to
have a shared random intercept. We consider two clus-
ters, i.e., community and household, since in most of
the cases NFHS provides information on children of
one mother chosen from a particular household. Thus,
we have,
zx
ij ij i ij
=′ + +
where z
ij
is the HAZ score for the child(re n) from the
j
th
household in the i
th
community. b is a vector of
regression coefficients corresponding to the effects of
fixed covariates x
ij
, which are the observed characteris-
tics of the child, the household and the community.
Where, ‘ i ’ is a random community effect denoting the
deviation of community i ’ s mean z-score from the grand
mean, ‘ j ’ is a random household effect that represents
deviation of household ij ’ s mean z-score from the i
th
community mean. The error terms δ
i
and μ
ij
are
assumed to be normal ly distributed with zero mean and
variances s
2 c
and s
2, h
respectively. As per our argu-
ments above, these terms are non-zero and estimated by
variance components models. To the extent that the
greater homogeneity of within-cluster observations is
not explained by the observed covariates, s
2 c
,a n d s
2, h
will be larger [55].
To evaluate the appropriateness of the multilevel
models, we test whether the variances of the random
part are different from zero over households and com-
munities. The resulting estimates from the models can
be used to assess the Intra Class Correlation (ICC) i.e.,
the extent to which child undernutrition is correlated
within households and communities, before and after
we have accounted for the obs erved effects of covariates
. A significantly different ICC from zero suggests
appropriateness of random effect models [54]. The ICC
coefficient describes the pro portion of variation that is
attributable to the higher level source of variation. The
correlations between the anthropometric outcomes of
children in the same commu nity and in the same family
are respectively:
cc c h
22 2
=+ /( )
Following this, the total variability in the individual
HAZ scores can be divided into its two components;
variance in children ’ s nutritional status among house-
holds within communities, and variance among commu-
nities. By including covariates at each le vel, the variance
components models allow to examine the extent to
which observed differences in the anthropometric scores
are attributable to factors operating at each level. Thus,
the variance components model described above intro-
duces a random intercept at each level or cluster assum-
ing a constant effect of each of the covariates (on the
If additionally, we consider the effect of certain covari-
ates to vary across the clusters (for e.g, differential
impact of household socio-economic status or mother ’ s
education across households and/or communities), we
need to introduce a random effect for the slopes as well,
leading to a random coefficients model. Under these
assumptions, the covariance of the disturbances, and
therefore the total variance at each level depend on the
values of the predictors [55].
As mentioned earlier, a subse t of 24,896 children have
been considered for the analysis from the hierarchically
clustered NFHS-3 da taset. Hence, our multilevel model s
are based on observations on 24,896 children from
18,078 households distributed in 2,440 communities/
clusters (PS Us). Inclusion of separ ate levels for children
and mothers were considered not necessary since these
were almost unitary to the number of households.
The analysis is presented in the form of five models,
apart from the conventional OLS model wit hout consid-
ering the cluster random effects, primaril y as a compari-
son: Model_Null is the null model, where the HAZ z
scores is the dependant variable with no covariates
and richest household asset quintile, other covariates are
introduced in a phased manner. Such as, Model_Kids
introduces ch ild specific predictors (be ing purely indivi-
dual attributes); Model_Moms introduces the mother-
specific cov ariates. Model_Full is t he full model with all
the model covariates at respective levels. These models
are three-level random intercept models with the two
clusters: community, and households. In Model_Ran-
dom_Slope, we introduce a random coefficient for
socio-economic status at the household level. We settled
for the random coefficient in the form of wealth quintile
dummies. The covariates included as controls in our
analytical models, with the primary aim of isolating the
effect of income or socioeconomic status (SES) on
chronic child undernutriti on are described below. In the
multilevel framework most of these variables can be
classified as individual-specific, household-specific or
community-specific covariates.
Kanjilal et al . International Journal for Equity in Health 2010, 9 :19
Variables in the regression model
As mentioned earlier, the paper uses height for age
(stunting) as the key outcome var iable, which is an indi-
cator of chronic nutritional status capable of reflecting
long-term deprivation of food [56] following the estab-
lished practice o f anthropometric measures of malnu tri-
tion. The measure is expressed in the form of z-scores
standard deviation (SD) from the median of the 2006
WHO International Reference Populati on. This continu-
ous standard deviation of HAZ score is capable of pro-
viding expected change in the value of the response
variable due to one unit change in the regressors regard-
less of whether a child is stunted or not [57]. Hence, the
present approach differs from the usual practice of
employing a dichotomous variable on probability of a
child being chronically malnourished (0 = otherwise, 1 =
stunted). Since here the attempt is not to model prob-
ability of stunting, but instead using a deterministic
model the paper attempts to find out the influencing
role of household asset o n childhood nutrition in fifteen
major states of India.
Explanatory variables
Asset quintile as the proxy for household socio-economic
status
Following the standard approach of assessing economic
status of the household [28], the paper uses household
asset index provided by the NFHS-3. The survey pro-
vides the household wealth index based on thirty-three
household characteristics and ownership of household
assets using a Principal Component analysis (for details
on the methodology refer to IIPS 2007) [12]. In the
paper we divided the household index into quintiles
based on the asset scores adj usted by sample weights.
Separate quintiles were developed for rural and urban
areas of each state by using state-specific sample
weights, to avoid questions on comparability [28].
Other explanatory variables used as controls
Apart from the above mentioned asset index, other
determinants of childhood malnutrition are chosen
based on approaches in literature and presented in the
conceptual framework (Figure 1) of the study [47]. We
consider certain indi vidual characteristics of child as the
proximate covar iate of chronic malnutrit ion. These pre-
disposing factors include child ’ s characteristics similar to
other studies, such as, child ’ s age in months, quadratic
form of age to elimi nate the effect on z-score [38 ] since
there exists non-linearity between age and HAZ, sex of
the child, birth order, size of child at birth (as a proxy
of birth weight) [57], incidence of recent illness, com-
plete doses of immunization and recommended feeding
practice; denoted by exclusive breast feeding for infants
below six months of age, introduction of nutritional
supplements along with or without breastmilk after six
months. In view of information provided by NFHS on
child feeding, we considered a child is introduced to
supplementary food, where ver the child was reported
having given any food-stuff irrespective of its breast
feeding status, a day preceding the survey date.
The controls on mother ’ s characteristics includes;
years of in terms of education, body mass index (BMI),
mothers status of anemia, autonomy for seeking medical
help for self [58,59] and place of birth for the child of
interest. On the household level, except for asset quin-
tile, controls was incl uded for household ethnicity, since
a large number of earlier st udies found a significant
linkage between scheduled tribe/scheduled caste house-
holds and childhood undernutrition [2,14]. Community
characteristic is regarded as the distant covariate of
child malnutrition in t he model and include rural-urban
Figure 2 Trend in Malnutrition in India among Children (0-35 months)
Kanjilal et al . International Journal for Equity in Health 2010, 9 :19
http://www.equityhealthj.com/content/9/1/19
place of residence and state. Keeping in mind the large
scale variation in childhood mortality and morbidity, the
states are consider ed for each of the models as contro ls,
or as fixed effects in multilevel models.
Results
Extent of socio-economic inequity in childhood stunting
As mentioned earlier, the successive waves of NFHS in
India indicates a declining trend in the prevalence of
child malnutrition among children aged below three
years (Figure 2).
Except for wasting, across the two different established
anthropometric measures of malnutrition; stunting and
underweight, a consistent decline is evident during
1992-2005 period (Figure 2). Overall, NFHS-3 reveals a
different ial scenario of chil d malnutrition acros s the fif-
teen major states of India (Table 1).
To describe further, the state of Kerala showed the low-
est prevalence of stunting among children (25 percent)
across all the major states, where the rural-urban differ-
ential is virt ually nonexistent. Whereas the opposit e side
of the spectrum, more than half the children below five
years were stunted in Uttar P radesh (57 percen t), Bihar
(56 percent), Gujarat (52 percent) and Madhya Pradesh
(50 percent) (Table 1). The rural-urban differentials are
also considerably high in these states, along with West
Bengal; which showed the highest (19 percent) d ifferen-
tial between rural-urba n prevalence of child malnutrition
which is unfavorable for rural areas, during NFHS-3.
Overall, all the three indicators of malnourishment are
found highly correlated with each other and hence it
was worthwhile to explore their association with the
incidence of poverty in the s tates, following the estab-
lished line of argument. It c an be said that the optimal
growth of the ch ildren (having standard height for thei r
age and weight for their height) have been strongly
associated with economic status of the population.
Table 1 Prevalence of Malnutrition among children (0-59 months) across fifteen major states of India (NFHS-3)
States/Country Underweight Stunting Wasting
Rural Urban Total Rural Urban Total Rural Urban Total
Haryana 41.3 34.6 39.6 48.1 38.3 45.7 19.7 17.3 19.1
Punjab 26.8 21.4 24.9 37.5 35.1 36.7 9.2 9.2 9.2
Rajasthan 42.5 30.1 39.9 46.3 33.9 43.7 20.3 20.8 20.4
Uttar Pradesh 44.1 34.8 42.4 58.4 50.1 56.8 15.2 12.9 14.8
Bihar 57 47.8 55.9 56.5 48.4 55.6 27.4 25.2 27.1
Orissa 42.3 29.7 40.7 46.5 34.9 45.0 20.5 13.4 19.5
West Bengal 42.2 24.7 38.7 48.4 29.3 44.6 17.8 13.5 16.9
Assam 37.7 26.1 36.4 47.8 35.6 46.5 13.6 14.2 13.7
Gujarat 47.9 39.2 44.6 54.8 46.6 51.7 19.9 16.7 18.7
Andhra Pradesh 34.8 28 32.5 45.8 36.7 42.7 13 10.7 12.2
Karnataka 41.1 30.7 37.6 47.7 36 43.7 18.2 16.5 17.6
Kerala 26.4 15.4 22.9 25.6 22.2 24.5 18.2 10.9 15.9
Tamilnadu 32.1 27.1 29.8 31.3 30.5 30.9 22.6 21.6 22.2
All 15 states 44.1 32.2 41.1 49.7 39.2 47.04 19.9 16.6 19.04
Source: Authors ’ Calculation from NFHS 3 unit data
Table 2 Concentration Index Values for Stunting across
States and Urban-Rural Locations, India, NFHS-3
States/Country Concentration Index (Stunting)
Rural Urban Total
Haryana -0.118** -0.257** -0.151**
Punjab -0.211** -0.259** -0.212**
Rajasthan -0.069** -0.182** -0.106**
Madhya Pradesh -0.032 -0.133** -0.063**
Bihar -0.082** -0.131** -0.094**
Orissa -0.169** -0.267** -0.183**
West Bengal -0.112** -0.3** -0.168**
Assam -0.101** -0.253** -0.116**
Gujarat -0.087** -0.132** -0.115**
Maharashtra -0.12** -0.167** -0.146**
Andhra Pradesh -0.104** -0.134** -0.14**
Karnataka -0.076** -0.185** -0.127**
Kerala -0.204** -0.061 -0.165**
Tamil Nadu -0.075 -0.196** -0.131**
All 15 states -0.092** -0.177** -0.121**
ALL INDIA -0.098** -0.169** -0.126**
Source: Authors ’ Calculation from NFHS 3 unit data
Significant at ***p < 0.01, ** p < 0.05, and * p < 0.10.
The CI values for chronic malnutrition in respect to
fifteen major st ates and at the country level cons istently
return negative values, reflecting a heavy burden of
malnutrition among the poor in India (Table 2).
The above table (Table 2) confirms the fact that across
children from poorer households share the higher bur-
den of sub-optimal gr owth due to undernourishment. It
needs speci al mention that chroni c malnutrition among
children is more concentrat ed among urban poor com-
paring their count erpart living in rural areas. This trend
is consistent across all thirt een states, except for Bihar
and Kerala; wh ere concentration of stun ting is observed
higher among poor children from rural areas.
It is also seen in a similar vein that aggregate eco-
nomic status of a population is associated with child
nutritional status. CI values for stunting and Net State
Domestic Product (NSDP; considered as the indicator
for economic devel opment for the aggregate level of the
state) share an inverse association (Figure 3), common
for most of the states.
Overall, the negative corre lation established between
CI values for stunting and NSDP per capita stands at
r = -0.603 (p < .001). The scatter plot of NSDP per
capita and CI values for stunted children across the
states (Figure 3) emerges few specific patterns. The
states like, Bihar, Uttar Pradesh, Madhya Pradesh and
Rajasthan exhibit a typical situation where per capita
0.134
(0.074)
Kanjilal et al . International Journal for Equity in Health 2010, 9 :19
http://www.equityhealthj.com/content/9/1/19
Page 8 of 13
per-capita NSDP as compared to the national average,
the state exhibits a noticeably higher burden of chronic
malnourishment among the poor.
Role of household socio-economic conditions
determining long-term nutritional status among children
The results shows (Table 3), significant association
between househ old asset quintiles and nutri tional status
of children.
Given the form of the dependent variable in the sub-
sequent models a higher coefficient indicates better
nutritional status among children from better off socio-
economic status quintiles (SES). It shows (Table 3)
nearly 50 percent better nutritional status (0.31 -
(-0.18)) among children from richest SES quintiles, com-
pared to ones those from the poorest quintile.
The variance component mo dels (i.e., Model_kids,
Model_moms and Model_full) and the random slope
model (Table 3) also support such finding. By introdu-
cing covariates at each level, the variance component
models allow to examine the extent to which observed
differences in the HAZ scores are attributed to the fac-
tors operating at each level. With the introduction of
child ’ s individual characteristics in the Mode l_kids along
with the state level fixed effect, the impact of richest &
poorest SES quintiles become much stronger. The result
s h o w so v e r8 0p e r c e n t( 0 . 5 4- (-0.29)) higher incidence
of worse nutritional status among children in the poor-
est quintile, than the ones hailing from richest SES
group. However, such richest-poorest gap decreases
with the phased introduction of covariates related to
mother ’ s characteristics, household ethnicity and place
of residence in the models (Table 3). Finally, similar to
the initial estimate by OLS, the variance component
models and random sl ope model indicates that the chil -
dren with the most favorable SES background enjoy
almost 50 percent better nutritional status than their
counterpart from the poorest SES groups.
The calculated ICC coefficient values presented in
Table 4 differ from zero. This indicates that child nutri-
tion is indeed correlated with households and commu-
nities (PSUs ). The ICC for household lev el shows much
higher correlation than the case of PSUs.
The lower panel of the Table 4 shows how the resi-
dual variance is distributed across PSUs and households.
Estimates f rom model 1(null model) , which contains no
observed covariates, indicate that the variation in
height-for-age has substanti al group level components.
The total variance 0. 548 (combined for PSU and house-
holds estimates), of which 63 percent is attributed to
household level variation i n anthropometric scores.
Consistent wit h this observation on null model var iance
decomposition, other model specifications show similar
variance distribution pattern across state, PSU and
household levels.
Estimation of househo ld random effects (Table 4) indi-
cates that h ousehold heterog eneity is accounte d for only
partially by the covariates in our model (Model_Full &
Model_random_slope). In other words the significantly
different values of s
2
c
and s
2
h
indicates that the
Table 3 Association ( b s) fro m Ordinary Least Squares and Multilevel Linea r Regression Models (Main Effects) between
Child Stunting (Height for Age) and Household Socio-Economic Status, controlling for various other covariates; Fifteen
Major States, India, NFHS-3 (Continued)
Madhya Pradesh 0.025
(0.056)
- 0.062
(0.071)
0.069
(0.067)
0.032
(0.067)
0.034
(0.067)
Gujarat -0.307***
(0.063)
- -0.281***
(0.079)
-0.272***
(0.074)
-0.314***
(0.075)
-0.311***
homogeneity withi n cluster observations is not explai ned
by the observed covariates s pecified in the model. The
intra-household correlation remains as large as 0.242
suggesting that the height outcomes of two children
belonging to the same family are more ho mogenous than
those of two children chosen at random, even after
adjusting for other observed covariates (Model_Full).
household level denotes existence of higher homogeneity
at the household level. These results further imply that
choice of one-level model with the similar data set
might yield underestimation of parameters.
Discussion
Successive waves of NFHS brings to the fore wid espread
under nutrition among the Indian children, however it
shows a declining trend duri ng the inter survey period.
Though, the latest estimates as provided by the NFHS 3,
highlights the cont inuance of high overall levels of child
malnutrition in India. As we find here, prevalence of
states and also across rural and urban areas. It needs
special mention that chronic malnutrition among chil-
dren is more concentrated among urban poor compared
to their counterpart living in rural areas (Table 2) where
inequalitie s are not as great but overall lev els of malnu-
trition are higher. This trend is consistent across all
thirteen states, except for Bihar and Kerala; where con-
centration of stunting is observed higher among poor
children from rural areas.
The intra-stat e inequality in child m alnutrition is stark
as we find through the divergent values of the Concentra-
tion Index highlighting the disproportionate burden
among the poor. The variance component models clearly
show clustering o f observation at community and ho use-
hold levels. In othe r words, for the fifteen major states in
India, children in the households that shared similar
communities do posses similar n utritional status. Intra-
household corr elation is the most substantia l, comparing
intra-PSU correlation. In other words, children from a
cluster or community do not se em to share stronger cor-
relation in terms of their nutritional status. But, at the
household level the observations are not independent. It
implies the fact that children belonging to a particular
household do share certain common characteristics while
growing up. The children who belong to households
from the poorest SES quintile have higher prevalence of
worse nutrit ional status. While, on t he contrary the chil-
dren hailing from richest asset quintile households are
associated with better nutrit ional status. The finding is
supportive of many earlier observations made based on
NFHS data [2]. Such association is consistent across the
different models applied to the researc h (Table 4); recon-
firming better nutritional status among children with
favourable household socio -economic background, even
after controlling for a range of individual, maternal and
community characteristics. T his further emphasizes the
impact of differential available resources to the families
that act as a major determinant of malnutrition. The
finding is supportive of studies conducted even in other
countries [60]. Hence the gradient of household socio-
economic status remains as a crucial determi nant of level
of nutritional achievement among children. Betterment
of such condition thus is exp ected to improve growth of
children likely through better nutritional intake and
reduced morbidity.
Table 4 Random Coefficients, Intra-class correlation and Variance Decomposition estimates from comparative models
Null_model Model_Kids Model_Mom Model_Full Model_Random_Slope
Random Effects
s
2 c
(Community - PSU) 0.202 0.091 0.056 0.055 0.055
(S.E.) (0.014) (0.009) (0.008) (0.008) (0.008)
Proportions of overall (null model) explained by the covariates of
the model (in %)
55.189 72.149 72.850 72.875
s
2 h
(Household) 0.346 0.462 0.436 0.431 0.366
(S.E.) (0.027) (0.025) (0.025) (0.025) (0.030)
Proportions of overall (null model) explained by the covariates of
the model (in %)
-33.578 -26.086 -24.575 -5.683
Residual
2
1.877 1.516 1.514 1.518 1.516
(S.E.) (0.029) (0.024) (0.025) (0.025) (0.025)
Intra-class correlation
r (PSU) 0.083* 0.044* 0.028* 0.027* 0.028*
r (household) 0.226* 0.267* 0.245* 0.242* 0.217*
Variance Decomposition (in %)
PSU 36.9 16.4 11.4 11.3 13.1
Household 63.1 83.6 88.6 88.7 86.9
Significance level: * p<0 5
Kanjilal et al . International Journal for Equity in Health 2010, 9 :19
However, at the more macro level i t is seen that abso-
lute levels of malnutrition prevalence across th e states is
not necessarily linearly correlated with the intra-state
inequality in malnutrition prevalence. In other words,
states that records higher prevalence of childhood mal-
nutrition are not always reflective of the disproportion-
ate burden shared by the poorest households.
Mazumdar (fo rthcoming) [61], while exploring the link-
age between povert y and inequality with child malnu tri-
tion in India suggests a po ssible conformation of
malnutrition inequality wi th overall socioeconomic
inequality that exists in the states. We too identify a
similar pattern; though with overall economic develop-
ment measured throug h NSDP is found to be negatively
correlated with the proportion of stunted children in the
state, emphasizing the role of development that pro-
motes equity in better nutritional outcome; the pattern
cannot be generalized.
In states like Punjab and Kerala with better develop-
ment, a typical scenario emerges. Here, higher inequality
in malnutrition pr evalence can be observed at the lower
levels of percentage of stun ted children. On the other
hand, states like Madhya Pradesh, Bihar, Gujarat and
Rajasthan the states wit h less economic develop ment or
at par with the national average, though have consider-
ably high prevalence of malnutrition exhibited lower
values of the concentration index suggesting lower levels
of inequality. It is particularly since a higher average
implies prevalence of malnutrition irrespective of SES
with fewer differentials. Hence a clear gradient of mal-
nutrition inequality, biased against the poor is more pro-
nounced in states where absolute levels of malnutrition
are low. This is largely due to the overall inequality in
household ass et [50,62] among the states, wi th the poor
accounting for a major share of the malnourished
children.
On the other hand, the states with higher levels of
child malnutrition, generally tend to have a uniform dis-
nomic distribution (Mazumdar forthcoming )[ 6 1 ] ,a n d
the poor in states with lower observed levels sharing a
higher disproportionate burden, vis-à-vis the poor in the
former group of states.
The situation in Orissa is however the worst and do es
not confirm to any of the pattern discussed above. Here,
with much lower per-capita NSDP as compared to the
national average, the state exhibits a noticeably higher
burden of chronic malnourishment among the poor.
Hence, perhaps economic development cannot be con-
sidered as the straightforward indicator for removing
overall disparity in various input and outcome indicators
among different income bracket, especially in a country
like India. It is argued that reduction in child malnutri-
tion does not seem to depend so much on economic
growth of a state per se or even on the efforts at redu-
cing income poverty at the state level [3]. Achieving bet-
ter nutritional status among children is found sharing
close nexus with the household socio-economic condi-
tions, efforts to influence households ’ economic status
thus might prove to be b eneficial. Alternatively, one can
only think of successf ul targeted interventions to ensur e
nutritiona l status among chil dren those belong to unfa-
vorable asset bracket.
Nevertheless, this issue of malnutrition and poverty
deserves special treatment incorporating other para-
meters reflecting the possible predictors of overall socio-
economic inequality and its bearing on malnutrition
inequality among the states, as future research in this
area. Attempts can be worthwhile to know the reasons
why the states with better economic development
coupled with noticeable success in arresting the overall
level of chronic child malnutrition, have failed to
remove its disproportion ate prevalence across the socio-
economic classes. It can be said that prevalence of
worse nutritio nal status among children in Indi a cannot
be addressed with utmost success unless, inequality in
prevalence across soci o-economic classes ar e taken care
of. A more state spec ific policy should be designed o n a
priority basis, to arrest such unequal prevalence.
Conclusions
Regional hete rogeneity in malnutrit ion across the major
states and rural-urban locations are observed to be
widespread during NFHS-3. The concerns amplify with
the disproportionate burden of malnutrition among
malnutrition is seen to be at the lower level, but where
they are experiencing better status of economic develop-
ment. Multilevel analyses with introduction of controls
on various covariates continue to indicate the household
SES-undernutrition gradi ent. Hence, an appropriate pol-
icy guideline that focuses on altering the nutritional
intake among the poor children, especially in the states
with apparent lower prevalence of childhood malnutri-
tion is need of the hour. In the high prevalence states
much stronger programme are awaited to reduce the
overall level. More focused programme attention tar-
geted at the poor to enhance the level of nutrition and
behavior al changes, through i nterventions lik e the posi-
tive deviance approach in a state like Orissa should be
further expanded in the near future.
Acknowledgements
The authors acknowledge the scientific support extended by ‘ Future Health
Systems: Innovations for equity ’ (http://www.futurehealthsystems.org) a
research program consortium of researchers from Johns Hopkins University
Bloomberg School of Public Health (JHSPH), USA; Institute of Development
Studies (IDS), UK; Center for Health and Population Research (ICDDR, B),
Bangladesh; Indian Institute of Health Management Research (IIHMR), India;
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is inversely related to child stunting in Andhra Pradesh, India. Maternal
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doi:10.1186/1475-9276-9-19
Cite this article as: Kanjilal et al .: Nutritional status of children in India:
household socio-economic condition as the contextual determinant.
... Nearly 165 million children, under the age of five, are malnourished in LMICs [4]. The proportion of undernourished children in 2017 accounted for 20.4% in Africa,
11
.4% in certain regions in Asia, and 6.1% in Latin America. Evidence indicates an increase in undernourishment and severe food insecurity in almost all the regions of Africa and South America, whereas, the undernourishment situation in Asia is observed to be stable [7]. ...
... A malnourished child is ten times more likely to die than a well-nourished child from a preventable cause [9]. The nutritional status of under-5 children in India, estimated using the anthropometric data on height and weight collected in the fifth round of the National Family Health Survey (NFHS-5;2019-20), indicates that 35·4% are stunted (height-for-age deficit), 32·08% are underweight Dialogues in Health 2 (2023) 100135 (weight-for-age deficit), and 19·35% are wasted (weight-for-height deficit) [10] India's progress in childhood nutrition status does not commensurate with its economic progress, and it is worse off than most Sub-Saharan nations
[11]
This paradoxical situation in India, as in most other South-Asian countries, is called the 'Asian Enigma'. ...
... Most studies treat tribal communities as an egalitarian group with a collective conscience, and, fail to capture and address the question of differentiation and inequality among them. Even though since Independence, various publicly financed initiatives have significantly improved the overall living conditions of the Tribal population across India, the inequality across all social classes and within ST communities continues
[11,
22]. Such inequalities are also reflected in the health status of the ST population. ...
Wealth inequalities in nutritional status among the tribal under-5 children in India: A temporal trend analysis using NFHS data of Jharkhand and Odisha states - 2006-21
Umakant Dash
... It is observed from NFHS-3 and NFHS-4 reports that the scenario of child malnutrition in West Bengal is lower than the national average, but the prevalence of malnutrition is not evenly distributed across the districts of the state (IIPS, 2017(IIPS, , 2021. Moreover, there are different studies done considering the role of bio-demographic factors in the prevalence of child malnutrition across the country
(Kanjilal et al., 2010;
Bisai et al., 2014;Panigrahi & Das, 2014;Amruth et al., 2015;Rengma et al., 2016;Ansuya et al., 2018; Aayog, 2021a), has been considered to study the prevalence of child malnutrition (Fig. 1). The proportion of rural populations in the district is 87.26%, which is quite high. ...
... But in this globalized world of the twenty-first century, the incidence of undernutrition is experienced by a wide range of pockets across the globe (UNICEF et al., 2019). Several studies observed that the bio-demographic and socioeconomic factors, such as BMI of mother, marriage age of mother, child birth weight, number of siblings, birth order, food intake, family income, education of parents, sanitation facility, source of drinking water, have a direct bearing in the prevalence of malnutrition of children (de Onis & Blossner, 1997;Cummins, 1998;Phillips, 2006;
Kanjilal et al., 2010;
Panigrahi & Das, 2014;Amruth et al., 2015;Rengma et al., 2016;Ansuya et al., 2018;De & Chattopadhyay, 2019;Islam & Biswas, 2020;Agarwal et al., 2021). In this present study, a total number of fifteen bio-demographic and socio-economic parameters are adopted as independent variables to find out the significant predictors of child malnutrition (Table 3). ...
... The prevalence of wasted children is observed in several works in different proportions across India, such as Arambag, West Bengal (2 to 6 years) 50% (Mandal et al., 2008); Paschim Medinipur, West Bengal (2 to 13 years) 22.70% (Bisai & Mallick, 2011); Paschim Medinipur, West Bengal (1 to 14 years) 19.40% (Bisai et al., 2008b); Darjeeling, West Bengal (5 to 12 years) 26.50% (Debnath et al., 2018); Odisha (1 to 6 years) 25% (Goswami, 2016); Assam (5 to 12 years) 17.15% ; Bhubaneswar, Orissa (3 to 9 years) 23.29% (Panigrahi & Das, 2014); Sullia, Karnataka (5 to 11 years) 26.50% (Amruth et al., 2015). It was documented in different studies that the variation in the prevalence of wasting mainly results from socio-economic-backgrounds and growth patterns of different age groups of children (Alemayehu et al., 2015;Amruth et al., 2015;Bisai et al., 2008aBisai et al., , 2008bDas & Bose, 2009;Debnath et al., 2018;Islam & Biswas, 2020;
Kanjilal et al., 2010;
Panigrahi & Das, 2014;Rengma et al., 2016;Singh, 2020;Stiller et al., 2020). The study does not observe any statistically significant difference in sex and age groups of children in the prevalence of wasting; it may be due to the low socio-economic profile of the households (Ghosh et al., 2021;Mandal, 2021;Mandal & Ghosh, 2019;Mandal et al., 2017). ...
Rural child health in India: the persistent nature of deprivation, undernutrition and the 2030 Agenda
... A high-quality diet is typically comprised of regular consumption of fruits, vegetables, whole grains, lean sources of protein, and dairy products, and infrequent consumption of foods rich in sugar, salt, and fat that are low in nutritional density. On a shortterm basis, a high-quality diet in preschoolers is positively related to better cognitive development and a lower prevalence of childhood overweight and obesity [1]
[2]
[3][4][5] . Meanwhile, in the longer term, diet quality during preschool may act as a lifelong predictor for an individual's risk of having poor or good health during adolescence and beyond 1-3 . ...
... Meanwhile, in the longer term, diet quality during preschool may act as a lifelong predictor for an individual's risk of having poor or good health during adolescence and beyond 1-3 . In the era of economic achievement and the advancement of the health industrial revolution, it has not yet guaranteed a better diet quality and nutrition status among all preschool children in the country
2,
3 . must be studied because it is an indicator and predictor of their future wellbeing and health conditions in adulthood 4 . ...
FAMILY FOOD CHOICES MOTIVE AMONG MALAYSIAN PRESCHOOL CHILDREN’S PARENTS
It is important to determine the factors influencing the family, specifically the parent's food choice motives (FFCMs). These factors are perceived to relate to the nutritional status, eating habits of the children and, subsequently, their future well-being. This study aimed to determine the FFCMs factors (including health concerns, natural content, sensory appeal, convenience, weight control, price, mood, and familiarity) of the parents who had preschool children in Selangor, Malaysia. A cross-sectional study was conducted among seventy-six pairs of mothers and children aged 4 to 6 years in six selected preschools in the Klang Valley, Selangor. A set of self-administered questionnaires measuring demographic data, dietary records, and FFCMs of the parents were answered by the mother, and anthropometric measurements of the children were then taken. The mean FFCMs score found that "health" (mean 3.5 ± 0.53) was reported as the most important factor in parents' ’food choices than the "familiarity" factor (mean 2.78 ± 0.67). Compared to the ethnic groups, both Chinese and Indians mostly chose "natural content”, compared to Malay parents who chose "health" (3.55 ± 0.50) as an important factor to consider when choosing food. In conclusion, this study showed that by determining the most important factors influencing a family’s food choices, it is likely to improve the nutritional status and well-being of children and their family members. Thus, this study proposed the utilization of FFCMs as an instrument to design and develop food- and nutrition-related interventions for further studies.
... Reducing poverty and increasing access to services for those in need are crucial to improving childhood health and nutritional outcomes. Kanjilal, Mazumdar, Mukherjee and Rahman
[5]
found that stunting disproportionately affects children from poor socio-economic backgrounds across all Indian states, and that there is a negative correlation between Net State Domestic Product and stunting prevalence. Larrea and Kawachi, [6] investigated the effect of economic inequality on chronic child malnutrition while considering various household and individual determinants in Ecuador. ...
A Study on Income Inequality and Nutritional Status of Children in Rural Areas of Jammu and Kashmir: Evidence from Jammu District, India
Children nutritional status is a powerful indicator of nutrition security and well-being of individual and reflects the nutritional and poverty situation of household. Good nutritional status of children under five years of age is very crucial for the foundation of a healthy life. This study is a small attempt to highlight the extent of malnutrition in rural areas of Jammu district on the basis of households’ economic status. It empirically investigates the relationship between income inequality and nutritional status of children under age of five years of age (stunting) in the rural areas of Jammu district of Jammu and Kashmir. To determine the prevalence of undernutrition among different income groups of rural households, the study uses the data of a primary household survey. In order to measure the level of undernutrition (stunting), gender-specific anthropometric z-scores for height-for-age are calculated by using new child growth standards which are developed by the World Health Organisation (WHO). The study finds that children from households in the poorest quintile have significantly higher odds of stunting compared to those in the highest income quintile. The study revealed a negative association between income and the prevalence of stunting in the study area. It means the proportion of stunted children under five years of age decreases as the level of income increases among rural households. The study suggests that the government can help improve the nutritional status of children by taking important policy initiatives that addresses income inequality and poverty in rural areas.
... In spite of the implementation of Revamped Public Distribution System and Targeted Public Distribution System since the 1990s, and the enactment of the National Food Security Act, 2013, India is suffering from a serious and acute level of hunger and malnutrition. According to a report of the National Family Health Survey, approximately 38% of children under the age of 5 years are categorized within the range from moderate to severely stunted (based on height for age); overall, 46% of the children are categorized within the range from moderate to severely underweight (based on weight for age), and around 19% are categorized within the range from moderate to severely futile based on weight for height (Rajaram et al. 2007;
... Therefore, it is necessary to design region-specific public health policies (Yu et al., 2019) to find early intervention strategies and mitigate the human resource and economic burden of those regions and ultimately to India by investigating the nutritional status. Several studies are there in this regard in different regions (Swain et al., 2018; on different age groups
Agarwalla et al., 2015;Padma et al., 2016) but most of the previous studies on nutritional status from Meghalaya, North-east India and Garos of East Garo Hills are conducted on children (Rao et al., 2005;Chyne et al., 2017;Singh et al., 2019;Meitei, 2020) and a very few on women (Chyne et al., 2017;Nongrum et al., 2021) while, research related to the prevalence of malnutrition among the adults (men and women) of North-eastern part of India, particularly from the Garo tribes of Meghalaya are meagre. ...
| https://www.researchgate.net/publication/45628665_Nutritional_status_of_children_in_India_Household_socio-economic_condition_as_the_contextual_determinant |
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Englund, Axel Englund, Axel Engström, Andreas Enikő, Gyenge Eno, Brian Enstice, Wayne Eősze, L Eötvös, P Epstein, Dan Epstein, Marcia Jenneth Epting, Chris Érdi, T Erdmann, Hans Erickson, Kris Ericson-Roos, Catarina Erika, Nyerges Erika, Simon Erika, Fernbach Eriksen, Dorthe Eriksen, Jan Eriksson, Gunnar Eriksson, Jeanette Eriksson, Karin L. Eriksson, Karin. Eriksson, Josef Eriksson, Maria Eriksson, Magnus Eriksson, Åke Eriksson, Torbjörn Eriksson, Maria Erlmann, Veit Ernő, Kiss Erricker, Jane Erwin, Max Escuer-Salcedo, Sara Eshbach, Robert Whitehouse Espada, Martín Espeland, Magne I. Espiña-Campos, Yolanda Espínola, Francisco Espinosa, Santiago Esse, Melina Essex, David Esteve-Faubel, José María Esteve-Roldán, Eva Esteve-Roldán, Eva Estévez-Sola, Juan A. Eszter, Gombocz Ethniko kai kapodistriako panepisti̲mio Etter, Brian K. 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Faulkner, Simon Faulkner, Robert Faure, Michel Fauré, Gabriel Fauser, Annegret Fay, Brendan Fazakas, I Fazekas, G Fazekas, Gergely Fazekas, G Fearnley, James Featherstone, Sally Federico, Gabriel Fedoszov, J Fedrová, Stanislava Fein, Michael Fejérvári, Boldizsár Fejérvári, B Fejős, J Fekete, A Fekete, Károly Feldman, Zev. Feldman, Morton. Feldman, Morton Feldman, Heidi Carolyn Feldman, Evan Feldman-Barrett, Christine Jacqueline Feldstein, Ruth Fell, Mark Fell, Alex Fellani, Matin Felton, Dickie. Feneyrou, Laurent Fenlon, Ian Fenlon, Iain Fenton, Kathryn Fényes, G Ferenc, Verseghy Ferenc, Liszt Ferenc, Szénási Ferenc, Rátkai Ferenc, Apró Ferenczi, I Ferge, Béla Ferguson, Paul Ferić, Mihael Fernandes, Cristina Fernández, Gabriel Fernández-de-Latorre, R. Fernández-Manzano, Reynaldo Ferrada-Noli, Nicholas Ringskog Ferraguto, Mark Ferraiuolo, Augusto Ferrari, Brunhild Ferrari, Giordano. 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Hanna, Emma Hannah, Jonny Hanns-Werner, Heister Hansén, Stig Hansen, Mads Hansen, Adam. Hansen, Lene Halskov Hansen, Pil Hansen, Kai Arne Hara, Nobuo. Harada, Theresa Harada, Kaori Hardasmal, Sergio Hardi, R Harding, Charlie Harding, J. T. Harding, Phil Hardy, Martha Hargittai, Esther Hargreaves, David J. Hargreaves, Sam Harkins, Paul Harley, John Harmsen, Sophie Harnoncourt, Nikolaus. Harper, Nancy Lee Harper, Sally Harper, Ben Harper, Ellen Harper, Adam. Harper-Scott, J. P. E. Harpham, Geoffrey Galt Harrandt, Andrea Harrán, Don Harries, Judith Harrington, James Harris, Paul Harris, Craig Harris-Warrick, Rebecca Harrison, Peter T. Harrison, Danny Harrison, Sarah Harrison, Brady Harrison, Carol Harrison, Chris Harsent, David Harsløf, Olav Hart, Colin Hart, Chris Hart, Chaz Harte, Frank Hartenberger, Russell Hartl, Karla Hartley, John Hartmann, Astrid Pernille Hartmann, Annette Hartnoll, Paul Hartnoll, Phil Hartse, Joel Heng Hartt, Jared C. 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Iazzetta, Fernando Ibn Ḥayyān, Abū Marwān H Iddon, Martin Ideguchi, Akinori Ideland, Jens Igbi, Oghenemudiakevwe Iges, José Iges-Lebrancón, José Iglesias-Iglesias, Iván Iglesias-Martínez, Nieves Ignácz, Á Ignácz, Ádám Ihnat, Kati Ikushima, Mikiko Ilari, Beatriz Senoi Ilić, Ivana Ilona, Ferenczi Ilona, Kovács Immler, Christian Impett, Jonathan Impey, Angela Imre, Harangozó Imre, Romsics Imre, Olsvai Information Resources Management Association, Ingalls, Monique Marie Ingalls, Monique Marie. Ingemark, Camilla Asplund Ingham, Chris. Ingham, Chris Ingham, Michael Inglis, Ian Inglis, Brian Ingolfsson., Árni Heimir Ingólfsson, Árni Heimir Ingraham, Mary I. Ingram, Catherine Inomata, Tokiwa Inose, Chihiro Inoue, Takahiro Inōe, Sayuri. Institute of Measurement and Control. International Conference Music Theory and Analysis (9 ; 2011 ; Beograd) International Council for Traditional Music. Study Group on Music and Dance in Southeastern Europe. Symposium (6 ; 2018 ; Sinj) International Music Education Research Centre. International Musicological Society International Society for Music Education. Internationale Richard-Strauss-Gesellschaft Internationale Stiftung Mozarteum Salzburg. Iommi, Tony. Iott, Sheryl Iovene, Paola Ippolito, J. M. Irby, Samantha Ireland, Brian Irons, Yoon Irvine, Thomas Irwin, William Irwin, Colin. Irwin, Colin Isacoff, Stuart Isacsson, Jonas Isakoff, Katia Ishida, Yutaka Isnard, Vincent. Isserlis, S Isserlis, Steven István, Pávai István, Bátori László István, Németh István, Kilián István, Gróf István, Elmer István, Korody-Paku István, Kereszty István, Mustos István, Balázs István, Bogárdi Szabó István, Berczelly István, Gáti Istvandity, Lauren Isusi-Fagoaga, Rosa Ittzés, M Ittzés, Mihály Ittzés, M Ittzésné, K Iturrioz-Petralanda, Nekane Iván, Cs Ivarson, Karin Iverson, Jennifer Ivković, Želimir Ž. Izabella, Bartalis Jaccard, JL Jacke, Christoph Jacks, Will H. 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Jian, Miaoju Jiang, Ying = 蒋英 Jimenez, Javier Jiménez, José Luis Jin, Tielin = 金铁霖 JLS (Musical group), Jnr., HOwie Morrison Johann, Lurf Johansen, Geir Johansen, Guro Gravem Johansson, Karin Johansson, Anna Johansson, Ola Johansson, Carina Johler, J John, Elton John, Elton John, Corner John, Graham St. John, Emma John Ireland Charitable Trust. John Merrill Foundation, Johnson, Sherry. Johnson, Stephen Johnson, Mark Johnson, Christopher Johnson, Sherry Johnson, Joan Johnson, Jake Johnson, Carol Johnson, Bruce Johnson, David Johnson, Julian Johnson, Henry Mabley Johnson, Curtis D. Johnson, Alan Johnston, Tom Johnston, Jean Johnston, Roy Johnston, Ben Johnston, A. J. B. Jonasson, Camilla Jonášová, Milada Jones, John Jones, Richard Jones, Jacqueline Jones, Rickie Lee Jones, Joseph E. Jones, Tudur Huws Jones, Gerry Jones, Barry O. Jones, Peter Jones, Kenney Jones, Ellis Jones, Kimberly A.. Jones, Thomas C. Jones, Danny Jones, J. S. Jones, Dylan Jones, David Wyn Jones, Nicholas Jones, Tom Jones, Lesley-Ann Jones, Mark Jones, Lesley-Ann Jonsson, Göran Jonsson, Bengt R. Jorba, Miquel Jordan, W. D. Jordan, Randolph Jordansson, Leif Jorgensen, Ian Jorgensen, Hanna Rose Jornadas de Zarzuela (4ª. 2016. Cuenca) Jovanović, Jelena Jovanovic, Rob. Jovanović, J Joyce, Sandra Joynson, Vernon Joynson, Vernon József, Szécsi József, Krénusz József, Fülöp József, Kozák József, Gál József, Béres József, Terék József, Brauer-Benke Józsefné, Dombi Jóri, Anita Jóri, Anita Ju, Kelin = 巨克林 Jubin, Olaf Judd, Harry Judit, Rácz Judit, Bogár Judit, Pokoly Juhász, Z Juhász, E Juhász, Zoltán Julia, Jaklin Júlia, Torda Julia, Craig-McFeely Júlia, Demeter Julich-Warpakowski, Nina Julien, Pauline Julien, Olivier Julin, Don. Jullander, Sverker Jung, Eunji Jung-Kaiser, Ute Juranić, Zoran Jurecic, Boštjan Jurij, Snoj Juslin, Patrik N. Juslin, Patrik N. Juslin, Patrik N Justice, Deborah Justice, Jacob Jørgensen, Jørgen Wenndorf K., Marquis H. Ka'ai, Tania Kaastra, Linda T. Kabeláč, Miloslav Kabir, Ayesha Kaczmarczyk, Adrienne Kádár, AJ Kagerland, Peter Kahn, Ashley Kahr, Michael Kaijser, Lars Kaiser, Martin Maxmilian Kajanová, Yvetta Kajfeš, Davor Kakubari, Wataru Kaldewey, Helma Kalinak, Kathryn Marie Kalish, Gilbert Kallberg, Jeffrey Kallio, Alexis Anja Kallis, Vasilis Kalman, Julie Kalmár, A Kaltmeier, Olaf Kälvemark, Torsten Kamilla, Dévai Nagy Kamlah, Ruprecht. Kammerchor Stuttgart, Kamp, S Kanbe, Satoru. Kanda, Kunihiko Kane, John Kaneko, Naoki Kaneko, Jun Kanellopoulos, Panagiotis A. Kanellopoulos, Panagiotis A. Kanellopoulou, Jenny Kania, Andrew Kanneh-Mason, Kadiatu Kapilow, Robert Káplán, Szofia Kapp, Reinhard Kapralova Society, Kaprálová, Vítězslava Kapronyi, Teréz Karath, Kym Karczag, M Kardamēs, Kōstas Kardaras, Chrēstos D. Kardos, Leah Karjalainen, Toni-Matti Karl, Kügle Karlin, Jason G. Karlík, Filip Karlsen, Sidsel Karlsen, Sidsel. Karlsson, Ove Karlsson, Petter Karlsson, Katarina A.. Karlsson, Lars Karnes, Kevin Károly, Libisch Károly, Fekete Károly, Sziklavári Karousos, Charalampos Kárpáti, J Karpf, Juanita Kartawidjaja, Yakub E. Karwen, Bernd. Kaschub, Michele Kasinitz, Philip Kasser, Tim Kassler, Michael Kassler, Jamie Croy Kastine, Jeremy Kata, Rácz Katalin, Juhász Katalin, Marczell Katalin, Lázár Katalin, Paksa Katalin, Kim Katalin, Szvitacsné Marton Katalinić, Vjera Katayama, Takeshi. Kathy-Horváth, L Katona, Zoltán Katona, Kerry Katz, Pamela. Katz, Jared Katz, Mark Kauffman, Deborah Kaufman, Will Kaufman, Brian Kawasaki, Mizuho Kay, Maria. Kay, Sarah Kayaki, Tōru Kaye, Lenny Kayes, Gillyanne. Kärjä, Antti-Ville Kärki, Kimi Kealing, Bob Kearney, Mark. Kearns, Robin A. Kearns, Peter Kecskeméti, I Kecskés, A Keefe, Simon P. Keegan, Josephine Kehrer, Lauron J. Keijser, Roland Kelemen, É Kelhoffer, James A. Keller, Hans Kelley, Robin D. G. Kelly, Ursula Anne Marga Kelly, Lynne Kelly, John Ellis Kelly, Steven N. Kelly, Barbara L. 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Leković, Biljana Leloup, Jean-Yves Lemaire, Frans C Leman, Marc Lemay, Denyse Lempesē, Litsa Lencsés, L Lendvay, Domonkos Leneman, Helen Lenneberg, Hans Lennon, John Lenti, Vincent A. Lenz, Risto León-Ara, Agustín León-Rodríguez, Ángel-Luis Leonard, Maurice. Leonard, Anne Leonard, Kendra Preston Leong, Daphne Leopold, Silke Leppert, Richard D. Lerch-Kalavrytinou, Irmgard Lerena-Gutiérrez, Mario LeRoy, Dan Lesaffre, Micheline Lesner, Frej Vammen Lespinasse, Patricia G. Lester, Paul Lestidau, shane Letchford, Michael Letellier, Robert Ignatius. Letellier, Robert Ignatius Letham, Andy Lethem, Jonathan Levaux, Christophe Leve, James Levenson, Steven Levente, Váradi Levente, Király Leverton, Marc Levey, Marie Therese Levi, Erik. Levine, Victoria Lindsay LeVine, Mark Levinson, Jerrold Levitin, Daniel J. Levitz, Tamara Levy, Daniel Lewenhaupt, Carl-Gustaf Lewin, David Lewin-Lane, Stephanie Lewis, Eric Lewis, George Lewis, Tony Lewisohn, Mark. 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Waldingbrett, Ingrid Waligórska, Magdalena Walker, STan Walker, Norman Walker, Stan Walker, Alan Walker, Lucy Walker, Jason P. Walker, Ian Walker, Michael Walker, David Walker, James Walker, A Walkling, Andrew R. Wallace, John Wallace, Robin Wallén, Göran Wallis, John Wallmark, Zachary Wallrup, Erik. Wallrup, Erik Wallrup, Erik Walls, Peter. Walsh, Stephen Walsh, Michael J. K. Walter, Meinrad Walter, Meinrad Walter de Gruyter GmbH & Co. KG Walthaus, Asing Walton, Chris Walton, Andrew Walton, Benjamin Walton, Chris Wan, Shuangwu Wang, Li Wang, Jing Wang, Jing Wang, Klavier J. Wang, Guiping Wang, Helen Wang, Chenwei Wang, Ka Wang, Oliver Wang, Hui = 王辉 Wang, Jin = 王进 Wang, Liping = 王黎平 Wang, Lixin = 王丽新 Wang, Min = 王敏 Wang, Peiyu = 王培瑜 Wang, Yaohua = 王耀华 Wang, Yarui = 王娅蕊 Wang, Yimeng = 王艺萌 Wang, Zonglin = 王纵林 Wannamaker, Rob Ward, Philip. Ward, Miranda. Ward, Christopher Wardhaugh, Benjamin Ware, Evan Warner, Daniel Warner, Andrea Warner, Alan Warren, Andrew Warren, Jeff R. Warwick, Dionne. Warwick, Jacqueline C. Wash, Martha Washabaugh, William Washida, Kiyokazu Watanabe, Yawara. Watanabe, Tamotsu Waterman, Bryan Waterman, Christopher Alan Waters, Keith Waters, Robert Watkins, Huw Watkins, Jane Watkinson, David Watson, Jada E. Watson, Laura Watson, Jada Watson, Allan Watson, Philip Watt, Paul Way, Lyndon C. S. Webb, Michael D. Webb, Jimmy Webb, Sioned Webb, Martin Weber, Zdenka Weber, William Webster, Patrick Webster, Emma Webster, Peter Richard Weel, Liva Wehn, Jan Weid, Jean-Noël von der. Weidinger, Hans Ernst. Weinel, Jonathan Weinstein, Anna Weiss, Jernej Weissglas, Birgitta Östlund Weissman, Dick Weitzman, Simon Welander-Berggren, Elsebeth Welch, Graham Welin, Cissi Weliver, Phyllis Wellings, Ben Wellington, Tony Wellmann, N Wellmer, Albrecht Wells, Christi Jay Welsh, Louise Welsh Association of Male Choirs. Welsh Folk-Song Society. Weltman, Sandy Wendler, Merete Wennberg, S Wenner-Gren Foundation for Anthropological Research. Wente, Allison Rebecca Werger, Carola Werley, Matthew Michael Werner, Goebl Wernlid, Eva Wertheimer, Alfred Wertheimer, Melissa E. West, Christopher West, Chad Wester, Bertil Westerlund, Heidi Western, Tom Westhoff, Ben Westminster Media Forum, Westrup, Laurel Westvall, Maria Wetterqvist, Anna Wheaton, R. J. Whedon, Joss Wheeldon, Marianne Whidden, Lynn Whineup, Tony Whitall, Susan. White, Danny White, Harry. White, Danny White, Michael White, Vernon White, Paul. White, Bryan White, Paul White, Matthew White, Timothy White, Harry White, John Whitehead, Gillian Whiteley, Sheila Whiteley, Jon Whiteoak, John Whitfield, Sarah Whitfield, Sarah Whiting Society of Ringers, Whitmer, Mariana Whitney, Karl Whittaker, Jason Whittaker, Sheila Whittall, Arnold Whyton, Tony Wicke, Peter Wickström, David-Emil Widdess, Richard Wide, Steve Widmer, Gerhard Wieczorek, Sławomir Wiegand, Gottfried Wienbibliothek im Rathaus, Wiener Institut für Strauss-Forschung, Wiener Volksliedwerk Wiens, Kathleen Wiersema, Robert J. Wierzbicki, James Eugene Wiesenfeldt, Christiane Wiffen, Charles. Wiggins, Jackie. Wiggins, Phil Wikström, Per Wikström, Patrik Wilbourne, Emily Wilcher, Phillip Wilcox, Beverly Wild, Andrew Wild, David Anthony. Wilder, Alec Wilding, Philip Wildmann, Daniel Wilentz, Sean Wilfing, Alexander. Wilfing-Albrecht, Meike. Wilheim, A Wilkie, Katie Wilkins, Frances Wilky, Pete Will, Richard James Willard, Timothy D. Wille, Irmgard Willemetz, Jacqueline. Willert, Søren Williams, James Williams, Alastair Williams, David A. Williams, Grace Williams, Katherine Williams, Stuart Williams, Liz Williams, Joseph Williams, John Williams, Georgina Williams, Alex Williams, David A. Williams, Hermine Weigel Williams, James Gordon Williams, Quentin Williams, Jonathan. Williams, Jane Q. Williams, William Lewis Williams, Sarah F. Williams, Sean Williams, David Anson Williamson, Brian Williamson, Victoria Williamson, John Williamson, Nigel Willin, Melvyn J. Willingham, Lee Willis, Peter Willis, Victoria Willson, Rachel Beckles. Willsteed, John Wilsmore, Robert Wilson, Blake McDowell Wilson, Mary Wilson, Joe Wilson, Brian Wilson, Christopher R. Wilson, Scott Wilson, Jason Wilson, Brett Wilson, Charles Wilson, Jen Wilson, Nick Winans, BeBe Windhager, Ákos Windhager, K Winehouse, Mitch. Winfried, Pauleit Winkler, Heinz-Jürgen Winkler, Amanda Eubanks Winnett, Susan Winslow, Luke Winter, Tomáš Winters, Ben Winterson, Julia Wintle, Christopher Wintle, Christopher. Wipplinger, Jonathan O. Wise, Stuart Wiseman, Bob Wiseman-Trowse, Nathan Wistreich, Richard. Wistreich, Richard Withers, Deborah M. Wittkowski, Désirée Witulski, Christopher Witvliet, John D. Wladika, Michael Wode Psalter Project Team. Woitas, Monika Wolf, Richard K. Wolf, Norbert Christian Wolf, Stacy Ellen Wolfe, Paula Wolff, Christoph Wolff, Loup. Wolff, Christian Wolin, Ada Wolke Verlagsgesellschaft mbH Wolkowicz, Vera Woller, Megan Wollman, Elizabeth L. Wolman, Baron. Womack, Kenneth Wong, Samuel Shengmiao Wong, Casey Philip Wood, Alistair Wood, David. Wood, Jo Wood, Caroline Woodcock, Rob. Woodford, Paul Woodhead, Leslie Woodhouse, Susi Woods, Clyde Adrian Woods, Paul A. Woodward, Ian Woodward, Keren Woody, Robert H. Woolaver, Lance Wooldike, Mogens Wooley, David Freeman. Woolf, Ray Woolford, Julian Woollacott, Ron Woolley, Robin E. H. Woolley, Andrew Wottle, Martin Woznicki, Lisa M. Wöllner, Clemens. Wrangsjö, Björn Wright, Jon Wright, James K. Wright, Lesley Alison Wright, Michael Wright, David C. H. Wright, Ruth Wright, Samuel Wright, Ruth. Wright, Dan Wright, Adrian Wright, Owen Wright, Joshua K. Wright, Julie Lobalzo Wright, Mark Peter Wu, Jiayue Cecilia Wu, Dequn = 吴德群 Wu, Ye = 吴叶 Wurnell, Mats Wyatt, Robert Wylde, Zakk Wyndham-Jones, Guy. Wynne, Ben X, King of Castile Xepapadakou, Avra Xiang, Hengfang = 项衡方 Xiang, Xiaogang = 项筱刚 Xiang, Yang = 项阳 Xiao, Dongfa = 肖东发 Xiao, Mei = 萧梅 Xiao, Wenli = 肖文礼 Xie, Jiaxing = 谢嘉幸 Xie, Yongxiong = 谢永雄 Xin, Xuefeng = 辛雪峰 Xiong, Qi = 熊琦 Xiong, Xiaoyu = 熊小玉 Xu, Chengbei Xu, Delei = 徐德雷 Xu, Ximao = 徐希茅 Xue, Ming = 薛明 Yakupov, Alexander N. Yamada, Kōsaku. Yamada, Chieko Yamada, Takafumi Yamaguchi, Mutsumi Yamakawa, Shizuo Yamamoto, Hiroko Yamamoto, Hiroyuki Yamashita, Hiroaki Yang, Zoua Sylvia Yang, Dingwang = 杨丁旺 Yang, Heping = 杨和平 Yang, Sai = 杨赛 Yang, Xifan = 杨曦帆 Yao, Zhihui = 姚志辉 Yard, Ryan Yawson, Jude Yeaman, G. E. Yearsley, David Gaynor Yearsley, David Gaynor Yeo, Douglas Yewdall, Julian Leonard Yi, Yŏng-mi Yi, Shucheng = 易述程 Yip, Joyce Yoon, Sunmin Yoon, Jean Yordanova, Iskrena Yordanova, Iskrena. York St John University. Yorkshire Association of Change Ringers. Yorkston, James. Yoshida, Tamao Yoshida, Yukako. Yoshida, Minosuke Yoshihara, Mari Yoshikami, Miyuki Yoshizaki, Masaki. You, Jingbo = 尤静波 Young, John Bell Young, Miriama Young, La Monte Young, Rob Young, Toby Young Classical Artists Trust. Young Musician Hebrides (Organization) Ystad, Sølvi Yu, Jun Yu, Danhong = 余丹红 Yuan, Quanyou Yudkin, Jeremy Yue, Kaifeng = 乐开丰 Yun, Isang Yusta, Miguel Ángel Yuste-Martínez, Luis Yusuke, Nakahara Zackrisson, Lasse Zadig, Sverker. Zaeri, Mehrdad Zagorski-Thomas, Simon Zakić, Mirjana Zamora-Caro, Katerine Žanić, Ivo Zapke, Susana Zarate, Rebecca Zatkalik, Miloš Zauner, Michelle Zazulia, Emily Zdanowicz, Gina Zebec, Tvrtko Zeck, Melanie Zeller, Regine. Zembylas, Tasos Zepf, Markus Zeppetelli, John Zerbe, Michael J. Zervos, Giōrgos Zhang, Deyu = 章德瑜 Zhang, Wei = 张巍 Zhang, Xiaoxia = 张笑侠 Zhang, Xin = 张欣 Zhang, Yingfen = 张迎芬 Zhang, Yishan = 张翼善 Zhang, Zhongqiao = 张仲樵 Zhang, Zonghong = 张宗红 Zhao, Sitong = 赵思童 Zhao, Talimu = 赵塔里木 Zhao, Zhi'an = 赵志安 Zheng, Yan = 郑艳 Zhong, Enfu = 钟恩富 Zhou, Danny Zhou, Ji = 周吉 Zhou, Liang = 周亮 Zhu, Hengfu = 朱恒夫 Zhu, Jian'er = 朱践耳 Zhu, Lixing = 朱理惺 Zhu, Yujiang = 朱玉江 Zhuo, Sun Zi, Yin = 紫茵 Zicari, Massimo Ziegler, Robert Ziegler, Lulu Ziemer, Hansjakob Ziemska, Joanna Zilli, Anna Zimmerman, Lee Zimmermann, Walter Zohn, Steven David Zöldi, Gergely Zoltán, Császár Zoltán, Bicskei Zoltán, Molnár Zoltán, Szabó Zoltán, Tumpek Zoltán, Göllesz Zoltán, Kodály Zoltán, Gergely Zoltán, Csermák Zolten, Jerome Zombie, Rob. Zomparelli, Elena Zon, Bennett. Zon, Bennett Zondi, Nompumelelo Bernadette Zornica Hagyományőrző Egyesület Zouhar, Vít Zoumpoulakēs, Petros Zsófia, Borz Zsombor, Németh Zsuzsa, Kővágó Zsuzsa, Czagány Zsuzsa, Czagány Zsuzsanna, Erdélyi Zsuzsanna, Pintér Márta Zsuzsanna, Domokos Zsuzsanna, Réfi Zsuzsanna, Glavina Zsuzsanna, Szepesi Zsuzsanna, Bálint Zubillaga, Igor Contreras Zuckermann, Moshe. Zunigo, Xavier. Zurmühl, Sabine Žuvela, Sanja Kiš Zürcher Hochschule der Künste Østergaard, Per Јанковић-Бегуш, Јелена Маринковић, Соња 국남., 배 음악사연구회 川﨑, 瑞穂 Type any Book Miscellaneous Conference Proceedings Journal Website Web Article Audiovisual Thesis Conference Paper Report Journal Article Presentation Term any Year any 2023 2022 2021 2020 2019 2018 2017 2016 2015 2014 2013 2012 2011 2009 2001 Keyword any 7 (CaQQLa)201-0000282 (CaQQLa)201-0001542 (CaQQLa)201-0004568 (CaQQLa)201-0005777 (CaQQLa)201-0009248 (CaQQLa)201-0010484 (CaQQLa)201-0013983 (CaQQLa)201-0013986 (CaQQLa)201-0017854 (CaQQLa)201-0022164 (CaQQLa)201-0032589 (CaQQLa)201-0038053 (CaQQLa)201-0038355 (CaQQLa)201-0041435 (CaQQLa)201-0046052 (CaQQLa)201-0046054 (CaQQLa)201-0046163 (CaQQLa)201-0053875 (CaQQLa)201-0066316 (CaQQLa)201-0070033 (CaQQLa)201-0081252 (CaQQLa)201-0093787 (CaQQLa)201-0117737 (CaQQLa)201-0164320 (CaQQLa)201-0164324 (CaQQLa)201-0278656 (CaQQLa)201-0343563 (CaQQLa)201-0356887 (CaQQLa)201-0387198 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(OCoLC)fst02021107 (OCoLC)fst02021978 (OCoLC)fst02022009 (OCoLC)fst02023092 (OCoLC)fst02023366 (OCoLC)fst02024003 (OCoLC)fst02027038 (OCoLC)fst02029199 (OCoLC)fst02031393 (OCoLC)fst02032989 (OCoLC)fst02033725 (OCoLC)fst02033891 (OCoLC)fst02033893 (OCoLC)fst02033910 (OCoLC)fst02040679 (RERO)A021003248 (RERO)A021096923 (RERO)A022509224 (RERO)A024797456 (uri) http://id.loc.gov/authorities/subjects/sh2008108258 (uri) http://id.loc.gov/authorities/subjects/sh85088762 (uri) http://id.worldcat.org/fast/fst01033799 13th century 15e siècle 15e siècle. 15th century 15th century. 16. century 16e siècle 16e siècle. 16th century 16th century. 17e siècle 17e siècle-18e siècle 17e siècle. 17th century 17th century. 17the century 18. století. 18.-20. století. 18.century 1814-1918 18e siècle 18e siècle. 18th century 18th century. 18th-20th centuries. 19. century 19.-20. století. 1900-1945. 1901-1910 1911-1920 1914 May 16- Auckland Boys' Choir -- History. 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Avant-garde (Aesthetics) Avant-garde (Music) Avante-garde (Music) New Zealand Awards Ästhetik Background music; Sociology of music Badalić Bagpipe Bagpipe music Bagpipe music, Arranged. Bagpipe music. Bagpipe. Bagpipers Bagpipers. Balkan Peninsula Balkan Peninsula. Ballader Ballades Ballads Ballads, English Ballads, English. Ballads, Japanese. Ballads, Scots Ballads. Ballet Ballet dancers Ballet dancers in art Ballet dancing. Ballet. Ballets Ballets. Ballroom dancing Ballroom dancing. Ballrooms Baloković Band music Bandes dessinées. Bands (Music) Bands (Music) Ireland Banjo Banjo. Bankers Barbados Barbados. Barcelona Bards and bardism. Baritō. Barnes, Jimmy. Baroque Baroque music Baroque music (c 1600 to c 1750). Barroco Barroque Bars (Drinking establishments) Bartók Bartol Đurđević/Jurjević Bass guitar Bass guitarists Batterie (Instrument de musique) Batteurs (Instrumentistes) Battle of Szigetvár Bawdy songs beat music Beatles. Bedeutung. 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Diversity in the workforce Diversity in the workplace Divine office Divine office (Music) Do-it-yourself work Documentary films Dohnányi Domenico Scarlatti Domkyrkor Domnérus, Arne, 1924-2008 Don Juan (Legendary character) Don Quijote Doo-wop (Music) Double bass Double bassists Double bassists. Double Happys (musical group) Double-bassists Douglas Lilburn Dōwa. Dōyō-Nihon. Drama Drama. Dramatic music Dramatic music. Dramatisk och scenisk musik Dramatists, American Dramatists, English Dramatists, German Dramaturgie. Dramaturgy Dramaturgy. Droit d'auteur Droit d'auteur. Drottningar Musik – historia S{\aa}ngerskor – historia Kulturliv – historia Drug addicts Drug addicts. Drugs and popular music. Druids and druidism. Drum Drum and bugle corps. Drum circles Drum circles. drum language. Drum machine Drum machine. Drum set Drum set. Drum. Drummers Drummers (Musicians) dřevěné dechové nástroje. 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Electronica (Music) Elegiac poetry, English Elegiac poetry, English. Elektroakustisk musik Elektronisk musik Elektronmusikstudion Elementary school teaching. Elever Elgitarr – historia Gitarr – historia Ellington, Duke, 1899-1974-- influenser Elvis Presley Elvis Presley impersonators Elvis Presley impersonators. Embellishment (Vocal music) embne Emeralds Emeralds. Emigration and immigration Emigration and immigration. Emotions Emotions in art. Emotions in children. Emotions in music Emotions in music. Emotions in the performing arts Emotions in the performing arts. Empathy. Employees Empowerment Encyclopedias Encyclopedias. Encyclopédies. End of the world. Engeki-Nihon. Engeki-Roshia. Engelskspråkiga författare-- historia Engineering instruments Engineering instruments. England England, North East England, North East. England, Northern England. English English language English literature English literature. English New Zealand. 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Écosse. Écoute (Philosophie) Écrits de musiciens rock. Écrivaines noires américaines. Écrivains autrichiens Éditeurs audionumériques. Éditeurs de musique Édition Éducation holistique. Éducation humaniste. Éducation. Église catholique Église luthérienne Église luthérienne. Églises protestantes. Électronica (Musique) Électrophones États arabes États-Unis États-Unis (Sud) États-Unis. Éthiopie. Éthiopiens Étude et enseignement Étude et enseignement. Études de cas. Facsimiles. Facteurs d'orgues Facteurs liés à l'âge. Facture Facture. Faculty of Music in Belgrade Fair use (Copyright) Fairy tales Faith. Fame Families Families. Family relationships Fan magazines Fan magazines. Fandangos Fanfares (Orchestres) Fängelser Musik och samhälle Fans (Persons) Fantasy fiction Fantasy fiction. Fantasy films Fantasy games. Fanzines Farm life Farmers Fascism and culture Fascism and culture. Fascism and music Fascism and music. Fascisme et musique Fashion Fashion designers Fashion in art. fast Fathers and daughters Fathers and daughters. Fathers and sons Fathers and sons. Faust (Legendary character) Fågelsång. Feasts for the Blessed Virgin Mary. Federico García Lorca Feliks Petančić Femininity in music. Femininity in popular culture Femininity in popular culture. Feminism Feminism & Feminist Theory. Feminism and literature Feminism and literature. Feminism and music Feminism and music. Femmes dans l'industrie musicale. Femmes dans la musique. Femmes mécènes de la musique Femmes sauvages dans la littérature. Femmes violonistes Fender guitar Fender guitar. Fernsehproduzent. Festivals Festivals de musique Festivals. Féminisme et musique. Fiddle tunes Fiddle tunes. Fiddlers Fiddlers. Fiddling Field recordings Fife and drum corps Fife and drum corps music Fife and drum corps music. Fife and drum corps. Fifre et tambour, Musique de Filipino American youth Filipino Americans Film Film adaptations. Film catalogs. Film composers Film composers. Film music Film soundtracks Film soundtracks. Film theory & criticism,Film: styles & genres,Opera. Film, Musique de Filmmusik Filmmusik Animerad film Publiker Filmmusik, USA. Filmmusik. Filmska umjetnost filosofi Musik – sociala aspekter Finance, Personal. Fingering Fingering. Finland Finlandssvenskar Finn, Liam Finn, Neil Flageolet Flamenco Flamenco dancers; Biographies Flamenco dancers; Homosexuality; Gender studies Flamenco music Flamenco singers Flamenco; Ethnomusicology; Work songs Flight in art. Flöjt Musikframträdanden Florida Floride Flute Flute music Flute music. Flute players Flute players. Flûte à bec Flying Nun Records - History 20th century Flying Nun Records - History; Sound recording industry - New Zealand - History; Rock musicians - New Zealand; Music trade - New Zealand - history Flying Nun Records history Folk art Folk art. folk custom Folk dance folk dance in Hungary Folk dance music Folk dance music. folk dance research Folk dancing Folk dancing, Irish Folk dancing, Irish. Folk dancing, Scottish. Folk dancing. folk epics folk instrument Folk music folk music collection Folk music festivals Folk music festivals. folk music history Folk music Hungarian folk music research Folk music Southern Slavs in Hungary Folk music symphosyum Folk music, Irish. Folk music. folk musical instruments Folk musicians Folk musicians. folk musicof South Slavs in Hungary Folk poetry, Arabic Folk poetry, Bakhtiari. Folk poetry, Greek (Modern) Folk poetry, Italian Folk poetry, Italian. Folk singers Folk singers. Folk songs Folk songs, Aboriginal Australian Folk songs, Arabic Folk songs, Bakhtiari. Folk songs, Chinese Folk songs, Czech Folk songs, Czech. Folk songs, English Folk songs, English. Folk songs, Indonesian Folk songs, Indonesian. Folk songs, Japanese Folk songs, Japanese. Folk songs, Kannada. Folk songs, Korean Folk songs, Ladino Folk songs, Ladino. Folk songs, Manx. Folk songs, Nenets Folk songs, Old French Folk songs, Scots Folk songs, Scots. Folk songs, Scottish Gaelic Folk songs, Welsh. Folk songs. Folk-rock music Folk-rock music. folkdance Folkliga koraler Folklore Folklore. Folklorists Folkmusik Folkmusik Spelmän Folkmusik-- historia Folkmusik-- sociala aspekter folksongs folktradition Folkvisor-- forskning Fonds d'archives. Food in music Food in music. Football (Soccer Association Football) Forecasting. Foreign influences. FOREIGN LANGUAGE STUDY / Multi-Language Phrasebooks. Förenta staterna Forests and forestry. formal analysis Formation. Former Yugoslav republics Former Yugoslav republics. Foster children Fourrures Fragmente. fragments. France France, Southern France, Southern. France. Francoism Francoist dictatorship Franjo Ksaver Kuhač = Franz Ksaver Koch Frankrike Franz Joseph (František) Gläser Franz Xaver Kleinheinz Französisch Frederick May Free jazz Free jazz. French influences. French language French poetry French poetry. French. Friendship Friendship. From Scratch(Musical Group) Fue. Functor theory. Fundamentalism Fundamentalism. Funds Preservation Funeral consultants Funeral music Funeral music. Funeral service Funk (Music) Funk musicians Fur trade Fur trade. Fur traders Futurism (Literary movement) Futurism (Music) Fuzzy logic. Gagaku Gagaku. gaita Gakufu-Rekishi. ganga Gangsta rap (Music) Gangsters Gangsters. Garamut García family Gardberg, Tom, 1941- Gasshō. Gay culture Gay culture. Gay men Gay men. Gay musicians Gay musicians. Gay musicologists Gehörslära Geijutsu-Indoneshia. Geishas. Geistliche Musik. Gender Gender identity in music Gender identity in music. Gender nonconformity Gender nonconformity. Gender studies Gender studies, gender groups. Gender studies: women. Gender studies; Pedagogy Gender-nonconforming people Gender-nonconforming people. General & world history. General certificate of education examination (Great Britain) General. Generation Y. Generation Z Genetic algorithms. Genres & Styles genusaspekter. George Frideric Handel Georgia Gerald Dawe German influences. German language German literature German literature. German poetry German speaking countries German. Germany Germany (East) Germany (West) Germany. Gesang Geschlechterrolle Gestes dans la musique. Gestion numérique des droits Gestion. Gesture in music. Géorgie (État) Gēmu sofuto. Ghana Ghana. Ghāna Ghāna. Gidayūbushi. gipsy musicians Girei. Girl groups (Musical groups) Gitarrer-- historia Giuseppe Verdi Glam metal (Music) Glam rock (Music) - New Zealand - History and criticism Glam rock music Glam rock music - History and criticism - New Zealand Glam rock music. Glam rock musicians Glasgow glazbeni nakladnici - Hrvatska - 20/21. st. Glee clubs Glee clubs. Globalisierung Globalization Globalization. Gluck-Piccinni controversy. gnd God (Christianity) Godfrey Gong Gospel Gospel music Gospel music. Gospel musicians Gospel musicians. Gospel singers Gospel singers. Govori Grading and marking (Students) Grainger, Percy, 1882-1961 Grammar. Grande-Bretagne Grande-Bretagne. Graphic novels. Greager, Richard, Great Britain Great Britain. Greece Greece. Greek Americans Greek influences. Greek literature Greek music Greek poetry, Modern Greek poetry, Modern. Greeks gregorian Gregorian chants Gregorian chants. Group identity Group identity in the performing arts Group identity. Groupes rock Groupes vocaux Groupies Growth Growth. Grunge (Musique) Grunge music Grunge music. gtt Guadeloupe Guadeloupe. Guerre mondiale, 1939-1945 Guidebooks. Guides touristiques (Personnes) Guinbri Guinea. Guitar Guitar makers Guitar makers. Guitar music Guitar music (Blues) Guitar music (Rock) Guitar music. Guitar teachers Guitar. Guitare Guitare, Musique de. Guitaristes Guitarists Guitarists. Gullahs Gunnar, Eriksson, 1936- Guralnick, Peter Gymnasieskolan Gypsy musicians Hagström Hainichi mondai. Haiyū. Håkanson, Knut, 1887-1929 Hallucinations and illusions. Handbooks, manuals, etc. Hardcore (Music) Hardcore (Musique) Hardcore musicians Harmonica Harmonica music. Harmonica players Harmonica players. Harmonicistes Harmonie (musique) Harmonie. Harmony Harmony of the spheres. Harmony. Harp Harp music Harpistes Harpists Harpists. Harpsichord Harpsichord. Harpsichordists Hassaniyya dialect Hate groups. Hawaii. Hayes, Roland, 1887-1977. hälsoaspekter. HEALTH & FITNESS / Healthy Living HEALTH & FITNESS / Work-Related Health Health and hygiene. Health aspects Health aspects. Health facilities Hearing Hearing Aids Hearing aids. Hearing impaired. Hearing. Heavy Metal Heavy metal (Music) Heavy metal (Musique) Heian period, 794-1185 Heike monogatari. Heritage tourism Heroines in opera. Higashinihon daishinsai. higher education. Hindu goddesses Hindu goddesses. Hindu music Hindu music. Hinduism Hindustani music Hindustani music. hip-hop Hip-hop dance Hip-hop in art. Hip-hop. Hiphop (musik) Samhällskritik Feminism Antirasism Musiksociologi Musik – sociala aspekter Hispanic Americans Histoire Histoire et critique Histoire et critique. Histoire. Histoires, intrigues, etc. Historia historia. Historically informed performance (Music) Historiographie Historiography historiography Croatia Historiography. History History & Criticism. HISTORY / Africa / South / Republic of South Africa. HISTORY / African American HISTORY / Asia / General HISTORY / Australia & New Zealand. HISTORY / Europe / France. HISTORY / Europe / Great Britain / General. HISTORY / Europe / Spain & Portugal HISTORY / Europe / Western HISTORY / General. HISTORY / Jewish HISTORY / Latin America / South America. HISTORY / Modern / General HISTORY / Oceania. HISTORY / Social History HISTORY / Social History. HISTORY / United States / 19th Century. HISTORY / United States / 20th Century. HISTORY / United States / General HISTORY / United States / State & Local / South (AL, AR, FL, GA, KY, LA, MS, NC, SC, TN, VA, WV) History and criticism History and criticism. History and criticsm. History and critisicm. History in literature. History in opera. History in popular culture History in popular culture. History of music history of opera History. Högstadiet Holistic education. Holistic Health Holocaust survivors Holocaust, Jewish (1939-1945) Homages Homeland in music. Homes and haunts. Homes. homoit Homosexualité et musique. Homosexuality Homosexuality and music. Homosexuality and popular music Homosexuality and popular music. Homosexuality. Hongrie Hongrie. Honnête homme Horn (Musical instrument) Horror films Horror films. Horses Hospital care. Hospital patients Hospitalers Hospitalers. Hospitals Hospitals. House music House music. Hōgaku-Rekishi. Hōgaku. hrvatska poezija - 20/21. st. - antologije http://id.loc.gov/authorities/subjects/sh2008106048 http://id.loc.gov/authorities/subjects/sh85069833 http://id.worldcat.org/fast/871620 http://id.worldcat.org/fast/871649 http://id.worldcat.org/fast/982165 http://id.worldcat.org/fast/982175 http://id.worldcat.org/fast/982185 https://id.kb.se/term/sao/Kultur https://id.kb.se/term/sao/Kulturhistoria https://id.kb.se/term/sao/Musik https://id.kb.se/term/sao/Musikhistoria https://id.kb.se/term/sao/Nazism%20och%20musik https://id.kb.se/term/sao/Orgel https://id.kb.se/term/sao/Propaganda--historia https://id.kb.se/term/sao/Reggae https://scigraph.springernature.com/ontologies/product-market-codes/I13022 https://scigraph.springernature.com/ontologies/product-market-codes/I14002 https://scigraph.springernature.com/ontologies/product-market-codes/I18067 https://scigraph.springernature.com/ontologies/product-market-codes/I21000 https://scigraph.springernature.com/ontologies/product-market-codes/I22005 https://scigraph.springernature.com/ontologies/product-market-codes/I24032 Huang zhong (Musical instrument) hudba hudebniny hudební kritici hudební kritika hudební sbírky hudební skladatelé hudební skladatelky hudební vzdělávání hudební život hudebníci Hugo Badalić Human body Human body in music. Human body. Human evolution. Human geography. Human rights Human rights workers Human rights workers. Human rights. Human sacrifice in opera. Human-animal relationships Human-computer interaction. Humaniora och konst. Humanism Humanism in music Humanism in music. Humanism. Humanisme dans la musique. Humanists Humanities and the Arts. Humor in music. Humor. Hungarian hungarian composers Hungarian folk music Hungarian Folk songs Hungarian folksongs Hungarian music life hungarian musiciians hungarian musicology hungarian pop music Hungarian song Hungary Hungary. Hurdy-gurdy. Husband and wife. Hydroponics Hymnes Hymnes. Hymns Hymns, English Hymns, English. Hymns, Pitjantjatjara. Hymns, Welsh. Hymns. IAML Ian McGillis Iberian Peninsula Iceland Iconography Identification Identification (Religion) Identification. Identité sexuelle dans la musique. Identity (Psychology) in adolescence Identity (Psychology) in adolescence. Identity politics. Identity. Ideology Igor Illinois Illumination of books and manuscripts. Illustrators Imagery (Psychology) Imagination. Imitation (Littérature) Imitation in literature. Immigrants Immigrants. Impresarios Impression Impression. Imprésarios Improvisation (Music) Improvisation (Musique) Improvisation in art Ina Boyle Incas Incas. Inclusive education Inde Inde (Sud) Inde. Indexes. India India, South. India. Indian influences. Indian women activists Indian women singers Indians of North America Indie culture. Indie pop music Indigenous musicians Indigenous peoples Individual Composer & Musician. Individual composers & musicians, specific bands & groups. Indonesia Indonesia. Industrial music Industrial music. Industrie Industrie de la musique et du son. Industrie. Influence (Literary, artistic, etc.) Influence africaine. Influence américaine. Influence. Information literacy Information resources Informatique. Ingénieurs du son Inlärning Inscriptions. Installations sonores (Art) Institute of Registered Music Teachers of New Zealand Institute of Registered Music Teachers of New Zealand history Institutional care institutional history Instruction & Study Instruction and study Instruction and study. Instrumental music Instrumental music. instrumental works Instrumentation and orchestration Instrumentation and orchestration. Instrumentation et orchestration Instruments à clavier Instruments à cordes Instruments de musique Instruments de musique électroniques Intangible property Intelectual property Intellectual life Intellectual life. Intellectual property Intelligence artificielle. Intercultural communication Intercultural communication. Interfaith worship. Interior decoration Interior decoration. Intermediality. International relations. International trade. Internationalism Internationalism. Interpersonal conflict Interpersonal conflict. Interpretation Interpretation (Phrasing, dynamics, etc.) Interpretation and construction Interpretation and construction. Interracial adoption Intertextuality. Interviews Interviews. Inuit Invective in music. Iolo Morganwg iPad (Computer) iPhone (Smartphone) iPod (Digital music player) Iran Iraq Ireland Ireland. Irish Irish American soldiers Irish American soldiers. Irish American. Irish Americans Irlandais Irlandais. Irlande Irlande. Irony in music. Irving, Dorothy, 1927- Islam Islam Semiotik Hiphop Islam. Islamic arts Islamic countries Islamic countries. Islamic influences. Islamic music Islamic music. Islands. Isle of Man Isle of Man. Israel Israel. Israël. Italian language Italian Opera Italian poetry Italian poetry. Italie Italie. Italy Italy. Itálie Ivan Kukuljević Sakcinski Ivan pl. Zajc Ivan Zajc Jacinto Guerrero Jacinto Valledor Jack Jam bands Jam bands. Jamaica Jamaica. Jamaicans Jamaïque Jamaïque. James Goodman James Wilson Japan Japan. Japanese drama Japanese drama. Japanese influences. Japanese literature Japanese poetry Japon. Japonism Järnbruk-- historia Jay-Z. Jazz Jazz au cinéma. Jazz clubs Jazz dance. Jazz dans la littérature. Jazz festivals jazz history in Hungary Jazz history in Spain Jazz in Croatia Jazz in literature. Jazz in motion pictures. Jazz musicians Jazz Musicians - New Zealand jazz musicians - New Zealand - anecdotes; Clark Jazz musicians. Jazz New Zealand jazz record history Jazz singers Jazz singers. jazz theory Jazz vocals Jazz-- historia Jazz. Jazzklubbar Jazzmusiker Jazzmusiker Basister Tonsättare Jefferies, Graeme Jelena Zrinska=Ilona Zrínyi Jenny Jeux vidéo, Musique de Jew's harp Jewelry Jewelry theft Jewelry theft. Jewelry. Jewish composers Jewish composers. Jewish jazz musicians Jewish music Jewish musicians Jewish musicians. Jewish studies. Jewish theater Jews Jews in the performing arts Jews, German Jews, German. Jews. jlabsh/4 Joan Denise Moriarty Job stress. Joe Dolan John Barry John Beckett John Buckley John Egan Jojk Folkmusikuppteckningar Josep Mestres-Quadreny Journalism (Film & Media) Journalism. Journalists Jōruri Jōruri-Rekishi. Jōruri. Judaism Judaïsme. Judenverfolgung Jugaku. Jugoton Juifs Jukebox musicals Jukebox musicals. Jungian psychology. Jusqu'à 1500 Jusqu'à 1901 Jusqu'à 1931 Justice sociale Justice sociale. Juvenile Juvenile literature. K-pop Kabuki Kabuki music Kabuki music. Kabuki plays Kabuki plays. Kabuki-Rekishi. Kabuki. Kageki. Kagura Kagura. Kaitito waiata reo Korero taumata Kaiwaiata. Kamengeki. Kansas Karl Goldmark Kashu. Kayō. Keiongaku. Kentucky Kenya Kenya Nairobi Kenya. Kerry Kevin (trumpeter) - anecdotes - Keyboard instrument music Keyboard instrument music. Keyboard instruments Keyboard instruments. Keyboard music Keyboard players Keyboards (Music) Keybord music Kildare Kinematografija Kirchenmusik Kirtana (Hinduism) Klangfärg Improvisation (musik) Preparerat piano Klangkunst. Klapa singing Klarinettister Klassische Musik Klassische Musik. Klassisk musik Konserter (framträdanden) Pianister Scenframträdanden Nervsystemet Prestations{\aa}ngest Klassisk musik-- historia Klassisk musik-- mottagande Klezmer music Klezmer music. Knowableness. Knowledge, Theory of (Religion) Knowledge, Theory of. Kokusai bunka kōryū. Komponist Komponistin Komposition (musik) Komposition Musikframträdanden Kompositörer Konserter (framträdanden) Rock Könsmaktsordning Könsroller Konst Konst. Konstfilosofi Konstmusik Konstnärlig forskning Konstnärligt skapande Konzert Kördirigering Korea Korea (South) Korea. Korean Americans Korean language materials. Körer-- historia Körledning Körsång-- forskning Körsångng Körs{\aa}ng – sociala aspekter Körs{\aa}ng – psykologiska aspekter Kōrero taumata. Kŏmunʼgo music Kŏmunʼgo music. Kranjčević Vladimir Kropp och själ Kultur. Kulturell identitet Migration Musik – sociala aspekter Kulturförderung Kulturhistoria. kulturni kapital ; vrijednosti ; mladi ; kulturna potrošnja ; glazbeni ukus ; televizijske preferencije ; Jadranska Hrvatska (cultural capital ; values ; youth ; cultural consumption ; taste in music ; television preferences ; Adriatic Croatia) Kulturpolitik Kulturpolitik Offentliga sektorn Musikliv Kurt Weil Kuyō. Künste Kvarner Kvinnliga musiker Kvinnliga tonsättare Kvinnliga tonsättare Tonsättare Kvinnoförtryck Musik – historia – genusaspekter Kvinnor i musiken – historia Kvinnlighet – historia Kärlekss{\aa}nger – historia – genusaspekter Kwansei Gakuin Glee Club Kyōdo geinō. kyōdogeinō Kyōgen Kyōgen plays Kyōgen plays. Kyōgen-Rekishi. Kyōgen. Kyrkomusik Kyrkomusik – historia Kyrkomusiker. Kyrkos{\aa}ng Kyrkomusik Labor productivity Labour law Laienspiel Landscape architecture. Landscapes in music. Language Language acquisition. Language and languages Language and languages. LANGUAGE ARTS & DISCIPLINES LANGUAGE ARTS & DISCIPLINES / Alphabets & Writing Systems. LANGUAGE ARTS & DISCIPLINES / Composition & Creative Writing LANGUAGE ARTS & DISCIPLINES / Grammar & Punctuation. LANGUAGE ARTS & DISCIPLINES / Linguistics / General. LANGUAGE ARTS & DISCIPLINES / Linguistics / Syntax. LANGUAGE ARTS & DISCIPLINES / Publishing LANGUAGE ARTS & DISCIPLINES / Readers. LANGUAGE ARTS & DISCIPLINES / Spelling. Language. Large type books. Larsson Gothe, Mats, 1965- Last years of a person's life. Latin America Latin America. Latin drama (Comedy) Law LAW / Jurisprudence Law and legislation Law and legislation. Lawyers lcgft Leadership. Learning Learning disabled children Legacies Legal status, laws, etc. Leisure Lent Lenten music Leonard Cohen Lesbian musicians Lesbian musicians. Letters Letters. Lésions et blessures. LGBT LGBT Studies. LGBT. LGBTQ+ musicians. Liberalism Libraries and minorities Libraries and minorities. Libraries. Librarinaship Library Library fund raising Library fund raising. Library outreach programs libreto Librettists Libretto Libretto Librettologi Libretto. Librettos Librettos. Licenses lidové hudební nástroje Lied Lieu (Philosophie) Life cycle, Human Lifestyle, sport and leisure / Sports and outdoor recreation / Active outdoor pursuits / Walking, hiking, trekking likovi kao alegorija nacije Lindblad, Adolf Fredrik, 1801-1878 Lindh, Björn J:son, 1944-2013 Lisa; Pearl (musical group Listening Listening (Philosophy) Listening. Literacy LITERARY COLLECTIONS / Essays. Literary collections. LITERARY CRITICISM LITERARY CRITICISM / American / Asian American & Pacific Islander. LITERARY CRITICISM / American / General LITERARY CRITICISM / American / General. LITERARY CRITICISM / European / English, Irish, Scottish, Welsh LITERARY CRITICISM / European / English, Irish, Scottish, Welsh. LITERARY CRITICISM / Feminist. LITERARY CRITICISM / General. LITERARY CRITICISM / Modern / General. LITERARY CRITICISM / Poetry Literary sources Literary themes, motives. Literatur Literature Literature on music. Literature, Modern Literature, Modern. Littérature Liturgical drama; Religious festivities; Oral tradition liturgical songs Liturgics. Liturgie. Liturgies liturgy. Livres d'heures Livret (Musique) Ljudeffekter Ljudevit Gaj Ljudkonst Loggers Logging. Logiciels. Logistik Streamad media Programvara Musikbranschen – tekniska aspekter Loisir loneliness Longitudinal studies. Lorde Loss (Psychology) Louisiana Louisiane Love poetry, Scottish. Love songs Ludwig van Luis de Pablo Lullabies. Lumber trade. Lur (Iranian people) Lute Lutheran Church Lutheran Church. Luthiers Lyric writing (Popular music) Lyricists Lyricists. Lyrics. Maček Ivo Machine learning. Madrid Madrigal. Madrigaler. Madrigalkomödie. Madrigals Madrigals. Maintenance and repair Maintenance and repair. Makerspaces Maksimilijan Vrhovac Malawi Malawi. Malaysia Male actors. Male musicians Male singers Male singers. Malec Ivo Malerei Malta Malta. Män Man-woman relationships. Management. Mandolin Mandolinists Mandolinists. Manners and customs Manners and customs. Manuel de Falla manufacture of musical instruments. Manuscripts Manuscripts, German Manuscripts, German. Manuscripts, Latin (Medieval and modern) Manuscripts. Manuscrits latins médiévaux et modernes Maori (New Zealand people) Maori (New Zealand people), Maori in the performing arts Maori; Maori (New Zealand people) - music; wood instruments - New Zealand; Birds - New Zealand - songs and music Marcus, Greil Markedness (Linguistics) Marketing Marketing. Marque (Linguistique) Marriage. Marshall Islands Marshall Islands. Marshallais Marshallese Martin P. anecdotes Martin, Hans, 1934- Masculinité dans la musique. Masculinity Masculinity in music. Maskanda Maskanda. Mass Mass (Music) Mass media Mass media and music Mass media and music. Mass media; Broadcasting Massachusetts Masses Mastering (Sound recordings) Materialität. materiality. Materials and instruments Materials and instruments. Materials. Mathematics MATHEMATICS / Applied MATHEMATICS / General Mathematics. Mathematik Mathématiques Mathématiques. Matsuri-Miyagiken. Matsuri-Nihon. Matsuri-Tōhoku chihō. Matsuri-Tōkyōto chiyodaku. McIntyre, Donald, 1934 McPherson, Suzanne Meaning (Philosophy) Means of communication. Mechanical aids. Mechanical musical instruments Media Studies. mediaeval music. MEDICAL MEDICAL / Alternative Medicine medicine Medicine and art. Medicine. Medieval influences. Medieval music Medieval. Medievalism in opera. Medievalism. Mediterranean Region. Melancholy in music. Melbourne Melbourne (Vic.) Melodi Svenska skillingtryck – historia Svenska skillingtryck – sociala aspekter – historia Svenska skillingtryck – politiska aspekter – historia Melodic analysis. Melodrama. memoir. memoires Memorials Memorials. Memory Memory in motion pictures. Memory in old age. Memory. Men's choirs Mennonite Church Canada. Mensch Mensural notation. Mental disorders Mentoring. Messe (Musique) Messes Messiah Mesure et rythme Mesure et rythme. Metaphor in musical criticism. Metaphysics. Metaphysique. Methodology Methodology. Methods Methods (Blues) Methods (Rock) Methods. Metronome. Mexican American cooking. Mexican Americans Mexican-American Border Region Mexican-American Border Region. Mexicans Mexico Mexico. Mexique Mezzo-sopranos Mécénat Médias et musique. Médias numériques Mémoire Mémoire collective Méthodes statistiques. Méthodologie Michael W. Balfe Michigan Microphone Microphone. Microtones. Middle Age Middle age. Middle Age; Carmina Burana Middle Ages Middle Ages, 600-1500 Middle Ages, 600-1500. Middle Ages. Middle East Middle East. Middle West Middle West. MIDI (Standard) MIDI controllers. migrations Miguel de Cervantes Miguel Fisac Miklós Zrinyi Mil neuf cent soixante-huit. Militärmusiker Military music Military occupation Military occupation. Military participation Military spouses Mills and mill-work Mind and body. Mindfulness (Psychology) Minimal music Minimal music. Minorités dans les arts du spectacle. Minorities Minorities in the performing arts. Minstrel music Minstrel show Minwa. Minzoku ongaku. Miscellanea. Miscellanées. Misogyny in music. Mississippi Mississippi River Valley mixed choir Mixed reality. Mod culture (Subculture) Modality (Linguistics) Modan dansu-Rekishi. Models (Persons) Modern Age - Spain Modern dance Modern dance music Modern dance music. Modern dance. Modern history to 20th century: c 1700 to c 1900. Modernism (Art) Modernism (Literature) Modernism (Music) Modulation (Music) Modulation (Musique) Moguchai͡a kuchka (Group of composers) Monarchy Monastic and religious life Monasticism and religious orders Mongolia Mongolia. Mongolie Mongolie. Mongols Monism. Monisme. monography Monologues with music (Chorus with orchestra) Monsters. Moog synthesizer. Moral and ethical aspects. Morale pratique. Mormons Mörne, Arvid, 1876-1946. Sjömansvisa Morocco Morocco. Morrison, Howard Motets Motets. Motette Motherhood and the arts. Mothers Mothers. Motion detectors Motion picture actors and actresses Motion picture actors and actresses. Motion picture music Motion picture music. Motion picture plays Motion picture plays. Motion picture producers and directors Motion picture theater managers Motion pictures Motion pictures and music Motion pictures and music. Motion pictures and opera. Motion pictures and the war. Motion pictures and transnationalism. Motion pictures in psychotherapy. Motion pictures, Hindi Motion pictures. Motiv Motocyclisme Motorcycling Mouvements des droits de l'homme Movement education. Movement, Aesthetics of. Mozambique Mozambique. Mozarabic chants Mozarabic rite (Catholic Church) Mozart Mridanga MUISC / Genres & Styles / Rock. Multi-sided platform businesses Multiagent systems. Multicultural education. Multiculturalism Multiculturalism. Munich Biennale For New Music Theatre. Munster Murai Jurica MUS020000. Museology & heritage studies. Museu de la Música de Barcelona museum history Museum Studies. Museum techniques. Museums Museums of Instruments Music Music & Sound Studies. Music - Church music - Hymns, Choruses and Carols. music - private collctions- New Zealand Music - private collections - Australia Music -- New Zealand -- Dunedin -- History and criticism. MUSIC / Business Aspects MUSIC / Discography & Buyer's Guides. MUSIC / Essays. MUSIC / Ethnic MUSIC / Ethnomusicology MUSIC / Ethnomusicology. MUSIC / General MUSIC / General. MUSIC / Genres & Styles / Ballet MUSIC / Genres & Styles / Blues MUSIC / Genres & Styles / Classical MUSIC / Genres & Styles / Classical. MUSIC / Genres & Styles / Dance. MUSIC / Genres & Styles / Folk & Traditional MUSIC / Genres & Styles / Folk & Traditional. MUSIC / Genres & Styles / General MUSIC / Genres & Styles / Heavy Metal. MUSIC / Genres & Styles / Jazz MUSIC / Genres & Styles / Jazz. MUSIC / Genres & Styles / Latin. MUSIC / Genres & Styles / Opera MUSIC / Genres & Styles / Opera. MUSIC / Genres & Styles / Pop Vocal MUSIC / Genres & Styles / Pop Vocal. MUSIC / Genres & Styles / Punk MUSIC / Genres & Styles / Punk. MUSIC / Genres & Styles / Rap & Hip Hop MUSIC / Genres & Styles / Rap & Hip Hop. MUSIC / Genres & Styles / Reggae MUSIC / Genres & Styles / Rock MUSIC / Genres & Styles / Rock. MUSIC / Genres & Styles / Soul & R 'n B. MUSIC / History & Criticism MUSIC / History & Criticism. MUSIC / History & Criticism. MUSIC / History ; Criticism. MUSIC / Individual Composer & Musician MUSIC / Individual Composer & Musician. MUSIC / Instruction & Study / Appreciation MUSIC / Instruction & Study / Composition MUSIC / Instruction & Study / General MUSIC / Instruction & Study / General. MUSIC / Instruction & Study / Songwriting MUSIC / Instruction & Study / Songwriting. MUSIC / Instruction & Study / Theory MUSIC / Instruction & Study / Theory. MUSIC / Instruction & Study / Voice MUSIC / Instruction & Study / Voice. Music / Italy / 16th century / History. MUSIC / Lyrics MUSIC / Lyrics. MUSIC / Musical Instruments / Guitar. MUSIC / Musical Instruments / Piano & Keyboard MUSIC / Musical Instruments / Piano & Keyboard. MUSIC / Musical Instruments / Strings MUSIC / Musical Instruments / Strings. MUSIC / Philosophy & Social Aspects. MUSIC / Printed Music / Percussion MUSIC / Printed Music / Percussion. MUSIC / Printed Music / Vocal MUSIC / Printed Music / Vocal. MUSIC / Recording & Reproduction MUSIC / Recording & Reproduction. MUSIC / Reference MUSIC / Reference. MUSIC / Religious / Christian MUSIC / Religious / General MUSIC / Religious / Jewish music academy music aesthetics music amateurism Music and anthropology. Music and antisemitism Music and antisemitism. Music and architecture. Music and aristocracy Music and children Music and children. Music and crime. Music and Culture (Music) Music and dance Music and dance. Music and diplomacy Music and diplomacy. Music and geography Music and geography. Music and globalization Music and globalization. Music and history Music and history. Music and identity politics. Music and intergenerational communication. Music and language Music and language. Music and literature Music and literature. Music and magic Music and magic. Music and Media (Music) Music and medicine Music and mythology Music and older people. music and painting Music and philosophy Music and philosophy. Music and politics music and potry Music and race Music and race. Music and rhetoric. Music and science Music and science. Music and sports. Music and state Music and state. Music and technology Music and technology. Music and text Music and the conflict. Music and the Internet Music and the Internet. Music and the war. Music and tourism Music and tourism. Music and transnationalism Music and transnationalism. Music and war Music and war. Music and youth Music and youth. Music appreciation Music appreciation. Music archaeology Music archaeology. music archive Music as recreation. music association Music Association of Ireland Music audiences. Music avantgarde Music Biographies (Music) Music by African American composers Music by African American composers. Music by black composers Music by women composers Music by women composers. Music chapells Music collections Music criticism Music critics Music critics New Zealand biography Music critics. music dictionary Music Documentation Music Drama Music Education Music education; Pedagogy music esthetic Music fans Music fans. Music festivals Music festivals. Music for people with mental disabilities. Music for people with visual disabilities. Music for the developmentally disabled. Music for the hearing impaired. Music history Music history and criticism music history in Hungary Music History; Occult sciences; Secret societies Music in advertising Music in advertising. Music in art Music in art. Music in Christian education Music in churches Music in churches. Music in Dubrovnik Music in education Music in education. Music in historic house museums. Music in intercultural communication Music in intercultural communication. Music in literature. Music in prisons Music in prisons. Music in synagogues Music in the Bible Music in the Bible. Music in the home Music in the home. Music in the theater Music in the theater. Music in universities and colleges Music in universities and colleges. Music instruction and study Music Instruments Music journalists Music journalists. Music libraires Music librarians Music librarians. Music librarianship Music librarianship. Music libraries Music libraries. music life Music life history music life in Hungary Music Linguistics Music Management. Music manuscripts Music memorizing. music migrations Music museums Music museums. Music New Zealand Auckland history and criticism music New Zealand Invercargill history and criticism Music patronage Music patronage. music pedagogy Music performance Music printing Music printing. Music publicity Music publicity. Music publishers Music publishers. Music publishing Music publishing. Music recording & reproduction. Music reviews & criticism. Music rooms and equipment music school Music stores Music students Music study and teaching New Zealand Christchurch history Music teachers Music teachers New Zealand biography Music teachers. Music teaching Music television Music thanatology. Music theater Music theater. Music Theatre New Zealand Auckland History Music theorists Music theory Music theory. Music therapists Music therapy Music therapy for children Music therapy for children. Music therapy for families Music therapy for older people. Music therapy for teenagers. Music therapy New Zealand Case studies; Music therapy; New Zealand poetry 21st century Music therapy. Music trade Music trade New Zealand Music Trade New Zealand 20th Century Music trade. Music videos Music videos. Music › Genres & Styles › Pop Vocal Music, Greek and Roman Music, Greek and Roman. Music, Influence of Music, Influence of. Music, Slovenian Music--20th century--Analysis Music--21st century--Analysis music--instruction and study--New Zealand; Educational change--New Zealand; Education Music--Latin America Music-halls Music-halls (Variety theaters, cabarets, etc.) Music-halls (Variety-theaters, cabarets, etc.) music-halls New Zealand 20th Century Music-halls. Music. Music: Genres & Styles / Classical. Music: History & Criticism. Music: Individual Composer & Musician. Music: styles & genres. Musica ficta. Musical ability in children Musical ability. Musical accompaniment Musical accompaniment. Musical aesthetics Musical analysis Musical analysis. Musical applications Musical applications. Musical bow Musical canon Musical canon. Musical chapells Musical creation Musical criticism Musical criticism. Musical dictation. Musical education Musical Encoding Musical films Musical films. Musical form Musical genres Musical groups Musical groups. Musical heritage management Musical heritage; Oral tradition; Ethnousicology musical instrument Musical instrument collections Musical instrument makers Musical instruments Musical instruments & instrumental ensembles. Musical instruments collections Musical instruments, Ancient Musical instruments. Musical instruments; Archeological sources; Islamic art; Al-Andalus Musical intervals and scales Musical intervals and scales. Musical inventions and patents. Musical landmarks Musical landmarks. Musical Libraries musical life Musical manuscripts Musical memory Musical meter and rhythm Musical meter and rhythm. musical migrations Musical New Zealand Auckland history Musical notation Musical notation. musical papers Musical perception Musical perception. musical performance Musical pitch Musical practice Musical scores, lyrics & libretti Musical settings Musical settings. Musical sources Musical structure musical tales Musical teaching Musical temperament Musical temperament. Musical theater Musical theater producers and directors Musical theater. Musical theatre New Zealand Auckland history Musical thought Musicalproduktion Musicals Musicals New Zealand Auckland History Musicals. Musician angels Musicians Musicians -- New Zealand -- Biography. Musicians -- New Zealand -- Portraits. Musicians -- New Zealand -- Tauranga -- History. Musicians as artists. Musicians as authors. Musicians Career Musicians Musicians in art Musicians in art. 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Musicothérapie. musictheory Musictherapy; Medicine Musik Musik i massmedia Musikinspelningar – historia Musik och samhälle – historia Musik Musikhistoria Musik och dans Musik och samhälle Invandrare Musiksociologi Folkmusik – sociala aspekter Musik och samhälle Musikframträdanden Koreografi Genus (socialt kön) Gester – sociala aspekter Gester – genusaspekter Musik och samhälle-- historia Musik-- historia Musik-- idéhistoriska aspekter Musik-- sociala aspekter Musik-- teori, filosofi Musik. Musik/Mittelalter. Musikalische Analyse Musikalische Semiotik. Musikalität Musikalitet Musikalitet Sinnen och förnimmelser Musikanschauung Musikdruck Musiker Musiker Ungdomar Datorspel Digitalisering Musikundervisning Musiker-- genusaspekter Musiker-- historia Musikethnologie Musiketnologi Musikfestivaler Musikfilosofi Instrumentalmusik Musikforskare Museimän Folkhögskolelärare Musikgeschichte. 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. Mozart's Portrait On A French Box Of Sweets : Remember Me /
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Schneider, Magnus Tessing , and Ruth Tatlow
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Mozart's La Clemenza Di Tito : A Reappraisal
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Mozarts »Idomeneo«
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Norton-Hale, Robin. , Wolfgang Amadeus Mozart , and Lorenzo Da Ponte
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. London: Oberon Books, 2011.
Vourch, Marianne , and Elléa Bird
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. 1. udgavest ed. [Odense]. Denmark: mellemgaard, 2021.
Brügge, Joachim
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Brophy, Brigid
. Mozart The Dramatist : The Value Of His Operas To Him, To His Age And To Us /
, 2013.
Freestone, Brian D
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, 2013.
Keefe, Simon P
. Mozart In Context
. United Kingdom: Cambridge, United Kingdom ; New York, NY, USA : Cambridge University Press, 2019.
Lajos, Főkövi
. Mozart És Haydn A Szabadkőmívességben
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Pastor-Comín, Juan-José , and Paulino Capdepón-Verdú
. Mozart En España : Estudios Y Recepción Musical /
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Resonemus Pariter : Műhelytanulmányok A Középkori Zenetörténethez
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Selby, Richard , Bethany Porter , and Benedict Please
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poulakis, Nikos
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Lempesē, Litsa , and Petros Zoumpoulakēs
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Mousikē Empneusmenē Apo Tēn Archaia Hellada Kai Tē Logotechnia : Hellēnes Kai Xenoi Synthetes /
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Stevenson, Mick
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Slobin, Mark
. Motor City Music : A Detroiter Looks Back /
. United States: New York, NY : Oxford University Press, 2019.
Julich-Warpakowski, Nina
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Cocker, Jarvis
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Senfl, Ludwig , Scott Lee Edwards , Stefan Gasch ,
Sonja Tröster , Ludwig Senfl , Ludwig Senfl ,
Ludwig Senfl , et al.
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draft-chen-bgp-avoid-transition-00
Avoid BGP Best Path Transition from One External to Another (Internet-Draft, 2003)
Network Working Group Enke Chen
Internet Draft Redback Networks
Expiration Date: December 2003 Srihari R. Sangli
Procket Networks
Avoid BGP Best Path Transition from One External to Another
draft-chen-bgp-avoid-transition-00.txt
1 . Status of this Memo
This document is an Internet-Draft and is in full conformance with
all provisions of
Section 10 of RFC2026
.
Internet-Drafts are working documents of the Internet Engineering
Task Force (IETF), its areas, and its working groups. Note that
other groups may also distribute working documents as Internet-
Drafts.
Internet-Drafts are draft documents valid for a maximum of six months
and may be updated, replaced, or obsoleted by other documents at any
time. It is inappropriate to use Internet-Drafts as reference
material or to cite them other than as ``work in progress.''
The list of current Internet-Drafts can be accessed at
http://www.ietf.org/ietf/1id-abstracts.txt
The list of Internet-Draft Shadow Directories can be accessed at
http://www.ietf.org/shadow.html
.
2 . Abstract
In this document we propose an algorithm that would help improve the
overall network stability by avoiding BGP best path transition from
one external to another (under certain conditions).
Chen & Sangli [Page 1]
Internet Draft draft-chen-bgp-avoid-transition-00.txt June 2003 3 . Introduction The last two steps of BGP route selection [ 1 ] involve comparing the
BGP identifiers and the peering addresses. The BGP identifier,
(treated either as an IP address, or just an integer [ 2 ]) for a BGP
speaker is allocated by the AS to which the speaker belongs. As a
result, for a local BGP speaker, the BGP identifier of a route
received from an external peer is just an random number. When paths
under consideration are from external peers, the result from the last
two steps of the route selection is therefore "random" as far as the
local speaker is concerned.
It is based on this observation that we propose an algorithm that
would help improve the overall network stability by avoiding BGP best
path transition from one external to another (under certain
conditions). 4 . The Algorithm Consider the case in which the existing best path is from an external
peer, and another external path is then selected as the new best path
by the route selection algorithm described in [ 1 ]. When neither path
is eliminated by the route selection algorithm prior to the step of
BGP identifier comparison, we propose that the existing best path be
kept as the best path (thus avoiding the best path transition).
This algorithm is not applicable when either path is from a BGP
Confederation peer.
In addition, the algorithm should not be applied when both paths are
from peers with identical BGP identifier (i.e., there exist parallel
BGP sessions between two routers). As the peering addresses for the
parallel sessions are typically allocated by one AS (possibly with
route selection considerations), the algorithm (if applied) could
impact the existing routing setup. Furthermore, by not applying the
algorithm, the allocation of peering addresses would remain as a
simple and effective tool in influencing route selection when
parallel BGP sessions exist. Chen & Sangli [Page 2]
Internet Draft draft-chen-bgp-avoid-transition-00.txt June 2003 5 . The Benefits The algorithm helps improve the overall network stability in the
following aspects. 5.1 . Favor a Stable Path The algorithm helps select a stable external path by avoiding the
best path transition. 5.2 . Reduce Route Oscillation The algorithm helps reduce the level of BGP dynamics. As a result, it
can be used as a simple and efficient tool to eliminate certain
permanent ibgp route oscillation [ 3 ].
Consider the example in Fig. 1 where
o R1, R2, R3 and R4 belong to one AS
o R1 is a route reflector with R3 as its client.
o R2 is a route reflector with R4 as its client.
o External paths (a), (b) and (c) are as described in Fig. 2.
+----+ 10 +----+
| R1 |--------------| R2 |
+----+ +----+
| |
| |
| 5 | 20
| |
| |
+----+ +----+
| R3 | | R4 |
+----+ +----+
/ \ |
/ \ |
(a) (b) (c)
Figure 1
Path AS MED Identifier
a 1 0 2
b 2 20 1
c 2 10 5 Chen & Sangli [Page 3]
Internet Draft draft-chen-bgp-avoid-transition-00.txt June 2003 Figure 2
With the proposed algorithm R3 would not switch the best path from
(a) to (b) even after R2 withdraws (c), and that is enough to stop
the permanent route oscillation. 6 . Security Considerations This extension does not introduce any security issues. 7 . Acknowledgments The idea presented was inspired by a route oscillation case observed
on the BBN/Genuity backbone around 1998/1999 while both authors were
at Cisco Systems. The algorithm was also implemented at that time.
The authors would like to thank Yakov Rekhter for his comment on the
initial idea. 8 . References [ 1 ] Y. Rekhter, T. Li, S. Hares, "A Border Gateway Protocol 4
(BGP-4)", draft-ietf-idr-bgp4-20.txt , 03/03
[ 2 ] E. Chen and J. Yuan, "AS-wide Unique BGP Identifier for BGP-4",
< draft-ietf-idr-bgp-identifier-02.txt >, April 2003.
[ 3 ] D. McPherson, V, Gill, D. Walton, and A. Retana, "Border Gateway
Protocol (BGP) Persistent Route Oscillation Condition", RFC 3345 ,
August 2002. 9 . Author Information Enke Chen
Redback Networks, Inc.
350 Holger Way
San Jose, CA 95134
e-mail: [email protected]
Srihari R. Sangli
Procket Networks, Inc.
1100 Cadillac Court
Milpitas, CA 95035
e-mail: [email protected] Chen & Sangli [Page 4]
Internet Draft draft-chen-bgp-avoid-transition-00.txt June 2003
Chen & Sangli [Page 5]
draft-chen-bgp-avoid-transition-00 Internet-Draft
Info
Contents
Prefs
Document Document type This is an older version of an Internet-Draft whose latest revision state is "Expired". Expired & archived Select version 00 01 Compare versions draft-chen-bgp-avoid-transition-01 draft-chen-bgp-avoid-transition-00 draft-chen-bgp-avoid-transition-00 draft-chen-bgp-avoid-transition-01 draft-chen-bgp-avoid-transition-00 draft-chen-bgp-avoid-transition-00 Side-by-side Inline Author RFC stream (None) Other formats txt pdf bibtex Report a datatracker bug
| https://datatracker.ietf.org/doc/html/draft-chen-bgp-avoid-transition-00.txt |
Gavin Bishop
Waikato,
Ngāti Mahuta,
Ngāti Awa
Ngāti Pūkeko
1946
-
Biography
Primary Sources
Gavin Bishop was born in Invercargill and educated at Kingston Primary School at Lake Wakatipu, Clifton Primary School, Invercargill, and Southland Technical College. He studied at the School of Fine Arts in Christchurch from 1964-68 graduating with Dip. F.A. (Hons) and in 1968 he attended Christchurch Teachers’ College and obtained a Teaching Diploma. Bishop taught Art at Linwood High School in Christchurch for twenty years and subsequently was Head of the Art Department at Christ’s College until 1998 when he became a full-time writer/illustrator of children’s books. He has won many awards for his books including the Russell Clark Medal for Illustration (1982), New Zealand Picturebook of the Year (1982, 1994 and 2000), and the Grand Prix of the Noma Concours, Japan, (1984). He was awarded NZ Children’s Book of the Year in 2000 and 2003. In 2000 he was presented with the Spectrum Print Award for the Best Use of Illustration in a New Zealand Book and was awarded the New Zealand Book Council Margaret Mahy medal for Services to Children’s literature – New Zealand’s highest honour for children’s literature. He was awarded a Christchurch Writers’ Walkway Bronze Plaque in 2002 and won the NZ Children’s Non-fiction Book of the Year in 2003. His children’s books are published internationally and articles about his work have appeared in the Library Association Journal, Times Education Supplement (London) and various other Australian, American and British publications. He was included in the 1990 edition of International Authors and Writers Who’s Who published by Burkes Peerage of London. In 1994 he designed 12 covers for a pre-school magazine for Chinese children published by the Shanghai Children and Juvenile Publishing House. In 1994 and 1995 he was a member of the Children’s Literature Grants committee of the NZ Arts Council. Bishop was author of a module on “Writing and Illustrating for Children” for the National Diploma of Children’s Literature at the Department of Extension Studies, College of Education, Christchurch. In 1996 he was guest lecturer at the Art Centre School of Design in Pasadena, California, and tutored “Drawing” and “Children’s Picturebook Design” for the spring semester at the Rhode Island School of Design. In 1997 he was awarded a QE II Arts Council Children’s Writers’ Project Grant to complete an historical picture book. Also in that year he gave lectures and ran a workshop on Children’s Picture Book Illustration and Design in Jakarta, and for the Asian Cultural Centre for UNESCO in Tokyo. From 1999-2001 he taught Image and Text at the Art & Design College of Aotearoa NZ.
Bishop is a member of the New Zealand Society of Authors (PEN New Zealand Inc.) and the New Zealand Illustrators’ Guild. He participated in the Words On Wheels Tour of Marlborough and Nelson in February 2000 with Elizabeth Knox, Vincent O’Sullivan, Catherine Chidgey, Briar Grace Smith and Lydia Wevers. In May of that year, Bishop was guest speaker at the Children’s Book Council of Australia Conference in Canberra, and later in 2000 presented two papers at the 18th World Congress of Reading in Auckland. In March 2001 he led the Words on Wheels Tour of Northland. In 2002 he was appointed to the Christchurch Books and Beyond Festival Trust and was also judge for the Noma Concours Children’s Picture book Art Competition in Tokyo. In 2003 he was Writer-in-Residence at the University of Canterbury and received a Smash Palace Art and Science Collaboration Grant with the HIT Lab, Canterbury University. Bishop was a Jury Member for the Noma Concours competition for international Picture Book Illustrators, UNESCO, Tokyo, Japan. In 2004 he had a major exhibition of art from The House that Jack Built (Scholastic, 1999) at the Dowse Gallery, Lower Hutt, which toured to Rotorua, Blenheim, Palmerston North, Nelson and Gisborne. Also in 2004 he had an exhibition of art from Weaving Earth and Sky at the Salamander Gallery in Christchurch. In 2005 he represented New Zealand at the 20th Biennale of Illustration held in Bratislava. Hinepau Capital E Production toured North Island in 2005 and had an Australian season in October 2006. In 2006 he an exhibition of original art at the Salamander Gallery in Christchurch.
"Bishop supplied illustration to Joy Cowley’s 2004 children’s book The Little Tractor (2004), and to Jean Prior’s The Waka, published by Scholastic in 2005. The latter of which was selected as a joint finalist in the Picture Book Category of the New Zealand Post Book Awards for Children and Young Adults. Between these projects, Bishop wrote and illustrated Taming The Sun: Four Mâori Myths (Random House, 2004), wherein he retells four essential Maori myths: Maui and the sun, Kahu and the taniwha, Maui and the big fish, and Rona and the moon. Taming The Sun: Four Mâori Myths was a finalist in the picture book category at the 2005 New Zealand Post Book Awards for Children & Young Adults, as well as for the Russell Clark Award at the 2005 LIANZA Children's Book Awards. Its sequel, Counting the Stars: Four Maori Myths, was published in 2009.
Kiwi Moon (2006) was published by Random House Publishing and won the The Russell Clark Award, a national distinction rewarding the finest pictures or illustrations for a children’s book. 'Kiwi Moon has all the appeal and promise of a future folktale classic', said the judging panel. 'It is an outstanding example of how text and illustrations can be interwoven to produce a marvellous whole.' Kiwi Moon traces the story of a little white kiwi that looks to the similarly-coloured moon as his mother-figure, with Bishop locating the kiwi in a changing Maori world where intertribal warfare, Pakeha interference, and the extinction of wildlife feature.
Bishop again lent his artistic hand in 2007 to illustrate Joy Cowley’s Snake & Lizard (Gecko Press, 2007), which the following year was awarded Best in Junior Fiction and Book of the Year at the New Zealand Post Book Awards for Children and Young Adults.
Venturing into the realm of early autobiography, Bishop wrote and illustrated Piano Rock in 2008 to immortalize his childhood memories from the railway town of Kingston. Piano Rock won the 2009 PANZ Book Design Award in the children's category.
The Storylines Gavin Bishop Award was established in 2009. It aims to encourage the publication of new and exciting high-quality picture books from New Zealand illustrators. It also recognises the contribution Gavin Bishop has made to the writing and illustrating of children’s picture books and gives an emerging talent the opportunity to benefit from his expertise. Fourteen of Bishop's works have been listed as Storylines Notable Books, including four in 2010: Tom Thumb (2002), The Three Billy Goats Gruff (2004), Taming the Sun: Four Maori Myths (2005), Kiwi Moon (2006), The Waka (2006), Te Waka (2006), Riding the Waves: Four Maori Myths (2007), Snake & Lizard (2008), Rats! (2008), Piano Rock: A 1950s Childhood (2009), There Was a Crooked Man (2010), Cowshed Christmas (2010), Friends: Snake & Lizard (2010), and Counting the Stars: Four Maori Myths (2010).
More recently, Bishop has continued his collaboration with Joy Cowley by illustrating her 2009 book Cowshed Christmas, a finalist in the picture book category of the 2010 New Zealand Post Book Awards for Children and Young Adults. Friends: Snake & Lizard, also written by Joy Cowley and illustrated by Gavin Bishop, was the Children's Choice Junior Fiction Category Winner.
A new edition of The House that Jack Built - and the first Te Reo Maori version - was published by Gecko Press in 2012 as Koinei te Whare na Haki i Hanga. Also published in 2012 was Mister Whistler, written by Margaret Mahy and illustrated by Gavin Bishop, which was awarded Best Picture Book at the 2013 New Zealand Post Children’s Book Awards. Also in 2013, Bishop received the Arts Foundation Mallinson Rendel Illustrator's Award.
In 2013, Bishop joined the New Zealand Book Council board.
Bishop’s latest written and illustrated work is Teddy One-Eye (2014). Within the book, Bishop continues the autobiographical trend that he previously established in Piano Rock (2008), and - via the central character of Teddy One-Eye - leads the reader through the incidences and joys of his childhood.
Bishop’s latest artistic offerings are to be found alongside Joy Cowley’s text in The Road to Ratenburg, where Cowley and Bishop imaginatively present the exploits of a group of rats who journey to find the blissful Ratenburg. The Road to Ratenburg is scheduled for release in April 2016."
Biographical sources
Correspondence with Gavin Bishop, 1992, 19 Aug and 15 Nov 1997, 12 July 1998, 14 March 2004, 2 February 2006 and 6 March 2008.
Arts Times Winter 1990: 18.
Bishop’s website is: www.gavinbishop.com
http://www.bookcouncil.org.nz/Writers/Profiles/Bishop,%20gavin 28 September 2016
A story of how a cucumber seedling bought at a “bring and buy” sale transformed the life of grumpy Mrs Delilah McGinty. Bishop won the New Zealand Library Association’s Russell Clark Medal for illustration of Mrs McGinty and the Bizarre Plant in 1982, and the book was a finalist in the New Zealand Children’s Picture Book of the Year in 1981. It was named by the NZ Listener as one of the ten “Most Significant New Zealand Children’s books”.
Bidibidi. Auckland, N.Z.: Oxford UP, 1982. Rpt. in a paperback edition. Auckland, N.Z.: Ashton Scholastic, 1991. Rpt as Bidibidi. [Māori version] Nā Gavin Bishop. Nā Apirana Mahuika i whakamāori. Auckland, N.Z. [N.Z.]: Scholastic, 2001. Written and illustrated by Gavin Bishop.
The adventures of a sheep called Bidibidi who set off to find the land of the rainbow. This book was a finalist for the New Zealand Picture Book of the Year in 1982 and prizewinner in the Asian section of the 1982 Noma Concours Award for children’s book illustration.
Mr Fox. Auckland, N.Z.: Oxford UP, 1982. Rpt. as Ta Pokiha [Māori edition] Trans. Katarina Mataira. Auckland, N.Z.: Oxford UP, 2001. Retold and illustrated by Gavin Bishop.
Bishop writes a retelling of the children’s story of the acquisitive Mr Fox who is finally outwitted by the little golden woman. This picture book was awarded the New Zealand Picture Book of the Year in 1983, was Grand Prix winner of Noma Concours, Japan, in 1984, and has been exhibited at Bratislava Biennale and the Bologna Book Fair. It was named by the NZ Listener as one of the ten “Great New Zealand Children’s books.”
Chicken Licken. Auckland, N.Z.: Oxford UP, 1984. Rpt. as P˚p˚ paopao. Kua kōrerohia anō, kua waituhia hoki e Gavin Bishop. Nā Kāterina Mataira i whakamāori. Auckland, N.Z.: Scholastic, 2001.
Retold and illustrated by Gavin Bishop.
The adventures of Chicken Licken who, when an acorn fell on its head one morning, set off to tell the queen that the sky was falling. This book was selected for exhibition at the Premi Catalonia D’ll-lustracio in Barcelona in 1984.
The Horror of Hickory Bay. Auckland, N.Z.: Oxford UP, 1984.
A fantasy about a great hungry monster at Hickory Bay who is finally destroyed by the sound of India Brown’s violin, Uncle Athol’s harmonica and Smudge’s barking. This book was selected for exhibition for the Bratislava Biennale 1985 and exhibited at Premi Catalonia D’ll-lustracio in Barcelona in 1986.
The Hungry Fox. Boston: Houghton Mifflin, 1985.
A commissioned reader for American publisher Houghton Mifflin.
Mother Hubbard. Auckland, N.Z.: Oxford UP, 1986.
This picture book is a retelling of the children’s nursery rhyme.
A Apple Pie. Auckland, N.Z.: Oxford UP, 1987.
A children’s alphabet book. A Chinese edition of A Apple Pie was published by the Beijing Children and Juvenile Publishing House in March 1995.
The Three Little Pigs. New York: Scholastic, 1989. Rpt. as Ngā Poaka e Toru. Kua kōrerohia anō kua whakaiorohia hoki e Gavin Bishop; nā Kāterina Mataira i whakamāori [Māori trans.]. Auckland, N.Z.: Scholastic, 2001.
Retold and illustrated by Gavin Bishop.
A retelling of the children’s story Three Little Pigs.
Katarina. Auckland, N.Z.: Black Cat, Random Century New Zealand Ltd (An imprint of the Random Century Group), 1990.
Bishop draws this story from the experiences of his great-aunt Katarina who left her whanau in the Waikato in 1861 and settled in Murihiku with her Scottish husband William McKay. Bishop portrays Katarina’s loneliness and homesickness for her Waikato whanau amidst the climate of the land wars and the gold rush.
Hinepau. Auckland, N.Z.: Ashton Scholastic, 1993. Rpt. 1994.
The story of Hinepau who although exiled from her tribe ultimately returns to save them from the wrath of Maungariri. Editorial notes state that “Hinepau carried [Bishop’s] mother’s name, an old family name which goes back hundreds of years, she is Ngåti Pukeko (Ngåti Awa) from near Whakatane, on the east coast of the North Island of New Zealand.” Hinepau won the New Zealand Picture Book of the Year in the 1994 Aim Book Awards.
Spider. [Hong Kong]: Wendy Pye, 1995.
There is a Planet. [Hong Kong]: Wendy Pye, 1995.
Illustrations by Andrew Trimmer.
An early reader. Bishop writes “this is a telescopic story which starts with, ‘There is a Planet...’ and finishes with, ‘And on that dog there is a flea, hee, hee, hee, hee, hee, hee.’”
I Like to Find Things. [Hong Kong]: Wendy Pye, 1995.
Graded reader. Illustrations by Neil Vesey.
An early reader in which “a small boy collects things like snails, frogs and so on and keeps them all in his bedroom.”
The Cracker Jack. [Hong Kong]: Wendy Pye, 1995.
Illustrations by Jill Allpress.
In this emergent reader the text “tells you how to do a dance called the Cracker Jack.”
Maui and the Sun. New York: North South Books, 1996.
A trade picture book. Bishop writes that in this story "Maui and his brothers capture and slow the sun to make the days longer." This book was a finalist in the NZ Post Children’s Book Awards.
Good Luck Elephant. [Hong Kong]: Wendy Pye, 1996.
Text and illustrations by Gavin Bishop. An early reader in which "an elephant goes for a walk down a scary road at night. He is not afraid because he has all his lucky charms with him, but the moon comes out from behind a cloud and casts a big shadow ‘monster’ on the road in front of him."
Cabbage Caterpillar. [Hong Kong]: Wendy Pye, 1996.
Illustrations by Jim Storey.
An early reader about a cabbage caterpillar. The caterpillar “moves from a cabbage to a cauliflower and then to some broccoli before running out of places to go as the farmer cuts vegetables for his lunch. The caterpillar escapes once and for all by turning into a cabbage butterfly and flying off to a new cabbage garden.”
Little Rabbit and the Sea. New York: North South Books, 1997. Words and pictures by Gavin Bishop.
Little Rabbit dreams of seeing the sea. A seagull gives him a shell to help him.
Jump Into Bed. Auckland, N.Z.: Shortland, 1997.
Illustrations by Craig Brown. An emergent reader in which "a young bear does not want to go to bed because there are lots of other things that he would rather do."
The Secret Lives of Mr and Mrs Smith. [Hong Kong]: Wendy Pye, 1997.
Illustrations by Korky Paul.
In this reader for older children “Mr and Mrs Smith lead secret lives as undercover agents and neither of them know about each other.”
Maui and the Goddess of Fire. Auckland, N.Z.: Scholastic NZ Ltd, 1998. Retold by Gavin Bishop. Illustrated by Gavin Bishop.
Bishop writes that in this book “Maui visits his grandmother to get some fire for his village but does not show enough respect for her mana.”
It Makes Me Smile. [Hong Kong}: Wendy Pye, 1998.
Illustrations by Emanuela Carletti.
Graded reader. Illustrations by Astrid Matijasevic.
The Wolf in Sheep’s Clothing. Auckland, N.Z.: Shortland, 1999.
Six Aesop fables.
The Lucky Grub. [Hong Kong]: Wendy Pye, 1999.
Illustrations by Jim Storey.
Stay Awake, Bear! New York: Orchard, 2000.
Text and illustrations by Gavin Bishop. Was shortlisted and was a CLFNZ Notable Book.
The House that Jack Built. Auckland, N.Z.: Scholastic NZ, 2000.
Won the Book of the Year and was a CLFNZ Notable Book in 2000.
Tom Thumb: The True History of Sir Thomas Thumb. Auckland, N.Z.: Random House, 2001. Paperback ed. 2002
Picture book produced for Random House NZ Ltd
The Three Billy Goats Gruff. Auckland, N.Z.: Scholastic NZ. 2003.
Was a finalist for the Russell Clark Medal for Illustration.
Hinepau. Auckland, N.Z.: Scholastic, 2004.
Taming the Sun: Four Māori Myths. Auckland, N.Z.: Random House, 2004
This collection was a finalist in both the 2005 Picture Book Category of the New Zealand Post Book Awards for Children and Young Adults, and The Russell Clark Award at the LIANZA Children’s Book Awards 2005.
Kiwi Moon. Auckland, N.Z.: Random House, 2005.
Riding the Waves: Four Māori Myths. Auckland, N.Z.: Random House, 2006. Translated into Māori as Whakaeke I Ngā Ngaru: E Whā Tino Purākau by Kāterina Te Heikōkō Mataira. Auckland, N.Z.: Random House New Zealand, 2006.Translation of Riding the Waves.
Rats. Auckland, N.Z.: Random House New Zealand, 2007.
There Was An Old Woman. Wellington, N.Z.: Gecko Press, 2008.
Counting the Stars: Four Māori Myths. Auckland, N.Z.: Random House, 2009.
There Was A Crooked Man. Wellington, N.Z.: Gecko Press, 2009.
Cowshed Springtime: A Kiwi Counting Book. Auckland, N.Z.: Random House, 2010.
Bruiser. Auckland, N.Z.: Random House New Zealand Ltd., 2011.
Māui and the goddess of fire. Auckland : Scholastic New Zealand, 2015. EditionA redesigned edition.
retold and illustrated by Gavin Bishop.
Quaky Cat helps out. Auckland, New Zealand : Scholastic, 2015.
written by Diana Noonan and Illustrated by Gavin Bishop.
The road to Ratenburg. Wellington, N.Z: Gecko Press, 2016.
written by Cowley, Joy and Illustrated by Bishop, Gavin.
Films/Video
Bidibidi. Dunedin, N.Z.: TVNZ Natural History Department, 1990.
Television series of 13 episodes for T.V.N.Z.’s Natural History Unit based on the Bishop’s book of the same title. This series was broadcast on television in November and December, 1990. Bishop writes "the story was extended with songs and live natural history footage. The characters were puppets and the settings were based very closely on the illustrations in the book."
Bidibidi to the Rescue. 1991.
This was a new story written for a television series of 13 episodes for T.V.N.Z.’s Natural History Unit as a follow-up to Bidibidi This series was broadcast in November and December 1991. Bishop writes that "it tells how Bidibidi the sheep, living in the mountains with the old rainbow maker, Rainbow Jackson, journeys to the West Coast to find a cure for her ailing friend, (Rainbow Jackson). She has many adventures including the discovery of a smuggling ring which captures native birds for illegal export to foreign zoos. Again there are lots of songs and live natural history footage spliced in from time to time."
Non-fiction
"Gavin Bishop; Kia ora Professor Cole." Inside Story: Year Book. 2000. 9-25.
Includes Bishop’s address at the Margaret Mahy Medal Award Lecture in 2000.
Other
Giant Jimmy Jones.
"Story and illustrations for the world’s first animated, 3-dimensional, pop-up picture book – produced in colaboration with One Glass eye and the HIT LAB University of Canterbury." See www.hitlabnz.org
Papers/Presentations
"Making Books That Matter and Surviving as a Writer at the Same Time." Author Luncheon - 18th World Congress of Reading. Auckland, N.Z., 12 July, 2000.
The text of this lecture can be found on Bishop’s website
"Putting It Together." Session Talk—18th World Congress. Auckland, N.Z., 12th July, 2000.
The text of this lecture can be found on Bishop’s website
"Kiaora Professor Cole Lecture for the Margaret Mahy Award 2000." Inside Story: Year Book 2000: 9-25.
The text of this lecture can be found on Bishop’s website
"Cinderellas of the Art World? Gavin Bishop Panel Session": Auckland, N.Z., Saturday 20th May 2000.
The text of this lecture can be found on Bishop’s website.
Performing Arts
Terrible Tom. 1985.
Bishop was responsible for the story and design of this commissioned ballet for the Royal New Zealand Ballet Company which toured nationally for 18 months and was performed at the Wellington Arts Festival in 1986 and 1994. Bishop writes "[t] he story tells of a naughty boy who runs away from his Grandma’s house to go to the park so that he can tease the birds in an aviary there." Philip Norman wrote the music for this hour-long ballet and Russell Kerr was the choreographer.
Te Maia and the Sea Devil. 1987.
Story and design for a commissioned ballet for the New Zealand Ballet Company which toured nationally. Bishop writes that the ballet is "set on the West Coast of the South Island [and that] it tells of a young Māori girl who lives with her father in a hut on the sea shore. Her mother mysteriously disappeared when she was a baby. One day a beautiful sea horse appears on the beach. She tells Te Maia to beware of the terrible sea devil, Taipo. There is a huge storm and Te Maia’s father is captured by Taipo and taken under the sea. Te Maia sets out to find her father and of course she does and as an added bonus she discovers that the sea horse is also her mother." Bishop designed the sets and costumes, Philip Norman composed the music and Russell Kerr did the choreography.
Reviews
"A Wink to the Grown-Ups." Rev. of The Night kite, by Peter Bland; Napoleon and the chicken farmer, by Lloyd Jones; Cat’s whiskers - 4 favourite Lynley Dodd stories, by Lynley Dodd. New Zealand Books 14.3 (2004): 5.
Theses
"Collective Ideas on Western Aesthetics and Māori Art. "Dip. FA Thesis. U of Canterbury, 1967.
Visual Arts
O’Brien, Katherine. The Year of the Yelvertons. Oxford UP, 1981.
Bishop was awarded the Ester Glenn Medal for these illustrations.
Leverich, Kathleen. The Hungry Fox. Boston. Houghton. 1986.
Dietz, Beveryley. The Lion and the Jackel. USA: Silver Burdett & Ginn, 1991.
Bailey, Philip H. The Wedding of Mistress Fox. New York, U.S.A.: North/South, 1994.
A re-telling of the original story by Jacob and Wilhelm Grimm. Bishop writes that "the Mistress Fox retires to her room when her husband, the old Mr Fox dies, and when a string of suitors come knocking at her door she sends them all away except one." In 1996, French, Dutch, Japanese and Chinese editions were published.
Bailey, Philip H. The Wedding of Mistress Fox. New York: North/South Books, 1994.
Retold from the Brothers Grimm.
Watson, Joy. Pets. Wellington, N.Z.: Learning Media NZ, 1988, 1997.
Cowley, Joy. The Bears’ Picnic. Auckland, N.Z.: Shortland, 1997.
Lawrence, Richard C.. Woodchuck’s New Helper. New York: Scott Foresman, 1999.
Cowley, Joy. The Video Shop Sparrow. Wellington, N.Z.: Mallinson Rendel NZ, 1999.
Cowley, Joy. Maui and the Sun. USA: Wright Group, 2000.
Cowley, Joy. Pip the Penguin. Auckland, N.Z.: Scholastic NZ, 2001.
Sullivan, Robert. Weaving Earth and Sky. New Zealand: Random House, 2002.
Winner of the non-fiction section of the New Zealand Post Children’s Book Awards in 2003. Winner of the New Zealand Post Book of the Year in 2003.
Cowley, Joy. The Little Tractor. Auckland, N.Z.: Scholastic New Zealand, 2004.
Cowley, Joy. Tarakihana Pakupaku. Māori trans. Katerina Mataira. Akarana, Aotearoa: Scholastic New Zealand, 2004.
Leask, Jeffry. Little Red Rocking Hood. Auckland, N.Z.: Ashton Scholastic, 1992. Rev. ed. Auckland, N.Z.: Scholastic, 2005.
A Rock Opera written by Jeffrey Leask. Illustrated by Gavin Bishop.
“Designed as part of the music programme for schools, sold also as a big book with pre recorded tape of music.” Accompanied by a dound disc. http://www.gavinbishop.com/red_rock.shtml
Leask, Jeff. Little Red Rocking Hood: A Rock Opera. Auckland, N.Z.: Scholastic, 2005.
Prior, Jean. The Waka. Auckland, N.Z.: Scholastic, 2005.
Prior, Jean. Te Waka. Auckland: N.Z.: Scholastic, 2005.
Maori translation by Katerina Te Heikōkō Mataira.
Cowley, Joy. Snake and Lizard. Wellington, N.Z.: Gecko Press, 2007.
Cowley, Joy. Friends: Snake and Lizard. Wellington, N.Z.: Gecko Press, 2009.
Cowley, Joy. Cowshed Christmas: A Kiwi Christmas Story. Auckland, N.Z.: Random House, 2009.
Noonan, Diana. Quaky Cat. Auckland, N.Z.: Scholastic, 2010.
Cowley, Joy. Just One More. Wellington, N.Z.: Gecko Press, 2011.
Stories by Joy Cowley, illus. by Gavin Bishop.
Other (30)
Reviews (60)
Other
Agnew, Trevor. "A Creative Collision: the Pop-Up Book of the Future." Magpies:Ttalking about Books for Children. 19.1 (2004): Sup.1-3.
Barley, Janet. "Gavin Bishop." Winter in July. New Jersey: Scarecrow, 1995. 51-64.
"Bishop, Gavin 1946-." Something about the Author. 97 (SATA) 199?. 15-18.
Booklist May 1, 1996: 1508
Darnell, Doreen. "An Interview with Gavin Bishop." Talespinner 8 (1999): 23-29.
Dunkle, Margaret. "Gavin Bishop." The Story Makers. Melbourne: Oxford UP, 1987. 7.
Dunlop, Celia. "Fresh Flair." Listener 4 Feb. 1991: 80.
Profiles Bishop.
Fitzgibbon, Tom. "Gavin Bishop." Beneath Southern Skies. Auckland, N.Z.: Ashton Scholastic, 1993. 16-17.
Garry, Arthur. "Katarina." The Press 5 Jan. 1991: 5.
An interview with Bishop.
Gaskin, Chris. "Gavin Bishop." Picture Book Magic. Auckland, N.Z.: Heinemann Reed, 1996. 24-28.
Gilling, Naomi. "Māoritanga, Green Message Woven." The Press 3 Nov. 1993: 2.
Guerin, Louise. "A lasting effect." Listener 25 Sep. 1993: 46-47.
Hunt, Peter. "New Zealand." Children’s Literature: An Illustrated History. Oxford UP, 1995. 346.
McKenzie, John. "Gavin Bishop: a Quintessential New Zealand Picture Book Artist." English in Aotearoa 46 (2002): 3-17.
Marantz, Sylvia and Kenneth. "Gavin Bishop." Artists of the Page. Jefferson, North Carolina: McFarland & Co, 1992. 28-34.
Interviews with 29 children’s book illustrators from around the world.
Nagelkerke, Bill. "Know the Author." Magpies: Talking about Books for Children 13.5 (1998): Sup. 4-6.
Packer, Ann. "Children’s Author’s Personal Odyssey." Evening Post 7 Apr. 1990. 30.
Packer, Ann. "Meet the Family." Listener 17 Nov. 2001. 58-59.
Packer, Ann. "Writing Heritage." North and South 215 (2004): 26-27.
Phelps, Karen. "Different Dimension." Sunday Star Times 8 June 2003: Sup. 32-33.
Publishers Weekly 28 Nov. 1994: 61.
Rewi, Adrienne. "Bishop’s Bunny is Winner." Sunday Star Times 23 Nov. 1997: E7.
Rewi, Adrienne. "It all Began with Roast Mutton." Press 13 Dec. 1997: Sup. 2.
School Library Journal Mar. 1990: 188
School Library Journal Dec. 1994: 122-123.
School Library Journal July 1996: 77.
Simpson, Peter. "Bishop Exhibition." Press 24 Aug. 1991: 29.
Slade, Colin. "Matching Picture with Text." Press 16 Aug. 1995: 13.
Thomson, Margie. "Writer-Artist Says Books for Kids Not Child’s Play." New Zealand Herald 1 Apr. 2000: J8.
Tyler, Janet. "Designs on Words." Quote Unquote 6 (1993): 11.
Reviews
A Apple Pie
Hebley, Diane. "Children’s Books: The One-Minute Novel." Listener 2 Apr. 1988: 66-67.
"In Review: Fiction." School Library Review 8.2 (1988): 9-16.
Bidibidi
Plumpton, Frances (and others). "Book Reviews." Magpies: Talking about Books for Children 17.4 (2002): Sup. 6-8.
Chicken Licken
Bulletin of the Center for Children’s Books (Apr. 1985): 141.
Lavender, Ralph. School Librarian (June 1985): 133.
Giant Jimmy Jones
Agnew, Trevor. "A Creative Collision: the Pop-Up Book of the Future." Magpies: Talking about Books for Children 19.1 (2004): Sup.1-3.
McKenzie, John. "Eyemagic: the Book of the Future?" Talespinner 17 (2004): 33-35.
Hinepau
Du Fresne, Karen. "Weaving Magic." Listener 5 Feb. 1994: 52-53.
Katarina
Arthur, Garry. "Katarina." The Press 5 Jan. 1991: 20.
Gilderdale, Betty. "Classic, Exuberant Efforts from Mahy." New Zealand Herald 25 May 1991: 6.
Hall, Mary. "Non-fiction." InfoChoice: A Buying Guide for Primary School Libraries 8 (1991): 8.
Hoben, Ngaire. "Non-fiction." New and Notable: Books for the Secondary School Library 8.1 (1991): 23.
Morris, Bruce. "Moving Tale of Old New Zealand." Dominion 19 Jan. 1991: 9.
Packer, Ann. "A Beautiful Bicultural Mix." Evening Post 25 Jan. 1991: 5.
Poole, Fiona Farrell. "TV Spinoff Gets it Right - For Once." Dominion Sunday Times 27 Jan. 1991: 24.
Kiwi Moon
Larsen, David. Listener Dec. 17, 2005. No further details.
Owen, Dylan. Dominion Post Dec. 3, 2005. No further details.
Agnew, Trevor. The Source (Australian/New Zealand website)l 2005. No further details.
Maui and the Goddess of Fire
Noonan, Diana. "Rabbits Are No-Go." New Zealand Books 9.2 (1999): 6.
Phillips, Margaret (and others). "Reviews." Magpies: Talking about Books for Children 13.4 (1998): Sup. 7-8.
Maui and the sun
Huber, Raymond. "Maui - Local Hero: a Teaching Resource." Talespinner 3 (1997): 29.
Mother Hubbard
Crouch, Marcus. Junior Bookshelf (Feb. 1988): 18.
Hebley, Diane. "Children’s Books: Four fantails flitting." Listener 15 Apr. 1987: 74-75.
Roberts, Cath. "Books." National Education 69.3 (1987): 127.
Mr. Fox
Fisher, Margery. Growing Point (May 1983): 4080.
Mr. Fox
Crouch, Marcus. Junior Bookshelf (June 1983): 107.
Mrs. McGinty and the Bizarre Plant
Mrs. McGinty and the Bizarre Plant. Junior Bookshelf (Aug. 1982): 128-129.
Sutherland, Zena. Bulletin of the Center for Children’s Books (May 1983): 163.
Stay awake, Bear
Dieringer, Julie. "Reviews of New Zealand Picture Books by German Students." Reading Forum NZ 2 (2002): 35-37.
Kedian, Margaret (and others). "Reviews." Magpies: Talking about Books for Children 15.4 (2000): Sup.6-8.
Taming the Sun
Booknotes 149, 2005. No further details.
Burgess, Linda. "Pinning Down The ‘Again’ Factor." New Zealand Books 15.2 (2005): 11.
Huber, Raymond (and others). "Book Reviews." Magpies: Talking about Books for Children 20.1 (2005): Sup. 5-6.
Terrible Tom
Flury, Roger. "Performances." Canzona 8.26 (1986): 23.
The House that Jack Built
Hebley, Diane. "Going into Detail." New Zealand Books 10.2 (2000): 3-4.
Holt, Jill. "Reading for the Pictures." Listener 5 Feb. 2000: 44-45.
Kedian, Margaret (and others). "Reviews." Magpies: talking about books for children 14.5 (1999): Sup. 6-7.
Keene, Howard. "Settlement Story In Nursery Rhyme." Press 6 Sep 1999. 24.
McKenzie, John L. "The Use (And Abuse?) Of History." Magpies: Talking about Books for Children 14.4 (1999): Sup.1-3.
Sharp, Iain and Joy MacKenzie. "Books." Sunday Star Times 19 Sep. 1999: F2.
The Little Tractor
Huber, Raymond. Magpies 24 Apr. 2004. No further details.
Reading Time 48.2, 2003. No further details.
Kedian, Margaret (and others). "Book reviews." Magpies: Talking about Books for Children 19.2 (2004): Sup.5-8.
The Three Little Pigs
Dunlop, Celia. "Children’s Books: "I’ll huff & I’ll puff."‘ Listener 30 Apr. 1990: 112.
Gilderdale, Betty. "Feline Felon Back in Print." New Zealand Herald 15 Sep. 1990: 6.
Griffiths, G J. "Recent NZ Titles." Otago Daily Times 9 Jun 1990: 21.
Jackett, Lynne. "Non-Fiction." InfoChoice: A Buying Guide for Primary School Libraries 6 (1990): 6.
Kirkus Reviews 15 Jan. 1990: 101-102.
Morris, Bruce. "Illustrations that Bring Piggy Tale up to Date." Dominion 5 May 1990: 7.
The Waka
Kedian, Margaret. Magpies Nov. 2005. No further details.
Baldwin, Charlotte, Shapland, Adrianne. "Book Reviews." Reading Forum NZ 20.3 (2005): 41-42.
The Children’s Bookshop Wellington, July 2005. No further details.
Three Billy Goats Gruff
Aluf, Kerry. "Book Reviews." Playcentre Journal 120 (2004): 34.
Kedian, Margaret (and others). "Book Reviews." Magpies: Talking about Books for Children 18.4 (2003): Sup. 6-8.
Tom Thumb
Jones, Jenny. "Book Reviews." Education Today 6 (2002): 30.
Kedian, Margaret and Bill Nagelkerke. "Book Reviews." Magpies: Talking about Books for Children 17.1 (2002): Sup. 5-6.
McKenzie, John. "The Spectator Gaze and the Other in Gavin Bishop’s Tom Thumb." English in Aotearoa 46 (2002): 18-26.
"Judges’ Report, NZ Post Children’s Book Awards, 2003. No details.
Manuel, Carol. "Myths and Legends from Aotearoa." Reading Forum NZ 3 (2003): 26-28.
Nagelkerke, Bill (and others). "Book Reviews." Magpies: Talking about Books for Children 18.1 (2003): Sup.7-8.
| https://komako.org.nz/person/71 |
Butterfly Plants for the Lower Rio Grande Valley Compiled By: Mike Quinn, Invertebrate Biologist Texas Parks & Wildlife, Sept - DocsLib
Butterfly Plants for the Lower Rio Grande Valley Compiled by: Mike Quinn, Invertebrate Biologist Texas Parks & Wildlife, Sept. 2002 Scientific Name Common
ButterflyPlantsfor the LowerRio GrandeValleyCompiled by: Mike Quinn, Invertebrate BiologistTexasParks & Wildlife, Sept. 2002
Scientific Name Common Name Sun Nectar Flwr Color Blooms Caterpillar FoodPlantfor these species: Remarks
Ground Covers
Justicia (Siph) pilosella Tube Tongue Full Sun Fair Lavender Sp-Fall Tiny & Elada Checkerspot, Vesta Crescent Phyla incisa Texas FrogFruitFull Sun Excel White Sp-Fall Phaon Crescent, White Peacock, Common Buckeye Phyla strigulosa Frog Fruit Full Sun Excel White Sp-Fall White Peacock Sedum texanum Stonecrop Full Sun Fair yellow Winter Xami Hairstreak succulent
Perennials (1 - 3 feet)
Asclepias oenotheroides Hierba de Zizotes Full Sun Fair Green/Yellow Sp-Fall Monarch Dicliptera vahliana Dicliptera Pt. Shade Fair Red Spring Banded Peacock, Rosita Patch, Texan & Cuban Crescents Eup. betonicifolium Betony Mistflower Pt/Full Sun Fair Bluish Purple Sp-Fall Rounded Metalmark Eupatorium greggii Gregg’s Mistflower Pt/Full Sun Excel Bluish Purple Sp-Fall Nectar for Queens, Food for Rawson's Metalmark not native Heliotrop (6) spp. Heliotrope Full Sun Excel White All Year Adult Nectar Source weed?! Hibiscus cardiophyllus HeartLeafHibiscus Full Sun Excel Deep Red Spring Yojoa & Mallow Scrub-Hairstreak native Justicia (3) spp. Water Willow Pt. Shade Good Purple Sum-Fall Malachite, Banded Peacock Lantana macropoda Desert Lantana Full Sun Good White Sp-Fall Adult Nectar Source Monarda citriodora Horsemint Full Sun Good White/Pink Sp-Fall Adult Nectar Source Pavonia lasiopetala Rose Pavonia Full Sun Excel Pink Sp-Fall Adult Nectar Source not nativePlumbagoscandens White Plumbago Sun-Shade Excel White Sp-Fall Marine & Cassius Blues Is native Prosopus reptans Screwbean Mesquite Full Sun Fair Yellow Sp-Fall Clytie Ministreak, TailedOrange, Blue Metalmark Rivina humilis Pigeon Berry Sun-Shade Poor White All Year Goodson's Greenstreak Salvia coccinea Scarlet Sage Full Sun Good Scarlet All Year Adult Nectar SourceVerbena(13) spp. Vervain Full Sun Good Purple-White Sp-varies Adult Nectar Source Zexmenia hispida Orange Zexmenia Full Sun Excel Orange Sp-Fall Adult Nectar Source Xeric
A few of the many butterfly and plant field guides that may be helpful:
Butterflies Through Binoculars, The West Plants of the Rio Grande Delta Jeffrey Glassberg, 2001. Oxford Univ. Press Alfred Richardson. 1995. Univ. of Texas Press
The Butterflies ofNorth America. Wildflowers and Other Plants of Texas Beaches and Islands James A. Scott. 1986. Stanford Univ. Press Alfred Richardson. 2002. Univ. of Texas Press
National Audubon Society Field Guide to North American ButterfliesTrees,Shrubsand Cacti ofSouth TexasRobert Michael Pyle, 1983. Alfred A. Knopf Everitt, J. H., & D. L. Drawe. 1993. Texas Tech Univ. Press Butterfly Plants for the Lower Rio Grande Valley Compiled by: Mike Quinn, Invertebrate Biologist Texas Parks & Wildlife, June 2002
Scientific Name Common Name Sun Nectar Flwr Color Blooms Caterpillar Food Plant for these species: Remarks
Shrubs (> 3 feet)
Acacia greggii Catclaw Acacia Full Sun Fair White/Cream Sp-Sum Marine Blue Adelia vaseyi Adelia Sun-Shade FairPetalsAbsnt Sp-Sum Mexican Bluewing Aloysia gratissima White Brush Full Sun Excel White Sp-Fall Adult Nectar Source Aloysia macrostachya Sweet Stem Full Sun Good Light Purple Sp-Sum Adult Nectar Source showy Amyris (2) spp. Torchwood Full Sun Fair White Sp-Fall Giant Swallowtail Asclepias curassavica Mexican Milkweed Sun-Shade Excel Red &Yellow Sp-Fall Queen, Monarch & Tiger Mimic-Queen not native Aster subulatus Aster Full Sun Excel Bluish Purple Sum-Fall Adult Nectar Source annual Buddleia davidii Butterfly Bush Full Sun Excel Various Adult Nectar Source not native Buddleia sessilifolia Butterfly Bush Part Sun Good Yellow Sp-Sum Adult Nectar Source Is native! Cassia fasciculata Partridge Pea Full Sun Fair Yellow Sp-Sum Cloudless Sulphur, Little Yellow annual Cassia lindheimeriana Lindheimer Senna Full Sun Fair Yellow Sum-Fall Sleepy Orange Cassia (4) spp. Senna Full Sun Fair Yellow Sum-FallCirsiumtexanum Thistle Full Sun Excel Pink Sp-Sum Adult Nectar Source annual Coursetia axillaris Baby Bonnets Full Sun Good Pink Sp-Fall Southern Dogface thornless Eupatorium azureum Blue Mistflower Pt/Full Sun Fair Bluish Purple Spring Adult Nectar Source Eupatorium incarnatum White Mistflower Pt/Full Sun Excel White Fall-Wint Adult Nectar Source Eupatorium odoratum Crucita Pt/Full Sun Excel Bluish Purple Fall-Wint Rounded Metalmark, one of the best nectar plants SUPERB Eysenhardtia Texana Texas Kidneywood Full Sun Good White Sp-Fall Southern Dogface Forestiera angustfolium Elbowbush Full Sun Excel Petals Absnt Sp-Fall Adult Nectar Source Karwinskia humboltiana Coyotillo Full Sun Excel (small) Sp-Sum Two-barred Flasher Lantana camara West India Lantana Full Sun Excel Pink/Yellow Sp-Fall Lantana Scrub, Tropical Green & Red-spotted Hair. not native Lantana horrida Texas Lantana Full Sun Excel Red/Yellow Sp-Fall Adult Nectar Source Lantana montivedensis Trailing Lantana Full Sun Good Magenta Adult Nectar Source Leucophyllum frutescens Cenizo Full Sun Fair Pink after Rain Theona Checkerspot xeric Lippia alba White Lippia Full Sun Good Reddish All Year White Peacock, Lantana Scrub-Hairstreak spreads Lippia graveolens Scented Lippia Full Sun Good White Sp-Fall White Peacock, Lantana Scrub-Hairstreak Malpighia glabra Barbados Cherry Sun-Shade Fair Pink Sp-Fall White-patched & Brown-banded Skip., Cassius Blue Malvaviscus arboreus Turk’s Cap Shade-Sun Excel Deep Red Sp-Fall Glassy-winged Skipper, Turk's-cap White-Skipper Palafoxia texana Palafoxia Sun-Shade Excel Pink Sp-Fall Adult Nectar Source annual Salvia ballotiflora Shrubby Blue Sage Full Sun Good Light Blue Sp-Fall Adult Nectar Source showy Solidago spp. Goldenrod Full Sun Excel Yellow Sum-Fall Adult Nectar Source annual Verbesina encelioides Cowpen Daisy Full Sun Good Yellow Sp-Fall Bordered Patch annual Viguiera stenoloba Golden Eye Daisy Full Sun Good Yellow Sp-Fall Adult Nectar Source showy Butterfly Plants for the Lower Rio Grande Valley Compiled by: Mike Quinn, Invertebrate Biologist Texas Parks & Wildlife, June 2002
Scientific Name Common Name Sun Nectar Flwr Color Blooms Caterpillar Food Plant for these species: Remarks
Trees
Acacia berlandieri Guajillo Full Sun Excel White/Cream Spring Adult Nectar Source SUPERB Bauhinia mexicana OrchidTreeFull Sun Good Pink or White Sp-Fall Tailed Aguna, Long-tailed Skipper, Gilbert's Flasher not native Bumelia lanuginosa La Coma Full Sun Excel White Sp-Sum Adult Nectar Source Caesalpinia mexicana Mexican Caesalpinia Full Sun Fair Bright Yellow Sp-Sum Curve-winged Metalmark, Apricot Sulphur Cephalanthus salicifolius Mex. Button-Bush Full Sun Excel Creamy/Wh Sum-Fall Adult Nectar Source SUPERBCitharexylumberlandieri Fiddlewood Full Sun Excel White Spring Adult Nectar Source Cordia boissieri Wild Olive Full Sun Excel White All Year Adult Nectar Source Ehretia anacua Anacua Full Sun Excel White Sp-Fall Adult Nectar Source Erythrina herbacea Coral Bean Full Sun Good Deep Coral Spring Adult Nectar Source showy Guaiacum angustifolia Guayacan Full Sun Fair Purple Sp-Sum Lyside Sulphur Helietta parvifolia Baretta Full Sun Fair Green/White Sp-Sum Giant Swallowtail Pithecellobium dulce Guamuchil Full Sun Red-bordered Pixie not native Psidium cattleianum Strawberry Guava Full Sun Guava Skipper not native Psidium guajava Common Guava Full Sun Guava Skipper not native Yucca treculeana Spanish Dagger Full Sun Fair Creamy Spring Yucca Giant-Skipper Zanthoxylum fagara Colima Full Sun Fair Green/White Spring Thaos Swtail/Sickle-winged Skipper/Dingy Purplewing
Vines
Aristolochia marshii PipeVineFull Sun Fair Reddish-Purp.Spring Pipevine & Polydamus Swallowtail, Cattle Heart Cardiospermum halicacabumCommon Ballon Vine Sun-Shade Fair (small) All Year Silver-banded & Red-lined Scrub-Hairstreak Clematis drummondii Old Man's Beard Full Sun poor Blond Sp-Fall Fatal Metalmark Cynanchum (2) spp. Climbing Milkweed Shade Fair Cream Sp-Fall Queen & Soldier Ipomoea (6) spp. Morning Glory Sun-Shade Fair Purplish all year Purplish-black Skipper, Morning Glory Pellicia Matelea reticulata Pearl Mikweed Shade poor Pearly Sp-Fall Queen & Monarch Mikania (1) sp. Climbing Hemp Weed Full Sun Fair White Sum-Fall Tropical GreenstreakPassiflorafilipes Spread-Lobe Passion Pt. Shade Fair Yellow/Green All YearPassiflora foetidaCorona de Cristo Full Sun Fair Light Purple Sp-FallGulf FritillaryaggressivePassiflora suberosa“Corky” Passion Vine Pt. Shade Fair Yellow/Green All Year Zebra Heliconian, Gulf Fritillary Passiflora tenuiloba Slender Lobe PassionFull Sun Fair Yellow/Green Sp-Fall Gulf Fritillary, Julia Heliconian Sarcostemma cynanchoidesClimbing Milkweed Sun-Shade Fair Greenish Sum-Fall Queen, Soldier & Monarch Serjania brachycarpa Serjania Full (Part) Fair Whitish-GreenSum-Fall Common Banner Tragia glanduligera Noseburn Full Sun Fair Creamy Sp-Fall Common Mestra, Red Rim
| https://docslib.org/doc/10943965/butterfly-plants-for-the-lower-rio-grande-valley-compiled-by-mike-quinn-invertebrate-biologist-texas-parks-wildlife-sept |
Climate Change Shifts Range and Behavior of Ocean Species - Scientific American
Scientific American is the essential guide to the most awe-inspiring advances in science and technology, explaining how they change our understanding of the world and shape our lives.
Biology
Climate Change Shifts Range and Behavior of Ocean Species
Despite slower temperature shifts in ocean waters, ocean life from plankton to fish have begun moving in response to global warming
Although this year hasn't been too unusual, Maine lobsterman Steve Train has noticed several new species appearing in his nets over the past few years. Red hake is more common than it used to be in Casco Bay, he said, as well as sea bass and squid. Lobster is also showing up earlier than Independence Day, when he used to begin his yearly catch.
"If you wait for the Fourth of July to get them now, you're going to miss them," Train said.
What Train is seeing in Casco Bay could be a small example of a global trend. Despite the fact that continents are warming about three times faster than the world's oceans, marine species are nonetheless reacting to climate change as much as -- or more than -- land-based species, a new study shows.
Twelve times more, in some cases. Bony fish and the tiny phytoplankton that form the base of the ocean food web shifted their range an average of 72 kilometers (45 miles) per decade in response to climate change, the study's authors found, while species on land shifted by an average of only 6 kilometers per decade.
The paper, published yesterday in the scientific journal Nature Climate Change, compiled more than 1,700 long-term observations on a wide range of ocean species, from algae to polar bears, finding that about 80 percent of these data reflected shifts in range, population and behavior consistent with what scientists expect with a changing climate.
Great expectations matched by data"What this data shows is that marine ecosystems are responding to environmental change, and they're responding at a faster rate than just simple metrics like mean global temperature rise would perhaps indicate," said Moore.
This meta-analysis will be included in the upcoming Intergovernmental Panel on Climate Change Fifth Assessment Report, and is the first comprehensive assessment of the impacts of climate change on the global marine system.
The authors focused on multi-species studies to avoid bias -- less than 11 percent of the observations used were based on single-species studies -- because journal editors are more likely to publish papers that exhibit larger, more dramatic results. They also chose studies that provided data for a span of at least 19 years and safely excluded impacts from other stressors like pollution and overfishing.
That 80 percent of the data are consistent with expectations under climate change is remarkable, said co-author William Sydeman, senior scientist with the Farallon Institute for Advanced Ecosystem Research in Petaluma, Calif. "The statistical significance of that is off the charts," he said.
Of the wide range of species studied, plankton showed some of the largest changes in distribution, said Sydeman, probably because these tiny animals and plants "go with the flow."
"Plankton, by definition, are organisms that go where the ocean takes them," Sydeman said. "Therefore, the movements or the changes of the distribution of planktonic organisms are really driving a lot of the differences that we saw between terrestrial organisms and marine organisms."
'Moving the dinner plate'The major shifts seen in the ocean's plankton communities are "a really big deal," said co-author Benjamin Halpern, a research biologist with the National Center for Ecological Analysis and Synthesis at the University of California, Santa Barbara, because these tiny organisms are "what everything else ultimately feeds on."
"That's like moving the dinner plate to a totally different place in the ocean," Halpern said.
The authors also saw substantial shifts in marine species' phenology, or the seasonal timing of life cycle events like breeding or migration. Spring phenological change in the ocean has advanced by more than four days per decade, the paper states, while the shift for land-based species is estimated to be between 2.3 and 2.8 days per decade.
Like on land, behavioral timing shifts do not happen equally for all species, making it possible for "mismatches" to occur.
"There actually are differences in the rate of response between different taxonomies," Moore said.
"You're seeing quite large changes or advances in the phenology of zooplankton and fish, for instance, but seeing much-reduced changes in phenology for seabirds," she said. "If you think that seabirds perhaps eat the plankton and eat the fish, the differences in response can lead to what's called a trophic mismatch, which means that perhaps when the seabirds arrive on their colony to nest, their food supply is not there anymore."
An 'unpredictable' reorganizationThe reason behind ocean species' swift adjustment to climate change is not explained in the paper. However, said Moore, it could be because parts of the ocean containing water of the same temperature, called isotherms, are changing location faster than land temperatures. Ocean isotherms span hundreds of miles, so marine creatures have to shift their ranges at a faster rate to stay comfortable.
Another unknown is exactly what the impact of these major shifts might be, but a major reorganization of underwater ecosystems seems likely.
"The structure and the functions of these ecosystems, and the services that they provide to society, are going to be more and more unpredictable," said Sydeman.
Halpern said that the impact of climate change on people like Train, whose livelihood depends on the distribution of different ocean species, is also worrisome: "It's not easy to move an entire community 200 miles up the coast when the fish move," he said.
"There's almost certainly going to be unexpected consequences from reshuffling species," he added. "Yes, nature and people can adapt, but I think at a pace slower than what we're seeing happening in response to what climate change suggests will be possible."
Reprinted from Climatewire with permission from Environment & Energy Publishing, LLC. www.eenews.net , 202-628-6500
| https://www.scientificamerican.com/article/climate-change-shifts-range-and-behavior-of-ocean-species/ |
IJERPH | Free Full-Text | The Association of Nutrition Quality with Frailty Syndrome among the Elderly
Low diet quality among the elderly may be correlated with some diseases, including Frailty Syndrome (FS). This decline in function restricts the activity of older people, resulting in higher assistance costs. The aim of this study was to increase knowledge of diet quality predictors. Dietary intake was assessed among 196 individuals aged 60+ years using the three-day record method and FS by Fried’s criteria. Based on the compliance with the intake recommendation (% of EAR/AI), we distinguished three clusters that were homogeneous in terms of the nutritional quality of the diet, using Kohonen’s neural networks. The prevalence of frailty in the entire group was 3.1%, pre-frailty 38.8%, and non-frailty 58.1%. Cluster 1 (91 people with the lowest diet quality) was composed of a statistically significant higher number of the elderly attending day care centers (20.7%), frail (6.9%), pre-frail (51.7%), very low vitamin D intake (23.8% of AI), using sun cream during the summer months (always 19.8% or often 39.6%), having diabetes (20.7%), having leg pain when walking (43.1%), and deteriorating health during the last year (53.5%). The study suggests the need to take initiatives leading to the improvement of the diet of the elderly, especially in day care senior centers, where there are more frail individuals, including nutritional education for the elderly and their caregivers.
The Association of Nutrition Quality with Frailty Syndrome among the Elderly
by Katarzyna Rolf 1,* , Aurelia Santoro 2 , Morena Martucci 2 and Barbara Pietruszka 3
1
Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, 40138 Bologna, Italy
3
Department of Human Nutrition, Warsaw University of Life Sciences—SGGW, 02-776 Warsaw, Poland
*
Author to whom correspondence should be addressed.
Int. J. Environ. Res. Public Health 2022 , 19 (6), 3379; https://doi.org/10.3390/ijerph19063379
Received: 26 January 2022 / Revised: 7 March 2022 / Accepted: 11 March 2022 / Published: 13 March 2022
(This article belongs to the Special Issue Minimizing the Burden of Aging Disorders )
Abstract
:
Low diet quality among the elderly may be correlated with some diseases, including Frailty Syndrome (FS). This decline in function restricts the activity of older people, resulting in higher assistance costs. The aim of this study was to increase knowledge of diet quality predictors. Dietary intake was assessed among 196 individuals aged 60+ years using the three-day record method and FS by Fried’s criteria. Based on the compliance with the intake recommendation (% of EAR/AI), we distinguished three clusters that were homogeneous in terms of the nutritional quality of the diet, using Kohonen’s neural networks. The prevalence of frailty in the entire group was 3.1%, pre-frailty 38.8%, and non-frailty 58.1%. Cluster 1 (91 people with the lowest diet quality) was composed of a statistically significant higher number of the elderly attending day care centers (20.7%), frail (6.9%), pre-frail (51.7%), very low vitamin D intake (23.8% of AI), using sun cream during the summer months (always 19.8% or often 39.6%), having diabetes (20.7%), having leg pain when walking (43.1%), and deteriorating health during the last year (53.5%). The study suggests the need to take initiatives leading to the improvement of the diet of the elderly, especially in day care senior centers, where there are more frail individuals, including nutritional education for the elderly and their caregivers.
Keywords:
elderly
;
diet
;
frailty
;
day care senior centers
1. Introduction
Aging means a gradual, physiological, but not linear, decrease in physical and mental capacity. These changes are loosely associated with a person’s age in years; however, the elderly are usually classified as 60 years or older. Demographic statistics show that the world’s population is aging rapidly. It is estimated that the number of older people in the world will double by 2050 [ 1 ]. Therefore, a better understanding of all aspects of the aging process is needed, in particular with regard to the long-term care requirement for the elderly, which may generate additional social costs [ 2 ].
Aging is associated with many changes in the body’s cells, tissues, and organs, which may affect the functioning of, for example, the musculoskeletal and digestive systems, causing decreased food intake, as well as digestion and absorption of nutrients. The poor nutritional value of meals and the decreased ability of the digestive system contribute to the development of malnutrition. In addition, the elderly take drugs, such as diuretics, with potential adverse effects [ 3 , 4 , 5 ]. Many studies have shown that malnutrition and the risk of malnutrition concern from 25% to even above 60% of the population of older people [ 6 , 7 , 8 , 9 ]. The criteria for the diagnosis of clinical malnutrition are different in the USA and Europe. The lack of accurate criteria for diagnosing malnutrition increases the risk of adverse health outcomes [ 10 , 11 ]. The diet of seniors should take into account their lower energy requirements, while they have a greater need for proteins, vitamin D, and B6 as well as calcium. An adequate intake of folate, vitamin B12, and antioxidants is also important [ 3 , 12 ]. Therefore, a diet should have high nutritional density [ 3 , 13 , 14 ]. Age-related changes in protein metabolism mean that the average daily protein intake for the elderly should be at least 1.0 to 1.2 g per kilogram of body weight per day [ 12 , 13 ]. As the elderly exhibit decreased thirst sensation and reduced fluid intake, this results in dehydration, which is a form of malnutrition [ 14 ].
The aging process is often associated with Frailty Syndrome (FS); this means there is a weakening of the physical and/or mental condition, which in turn increases the risk of mortality [ 15 , 16 ]. One of the causes of FS may be malnutrition, especially a deficiency of energy and protein [ 17 ]. However, insufficient vitamin D status is also strongly associated with FS [ 18 ]. There is a correlation between FS and nutritional inadequacy [ 19 ]. Sarcopenia, i.e., the loss of muscle mass and strength progressing with age, is also associated with FS [ 20 ]. The frequency of the appearance of FS is higher among the elderly with sarcopenia [ 17 ]. It appears that higher protein intake by the elderly can be associated with a lower risk of FS [ 21 ] and sarcopenia [ 17 ].
Therefore, the aim of this study was to assess the relationship between the quality of nutrition and various determinants, including the FS, among individuals aged 60+ years.
2. Materials and Methods
2.1. Participants
The cross-sectional study was conducted at the Department of Human Nutrition, Warsaw University of Life Sciences—SGGW, Warsaw, Poland between 2012 and 2016. Independently-living participants aged 60 years and over were recruited. People applied for the study on the basis of information disseminated through leaflets, advertisements in the local press, as well as information provided in seniors’ clubs and the Universities of the Third Age. All respondents taking part in the study were volunteers. Some of them participated in the randomized and controlled NU-AGE project, previously described [
22
], and some were outside the project. Exclusion criteria were: 1. inability to perform daily activity (inability to walk), 2. advanced dementia (inability to sign informed consent), 3. failure to complete the three-day record, and 4. aged below 60 years. From the 229 recruited individuals, 33 did not fill in the three-day records, so 196 people were included in the study.
The study protocol was approved on 3 April 2012 by the ethical commission of the National Food and Nutrition Institute in Warsaw, Poland. The study followed the principals of the Declaration of Helsinki.
2.2. Dietary Assessment
Dietary intake was assessed using the three-day record method, including one weekend day and two weekdays (nonconsecutive). Participants were instructed to take detailed notes on the food and beverages consumed, as well as the dietary supplement intakes, which were included in the analysis. Data on the amount of food consumed were collected using the weight method, and when it was not possible, the portion size was determined using home measures. The correctness of completing the questionnaires was verified by a qualified nutrition specialist. Based on the food consumption data, the nutrient content was calculated using the computer database ”Dieta 5”, which was based on Polish food composition tables [
23
]. The mean daily energy intake, as well as the intake of protein, fat, digestible carbohydrate, calcium, phosphorus, magnesium, iron, copper, zinc, iodine, vitamins A, B1, B2, B6, and B12, niacin, and folate was individually compared with the Estimated Average Requirements (EAR) for every respondent, while the consumption of water, dietary fiber, sodium, potassium, vitamin D and E, and also of eicosapentaenoic, docosahexaenoic, linoleic and alfa-linolenic fatty acids, was compared with the Adequate Intake (AI) [
12
].
2.3. Frailty Syndrome
Frailty syndrome (FS) was evaluated according to the five criteria proposed by Fried et al. [
15
]: (1) unintentional weight loss (shrinking); (2) weakness; (3) exhaustion; (4) low walking speed; and (5) physical inactivity. Unintentional weight loss concerned a loss of more than 4.5 kg or 5% body weight in the previous year, based on self-reporting. Weakness was assessed as the mean value of three grip strength measurements using a handheld dynamometer (dominant hand). The results were considered separately for men and women, and additionally for BMI. Exhaustion was determined on the basis of the participants’ responses to two questions about how energetic and active they felt over the previous two weeks. Walking speed was measured over a distance of 4.5 m. The results were considered separately for men and women, and additionally for body height. The participants’ physical inactivity was determined on the basis of self-reported physical activity over previous year. In this case, participants answered how much sport or physical activity they usually did. Less than 2 h per week was considered as a criterion of frailty. Individuals were considered to be “frail” if they met ≥ 3 criteria, and those who had 1–2 criteria were classified as “pre-frail”. If participants did not have any of the described characteristics, they were categorized as “non-frail”. The original questionnaire was translated into Polish as part of the NU-AGE project.
2.4. Statistical Analysis
Data were analyzed using Statistica software version 13.3 (TIBCO Software Inc., Palo Alto, CA, USA). Based on the comparison of the mean level of compliance with nutrient requirements (% of EAR or AI) between individuals depending on frailty status, we distinguished groups that were more homogeneous in terms of the nutritional quality of the diet, using the Kohonen’s neural networks (KNN). First, we performed the statistical analysis of association between FS and nutrients intake, using the Mann-Whitney U test. Energy intake, as well as intake of protein, fat, calcium, iron, zinc, copper, vitamins B1, B6, B12 were included in the KNN analysis, due to the statistically significant correlation with FS. The final number of clusters and their size were determined on the basis of the analysis of variance and the Pearson correlation coefficient between the clusters and nutrients included in the cluster analysis, as well as the correlation between the clusters and the prevalence of FS. In
Figure 1
, showing the division of population under study into 3 clusters, the lines connecting the points have been preserved due to better data visualization and easier location of individual points. There is also a “neutral value” line showing 100% of compliance with the recommended nutrient intake. The Pearson’s chi-squared test was used to determine the association between clusters and categorical variables; for continuous variables the Kruskal-Wallis test and post hoc analysis was used. The results with
p
-values ≤ 0.05 were considered statistically significant.
3. Results
Cluster analysis showed three clusters clearly differing in the degree of implementation of nutritional standards for energy, protein, fat, calcium, iron, copper, and vitamin B1, B6, and B12. The first cluster covered 91 people with nutritional standards on average below the EAR for six out of ten analyzed nutrients (energy, protein, fat, calcium, zinc, and vitamin B1). The second cluster included 58 people with the norms below the EAR for only two nutrients (fat and calcium), and the third one (47 people) with all nutrients above the EAR (
Figure 1
). Neither gender, age, marital status, education level, nor occupation were different among clusters. Over 20% of the individuals in cluster 1 attended day care senior centers, while in cluster 3 it was only about 2% (
p
= 0.0067) (
Table 1
).
Although the total number of frail subjects was only six (3.1%) in the entire sample size, cluster 1 was characterized by a statistically significantly greater number of frail and pre-frail individuals, and fewer non-frail individuals ( p = 0.0096). In individuals from cluster 1, weakness, exhaustion, and lower walking speed were observed much more often in comparison with the clusters 2 and 3 but no shrinking or physical activity ( Table 2 ).
In the entire study group the majority of respondents reported their health as good (49.5%) or average (42.9%); however, in cluster 1 there were significantly more individuals who perceived a deterioration in health compared to the previous year ( p = 0.0373; Table 2 ). Diabetes and leg pain during walking were observed significantly more often also among the elderly in cluster 1. Median BMI was the highest in cluster 1, but the difference with other clusters was not statistically significant ( Table 2 ).
We found statistically significant differences in summer sun exposure, sunscreen use, and vitamin D intake between the elderly from individual clusters (
Table 3
). In the first cluster, the fewest people declared no sun exposure in the year preceding the study (2.2%); simultaneously, they used sun cream the most during the summer months (39.6%) and had the lowest number of people who never used it (36.6%). Moreover, the consumption of vitamin D expressed as % of the AI norm was the lowest both with the diet alone (22% of AI) and after taking into account the consumption of this vitamin in the form of dietary supplements (23.8% of AI).
4. Discussion
Nutrition is considered to be one of the main factors in the pathophysiology of frailty syndrome (FS); therefore, proper nutrition is the goal of not only prevention but also treatment strategies [ 24 ]. Therefore, this cross-sectional study investigated whether malnutrition was related to those already confirmed to have frailty syndrome.
Our survey was conducted among voluntarily enrolled participants, and recruitment took place, among others, at senior clubs and at Third Age Universities. Elderly people attending such institutions are more interested in a healthy lifestyle, do not have cognitive decline—which is associated with FS [ 25 ], and are more willing to participate in research, while weakened/frail elderly are usually less cooperative. The incidence of frailty syndrome in our study was low (3.1%) in comparison with the results of other studies, where the FS prevalence varied from below 10% [ 26 , 27 ], through over ten percent [ 25 , 28 , 29 ], to above 30% [ 19 ]. More frail people can be recruited in studies conducted in primary health care clinics, specialized outpatient clinics, or as a part of medical examinations, because there is a higher possibility to encounter such individuals [ 19 , 25 ]. Moreover, it is known that the average interest of frail people in taking part in research in such conditions is higher [ 30 ]. However, neither community-dwelling nor outpatient clinic recruitment would be representative, so the proportion of the frail elderly did not reflect the real number.
The characteristics of the subjects were conducted within the division into three nutritional clusters. Among all the parameters presented in Table 1 , a statistically significant relationship was found only for the parameter “Attending day care senior centers”. Among individuals attending this type of institution, the majority was in cluster 1. This is surprising, because in this type of senior center, the elderly receive meals. The reason for this should be further investigated, as our result may indicate some nutritional deficiencies in meals at such centers.
Our results showed that although a lack of association between age and nutritional quality of the diet was observed, the median age was a little higher among individuals with a poorer diet (cluster 1). Similarly, Engelheart and Akner [ 31 ] as well as Fakhruddin et al. [ 32 ] did not find correlation between age and food intake. However, in another Polish study, authors found a strong impact of age on poor nutritional status [ 33 ]. The difference between our study and the one quoted may be due to research methods. We analyzed the dietary intake, using the three-day record method, whereas Krzymińska-Siemaszko et al. [ 33 ] examined nutritional status, using the MNA questionnaire. The diet may not fully reflect the nutritional status, because, as mentioned earlier, it can be related to changes in the digestive system of the elderly [ 3 , 5 ].
Frailty syndrome can be related to the nutritional value of diets, especially as it can be the consequence of malnutrition or catabolism, which increase with age [ 15 ]. In our study, respondents with a low nutritional value diet were more likely to have at least one symptom of FS (frail and pre-frail). Several studies indicate a poorer diet in frail elderly people [ 27 , 34 , 35 , 36 ] and a generally lower density of nutrients in a diet [ 34 ]; however, no causal relationship data are available. Importantly, improving dietary habits reduces the odds of developing frailty [ 35 ]. However, it should be note that caloric/protein supplementation should be considered only for frail persons when weight loss or undernutrition is diagnosed [ 37 ]. On the other hand, research indicates that improving health status and extending life is associated with reducing the energy value of the diet, but with an adequate supply of macro-, and especially microelements, preventing malnutrition among healthy elderly [ 38 ]. Unfortunately, calorie restrictions survey are largely based on animals models. A nonhuman primate study showed that calorie reduction decreases the incidence of FS and increases the healthy life span [ 39 ].
In contrast to other studies [ 15 , 25 , 36 ], we found no differences between nutritional value of the diet (that is between clusters) in self-assessment of health. This could be due to the aforementioned form of recruitment elderly to the study. However, in cluster 1 there were significantly more people who reported a deterioration in health over the past year, as well as diabetics, and those who reported leg pain while walking, as in another study [ 15 ]. Taking into account that cluster 1 had the most people with FS, it can be concluded that there was an association between the occurrence of FS and these factors. Leg pain may accompany disability, which is strongly associated with FS [ 25 ], but may also contribute to the development of FS as an element of locomotive syndrome. Such people are at a higher risk of further deterioration of their health [ 40 ].
Among other analyzed factors related to diet quality, a statistically significant relationship was found with factors related to vitamin D metabolism. Vitamin D deficiency may affect up to 50% of the elderly population in Europe, therefore many countries have introduced mandatory fortification of some food products, for example, milk in Sweden and margarine in the United Kingdom [ 41 ]. In Poland, all table spreads, except milk fat, are mandatorily vitamin D fortified, so that the maximum amount in 100 g of the final product is not more than 7.5 μg [ 42 ].
It is worrying that almost 30% of our respondents avoided sunlight exposure during summer months, when endogenous vitamin D synthesis in Europe is the highest [ 43 ]. Although there were the least such individuals in cluster 1, that is, in the group with the highest percentage of frail and pre-frail people, in this cluster, there were a higher number of respondents using sun cream, which blocks vitamin D synthesis [ 43 ]. Moreover, vitamin D intake was very low in cluster 1, either with diet and supplements combined or with diet alone, as evidenced by only slightly higher median intake combined, compared to the diet only. It is equally important that synthesis of 1,25-dihydroxy-vitamin D decreases with age, among others reasons because of renal function decline [ 44 ]. As a consequence, the elderly are more likely to suffer from vitamin D deficiency, which may intensify FS symptoms. Wilhelm-Leen et al. [ 45 ], as well as Pabst et al. [ 46 ], found an inverse association between FS and 25-hydroxy-vitamin D serum concentration. One of the results of FS is an increased risk of falls [ 15 ]. In a randomized intervention study, ergocalciferol supplementation at an amount of 600,000 I.U. (15,000 µg) significantly improved functional performance, psychomotor skills, and balance in the elderly [ 47 ]. One of the mechanisms responsible for this may be the improvement in neuromuscular function by vitamin D [ 48 ], as atrophy in the first reacting fast-twitch type II muscle fibers has been observed in people with this deficiency, which may predispose them to more frequent falls and bone fractures [ 46 ]. Considering the above research, as well as Hirani et al. [ 18 ], confirming the benefits of a higher vitamin D level, it is worrying that in our study there were elderly with an intake at a level of 3% of AI norm, that is 0.45 µg (the Adequate Intake is 15 µg per day) [ 12 ]. Similarly, Verlaan et al. [ 17 ] found a very low intake of vitamin D in the entire study group, and among the elderly with sarcopenia the amount was much lower than among those without sarcopenia. Bartali et al. [ 34 ] also discovered a lower intake of this nutrient by frail elderly.
One of the limitations of our study is its cross-sectional nature, which makes it impossible to assess the causal relationship between the intake of nutrients and analyzed factors, such FS. Another is the recruitment method, as mentioned above. This is probably why the percentage of elderly with ≥3 symptoms of FS was so low. Furthermore, this is perhaps why the respondents’ dietary habits were better than that of the average elderly person in Poland, because malnutrition can occur in as much as 44% of community-dwelling elderly [
33
]. On the other hand, such a selection can also be an advantage, because such people are more willing to take part in this type of research and fill in the questionnaires more meticulously, which translates into greater credibility of the results. Another strength of our study was the comparison of nutrient intake to the recommendations, not just the absolute values in kcal, g, etc., as in other research, because recommendations sometime differ depending on the gender.
Overall, there was a large correlation between diet and the prevalence of FS, so it is necessary to undertake initiatives leading to improve the quality of diet of the elderly such as nutritional education for them and their care-givers, including senior center workers. Perhaps an additional educational campaign for Central Europeans should be introduced to explain the need for moderate balanced sun exposure without sunscreen or regular vitamin D supplementation [
49
]. As well, it would be good for primary care physicians to conduct obligatorily simple FS tests for the elderly, and then, depending on the results, recommend therapy or refer to another specialist, such as a dietician.
The above actions may consequently improve the nutritional status and health of older people.
5. Conclusions
We observed a relationship between the nutritional value of the diet and a few factors, especially the prevalence of frailty syndrome, attending a day care senior center, and probably vitamin D status (inadequate vitamin D intake and using sun cream during the summer months). Therefore, initiatives to improve the diet and vitamin D nutritional status of the elderly, especially with FS, are needed.
Informed consent was obtained from all subjects involved in the study.
Data Availability Statement
References
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Figure 1. Division of the respondents into clusters, by the Kohonen’s neural networks.
Figure 1. Division of the respondents into clusters, by the Kohonen’s neural networks.
Table 1. Sociodemographic characteristics of the study population by clusters.
Table 1. Sociodemographic characteristics of the study population by clusters.
Variable Cluster 1 [%] Cluster 2 [%] Cluster 3 [%] p Total n = 196 [%] n = 91 [46.4] n = 58 [29.6] n = 47 [24.0] Gender Men [ n = 82] 37.9 41.8 46.8 Ns (1) Women [ n = 114] 62.1 58.2 53.2 Age [years] Median (IQR) (range) 73 (8) 60–96 72 (6) 63–91 70 (6) 60–79 Ns (2) Marital status Lives alone [ n = 97] 53.5 47.3 48.9 Ns (1) Married/cohabiting [ n = 99] 46.5 52.7 51.1 Attending day care senior centers Yes [ n = 21] 20.7 8.8 2.1 0.0067 (1) Education level Primary [ n = 5] 5.2 2.2 0.0 Ns (1) Secondary [ n = 77] 50.0 34.1 36.2 Higher [ n = 114] 44.8 63.7 63.8 Occupation Yes [ n = 24] 6.9 13.2 17.0 Ns (1)
Clusters differ by the implementation level of nutritional standards for energy, protein, fat, calcium, iron, copper, and vitamins B1, B6, and B12—cluster 1, the lowest; cluster 2, moderate; cluster 3, the highest implementation; IQR—interquartile range; (1) Pearson Chi 2 test; (2) Kruskal-Wallis test; p -value ≤ 0.05; Ns—not statistically significant.
Table 2. Health variables of the study population by clusters.
Table 2. Health variables of the study population by clusters.
Variable Cluster 1 [%] Cluster 2 [%] Cluster 3 [%] p BMI [kg/m 2 ] Median (IQR) (range) 28.4 (7.6) (21.5–40.8) 27.5 (4.8) (20.2–38.6) 26.3 (6.3) (21.0–43.5) Ns (1) Self-rated health Good [ n = 98] 48.3 51.6 48.9 Ns (2) Average [ n = 85] 44.8 42.9 42.6 Poor [ n = 13] 6.9 5.5 8.5 Self-rated changes in health compared to last year Now better ab [ n = 15] 10.3 5.5 8.5 0.0373 (2) No change a [ n = 103] 36.2 57.1 63.8 Now worse b [ n = 78] 53.5 37.4 27.7 Cardiovascular disease Yes [ n = 68] 74.1 70.3 66.0 Ns (2) Chronic lung disease Yes [ n = 15] 6.9 6.6 10.6 Ns (2) Diabetes Yes [ n = 23] 20.7 9.9 4.3 0.0256 (2) Hospitalization Yes [ n = 37] 17.2 20.9 17.0 Ns (2) Leg pain when walking Yes [ n = 56] 43.1 24.2 19.1 0.0116 (2) Falls over the past year Yes [ n = 35] 20.7 20.9 8.5 Ns (2) Frailty syndrome Frail a [ n = 6] 6.9 1.1 2.1 0.0096 (2) Pre-frail a [ n = 76] 51.7 37.4 25.5 Non-frail b [ n = 114] 41.4 61.5 72.4 shrinking Yes [ n = 7] 6.9 3.3 0.0 Ns (2) weakness Yes [ n = 50] 36.2 23.1 17.0 0.0421 (2) exhaustion Yes [ n = 36] 29.3 13.2 14.9 0.0362 (2) low walking speed Yes [ n = 11] 13.8 2.2 2.1 0.0055 (2) physical inactivity Yes [ n = 16] 6.9 11.0 4.3 Ns (2) Sum of FS criteria 0 a [ n = 114] 41.4 61.5 72.3 0.0446 (2) 1 b [ n = 52] 32.7 26.4 19.2 2 b [ n = 24] 19.0 11.0 6.4 3 b [ n = 4] 5.2 0.0 2.1 4 ab [ n = 2] 1.7 1.1 0.0
Table 3. Variables of lifestyle and vitamin D intake of the study population by clusters.
Table 3. Variables of lifestyle and vitamin D intake of the study population by clusters.
Variable Cluster 1 [%] Cluster 2 [%] Cluster 3 [%] p Current smoking Yes [ n = 16] 8.6 5.5 12.8 Ns (1) Alkohol drinking Yes [ n = 140] 63.8 75.8 72.3 Ns (1) Self-rated physical activity High [ n = 52] 17.2 26.4 38.3 Ns (1) Average [ n = 104] 60.4 51.6 46.8 Low [ n = 40] 22.4 22.0 14.9 Exposed to sunlight last summer Never a [ n = 14] 2.2 15.5 6.4 0.0424 (1) Sometimes b [ n = 43] 24.2 20.7 19.2 Often b [ n = 139] 73.6 63.8 74.5 Use sun cream during summer months Always ab [ n = 32] 19.8 15.5 10.6 0.0291 (1) Often a [ n = 63] 39.6 19.0 34.0 Never b [ n = 101] 36.6 65.5 55.4 Dietary supplement use Yes [ n = 121] 56.9 68.1 55.3 Ns (1) Vitamin D supplementation Yes [ n = 56] 35.2 19.0 27.7 Ns (1) Vitamin D intake as % of AI (diet + supplements) Median (IQR) (range) 23.8 (23.2) (3.0–392.9) 38.4 (91.4) (8.2–519.9) 53.2 (73.7) (11.4–494.1) 0.0000 (2) Vitamin D intake as % of AI (diet only) Median (IQR) (range) 22.0 (19.0) (3.0–153.6) 26.2 (31.1) (8.2–189.1) 45.4 (48.3) (11.4–177.2) 0.0000 (2)
Clusters differ by the implementation level of nutritional standards for energy, protein, fat, calcium, iron, copper, and vitamins B1, B6, and B12—cluster 1, the lowest; cluster 2, moderate; cluster 3, the highest implementation; AI—Adequate Intake; IQR—interquartile range; (1) Pearson Chi 2 test; (2) Kruskal-Wallis test; a, b —different letters indicate a statistically significant differences between groups ( p -value ≤ 0.05); Ns—not statistically significant.
Article Metrics
MDPI and ACS Style
Rolf, K.; Santoro, A.; Martucci, M.; Pietruszka, B. The Association of Nutrition Quality with Frailty Syndrome among the Elderly. Int. J. Environ. Res. Public Health 2022, 19, 3379.
https://doi.org/10.3390/ijerph19063379
AMA Style
Rolf K, Santoro A, Martucci M, Pietruszka B. The Association of Nutrition Quality with Frailty Syndrome among the Elderly. International Journal of Environmental Research and Public Health. 2022; 19(6):3379.
https://doi.org/10.3390/ijerph19063379
Chicago/Turabian Style
Rolf, Katarzyna, Aurelia Santoro, Morena Martucci, and Barbara Pietruszka. 2022. "The Association of Nutrition Quality with Frailty Syndrome among the Elderly" International Journal of Environmental Research and Public Health19, no. 6: 3379.
https://doi.org/10.3390/ijerph19063379
| https://www.mdpi.com/1660-4601/19/6/3379 |
A History Of Costumes: Vintage Halloween Photos - Paperblog
Dressing up is a really important part of human life. We don’t dress up only in everyday or function clothing, but in the global culture we also dress up as someone else for certain occasion.
A History Of Costumes: Vintage Halloween Photos
Dressing up is a really important part of human life. We don’t dress up only in everyday or function clothing, but in the global culture we also dress up as someone else for certain occasion. This goes for almost every culture and every space in any time. The people who lived in African tribes used to wear masks for certain rituals, while others wore masks on holidays.
Wearing a mask is something embedded in the human spirit. It’s context is wide and somewhat unclear. By wearing a mask, you become someone else. In ancient times, it was a normal thing to wear a mask when you wanted to do something or take on a role. To give you an example, certain groups used to wear masks or paint their bodies (another form of the same concept) when they would go to war. This way, the war spirits would take over their bodies, or better said, they would become these war spirits and their victory was easier to obtain. In a way we can say that this is associated with unexpressed guilt, since it was acceptable to do certain things while wearing a mask that were otherwise unacceptable. But we can’t dig too deep into this, since we can’t exactly know how people thought in those days.
Halloween is one of the most known and celebrated costume-related holidays in the Western world today. It’s not similar to other holidays where people dress up such as the Italian carnival or the Jewish holiday of Purim.
An ancient turnip lantern found in Ireland
Halloween is a rather somber holiday. It originated in the old Celtic civilization (today’s Ireland and Scotland),even though it seems that it’s actual origin was in the Bronze Age. The Celts would call it Samhain (pronounced sah-win). At that time, October 31st marked the end of the old year; the end of the summer and the death of the sun; hence the whole death-element that Halloween has attached to it. In short, it was believed that people could actually come into contact with the spirits of the other world in this night. The holiday itself derived many legends and customs, the most known is of course the Jack O’Lantern pumpkin, which originated in the custom of farmers putting candles in turnips to light their way home from the land they worked. Many years later, when the immigrants came to America, they kept the custom, just that they used pumpkins.
Let’s come back to the dressing up part of it though. It appears that the custom of dressing up appeared in the Middle Ages and includesChristmaswassailing. By the way, an alternate name for Halloween is All Hallows’ Eve or Hallowmas (resembling the name Christmas). However, it was only in the late 1800s when people started throwing costume parties.
The tradition of trick-or-treat-ing appeared as we know it in the 1930s, when, because of many violent happenings on the night of Halloween, the American authorities decided to transform the holiday into a kid’s holiday. However, the custom has it’s origins in the late medieval concept of “souling”. Souling means that a poor person would go from door to door on Hallowmas (November 1st) to ask for food. That person was given food in the return of his prayers on All Souls Day (November 2nd). Of course, there is a big Christian, especially Catholic influence there, which mixed the old pagan holiday with the Celtic New Year, the holiday of the dead and All Saints’ Day.
It’s really hard to actually trace the history and concept of Halloween without having to constantly go back and forth, since traditions, concepts and ideas seem to overlap. They are all tight up to each other in a way. Souling became trick-or-trat-ing, now done by kids in costumes. According to several sources, people used to dress up on Halloween to scare the bad spirits away or to please them. It is kind of complicated to understand this: did they want to scare them or to please them? Probably both, but at different times in history. It would make sense if we agree that the people of the past thought this night was a gateway to another world, and that they would do anything to avoid creatures from another world, by either scaring them away (although if you wish to scare a ghost away, why dress like one?) or to make them think you’re one of them. Just imagine what this would have been like. There are very few documents to speak about Halloween from the past.
It remains to be seen where Halloween is heading in the future, but one thing is for sure: it’s a more complicated holiday than we think and it’s really the expression of our history and the way we changed and evolved from ancient times to the modern era.
Fraquoh and Franchomme
P.S. What do you think of Halloween? Is it celebrated where you live? Share your thoughts in the comments below!
| https://en.paperblog.com/a-history-of-costumes-vintage-halloween-photos-685788/ |
Icentia11k Single Lead Continuous Raw Electrocardiogram Dataset v1.0
This is a dataset of continuous raw electrocardiogram (ECG) signals for representation learning containing 11 thousand patients and 2 billion labelled beats.
Icentia11k Single Lead Continuous Raw Electrocardiogram Dataset
Shawn Tan, Satya Ortiz-Gagné, Nicolas Beaudoin-Gagnon, Pierre Fecteau, Aaron Courville, Yoshua Bengio, Joseph Paul Cohen
Published: April 12, 2022. Version:
1.0
When using this resource, please cite:(show more options) Tan, S., Ortiz-Gagné, S., Beaudoin-Gagnon, N., Fecteau, P., Courville, A., Bengio, Y., & Cohen, J. P. (2022). Icentia11k Single Lead Continuous Raw Electrocardiogram Dataset (version 1.0). PhysioNet . https://doi.org/10.13026/kk0v-r952 .
Additionally, please cite the original publication:
Tan, S., Androz, G., Ortiz-Gagné, S., Chamseddine, A., Fecteau, P., Courville, A., Bengio, Y., & Cohen, J. P. (2021, October 21). Icentia11K: An Unsupervised Representation Learning Dataset for Arrhythmia Subtype Discovery. Computing in Cardiology Conference (CinC).
Please include the standard citation for PhysioNet:(show more options) Goldberger, A., Amaral, L., Glass, L., Hausdorff, J., Ivanov, P. C., Mark, R., ... & Stanley, H. E. (2000). PhysioBank, PhysioToolkit, and PhysioNet: Components of a new research resource for complex physiologic signals. Circulation [Online]. 101 (23), pp. e215–e220.
Abstract
This is a dataset of continuous raw electrocardiogram (ECG) signals containing 11 thousand patients and 2 billion labelled beats. The signals were recorded with a 16-bit resolution at 250Hz with a fixed chest mounted single lead probe for up to 2 weeks. The average age of the patient is 62.2±17.4 years. 20 technologists annotated each beat's type (Normal, Premature Atrial Contraction, Premature Ventricular contraction) and rhythm (Normal Sinusal Rhythm, Atrial Fibrillation, Atrial Flutter).
Background
Arrhythmia detection is presently performed by cardiologists or technologists familiar with ECG readings. Recently, supervised machine learning has been successfully applied to perform automated detection of many arrhythmias [1,2,3,4]. However, there may be ECG anomalies that warrant further investigation because they do not fit the morphology of presently known arrhythmia. We seek to use a data driven approach to finding these differences that cardiologists have anecdotally observed. Existing public ECG datasets include the the MIMIC-III Waveform Database and the ECG-ViEW II dataset [5,6]. Here we present Icentia11k, a dataset of continuous raw electrocardiogram (ECG) signals containing 11 thousand patients and 2 billion labelled beats
Methods
Our data is collected by the CardioSTAT, a single-lead heart monitor device from Icentia [7]. The raw signals were recorded with a 16-bit resolution and sampled at 250Hz with the CardioSTAT in a modified lead 1 position. The wealth of data this provides us can allow us to improve on the techniques currently used by the medical industry to process days worth of ECG data, and perhaps to catch anomalous events earlier than currently possible.
The dataset is processed from data provided by 11,000 patients who used the CardioSTAT device predominantly in Ontario, Canada, from various medical centers. While the device captures ECG data for up to two weeks, the majority of the prescribed duration of wear was one week.
The data is analyzed by Icentia's team of 20 technologists who performed annotation using proprietary analysis tools. Initial beat detection is performed automatically and then a technologist analyses the record labelling beat and rhythm types performing a full disclosure analysis (i.e. they see the whole recording). Finally the analysis is approved by a senior technologist before making it to the dataset.
The ethics institutional review boards at the Université de Montréal approved the study and release of data (CERSES-19-065-D).
Data Description
We segment each patient record into segments of 2 20 + 1signal samples (≈70 minutes). This longer time context was informed by discussions with technologists: the context is useful for rhythm detection. We made it a power of two with a middle sample to allow for easier convolution stack parameterization. From this, we randomly select 50 of the segments and their respective labels from the list of segments. The goal here is to reduce the size of the dataset while maintaining a fair representation of each patient.
Data structure
The data is structured into patients and segments.
Patient level (3-14 days)
At this level, the data can capture features which vary in a systematic way and not isolated events, like the placement of the probes or patient specific noise.
Segment level (1,048,577 int16 samples, approximately 1 hour)
A cardiologist can look at a specific segment and identify patterns which indicate a disease while ignoring noise from the signal such as a unique signal amplitude. Looking at trends in the segment help to correctly identify arrhythmia as half an hour provides the necessary context to observe the stress of a specific activity.
Aggregate statistics
Aggregate statistics are shown below:
Statistic # (units) Number of patients 11,000 Number of labeled beats 2,774,054,987 Sample rate 250Hz Segment size 2 20 + 1 = 1,048,577 Total number of segments 541,794 (not all patients have enough for 50 segments)
Beats are annotated in ann.symbols at the R timepoint in the QRS complex. The timepoint in the rec.signal for each annotation is found in ann.sample Below shows the counts for beats over the entire dataset. There are also annotations with a '+' symbol which just mean there is a rhythm annotation (next table).
Symbol Beat Description Count
N Normal 2,061,141,216
S ESSV (PAC): Premature or ectopic supraventricular beat, premature atrial contraction 19,346,728
V ESV (PVC): Premature ventricular contraction, premature ventricular contraction 17,203,041
Q Undefined: Unclassifiable beat 676,364,002
Rhythms are annotated in ann.aux_note at each timepoint. For example a normal sinusal rhythm will start with a '(N' annotation and then end with a ')' annotation. The entire sequence in between is annotated as a normal sinusal rhythm. Below are the counts of each annotated region which could be one beat or thousands.
Symbol Rhythm Labels Count (N ... ) NSR (Normal sinusal rhythm) 16,083,158 (AFIB ... ) AFib (Atrial fibrillation) 848,564 (AFL ... ) AFlutter (Atrial flutter) 313,251
Details on how the dataset is encoded into wfdb format are available on GitHub [8].
Usage Notes
By releasing this dataset, we seek to enable the research community to develop better models for detection of arrhythmia and related heart disease. The dataset is described in more detail in our accompanying paper [9], which also describes our efforts to evaluation existing models for classification of arrhythmia. Code for working with the data, including executable notebooks, is available on GitHub [8].
Example code
To look at patient 9000 and segment 0 the filename would be: p09/09000/p09000_s00 and it can loaded using wfdb as follows:
import wfdb
patient_id=9000
segment_id=0
start=2000
length=1024
filename = f'{data_path}/p0{str(patient_id)[:1]}/p{patient_id:05d}/p{patient_id:05d}_s{segment_id:02d}'
rec = wfdb.rdrecord(filename, sampfrom=start, sampto=start+length)
ann = wfdb.rdann(filename, "atr" , sampfrom=start, sampto=start+length, shift_samps=True)
wfdb.plot_wfdb(rec, ann, plot_sym=True, figsize=(15,4));
Limitations
It should be noted that since the people who wear the device are patients, the dataset does not represent a true random sample of the global population. For one, the average age of the patient is 62.2±17.4 years of age. Furthermore, whereas the CardioSTAT can be worn by any patient, it is mostly used for third line exam, so the majority of records in the dataset exhibit arrhythmias. No particular effort has been done on patient selection except data collection has been conducted over years 2017 and 2018.
Release Notes
Version 1.0: First release on PhysioNet. Prior to this release data was made available on AcademicTorrents [10].
Ethics
The authors declare no ethics concerns. The ethics institutional review boards at the University of Montreal approved the study and release of data (#CERSES-19-065-D).
Acknowledgements
We thank Leon Glass, Yannick Le Devehat, Germain Ethier, and Margaux Luck, Kris Sankaran, and Gabriele Prato for useful discussions. This work is partially funded by a grant from Icentia, Fonds de Recherche en Santé du Québec, and the Institut de valorisation des donnees (IVADO). This work utilized the supercomputing facilities managed by Compute Canada and Calcul Quebec. We thank AcademicTorrents.com for making data available for our research.
Conflicts of Interest
None
References
Hannun AY, Rajpurkar P, Haghpanahi M, Tison GH, Bourn C, Turakhia MP, Ng AY. Cardiologist-level arrhythmia detection and classification in ambulatory electrocardiograms using a deep neural network. Nature Medicine 2019
Yıldırım O, Pławiak P, Tan RS, Acharya UR. Arrhythmia detection using deep convolutional neural network with long duration ecg signals. Computers in biology and medicine 2018.
Minchole A, Rodriguez B. Artificial intelligence for the electrocardiogram. Nature Medicine 1 2019.
Porumb M, Iadanza E, Massaro S, Pecchia L. A convolutional neural network approach to detect congestive heart failure. Biomedical Signal Processing and Control 2020.
Johnson, A., Pollard, T., & Mark, R. (2016). MIMIC-III Clinical Database (version 1.4). PhysioNet. https://doi.org/10.13026/C2XW26.
Kim YG, Shin D, Park MY, Lee S, Jeon MS, Yoon D, Park RW. ECG-ViEW II, a freely accessible electrocardiogram database. PloS one 2017.
Icentia website. https://www.icentia.com/
Icentia11k project on GitHub. https://github.com/shawntan/icentia-ecg/tree/master/physionet
Tan, S., Androz, G., Ortiz-Gagné, S., Chamseddine, A., Fecteau, P., Courville, A., Bengio, Y., & Cohen, J. P. (2021, October 21). Icentia11K: An Unsupervised Representation Learning Dataset for Arrhythmia Subtype Discovery. Computing in Cardiology Conference (CinC). https://www.cinc.org/2021/Program/accepted/229_Preprint.pdf
Icentia11k Dataset on Academic Torrents. https://academictorrents.com/details/af04abfe9a3c96b30e5dd029eb185e19a7055272
License (for files):Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International Public License
Discovery
DOI:https://doi.org/10.13026/kk0v-r952
Topics: representation learning ecg
Project Website:https://github.com/shawntan/icentia-ecg
Corresponding Author
Files
Total uncompressed size: 1.1 TB.
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Download the ZIP file (188.3 GB)
Download the files using your terminal:
wget -r -N -c -np https://physionet.org/files/icentia11k-continuous-ecg/1.0/
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(PDF) Analysis of Urban Morphological Effect on the Microclimate of the Urban Residential Area of Kampung Baru in Kuala Lumpur Using a Geospatial Approach
PDF | As a Malay Agricultural Settlement established in 1900, Kampung Baru which is located in Kuala Lumpur, has become a subject of prolonged national... | Find, read and cite all the research you need on ResearchGate
Analysis of Urban Morphological Effect on the Microclimate of the Urban Residential Area of Kampung Baru in Kuala Lumpur Using a Geospatial Approach
September 2020
Sustainability 12(18):7301
DOI: 10.3390/su12187301
Show all 8 authors Hide
Abstract and Figures
As a Malay Agricultural Settlement established in 1900, Kampung Baru which is located in Kuala Lumpur, has become a subject of prolonged national interests in terms of economic, social, environment, and political issues along with the pressure of modern and future development. This study investigated the urban morphological impact of Kampung Baru on the intensity of urban heat island (UHI) by developing a smart geodatabase for urban climatic mapping. The database provided baseline data which was crucial to unveil the spatiotemporal characteristics of UHI in Kampung Baru. Determination of the urban heat island intensity (UHII) in Kampung Baru was carried out through two approaches, mobile and fixed measurements. In a period of six days, the mobile measurement was conducted within the target area at night using a motorcycle equipped with the temperature and relative humidity data logger while the fixed measurement was conducted using the similar equipment installed at a school building in the area. Building height data were also collected while building footprints were digitized using a topographical map and the satellite image was used as the base map. To estimate the UHII, the reference data for rural temperature was obtained from the Malaysian Meteorological Department (MMD). All of the data were analyzed using ArcGIS to portray the temperature pattern in the study area. The analysis revealed the presence of UHI effect in Kampung Baru at the average building height of six to ten metres. The results of the fixed measurement showed an island-like local maximum in the study area with the average and maximum UHII values of 4.4 °C and 6.0 °C, respectively. The results from the mobile measurement also showed that the highest temperature was recorded in Kampung Baru rather than in the surrounding areas of different land-use types throughout the observation days. The spatial temperature distribution in the study area also showed that the most affected part was the south-west of Kampung Baru which is surrounded by tall buildings. The findings of this study could be utilized in the planning of new development in the city of Kuala Lumpur.
Route of the mobile measurement (red line) which covered the study area of Kampung Baru and 500 m in the vicinity (Source: Google Wikimapia, 2017). …
3D view of Kampung Baru. Buildings are color-coded based on land-use classification. Figure 8. 3D view of Kampung Baru. Buildings are color-coded based on land-use classification. …
Example of the temperature distribution in Kampung Baru. Figure 11. Example of the temperature distribution in Kampung Baru. …
Cont. …
Instrument specifications and settings of the MJIIT-CS weather station. …
Figures - available via license: Creative Commons Attribution 4.0 International
Content may be subject to copyright.
sustainability
Article
Analysis of Urban Morphological E ff ect on the
Microclimate of the Urban Residential Area of
Kampung Baru in Kuala Lumpur Using a
Geospatial Approach
Sheikh Ahmad Zaki 1, * , Nor Suhada Azid 1 , Mohd Fairuz Shahidan 2, * ,
Mohamad Zaki Hassan 3 , Mohd Yusof Md Daud 3 , Nor Azlina Abu Bakar 2 ,
Mohamed Sukri Mat Ali 1 and Fitri Yakub 1
1 Malaysia-Japan International Institute of T echnology , Universiti T eknologi Malaysia, Jalan Semarak,
Kuala Lumpur 54100, Malaysia; [email protected] (N.S.A.); [email protected] (M.S.M.A.);
mfi[email protected] (F .Y .)
2 Faculty of Design and Architecture, Universiti Putra Malaysia, Serdang 43400, Selangor , Malaysia;
[email protected]
3 Razak Faculty of T echnology and Informatics, Universiti T eknologi Malaysia, Jalan Sultan Y ahya Petra,
Kuala Lumpur 54100, Malaysia; [email protected] (M.Z.H.); [email protected] (M.Y .M.D.)
* Correspondence: [email protected] (S.A.Z.); [email protected] (M.F.S.)
Received: 8 August 2020; Accepted: 3 September 2020; Published: 6 September 2020
Abstract:
As a Malay Agricultural Settlement established in 1900, Kampung Baru which is located in
Kuala Lumpur, has become a subject of pr olonged national interests in terms of economic, social,
environment, and political issues along with the pressure of modern and future development.
This study investigated the urban morphological impact of Kampung Baru on the intensity of urban
heat island (UHI) by developing a smart geodatabase for urban climatic mapping. The database
provided baseline data which was crucial to unveil the spatiotemporal characteristics of UHI in
Kampung Baru. Determination of the urban heat island intensity (UHII) in Kampung Baru was carried
out through two approaches, mobile and fixed measurements. In a period of six days, the mobile
measurement was conducted within the target area at night using a motor cycle equipped with the
temperature and relative humidity data logger while the fixed measurement was conducted using the
similar equipment installed at a school building in the area. Building height data were also collected
while building footprints were digitized using a topographical map and the satellite image was
used as the base map. To estimate the UHII, the refer ence data for rural temperature was obtained
from the Malaysian Meteorological Department (MMD). All of the data were analyzed using ArcGIS
to portray the temperature pattern in the study area. The analysis revealed the presence of UHI
e ff ect in Kampung Baru at the average building height of six to ten metres. The results of the fixed
measurement showed an island-like local maximum in the study area with the average and maximum
UHII values of 4.4
◦
C and 6.0
◦
C, respectively . The results from the mobile measurement also showed
that the highest temperature was recorded in Kampung Baru rather than in the surr ounding areas of
di ff erent land-use types throughout the observation days. The spatial temperature distribution in the
study area also showed that the most a ff ected part was the south-west of Kampung Baru which is
surrounded by tall buildings. The findings of this study could be utilized in the planning of new
development in the city of Kuala Lumpur.
Keywords: urban heat island; ArcGIS; urban climatic mapping; mobile measurement
Sustainability 2020 , 12 , 7301; doi:10.3390 / su12187301 www.mdpi.com / journal / sustainability
Sustainability 2020 , 12 , 7301 2 of 29
1. Introduction
The local climate of an urban area is usually di ff erent from that of the surrounding ar ea.
Urban climate
is influenced by urban heat island (UHI) which refers to the relative warmness of a
city [
1
]. UHI was determined in some studies as a comparison of the mean and maximum temperatures
between urban and rural areas. In certain research, the temperatures were compar ed, such as between
seasons, months, years or days. Study has shown that UHI problems are worsening as a result of urban
growth and heavy industrialization that tends to trigger changes in the urban temperature [
2
]. With the
increase in the global urban population as a result of urbanization, the e ff ect of the UHI phenomenon
is getting worse. It has worsened as more vegetated areas and permeable lands are transformed into
urban areas, hence resulting in the increase of albedo [
3
,
4
]. Albedo is the amount of solar energy that
is reflected by the surface to the surrounding area. Other factors that contribute to UHI e ff ects ar e
building thermal properties, urban form, and anthropogenic heat release [
5
,
6
]. Magee [
7
] described
UHI as the average temperature change between the urban and rural areas in Fairbanks, Alaska.
Mean urban and rural temperature patterns were used to determine the occurrence of UHI. Moreover ,
the temperature trends of an area before and after urbanization illustrated the influence of urbanization
on the occurrence of UHI. However , historical records of temperature data obtained before urbanization
of most cities are not available, and this creates an obstacle for studying UHI. This trend has become
significant in the tropics where the lack of shade and greenery has r esulted in a failure to o ff set the heat
from direct solar gain. Moreover , the use of dark materials in buildings and hard pavements causes the
increase in heat absorption, thereby contributing to high urban temperature. Besides, changes in urban
morphology , particularly in the tropical urban areas, influence local microclimates which directly
increases the UHI e ff ect [
8
–
10
]. A report by Nieuwolt [
11
], which was one of the earliest tropical urban
microclimatic studies, was conducted in Singapore. This was followed by numerous studies on the
heat island intensity in tropical cities around the globe, which contributed to the understanding of
the UHI phenomenon [
8
,
12
]. In regar d to Malaysia, work in this field was pioneered by Sham [
13
]
who investigated the UHI intensity in selected Malaysian cities and discovered that the heat island
intensity ranged from 2
◦
C to 7
◦
C.
More specifically
, the study found that the heat island intensity on
clear days in Kuala Lumpur was about 6
◦
C. Several studies have since been carried out to evaluate the
heat island intensity in other urban centers in Malaysia [
14
,
15
]. Moreover, previous studies on UHI in
Kuala Lumpur have reported that UHI has major e ff ects on thermal comfort, human health, pollution,
societal economy , and meteorology and climate. Policymakers, local governments, and engineers must
therefore consider the factors that contribute to the UHI phenomenon before designing and developing
new urban areas [
16
–
19
]. Nevertheless, there has been no detailed study to investigate the microclimate
of Kampung Baru in terms of weather patterns and e ff ects of UHI. Kampung Baru is chosen as a case
study since it is one of the most densely populated suburban areas in Kuala Lumpur . Moreover, it is
located less than 5 km from the city center where high-rise buildings such as the Petronas T win T ower
and the Kuala Lumpur T ower (KL Tower) dominate the city’s skyline. The development of an urban
area should prioritize the mitigation of UHI e ff ects [
16
–
20
]. Specific considerations are investigated
for determining UHI e ff ects from urban morphological characteristics. These include diminishing
greenery due to increased urban growth, materials used to construct skyscrapers, reshaping of the
city’s architectural forms, building scale extension, growing anthropogenic heat production, and other
additional factors such as climate change and spatial location of the area [ 21 , 22 ].
In order to carry out the comprehensive analysis of UHI, acquisition and processing of r emote
sensing data were implemented by the ArcGIS software. Daytime and nighttime thermal data were
loaded into the ArcGIS software and analyzed by a spatial analyst module. Besides, the land-use
layer was used to extract the statistical data of each individual land-use type [
22
]. Urban morphology
database can be used widely in many applications, and one of the applications is the UHI analysis that
had been used in previous researches [
23
,
24
]. Mapping, monitoring, and modeling of urbanization
progress with regard to climate change r equires holistic and integrated approaches. Geo-information
technology is one of the promising tools to analyze the UHI phenomenon in terms of spatial and
Sustainability 2020 , 12 , 7301 3 of 29
temporal resolutions more e ff ectively [
24
,
25
]. Utilizing the aforementioned tools and comprehensive
approaches, this study investigated the urban morphological impact of Kampung Baru on the intensity
of urban heat island (UHI) by developing a smart geodatabase for urban climatic mapping.
2. Methodology
2.1. Study Area
Kampung Baru, Kuala Lumpur, is geographically located at latitude 3
◦
09
0
N and longitude 101
◦
43
0
E, covering approximately 301.38 acres lying between the Klang River and Batu Road, as shown in
Figure 1 . Kampung Baru has been established since 1899 by the British government and was put under
the administration of the Kuala Lumpur City Hall in February 1972 [
26
]. The surrounding environment
of the study area presents the topography of a compact urban area, surr ounded by various commercial
buildings such as the Kuala Lumpur City Center (KLCC). It is a traditional and contemporary domestic
residential area situated within the capital of Malaysia.
Sustainability 2020 , 12 , x FOR PEER REVIEW 3 of 31
comprehensive approaches, this study investigated the urban morphological impact of Kampung
Baru on the intensity of urban heat island (UHI) by developing a smart geodatabase for urban climatic
mapping.
2. Methodology
2.1. Study Area
Kampung Baru, Kuala Lumpur, is geographically located at latitude 3°09 ′ N and longitude
101°43 ′ E, covering approximately 301.38 acres lying between the Klang River and Batu Road, as
shown in Figure 1. Kampung Baru has been established since 1899 by the British government and
was put under the administration of the Kuala Lumpur City Hall in February 1972 [26]. The
surrounding environment of the study area presents the topography of a compact urban area,
surrounded by various commercial buildings such as the Kuala Lumpu r City Center (KLCC). It is a
traditional and contemporary domestic residential area situated within the capital of Malaysia.
Figure 1. Study area at Kampung Baru, Kuala Lumpur (Google Maps, 2018).
The older part of Kampung Baru was characterized by densely packed buildings of single and
double ‐ story houses with non ‐ uniform footprints. A large part of this enclave is full of traditional
houses, built about 100 years ago. Some parts of this area generally have taller buildings that are
mainly residential apartments or commercial buildings. In this study, the whole area of Kampung
Baru was focused on the investigation of the influence of a densely packed built area on the urban
climate. The vicinity located within 500 m from the study area was also included in this investigation.
2.2. Building Morphology
In this study, 3D building models were created using a low ‐ cost technique (i.e., utilizing the on ‐
site database and human resources) rather than using a satellite image and aerial photography or
Light Detection and Ranging (LIDAR). In fact, the low ‐ cost technique was preferred to be used in this
study since the on ‐ site database and human resources were readily available and easily handled . In
the past, one of the main difficulties of the morphometric approach was the limited availability of
Figure 1. Study area at Kampung Baru, Kuala Lumpur (Google Maps, 2018).
The older part of Kampung Baru was characterized by densely packed buildings of single and
double-story houses with non-uniform footprints. A large part of this enclave is full of traditional
houses, built about 100 years ago. Some parts of this area generally have taller buildings that are
mainly residential apartments or commercial buildings. In this study, the whole area of Kampung
Baru was focused on the investigation of the influence of a densely packed built area on the urban
climate. The vicinity located within 500 m from the study area was also included in this investigation.
2.2. Building Morphology
In this study , 3D building models were created using a low-cost technique (i.e., utilizing the
on-site database and human resources) rather than using a satellite image and aerial photography or
Light Detection and Ranging (LIDAR). In fact, the low-cost technique was preferred to be used in this
study since the on-site database and human resources were r eadily available and easily handled. In the
Sustainability 2020 , 12 , 7301 4 of 29
past, one of the main di ffi culties of the morphometric approach was the limited availability of data
describing urban texture. In this study , the purpose of using a low-cost instrument to comprehensively
collect building height data is relevant. Collection of the building height data in the study area was
completed in about two months. All buildings on the map were individually checked and identified
on the study site.
Building height was measured from the ground level using the T ruPulse 200L laser rangefinder.
This method of building height determination was based on the development of digital elevation
models (DEM) and comparative morphological analysis in the Northern European and North American
cities [ 27 ].
Building height data was used to calculate urban morphological parameters. The measuring
instrument is able to distinguish between near and far objects. To make use of the full nominal accuracy
of the instrument (0.5 m), it was placed in front of a building’s façade and a set of three auxiliary
measurements were then performed.
The measurement was performed repeatedly on multiple targets, and the results wer e compared
to detect any uncertainty in the data. Basically , three to five measurements were found to be enough
because the results of each measurement were almost constant. Besides, the instrument that was new
was calibrated by the manufacturer and used for the first time in this data collection. This contributed
to the accuracy and consistency of measured data.
In this study , building footprints were digitized from the topographic map of Kuala Lumpur,
for which the last survey was in 2004. The sheet number of the map is 16 and the scale of the map is
1:10,000. The building footprints depict the placement of each building and are possibly linked with
data acquisition of the building height collected in a particular area. The building footprints were
digitized for all buildings using the ArcGIS software. The high-resolution satellite image taken in 2013
was overlaid with the topographic map to update the existing buildings in the study area. All buildings
on the map and satellite image were checked and identified on the site. For some buildings, the building
footprint was found to be less accurate and this would be corrected after identifying and measuring
them on the site. Every building was described by a 2D polygon with specific attributes corresponding
to its footprint and rooftop elevation.
The building height data collection is one of the most critical parts in constructing the 3D model
of the building footprints that had been digitized. The building height was measured from the ground
level using a distance meter, T ruPulse 200L. The instrument was positioned at two to three meters
from the building façade, as shown in Figure 2 . Using the TruPulse 200L, two measurements wer e
taken, perpendicular to the desired length and the other two measurements were at inclination. For the
building morphology application, each building is simply represented by a single polygon of uniform
shape with height [ 28 ].
The method used to measure height of a building is known as the technique of three shots. First,
to measure slope distance, the laser rangefinder was directed straight to the building’s line of sight, d .
Next, the laser rangefinder was specifically aimed at the bottom of the building to measure the slope
angle of
θ 2
, and next to the building’s highest point to measure the slope angle of
θ 1
. Based on the
Pythagorean theorem, the building height was then calculated.
A verage building height of an area represents the depth of the buildings in urban canopy .
The information
can be used as a first-order approximation of the surface roughness, z
0
, when
multiplied by the proportionality constant [
29
]. In this section, the height characteristics were
summarized for the case study of Kampung Baru. Equations (1) and (2) were used to calculate the
mean and standard deviation of building height.
h = P N
i = 1 h i
N (1)
S h = P N
i = 1 h i − h 2
N (2)
Sustainability 2020 , 12 , 7301 5 of 29
where,
h
is the average building height,
s h
is the standard deviation of building height,
h i
is the height
of building
i
, and
N
is the total number of buildings in the area. The mean building height of Kampung
Baru varies depending on the land-use type.
Sustainability 2020 , 12 , x FOR PEER REVIEW 5 of 31
Figure 2. Schematic diagram of building height measurement performed using TruPulse 2 00L. Letters
( a and b ) refer to the segmented distances measured based on the slope angles, θ 1 and θ 2 , to obtain the
height of building, H while c , d , and e represent the measured slope distance.
Building plan area fraction, λ p , is defined as the ratio of the plan area of buildings to the total
surface area of the target region. This parameter represents the density of buildings in an area
whereby a higher λ p indicates a higher density of the buildings in a particular area. λ p is calcula ted
using Equation (3):
𝜆
𝐴
𝐴
(3)
where, 𝐴 is the sum of the areas of the building footprints and 𝐴 is the total plan area.
2.3. Field Measurement
In this study, two methods of data collection were conducted. The first measurement was done
using a fixed station and the second method was done using a mobile measurement technique. This
section briefly explains about the instruments used to collect the climate data and data collection
procedure.
2.3.1. Instrumentation
Campbell Scientific CR1000 data logger is the instrument used as a fixed station (hereaft er
referred to as ‘MJIIT ‐ CS’). It was installed at the rooftop of MJIIT, UTMKL (3°10 ′ N, 101°43 ′ E) at the
height of 68.0 m from the ground level. The MJIIT building is situated approximately one kilometer
from the study area (i.e., Kampung Baru). It was set to log the data at a one ‐ min interval. The sensors
can measure air temperature, relative humidity, and solar radiation. The data logger was attached to
the CS215 temperature and humidity sensor probe and Apogee SP110 self ‐ powered pyranometer,
and covered by a so lar radiation shield as shown in Figure 3. The collected data is stored in the built ‐
in data logger. Table 1 summarizes the instrument spe cifications and settings of the MJIIT ‐ CS weather
station.
Figure 2.
Schematic diagram of building height measurement performed using T ruPulse 200L. Letters
( a and b ) refer to the segmented distances measured based on the slope angles,
θ 1
and
θ 2
, to obtain the
height of building, H while c , d , and e represent the measured slope distance.
Building plan area fraction,
λ p
, is defined as the ratio of the plan area of buildings to the total
surface area of the target region. This parameter represents the density of buildings in an area whereby
a higher
λ p
indicates a higher density of the buildings in a particular area.
λ p
is calculated using
Equation (3):
λ p =
A p
A T
(3)
where, A p is the sum of the areas of the building footprints and A T is the total plan area.
2.3. Field Measurement
In this study , two methods of data collection were conducted. The first measurement was done
using a fixed station and the second method was done using a mobile measurement technique.
This section briefly explains about the instruments used to collect the climate data and data
collection procedure.
2.3.1. Instrumentation
Campbell Scientific CR1000 data logger is the instrument used as a fixed station (hereafter referred
to as ‘MJIIT-CS’). It was installed at the rooftop of MJIIT , UTMKL (3
◦
10
0
N, 101
◦
43
0
E) at the height
of 68.0 m from the ground level. The MJIIT building is situated approximately one kilometer from
the study area (i.e., Kampung Baru). It was set to log the data at a one-min interval. The sensors
Sustainability 2020 , 12 , 7301 6 of 29
can measure air temperature, relative humidity , and solar radiation. The data logger was attached
to the CS215 temperature and humidity sensor probe and Apogee SP110 self-powered pyranometer ,
and covered by a solar radiation shield as shown in Figure 3 . The collected data is stored in the
built-in data logger. Table 1 summarizes the instrument specifications and settings of the MJIIT -CS
weather station.
Sustainability 2020 , 12 , x FOR PEER REVIEW 6 of 31
( a ) ( b )
( c )
Figure 3. Campbell Scientific weather station: ( a ) Campbell Scientific CR1000 data logger installed at
MJIIT rooftop, ( b ) CR1000 data loggers and ( c ) Apogee SP100 pyranometer.
Table 1. Instrument specifications and settings of the MJIIT ‐ CS weather station.
Data Logger Model Climatic Variables Accuracy T.I.
H.A.G.
(m) Period
Campbell
Scientific CR1000
CSL 215 ‐ L
Temp/RH Probe
Air Temp. ±0.3 °C
10.0
min ~68.0 March 2014–
February 2015
Relative Humidity ±4.0%
SP 110 ‐ L
Apogee
Silicon Pyranometer
Solar Radiation ±5.0% for daily
total radiation
Note: T.I. = time interval and H.A.G. = height above ground.
The data logger, Hobo pro ‐ V2, was fitted with built ‐ in air temperature and relative humidity
sensors. This data logger was used for mobile measurement and as a fixed station at the study area,
as shown in Figure 4. One set of Hobo pro ‐ V2 data logger was used as a fixed station for six days at
a one ‐ second time interval. Meanwhile, three (3) sets of Hobo pro ‐ V2 were used during the mobile
measurement. The sensors were mounted at a height of 2.5 m above the ground and sh ielded with a
solar radiation shield to prevent direct solar radiation exposure; otherwise, that will impact the
± 0.21 ◦ C from 0 ◦ to 50 ◦ C
( ± 0.38 ◦ F from 32 ◦ to 122 ◦ F)
5 min in air moving
at 1 m / s
Relative humidity 0% to 95% RH
± 2.5% from 10% to 90% RH
(typical), to a maximum of
± 3.5%
5 min in air moving
at 1 m / s with
protective cap
2.3.2. Site Selection
In this study , the selected locations were referenced as ‘environmental settings’ during the data
collection. Table 3 summarizes the types of land-use categories for urban climate data collection.
In fact, the six land-use categories that were selected in this study represent the majority and diversity
of environmental settings in Kampung Baru and its surrounding area. This is essential for better
understanding of the local microclimate during the site investigation.
The first element represents a body of water , i.e., pond, which is situated at Titiwangsa Lake
Gardens. The second element is a park which is also situated at Titiwangsa Lake Gardens. The next
Sustainability 2020 , 12 , 7301 8 of 29
element is a highway which refers to Jalan T un Razak. Along the highway , there are buildings such as
hospitals, schools, petrol stations, shop lots, and so on.
T able 3.
Di ff erent types of land-use categories for urban climate data collection using mobile
measurement.
No. Element Location Picture Location
1. W ater / pond
Sustainability 2020 , 12 , x FOR PEER REVIEW 8 of 31
Table 3. Different types of land ‐ use categories for urban climate data collection using mobile
measurement.
No. Element Location Picture Location
1. Water/pond
Titiwangsa
Lake Gardens
2. Park
Titiwangsa
Lake Gardens
3. Highway
Along Jalan
Tun Razak
4. Urban Residential
Kampung Baru
5. Downtown
Kuala Lumpur City
Center
Titiwangsa Lake Gardens
2. Park
Sustainability 2020 , 12 , x FOR PEER REVIEW 8 of 31
Table 3. Different types of land ‐ use categories for urban climate data collection using mobile
measurement.
No. Element Location Picture Location
1. Water/pond
Titiwangsa
Lake Gardens
2. Park
Titiwangsa
Lake Gardens
3. Highway
Along Jalan
Tun Razak
4. Urban Residential
Kampung Baru
5. Downtown
Kuala Lumpur City
Center
Titiwangsa Lake Gardens
3. Highway
Sustainability 2020 , 12 , x FOR PEER REVIEW 8 of 31
Table 3. Different types of land ‐ use categories for urban climate data collection using mobile
measurement.
No. Element Location Picture Location
1. Water/pond
Titiwangsa
Lake Gardens
2. Park
Titiwangsa
Lake Gardens
3. Highway
Along Jalan
instruments continuously collected the data on temperature and relative humidity at an interval of
one second. Th e observation was made for seven days from 20:30 to 22:30, i.e., from 24 April 2015 to
8 May 2015, with a vehicle speed of approximately 20–30 km/h.
Bukit Nenas Reserve
Forest
Sustainability 2020 , 12 , 7301 9 of 29
Another important element considered is urban residential area. Urban residential area is the
study area which is Kampung Baru. This is the most important element to be studied since Kampung
Baru is a crowded urban area with low-rise buildings surrounded by high-rise buildings.
The next element is downtown. A downtown area refers to the downtown of Kuala Lumpur where
buildings in this area are mostly skyscrapers. The last element is rural and mountain.
This element
refers to the forest reserve area located in the center of Kuala Lumpur . A government reserve area
is located to the west of the center of Kuala Lumpur, wher eas a commercial and residential area is
located to the east. In this study, observation was done along the r oad next to the forest reserve instead
of in the forest reserve area.
2.3.3. Fixed Measurement
Urban climate data for a complete one-year period was collected from MJIIT-CS. In this study ,
only air temperature and relative humidity were analyzed. The data logger was set up at a 10-min
interval. The measurement was carried out from March 2014 until February 2015.
Four monsoon seasons which are Southwest monsoon, Northeast monsoon, and two inter-monsoon
seasons took place throughout the measurement period. The weather phenomena of El Niño and
La Niña were also observed within the measurement period.
2.3.4. Mobile Measurement
The handheld measuring technique was carried out for six (6) selected days in April and May 2015
in Kampung Baru. In addition, the measurement also covered approximately 500 m from the boundary
of the study area. Figure 5 shows the route of the mobile survey which covered di ff erent types of land
uses. Details on di ff erent land uses can be referred to in T able 2 . The mobile measurement route was
planned to have a better understanding of how the pattern of land use would a ff ect the surrounding
urban microclimate. The various land uses along the route are indicated in Figure 6 . During mobile
measurement, the air temperature and relative humidity data were collected.
Sustainability 2020 , 12 , x FOR PEER REVIEW 10 of 31
Figure 5. Route of the mobile measurement (red line) which covered the study area of Kampung Baru
and 500 m in the vicinity (Source: Google Wikimapia, 2017).
Figure 6. Land ‐ use categories along the mobile survey route (Source: Google Wikimapia, 2017).
Table 4 summarizes mobile measurement details. Two (2) instruments were used during the
mobile measurement. Other than the installed instruments for mobile measurement, one instrument
was installed temporarily at the study area (school) as a control during the mobile measurement. This
control is important to check if data recorded by the two instruments were different or containing
error.
Figure 5.
Route of the mobile measurement (red line) which covered the study area of Kampung Bar u
and 500 m in the vicinity (Source: Google Wikimapia, 2017).
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Figure 5. Route of the mobile measurement (red line) which covered the study area of Kampung Baru
and 500 m in the vicinity (Source: Google Wikimapia, 2017).
Figure 6. Land ‐ use categories along the mobile survey route (Source: Google Wikimapia, 2017).
Table 4 summarizes mobile measurement details. Two (2) instruments were used during the
mobile measurement. Other than the installed instruments for mobile measurement, one instrument
was installed temporarily at the study area (school) as a control during the mobile measurement. This
control is important to check if data recorded by the two instruments were different or containing
error.
Figure 6. Land-use categories along the mobile survey route (Source: Google Wikimapia, 2017).
The mobile measurement was conducted using a motorcycle equipped with a handheld Global
Positioning System (GPS) and two separated Hobo pro-V2 with a solar radiation shield. One set of
Hobo pro-V2 data logger was also installed at the fixed station in the study area as a control. All the
instruments continuously collected the data on temperature and relative humidity at an interval of one
second. The observation was made for seven days from 20:30 to 22:30, i.e., from 24 April 2015 to 8 May
2015, with a vehicle speed of approximately 20–30 km / h.
T able 4 summarizes mobile measurement details. Two (2) instruments were used during the mobile
measurement. Other than the installed instruments for mobile measurement, one instrument was
installed temporarily at the study area (school) as a control during the mobile measurement. This control
is important to check if data recorded by the two instruments were di ff er ent or containing error .
T able 4. Details of the mobile measurement.
Item Description
Date 24–26 April 2015, 4–8 May 2015
Time Night time (20:30–22:30)
V ehicle Motorcycle
Speed of vehicle 20–30 km / h
Instruments Hobo temperature / RH mini data logger with radiation shield
Intervals 1 s
Instrument’s height 1.4 m
Sustainability 2020 , 12 , 7301 11 of 29
2.4. Geospatial GIS Data
The GIS spatial database of Kampung Baru was developed using various sources of data.
The primary
sources of data were obtained from the Department of Survey and Mapping Malaysia
(DSMM). However, the existing spatial data of Kampung Bar u could not be updated using the Kuala
Lumpur topography map from the DSMM as it was last updated in 2006. Therefore, the W orldView2
satellite image, which was last updated in 2010, and the Google Earth image, which was last updated
in October 2017, was used to develop the spatial data of Kampung Baru.
The geodatabase of Kampung Baru was developed using ArcGIS 10.1, which consists of 3D
building geometry (i.e., footprint and height) and urban climate data. The map was geo-referenced to
the Geodetic Datum of Malaysia 2000 (GDM2000) coordinate system. The limitation of the available
topographic map is the outdated spatial and attribute data. To overcome this limitation, field mapping
and detailed site investigation are occasionally organized to evaluate the available topographic
information and obtain updates from the field observations.
Building data sets were obtained from the satellite image and the field measurement at Kampung
Baru. The satellite image, however, does not contain the information of building height. Hence,
the footprint must be firstly digitized. The building footprints are represented as 2D polygons in the
AutoCAD file as shown in Figure 7 , while the 3D buildings, which are the buildings extruded based on
their respective heights, are shown in Figure 8 , in which the buildings are color -coded based on height.
Buildings were manually digitized using aerial photos. The tree canopy data were not included in
the analysis of the case study area because the analysis of the urban morphology was only focused
on the buildings. Nevertheless, the influence of tree canopy might be inherently present on the field
measurement data which is representative of actual data for the envir onmental settings in Kampung
Baru and its surrounding area. The lack of the tree canopy data in the developed GIS database is a
limitation that can be addressed and overcome in future studies.
The GIS spatial database of Kampung Baru consists of various types of buildings such as
residential, educational, commercial, religious (i.e., building of worship), and petrol station as shown
in
Figures 7 and 8
. The spatial characteristics of Kampung Baru were mapped using GIS to present
the current land cover of Kampung Baru. The detailed information of various building types such as
building name, building coordinates, building area, and building height were stored and managed in
the attribute table.
GIS is a modern application used to store, manage, and geo-spatially analyze various information.
This study utilized GIS in managing climatic variables at Kampung Baru in a GIS database. The general
workflow of the development of the GIS database is shown in Figure 9 .
The first step in handling spatial data information was geo-referencing the various data sources
into a single coordinate system. The base map obtained from the Department of Survey and
Mapping Malaysia (DSMM) with the projected coordinate system of GDM2000 Malayan Rectified
Skew Orthomorphic (MRSO) was used as a reference to geo-reference other data sour ces such as the
W orldView2 satellite image and the topographic map in one coordinate system. Next, the land cover
data such as the land-use categories were identified.
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Figure 7. 2D view of Kampung Baru. Buildings are color ‐ coded based on land ‐ use classification.
Figure 7. 2D view of Kampung Baru. Buildings are color-coded based on land-use classification.
Sustainability 2020 , 12 , 7301 13 of 29
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Figure 8. 3D view of Kampung Baru. Buildings are color ‐ coded based on land ‐ use classification.
Figure 8. 3D view of Kampung Baru. Buildings are color-coded based on land-use classification.
Sustainability 2020 , 12 , 7301 14 of 29
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The GIS spatial database of Kampung Baru consists of various types of buildings such as
residential, educational, commercial, religious (i.e., building of worship), and petrol station as shown
in Figures 7 and 8. The spatial characteristics of Kampung Baru were mapped using GIS to present
the current land cover of Kampung Baru. The detailed information of various building types such as
building name, building coordinates, building area, and building height were stored and managed
in the attribute table.
GIS is a modern application used to store, manage, and geo ‐ spatially analyze various
information. This study utilized GIS in managing climatic variables at Kampung Baru in a GIS
database. The general workflow of the development of the GIS database is shown in Figure 9.
Figure 9. General work flow of the GIS database development.
The first step in handling spatial data information was geo ‐ referencing the various data sources
into a single coordinate system. The base map obtained from the Department of Survey and Mapping
Malaysia (DSMM) with the projected coordinate system of GDM2000 Malayan Rectified Skew
Orthomorphic (MRSO) was used as a reference to geo ‐ reference other data sources such as the
WorldView2 satellite im age and the topographic map in one coordinate system. Next, the land cover
data such as the land ‐ use categories were identified.
The land cover data were digitized into vectors to produce the map of Kampung Baru which
includes different land categories and features. The land cover data were classified based on the
feature class. For each feature class, detailed feat ure information such as the name, location, and area
of the block was managed in the attribute table. The characteristics of spatial dat a were then analyzed
using GIS geo ‐ processing tools. Figure 10 shows the workflow in analyzing the temperature
distribution in Kampung Baru. In this study, the spatial analyst tool (i.e., the ‘Natural Neighbor’
function) was used to interpolate the data of the measurement days from the selected points in the
whole area of Kampung Baru.
Figure 10. Workflow of analyzing the temperature distribution using Natural Neighbor.
Figure 9. General work flow of the GIS database development.
The land cover data were digitized into vectors to produce the map of Kampung Baru which
includes di ff erent land categories and features. The land cover data were classified based on the feature
class. For each feature class, detailed feature information such as the name, location, and area of the
block was managed in the attribute table. The characteristics of spatial data were then analyzed using
GIS geo-processing tools. Figure 10 shows the workflow in analyzing the temperature distribution
in Kampung Baru. In this study, the spatial analyst tool (i.e., the ‘Natural Neighbor’ function) was
used to interpolate the data of the measurement days from the selected points in the whole area of
Kampung Baru.
Sustainability 2020 , 12 , x FOR PEER REVIEW 14 of 31
The GIS spatial database of Kampung Baru consists of various types of buildings such as
residential, educational, commercial, religious (i.e., building of worship), and petrol station as shown
in Figures 7 and 8. The spatial characteristics of Kampung Baru were mapped using GIS to present
the current land cover of Kampung Baru. The detailed information of various building types such as
building name, building coordinates, building area, and building height were stored and managed
in the attribute table.
GIS is a modern application used to store, manage, and geo ‐ spatially analyze various
information. This study utilized GIS in managing climatic variables at Kampung Baru in a GIS
database. The general workflow of the development of the GIS database is shown in Figure 9.
Figure 9. General work flow of the GIS database development.
The first step in handling spatial data information was geo ‐ referencing the various data sources
into a single coordinate system. The base map obtained from the Department of Survey and Mapping
Malaysia (DSMM) with the projected coordinate system of GDM2000 Malayan Rectified Skew
Orthomorphic (MRSO) was used as a reference to geo ‐ reference other data sources such as the
WorldView2 satellite im age and the topographic map in one coordinate system. Next, the land cover
data such as the land ‐ use categories were identified.
The land cover data were digitized into vectors to produce the map of Kampung Baru which
includes different land categories and features. The land cover data were classified based on the
feature class. For each feature class, detailed feat ure information such as the name, location, and area
of the block was managed in the attribute table. The characteristics of spatial dat a were then analyzed
using GIS geo ‐ processing tools. Figure 10 shows the workflow in analyzing the temperature
distribution in Kampung Baru. In this study, the spatial analyst tool (i.e., the ‘Natural Neighbor’
function) was used to interpolate the data of the measurement days from the selected points in the
whole area of Kampung Baru.
Figure 10. Workflow of analyzing the temperature distribution using Natural Neighbor.
Figure 10. W orkflow of analyzing the temperature distribution using Natural Neighbor .
Figure 11 shows an example of the temperature distribution in Kampung Baru developed using
ArcGIS. Urban climatic data (i.e., temperature and relative humidity) were imported into ArcGIS
10.1 to create a complete database coupled with the building morphology . The analysis was done to
map out areas with a higher risk of UHI in Kampung Baru indicated by high temperatures shown in
the figure and analyze the factors a ff ecting UHI based on Land Use Land Cover (LULC). In the GIS
environment (ArcGIS 10.1), the analysis of fixed and mobile measurements involved air temperature
data. For each station, the daily average air temperatures for seven days were inserted into the attribute
table. Further analyses were carried out in the GIS interface using the ArcGIS software. When the
building morphology database was ready to be used and the analysis of building statistics was done,
the urban climate data was then overlaid on the building morphology database using a 3D analyst
function (i.e., Natural Neighbor) in ArcGIS. Figure 11 displays the results of interpolation between
these two elements, urban climate data and building morphology . It can be deduced that the spatial
variation of the urban morphology has an impact on urban climate and outdoor thermal comfort.
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Figure 11. Example of the temperature distribution in Kampung Baru.
Figure 11. Example of the temperature distribution in Kampung Baru.
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Natural Neighbor is a type of interpolation method to predict weather at locations where
measurement was not performed. The interpolation method uses real weather information (e.g.,
precipitation, elevation or mineral content) obtained from measurements performed at particular
locations. The GIS interpolation mapping shows the variation of the average daily air temperature
across the Kampung Baru area. The air temperature interpolation a ff ected building morphology which
contributed by variation of building shadow , land cover features, sky view factor, and height / width
ratio [
21
,
22
]. This has a potential application in future research related to the impact of urban
development on local weather or climate.
T o classify each land-use type, MS1759:2005 (Geographic Information / Geomatics—Feature and
Attribute Codes), which is the standard code used to develop a database in Malaysia, was used. Table 5
summarizes the main land-use classifications in MS1759:2005. Currently there are 12 feature categories
including X which has been reserved for a special use (dataset-specific) in each classification scheme.
In this study , the mostly used category is B-Built Environment. Each category is then divided into
many sub-categories depending on the purpose of classification.
T able 5.
Urban land-use classification schemes in MS1759:2005 (Geographic Information /
Geomatics—Feature and Attribute Codes).
Code Category
A Aeronautical
B Built Environment
D Demarcation
G Geology
H Hydrography
S Soil
T T ransportation
U Utility
V V egetation
X Special Use (Dataset-specific)
Z General
3. Results and Discussion
3.1. T emporal Analysis of Urban T emperatures
Figure 12 shows the mean temperature profiles of an eight-month observation obtained
from MJIIT-CS and thr ee meteorological stations of Malaysia Meteorological Department (MMD).
T wo meteorological stations are located in Petaling Jaya (3
◦
06
0
N, 101
◦
39
0
E) and KLIA (2
◦
44
0
N,
101
◦
42
0
E), whereas one auxiliary station is located in FRIM Kepong (3
◦
14
0
N, 101
◦
38
0
E) which lies in a
rural area. All stations, which were at fixed locations, were analyzed for the weather pattern in Klang
V alley. The minimum temperature, which was between 25.2
◦
C and 27.1
◦
C, was recorded in January
2014. During this period, there were a few areas all over the country including Sabah and Sarawak
that were a ff ected by floods. The maximum temperature, which was between 28.4
◦
C and 30.0
◦
C,
was recorded in June 2014 and found to be consistent with the recor ded values from other stations in
the same month.
Additionally , the result also revealed higher temperatures were recorded by MJIIT -CS and the
temperature was recorded by the weather station located in the Forest Resear ch Institute Malaysia
(FRIM) Kepong, which lies in a rural area. In addition, Kampung Baru had a higher temperature,
between 1 and 2
◦
C higher compared to that of FRIM Kepong. According to [
1
], the annual mean
temperature of an urban area varies between 1 and 2
◦
C greater than that of a rural area, indicating
the higher probability of UHI occurrence in an urban area. Based on the findings, many factors,
for instance, urban structure, building materials, width of street, sky view factor , and anthropogenic
Sustainability 2020 , 12 , 7301 17 of 29
heat contribute to the occurrence of UHI in urban areas [
1
]. It is remarkably important to evaluate the
UHI phenomenon in the study area through spatial and temporal analysis.
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contribute to the occurrence of UHI in urban areas [1 ]. It is remarkably important to evaluate the UHI
phenomenon in the study area through spatial and temporal analysis.
Figure 12. Daily average temperature distributions from the MJIIT ‐ CS weather station and three
observation.
3.2. Temperature Variation under Different Environmental Settings
Figure 13 presents air temperature distributions obtained in various types of loca tions during
the mobile measurement. As stated earlier, the route of measurement passed through various types
of land use such as pond (water), commercial, park, urban residential (Kampung Baru), downtown,
and mountain.
Figure 13. Temperature d istributions based on mobile measurement at different land ‐ use categories.
8
Figure 12.
Daily average temperature distributions from the MJIIT -CS weather station and three
selected Malaysia Meteorological Department (MMD) weather stations for eight months of observation.
3.2. T emperature V ariation under Di ff erent Environmental Settings
Figure 13 presents air temperature distributions obtained in various types of locations during
the mobile measurement. As stated earlier, the r oute of measurement passed through various types
of land use such as pond (water), commercial, park, urban residential (Kampung Baru), downtown,
and mountain.
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contribute to the occurrence of UHI in urban areas [1]. It is remarkably important to evaluate the UHI
phenomenon in the study area through spatial and temporal analysis.
Figure 12. Daily average temperature distributions from the MJIIT ‐ CS weather station and three
selected Malaysia Meteorological Department (MMD) weather stations for eight months of
observation.
3.2. Temperature Variation under Different Environmental Settings
the mobile measurement. As stated earlier, the route of measurement passed through various types
of land use such as pond (water), commercial, park, urban residential (Kampung Baru), downtown,
and mountain.
Figure 13. Temperature d istributions based on mobile measurement at different land ‐ use categories.
4
th
Ma
y
2015
8
M ay 2015
th
April 2015
24
May 2015
May 2015
Figure 13. T emperature distributions based on mobile measurement at di ff erent land-use categories.
Sustainability 2020 , 12 , 7301 18 of 29
Figure 13 shows that air temperatures at the water area (pond) and mountain (Bukit Nanas
Reserve Forest) are mostly low compared to the other areas due to the extensive presence of cooling
elements such as water and vegetation. However, the air temperature trend obtained on 4 May 2015
contradict with the aforementioned finding since the measurement on 4 May 2015 was carried out
directly after the rain stopped, and this was considered as a wet day . Hence, the e ff ect of UHI is not
significant from the air temperature distribution obtained during or after the rain (wet day).
With the exception of the data reported on 4 May 2015, the graph r eveals that the urban residential
area (Kampung Baru) is the hottest region compared to the other ar eas on all observation days that were
dry days since there was no rain or the environment was fairly bright and sunny . The results clearly
show that the study area is much hotter than the downtown area. It is worth noting that this finding is
consistent with any day of observation. While the di ff erential is less than 0.4
◦
C, it is counter to the
belief that the downtown area will be the hottest during the night relative to other areas. Nonetheless,
Kampung Baru is not seen as a high-rise development zone. Most possibly , the key explanation for
the highest temperatures reported in Kampung Baru is the prevalence of nearby infrastructur es such
as highways (which frequently have heavy tra ffi c) and high-rise buildings, as well as being a very
compact area.
The findings also indicate that the green areas with roadside trees wer e leading to the cooler
lower on each day of the measurement relative to the air temperature in the Bukit Nanas Reserve
Forest. This finding is consistent for every day of observation except 4 May 2015. This is due to the
presence of roadside trees in the T itiwangsa Lake Gardens Park, as opposed to the location of Bukit
Nanas Reserve Forest which is restricted by the commercial highway zoning. A combination of a green
area with a water element will lower the air temperature as opposed to a stand-alone green area.
3.3. T emporal Analysis of UHI Intensity (UHII)
In an attempt to investigate the urban heat island intensity (UHII) in the study area, outdoor air
temperature measurements were performed in situ and the measured r esults were compared with
the rural weather station MMD in Jakoa, Gombak, during the same period from 14 to 19 October
2015. The minimum and maximum values of UHII from each day of observation are listed in T able 6 .
In addition, Figure 14 shows the recorded temperatures at Kampung Baru (urban ar ea) and Jakoa
(rural area) and the temperature di ff erence between the two ar eas.
T able 6. Minimum and maximum values of UHII (urban heat island intensity) at Kampung Baru.
Date Minimum Maximum
14 October 2015 − 0.7 4.4
15 October 2015 0.0 4.4
16 October 2015 − 2.3 4.2
17 October 2015 − 1.8 3.2
18 October 2015 − 0.8 4.5
19 October 2015 0.3 6.0
From the table, the maximum intensity of UHI was 6.0
◦
air temperature at Jakoa, Gombak, is higher compared to Kampung Baru. The negative result only
happened for one or two hours in a day . This is because of rainfall at Kampung Baru at that particular
time which cooled down the local environment. The minimum air temperature was recorded at 06:00
at the urban station and 07:00 at the rural station. Meanwhile, the maximum temperature at the rural
station occurred one hour after the recorded maximum temperature at the urban ar ea on each day of
observation. This is because the condition in the urban area, which has a higher density of buildings
and pavements, allows the absorption of heat during the daytime. However, the release of heat occurs
much slower at the nighttime. In contradiction to the urban area, the rural area is normally surrounded
Sustainability 2020 , 12 , 7301 19 of 29
by greenery . From all of the observation days, the UHI intensity was found higher during the nighttime
and lowest during the daytime. The UHI intensity continued to increase after 18:00 and peaked at
about 06:00, as shown in Figure 14 . It can be seen in Figure 14 a–c that the UHI peak was found early in
the morning due to heavy precipitation that occurred in the evenings of three consecutive days, fr om
14 to 16 October . This is contrary to the observation in Figure 14 d–f in which the UHI peak occurred in
the evening as a result of clear sky for the rest of the days.
Sustainability 2020 , 12 , x FOR PEER REVIEW 20 of 31
surrounded by greenery. From all of the observation days, the UHI intensity was found higher during
the nighttime and lowest during the daytime. The UHI intensity continued to increase after 18:00 and
peaked at about 06:00, as shown in Figure 14. It can be seen in Figure 14a–c that the UHI peak was
found early in the morning due to heavy precipitation that occurred in the evenings of three
consecutive days, from 14 to 16 October. This is contrary to the observation in Figure 14d–f in which
-1
0
1
2
3
4
5
22
24
26
28
30
32
34
36
12 18 0 6 12
Time (h)
UHII (∆T)
Temperature (°C)
Kampung Baru Jakoa UHII
Figure 14. Cont.
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( f )
Figure 14. Temperature distributions obtained from fixed measurement at the study area of Kampung
Baru (urban area) and Jakoa, Gombak (rural area) on ( a ) 14 October 2015, ( b ) 15 October 2015, ( c ) 16
October 2015, ( d ) 17 October 2015, ( e ) 18 October 2015, and ( f ) 19 October 2015.
Figure 15 shows the hourly average of UHI intensity over six (6) days. Overall, the hourly
average of UHII ranged between 1.0 °C and 4.0 °C, which was equal between the urban and rural
areas. The nighttime temperature in the urban area is higher than in the rural area. The highest value
of hourly average UHII was recorded at 09:00 and the lowest value were recorded at 16:00. All
calculated values of UHII are positive values, indicating that the high temperature recorded at
Kampung Baru contributed to the UHI phenomenon.
Figure 15. Comparison of temperature distributions obtained from fixed measurement for six days.
0
24
26
28
30
32
34
36
12 18 0 6 12
Time (h)
UHII (∆T)
Temperature (°C)
Kampung Baru Jakoa UHII
0
1
2
3
4
22
24
26
28
34
36
12 18 0 6 12
UHII (∆T)
Temperature (°C)
Time (h)
Kampung Baru Jakoa UHII
Figure 14.
T emperature distributions obtained from fixed measurement at the study area of Kampung
Baru (urban area) and Jakoa, Gombak (rural area) on (
a
) 14 October 2015, (
b
) 15 October 2015,
( c ) 16 October 2015, ( d ) 17 October 2015, ( e ) 18 October 2015, and ( f ) 19 October 2015.
Figure 15 shows the hourly average of UHI intensity over six (6) days. Overall, the hourly average
of UHII ranged between 1.0
◦
C and 4.0
◦
C, which was equal between the urban and rural areas.
The nighttime temperature in the urban area is higher than in the rural area. The highest value of
| https://www.researchgate.net/publication/344644396_Analysis_of_Urban_Morphological_Effect_on_the_Microclimate_of_the_Urban_Residential_Area_of_Kampung_Baru_in_Kuala_Lumpur_Using_a_Geospatial_Approach |
Buildings | Free Full-Text | Sustainability Assessment of Urban Heritage Sites
The purpose of this research was to create a framework of indicators that enabled us to measure the classic dimensions of sustainable development (SD): People, Planet, and Profit, in combination with the sustainability of the heritage values and the policy dimension. Methods developed as an approach to sustainable urban planning and that were based on system analysis models were modified, streamlined, and adapted into a concrete set of indicators for historical city sites. This framework, a multimodal system which maps out the holistic sustainability could serve as an incentive from the policy to the heritage world to implement sustainable objectives; and it could be used as an extra argument for the broader social relevance of heritage care.
by Maria Leus 1,* and Wouter Verhelst 2
1
Faculty of Design Sciences, University of Antwerp, Mutsaardstraat 31, 2000 Antwerp, Belgium
2
WVI (West-Vlaamse Intercommunale), Baron Ruzettelaan 35, 8310 Brugge, Belgium
*
Author to whom correspondence should be addressed.
Buildings 2018 , 8 (8), 107; https://doi.org/10.3390/buildings8080107
Received: 11 April 2018 / Revised: 31 July 2018 / Accepted: 7 August 2018 / Published: 12 August 2018
(This article belongs to the Special Issue Building Sustainability Assessment )
Abstract
The purpose of this research was to create a framework of indicators that enabled us to measure the classic dimensions of sustainable development (SD): People, Planet, and Profit, in combination with the sustainability of the heritage values and the policy dimension. Methods developed as an approach to sustainable urban planning and that were based on system analysis models were modified, streamlined, and adapted into a concrete set of indicators for historical city sites. This framework, a multimodal system which maps out the holistic sustainability could serve as an incentive from the policy to the heritage world to implement sustainable objectives; and it could be used as an extra argument for the broader social relevance of heritage care.
Keywords:
indicators
;
urban heritage sites
1. Introduction
In the field of urban planning, hundreds of different methods and tools have been developed to measure the sustainability of the built environment, each with its own perspective, approach, or goal. Unfortunately, none of these urban planning tools is adapted to the specific characteristics of a heritage site, which in turn makes them unsuitable in heritage conservation. In the best case, heritage aspects receive limited attention as a single indicator or sub-indicator. Many elements that are essential for an integrated sustainability assessment of specific cases, like cultural heritage sites, are simply overlooked in heritage value-based management. Avrami states that “Now, more than ever before, the heritage field is faced with the need to qualify and quantify its fundamental contributions to society and sustainability. Whether through environmental, economic, or social benefits, the field must robustly demonstrate how it improves quality of life for communities. Realigning the goals of heritage conservation to ensure that they serve the greater good of the sustainability cause is an important first step” [
1
] (p. 9).
1.1. The Brundlandt Definition as a Starting Point
Employing an analogy with the Brundtland definition, sustainable management of heritage sites is about how we can optimize the appreciation of our heritage in such a way, that it will still be relevant in the future [
2
]. Although the Brundtland definition originally starts from holistic sustainability, in recent years due to the presence of climate change and energy efficiency in planning processes, the focus has shifted to the Planet pillar. To most policymakers, social and economic sustainability are rather hazy concepts, which are difficult to communicate in contrast to climate problems. David Throsby points out that a holistic, multidisciplinary evaluation method is therefore necessary to overcome the shortcomings of environmental technology evaluation systems [
3
] (pp. 8–9); for example, social aspects also play an important role, particularly, architectural heritage is more preserved when social aspects have a high score.
1.2. Diachronic and Synchronic Relationships of Sustainable Development (SD)
When considering sustainable development (SD) in a heritage context, usually two approaches can be distinguished. In the first approach, the site is evaluated with the same criteria and instruments used for the SD of modern buildings or urban projects (sustainable development in general), whilst in the second approach the sustainability of heritage values is evaluated (sustainable heritage management). In the first case, the methodology is not adapted to heritage sites, so many specific heritage aspects are not covered. In the second case, the evaluation remains limited to cultural heritage management, and most quality aspects related to the contemporary and future functional use of the site are disregarded.
A tool that incorporates both approaches means that the two columns in Figure 1 are merged, and by merging the diachronic relationships and the synchronous analogies, new connections become clear. Whilst the two approaches were separated in the first scheme and only diachronic relationships were important, in the integrated approach, the synchronous and combined syn–diachronic connections are taken into account.
Figure 1. Integrated approach of SD of heritage sites.
In this integrated approach, optimal appreciation of heritage values goes hand in hand in the three directions, which results in:
The improvement of the quality of life, according to current needs (synchronic).
The protection of future needs, in terms of quality of life (syn–diachronic).
The enjoyment of these heritage values by future generations (diachronic).
The same applies in any case, in three directions, for each of the four components in this scheme.
2. Aim and Methodology: Search for a Holistic Vision
The aim of our research is to create a holistic framework, based on a set of indicators to advocate the benefits of heritage preservation in terms of SD-tailored protection of historic city fragments. The importance of a holistic approach in the planning of historic urban areas was already stressed in the Granada Convention [ 4 ] and the Charter of Washington [ 5 ].
Cultural heritage and sustainability are dynamic systems, hence a multimodal system is required that describes all the aspects and their mutual interrelations in an integrated way. The multimodal system analysis of the Dutch lawyer–philosopher Dooyeweerd, is used as a frame of reference to approach this complex problem in a holistic way. Furthermore, Lombardi and Brandon [
6
,
7
] and Vandevyvere [
8
] adopted this multimodal system analysis to evaluate sustainability in the built environment. The modal spheres or law spheres as developed by Dooyeweerd, do not refer to “what”, but to “how” the reality manifests itself to the human experience [
9
]. These modalities ground things or objects in terms of significance rather than in terms of existence. This theory can be used as an epistemological exercise to check the proposed set of indicators on completeness and coherence.
The methodology of this research was based on two surveys. On the one hand, we followed a theoretical track in which a literature study involving insights and methods from other disciplines can be applied to heritage sites. On the other hand, an empirical track was followed to create a conceptual framework in which the indicators were chosen based on the conclusions of the theoretical and comparative study of existing tools, frameworks, and strategies.
The proposed holistic and participatory evaluation method may be a tool that could be integrated in the management of world heritage sites. In the same vein is the Historic Urban Landscape approach (HUL-approach). This concept, proposed by UNESCO, approaches historic city fragments as landscapes in a broad context, with a stratification that goes beyond the pure architectural characteristics. It considers intangible aspects, contemporary social and cultural values, economic processes, and physico-spatial characteristics [
8
] art. 4 and 6. The HUL-approach aims to integrate urban heritage management into a general framework for sustainable development and is opposite to this research. The uniqueness of the proposed framework lies in the fact that it starts from existing urban tools, which are adapted to a heritage context.
3. Theoretical Track: The Multimodal System as an Epistemological Exercise
The spheres of the multimodal system of Dooyeweerd are adjusted in order to be applied to cultural heritage. Fifteen aspects of temporal reality, or modalities/spheres, or ways of being are distinguished: numerical (quantitative), spatial, kinematic, physical, biotic, psychic (sensitive), analytical (logic), historic (cultural), communicative, social, economic, aesthetic, juridical, ethical, and pistic (faith).
The first three modal spheres (numerical, spatial and kinematic), are the most fundamental and determinative ones. The higher in the ranking, the more the normative character is highlighted. The highest modal spheres (e.g., pistic, ethical, legal), are based more on human value judgments than the lower ones. The spheres refer to each other by anticipations and retrocipations. In this way, one modality is metaphorically described by the idiom of another [
9
] (p. 109). Heritage, for example, can be described on the basis of economic value, which in turn can be expressed in price (the numerical aspect). Such a “backward” relationship, although it is accompanied by the loss of a certain meaning, is called a retrocipation by Dooyeweerd. Additionally, in the reverse sense heritage is anticipatory, related to the legal, ethical and pistic aspects, for example in the form a protected monument prescribed by law, a site that is accessible to everyone, or a memorial, thus gaining in significance. Dooyeweerd considered this system of modal spheres, anticipation and retrocipation, the “cosmic order of time”.
A holistic point of view to sustainability ensures a system that functions in a way that all spheres are covered, and their appropriate laws are respected see Figure 2 .
Figure 2. The modal spheres of Dooyeweerd [ 10 ]: When all the law spheres are respected, a good balance and sustainability are received.
From the point of view of protected historic city fragments, or World Heritage sites, the multimodal analysis these valuable sites are situated in the historic ‘law sphere’. To neglect SD can have a destructive impact on several levels in the form of a decrease of legibility due to too many tourist facilities (communication), the unravelling of the social fabric (social), loss of employment (economic), and a reduction of the image quality because of degradation and vacancy (aesthetic) with legal consequences (juridical). This will finally result in less intergenerational responsibility (ethical) and no voluntarism (pistic). In this case, due to unsustainable heritage management, the historic modality is affected, and because this aspect is also a basis or substratum of the higher modalities (superstrata), in the long term the latter will be undermined in an anticipative way. On the other hand, this historic modality as superstratum is retrocipatively connected with its lower modalities and will have a destructive effect on them in the form of the loss of scientific knowledge (analytic), perception of a harsh environment (sensitive), environmental pollution (biotic), safety problems (kinematic), and inefficient use of space and buildings (spatial).
The relevance of the multimodal system analysis is also illustrated by the research of Lombardi and Brandon [
6
,
7
]. They reported on the example of a spatial development project in Italy, where four different parties proposed their own project scenario. A multimodal analysis was conducted to identify the differences and interfaces. In terms of differences, primarily the pistic aspect revealed the underlying interests. The result of this explication and the discovery of new interfaces, was that finally the debate was forced into the open and made it more transparent, so that new opportunities arose that led to a negotiated compromise. By way of illustration, we look at a discussion on the application of insulating measures in a monument by two different parties, a heritage expert and an ecologist, both putting forward their own sustainability scenarios. The heritage expert, who is in favor of energy savings, will rigorously combat every disruptive impact from the point of view of heritage conservation, whilst the ecologist, who recognizes the importance of heritage for integral sustainability, will propose drastic interventions from the point of view of energy saving. Although both parties situate themselves within the same ethical value perspective that implies maximum integrated SD, they monopolize the discussion by focusing on only one modal aspect (historical versus economical or physical). Mapping of the different interests, perspectives, and definitions on sustainability ensures clearance in order to find a creative, interdisciplinary solution. The search for a “common ground” and awareness of the influence of value perspectives “perspective adoption”, are indeed basic conditions of each interdisciplinary research.
4. Empirical Track: Creation of a Set of Indicators
In the creation of a set of indicators, a holistic vision is indispensable [ 11 ] (pp. 57–58). As Rotmans and de Vries pointed out that “Indicators describe complex phenomena in a (quasi-) quantitative way by simplifying them in such a way that communication is possible with specific user groups” [ 12 ].
4.1. References and Principles for a Set of Indicators
The Dutch DuMo model is not a holistic instrument, which is why the 20 strategies for sustainable preservation of monuments listed at the DuMo-calculation were used as inspiration and illustration, for the indicators of the Planet and Patrimony (Heritage) pillars [ 13 ]. These strategies are no indicators by themselves, but they are formulated in the form of recommendations and are in fact designed to create a customized solution.
In addition, Stubbs framework based on his experiences with 3 heritage projects in England, with a high content of social participation and local anchoring, acts as a reference for our set of indicators [ 14 ]. Stubbs framework had a specific focus on sense of place, community building, and public perception (social aspects of SD) reflecting the social turn [ 14 , 15 , 16 ]. For the fourth pillar, Stubbs [ 14 ] classified the indicators in analogy with Vandevyvere [ 9 ], except that for the fourth pillar he used the undemanding name ‘generic’ to accommodate public perception. The theme ‘generic’ in the framework of Stubbs’ can be regarded as being multimodal in reference to the ethical and pistic spheres. It is also interesting to note that Stubbs in the Planet pillar provided an indicator for climate change adaptation. This indicator is not included in this research because until now, there is hardly any research in Flanders about the impact of climate change on the built heritage.
Vandevyvere streamlined this method to a concrete set of indicators for the city districts based on a thorough comparative study by selecting the best known evaluation tools of that moment [
9
]. This research, was used as a guideline because of its strong substantive basis and the fact that Vandevyvere used the same principles, the multimodal perspective, and the same scale as the research object. Lombardi and Brandon outlined the 15 modal aspects of Dooyeweerd into a questionnaire [
6
]. Vandevyvere reversed this way of working by selecting a number of indicators, which were tested in a multimodal framework [
9
] (pp. 109–110, 116).
4.2. Criteria for the Selection of the Appropriate Indicators
The selection of the appropriate indicators depends firstly, on pragmatic factors, such as system boundaries (scale and typology of heritage) and availability of data, and secondly, on rather subjective aspects, such as the L, C, S-criteria, as defined by Clark et al.: “
The most influential assessments are those that are simultaneously perceived by a broad array of actors to possess 3 attributes: legitimacy, credibility and salience
” [
17
] p. 7. Creating a set of indicators is a methodological compromise between local relevance, practical feasibility, availability of data, and theoretical justification. Several authors have set down criteria that sustainable indicators should meet [
18
,
19
,
20
]. Although they all provide useful guidance, all these criteria can be reduced to the L, C, S criteria.
Salience : Is the indicator relevant to the type and scale of the heritage? Does the indicator meet the adequate scope of Bellagio-principle 5 [ 21 ] (pp. 1–4)? Is the indicator relevant for long-term sustainability and does it play an important role at higher levels than the local one? Is the indicator significant for the actors involved (both policy and public), but also, is the indicator clear, unambiguous, and usable to communicate?
Credibility (realistic measurability) : Are the collected data for the indicator available, and in terms of time budget, are they technically feasible?
Legitimacy : Is the indicator acceptable for all parties involved, both for experts (scientific validity) and stakeholders? This can be adequately consulted by the questionnaires in the context of the weighting.
4.3. Five Pillars of Sustainable Development
In addressing the question of how SD and heritage are interconnected, the classical three-pillar structure is extended to five pillars, including Policy and Patrimony (heritage). In order to realize a sustainable cultural development and management, it is important that these pillars are of equal value and that there is a constant interaction between them.
Although in principle, there is no hierarchy between the original sustainability pillars, the relative position of each pillar in this model is important as shown in
Figure 3
. Given that the Policy-pillar contains the highest normative modalities and has a steering function, it can be seen as overarching against the other pillars. Secondly, in this research the theme of the Patrimony-pillar is basically the central starting point, a kind of ‘heritage’ bias. In this way, we can imagine sustainable heritage management as a three-dimensional tetrahedral molecule. The idea to add an overarching institutional pillar to the three dimensional version is indebted to Valentin and Spangenberg, and gives a clear presentation of both the differences and the interconnectedness of the different components of SD [
22
].
Figure 3. The tetrahedron presentation of sustainable development (SD) of Patrimony (heritage).
The indicators can be located on the corner points (vertices), or on the ribs of the prism to display individual sustainability themes, or aspects that indicate the interconnectivity. Applied to the proposed indicators, a tetrahedron which starts from the point of view of the heritage (Patrimony) contains many indicators that will be located on the connections (the ribs), between the central Patrimony pool and the four vertices. For example, an indicator about the enclosure or opening-up of heritage could be located on the connection between People and Patrimony (heritage). A (sub) indicator on successful integration of modern facilities for energy efficiency in a heritage context, is located on the connection between Patrimony and Planet, and so on. On the other hand, there will be indicators that are only positioned in this or that vertex, e.g., the mere use of green energy in the Planet vertex, and an indicator on the presence of policy planning in the Policy vertex
A project on sustainability of heritage can be considered as a point within this three-dimensional structure where its positioning displays the average of all indicators. A heritage project is sustainable, as long as it remains within the five P-tetrahedron. The positioning, with regard to the vertices can be different according to other emphases (weights). This multidimensional presentation shows that SD has no unambiguously definable optimum, as would be the case in a two-dimensional model. It illustrates the fact that, although an evaluation will be based on a whole set of various indicators, one indicator can get more priority (weight) than another, as long as the total project is located within the limits of the tetrahedron.
4.4. Creation of a Set of Indicators
Based on these theoretical conclusions and built on existing models, 22 indicators were defined, most of them subdivided into sub-indicators. In Figure 4 the modal spheres of Dooyeweerd are related with the pillars of sustainability and the indicators developed on the scale of historic urban fragments.
Figure 4. The modal spheres of Dooyeweerd in relationship with the pillars of sustainability and the indicators developed on the scale of historic urban fragments.
• People indicators: ‘sense of place’, ‘community building’ and ‘safety’.
The indicator ‘sense of place’ assesses the experience of people within a specific setting; the associations, the feelings, and the sentiments that are evoked by a historic space. The indicator community building refers to the degree with which a site is able to create a balanced, coherent, and well-functioning community and refers to the sub-indicators: integration or social inclusiveness and sociability or the way a built environment encourages social life. Safety is an essential condition for the attractiveness of the site and for improving the well-being of a neighborhood [
23
]. Physical and social safety mutually reinforce each other [
24
].
• Planet indicators: ‘Use of material’, ‘energy’, ‘water’, ‘mobility’, ‘biodiversity’, ‘use of space’, and ‘pollution/nuisance’.
‘Planet’ refers to the testing of sustainable environmental aspects. The indicator ‘use of materials’ evaluates the conscious choice, or at least demonstrable sustainable materials for the refurbishment or replacement of restorations or modern additions of the site. The indicator ‘energy’ describes the sustainability of energy consumption, in terms of the trias energetica [
25
] (pp. 43–45). Moreover, the rational and sustainable use of ‘water’, both in terms of consumption and the drainage of rain water is assessed by this indicator. ‘Mobility’ refers to the extent to which the site is easily accessible by public transportation, and soft traffic is encouraged. The overall quality of the ecosystem, ‘biodiversity’, is conceived in biological sense. It comes as both the biodiversity on measures for conservation, restoration, and compensation. The indicator ‘use of space’ is related to the appropriate and effective spatial use of the site. ‘Pollution/nuisance’ is a container indicator that maps out all forms of pollution or nuisance.
• Profit indicators: ‘Local employment’, ‘economic embedding’, and ‘future value’.
When considering economic sustainability, we think in the first place of the so-called return on investment. Ideally, this should be measured with a CBA (cost-benefit analysis). However, it is clear that a full CBA, as part of a sustainability analysis, in terms of data gathering is not always realistic. Therefore this pillar is limited to indicators like, ‘local employment’, which is relatively simple to measure, and ‘economic embedding’, and ‘future value’, which are indicators with a qualitative score. ‘Economic embedding’ evaluates the economic role of the site in a broader context, and particularly the influence on tourism. ‘Future value’ is by definition what SD is about. Here the functional flexibility of the site is examined in relation to future developments; financial capacity in the sense of the financial resources that are available for the heritage project is measured in the Policy pillar by the indicator ‘legal certainty’.
• Policy indicators: ‘planning/process quality’, ‘legal certainty’, ‘integrity’ and ‘voluntarism’.
The first indicator ‘planning and process quality’, measures to what extent a kind of planning is present, as well as a follow-up of the realization of the objectives of this planning. ‘Legal certainty’ assesses if economic, social, and heritage aspects of the site are supported and encouraged by the government. ‘Integrity’ evaluates the extent to which stakeholders endorse the Brundtland definition of SD, in a holistic way. ‘Voluntarism’ is an indicator that refers to the pistic modality of Dooyeweerd [
10
] and the category “generic” of Stubbs [
14
]; and it measures the extent to which the parties involved are convinced of the overriding importance of SD for heritage care and vice versa.
•
Patrimony indicators: ‘integration of modern techniques’, ‘physical and psychological accessibility’ (enclosure or opening up), ‘knowledge building’, ‘spatial aesthetics’ (tangible aspects), and ‘immaterial cultural heritage’ (intangible aspects).
Whilst in the other pillars, the environmental, social, and economic impact of the heritage and the political focus and care are assessed, the Patrimony pillar measures the way in which the heritage itself is valued. The indicators of this pillar should be seen in relation to the manner in which a site is managed and developed to ensure optimal appreciation, and in the context of how the sustainability of the heritage values is guaranteed. The Patrimony indicators are summarized in five indicators, which on one hand are based on the listed practical input and inspirational references (
4.1 References and principles for set of indicators
), and on the other hand, on the most important charters of the last decades. The related indicators are underpinned by international charters.
The indicator ‘integration of modern techniques’, assesses if modern requirements are applied in a harmonic way with the surroundings and without prejudicing the values of the heritage. ‘Physical and inclusive psychological’ inclusion of information is important, and is a constant theme in the international charters [ 26 ] (art. 16); [ 5 ] (art. 15); [ 27 ] (art. 25); [ 28 ] (art. 6–10); [ 29 ] (art. 25). ‘Spatial aesthetics’ addresses the integration of green, water, and art, as well as the overall multi-sensorial aesthetic quality. ‘ Immaterial heritage’ covers besides legends, stories also, museum initiatives, cultural activities, and material elements on the site that have a link with the immaterial heritage.
Figure 4 shows the relationship between the model spheres of Dooyeweerd and the 5 pillars of SD, with their corresponding indicators and sub-indicators.
A holistic approach includes a wide range of modalities that extend from extremely determinative or substantive, to very normative or subjective. The determinative (quantitative) aspects can be assessed by quantitative methods; the normative aspects (pistic) by qualitative ones. To assess the aspects in between, a combination of quantitative and qualitative techniques is useful. SD, as well as preservation of heritage, are strongly value-based disciplines; hence the complete exclusion of subjectivity is utopian. A multi-criteria analysis is proposed as an efficient means to evaluate the quantitative, as well as the qualitative, indicators.
In a set of indicators, certain indicators get more weight than others because of a thematic focus. From an objective point of view there is no absolute, value-free standard for sustainability. By applying a set of indicators; SD of heritage sites will be measurable and presented clearly, but we should be aware that the creation of such a framework in itself is never a value-free concern.
5. Case Study: The Beguinage of the Minnewater Site in Bruges, Belgium (World Heritage Site)
The set of indicators was tested in a case study of the protected cityscape of Minnewater, in Bruges. The site, Minnewater,
Figure 5
, is about 16 hectares and is located in the southern part of the historic world heritage city Bruges. For many tourists this site is the gate to enter Bruges because the site is very accessible by public and soft transport. The site consists of a number of protected relics and iconic landscape elements, which are grouped around the Lake Minnewater. The site comprises of nine sub-areas and is characterized by little spatial cohesion. In the Northwest of the site, the Beguinage is located. This Beguinage of the 13th century,
Figure 6
, is a protected site since 1996 and in 1998, together with the 12 other Flemish Beguinages was included on the UNESCO world heritage list because
‘beguinages are exceptional witnesses to the cultural tradition of independent religious women in north-western Europe in the Middle Ages.’
Figure 5. Minnewater site in Bruges, Belgium, Beguinage (red indicated).
Figure 6. The Beguinage of the Minnewater site in Bruges, Belgium [ 30 ].
5.1. Quick Scan as a Test
A quick-scan was used as an illustration and test of the proposed methodology. The information was collected using questionnaires and in-depth interviews of experts of the heritage and urban department of the city of Bruges, and local heritage experts. To obtain an assessment of the indicators by the habitants, a questionnaire was submitted to 18 inhabitants, where 15 of them wanted to participate. In addition, 15 local employers were interrogated separately on the economic indicators. Respondents were asked to fill in an excel file, distributing 100 points on the 22 indicators, depending on the relative importance that he or she attached to the indicator in question. The weight of the indicator was defined by different groups of stakeholders related with the heritage site, and mainly those concerned with decision-making process. The scores of the indicators were multiplied by average weighting factors to obtain a weighted final score.
5.2. Chart Beguinage Area—Minnewater
Most instruments for sustainability that analyze the partial scores are displayed by the radar chart. The circular structure emphasizes the unity and principled equality of the indicators, and is therefore an appropriate visual representation of the holistic approach.
The global high score also indicates that the sectoral focus on heritage, successfully goes hand in hand with other aspects of sustainable development. Sense of place, community building, and future value get the highest weight. The cityscape Minnewater, is an example of a site where there is an intrinsic and sustained consideration of the values of the heritage, on the one hand, by the high degree of legal protection and on the other hand, by the enormous heritage tradition and expertise of the heritage and urban planning department of the city of Bruges. Energy is the only ecological indicator that scores just a pass grade. Therefore the use of renewable energy must be stimulated.
5.3. SWOT Analysis
The SWOT analysis of this survey as shown in Figure 7 revealed that the strengths were sense of place where people are proud to live in this area; also, a strong economic embedding and a strong planning and cross-sectorial consultation. Furthermore, financial support of the government is important for qualitative preservation of the cultural heritage site. Voluntarism, a spontaneous stewardship, is especially present with the inhabitants of the Beguinage.
Figure 7. Chart Beguinage area—Minnewater.
Points of weakness for the Heritage-pillar were the information disclosure or opening up of the cultural heritage. The power of communication draws attention because only a little information on the cultural heritage is accessible, in particular, the consideration of intangible heritage aspects is an aspect of concern. Minnewater is an area with little or no local participation, only a few inhabitants are passive members of a Heritage Association. There is no social mix and in general, the properties of this site are in a higher price range. Many buildings have a low energy performance, resulting in a low level comfort for users.
Analysis reveals that the most important aspect that offers an opportunity for a long term sustainable development is heritage participation. However, there were no real consultation structures for local participation and many residents had a feeling of uncertainty about the heritage policy, and especially about the UNESCO status. There is a need for an intermediate point of contact, to provide clear communication about the UNESCO protection to the citizens, as well as to the local authorities. A second point that needs to be improved, is the unlocking of intangible heritage because currently the history and anecdotes of the site are only sporadically explained on information boards in situ. Moreover, public knowledge about energy efficiency in historic buildings should be increased by means of awareness-raising activities. On the economic level, the site had some interesting sustainable assets. Firstly, there were some major employers, and secondly, the site had a strategic function for local tourism.
The threats revealed by the analysis were that a heritage bias may inhibit innovation in the field of energetic sustainability. In addition, the ageing residents' profile of the inhabitants of this site was a problem. On average, the inhabitants were between 45–70 years old, and there were almost no young families who lived in this area.
5.4. Conclusion Case Study
The quick scan revealed that for the future, it is clear that the social pillar has an important task in the evaluation of the management of heritage sites, in relationship with sustainable development. Opportunities include local heritage participation, acting as local barometer, identifying the core problems of sustainability, enabling heritage to be an essential part of the sustainable development debate, and the link with the UNESCO policy. Threats lie in the lack of local support through a top-down approach, and the time-consuming procedure that discourages uptake.
Research of Vandevyvere showed that in a non-heritage context, energy, land use, and mobility were the most important factors that made a site sustainable, followed by the indicators: process quality and participation. However, in our research the conclusion is that sustainability of heritage sites, more than in other situations, is related with a broad social consensus.
6. Conclusions
A major strength of this study is that for the first time, a holistic evaluation tool was created with a robust base, both on a theoretical and practical level which addressed the subjectivity of SD. The sporadic inclusion of general indicators, in addition to very specific indicators and sub-indicators, introduces more flexibility for contextual assessment. This is a methodological asset. Sustainability is an anthropocentric and dynamic concept, which reflects the expectations and values of a group of people, and that also involves a learning process. Our vision on the factors that contribute to the effectiveness and efficiency of SD, will also change as we will be increasingly able to assess the effects of a sustainability policy. Bell and Morse concluded in their research on the measurability of SD highlighting that “Like the term environment, but far more so, sustainability is what we want it to be and can change as we change. It is an organic and evolving construct of our mind and not an inorganic and static entity that can be physically probed. Indeed, the very action of trying to implement what one thinks is sustainability, may change one’s vision of what it is. The best we can achieve is to acknowledge the centrality of people…” [
31
] (p. 200).
This research, also has the merit of integrating heritage into the broad public debate, which should be seen as an opportunity to highlight the undeniable contribution of heritage to SD. In other words, SD offers new opportunities to heritage in order to prove its added value for the society.
Author Contributions
Both Wouter Verhelst and Maria Leus contributed to the final version of the manuscript.
Funding
This research received no external funding.
Acknowledgments
We would also like to show our gratitude to Brecht Vandekerckhove and Han Vandevyvere for sharing their knowledge with us during this research, and we thank the reviewers for their insights and recommendations.
Conflicts of Interest
The authors declare no conflicts of interest.
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Figure 1. Integrated approach of SD of heritage sites.
Figure 2. The modal spheres of Dooyeweerd [ 10 ]: When all the law spheres are respected, a good balance and sustainability are received.
Figure 3. The tetrahedron presentation of sustainable development (SD) of Patrimony (heritage).
Figure 4. The modal spheres of Dooyeweerd in relationship with the pillars of sustainability and the indicators developed on the scale of historic urban fragments.
Figure 5. Minnewater site in Bruges, Belgium, Beguinage (red indicated).
Figure 6. The Beguinage of the Minnewater site in Bruges, Belgium [ 30 ].
Figure 7. Chart Beguinage area—Minnewater.
MDPI and ACS Style
Leus, M.; Verhelst, W. Sustainability Assessment of Urban Heritage Sites. Buildings 2018, 8, 107.
https://doi.org/10.3390/buildings8080107
AMA Style
Leus M, Verhelst W. Sustainability Assessment of Urban Heritage Sites. Buildings. 2018; 8(8):107.
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Chicago/Turabian Style
Leus, Maria, and Wouter Verhelst. 2018. "Sustainability Assessment of Urban Heritage Sites" Buildings8, no. 8: 107.
https://doi.org/10.3390/buildings8080107
| https://www.mdpi.com/2075-5309/8/8/107/html |
Trangenerational Trauma – Context And Reflection Of Changes In Scenic Symbolic Work | European Proceedings
Trangenerational Trauma – Context And Reflection Of Changes In Scenic Symbolic Work
Gabriela Slaninova ,
Zuzana Kucerova
Abstract
The present study aims at describing and analysing transgenerational trauma and identifying changes over the course of psychotherapeutic process. For that reason, Pesso Boyden psychomotor therapy (PBSP) is employed. Furthermore, its purpose is to point out the possibilities and competencies of social pedagogues regarding the use of elements and techniques of PBSP. This study discovered that in scenic symbolic work in PBSP, uncovering and becoming conscious of trauma repetition occurs, and a client gradually achieves self-acceptance and actively participates in cognitive, emotional, and behavioural changes. This progressively results in the client being able to integrate the traumatic experience into a personal history and step out of unconscious replication of family traumatisation. The social pedagogue is able to participate in the cognitive changes, primarily using PBSP theory, micro tracking and local placeholders.Keywords:ClientTraumaTransgenerational TransmissionPBSPSocial Pedagogy
Introduction
Transgenerational transmission tends to be realised by emotional family dynamics. ( Tóthová, 2011) What is meant by family here follows Trapková and Chvála ( 2009) who consider it a space of reproduction of language and meanings, in which generational replication is realised and intergenerational transmissions occur. As Tóthová argues, the transmission is caused among other aspects by the quality of emotional bond, social separation, anniversary syndrome, emotional severance, unhealed emotions as well as due to family communication dynamics ( Tóthová, 2011). The author’s practice also confirmed transgenerational transmission of family lines and patterns usually occurs unconsciously and above all, covertly. Within the transgenerational psychogenealogy framework, Schützenberger ( 1998) introduced the concept of ancestor syndrome (concealed devotion to past generations caused by unfinished aspects of emotional or psychosocial dynamics). Thus, she pointed out repetitive patterns of family traumatisation and generational parallels. As this concept is supported by the present author’s practice, it is considered crucial and decisive of the course of this research.
The theoretical concept of trauma draws on Praško et al. ( 2003), and Vizinová and Preiss ( 1999), who consider trauma a short- or long-term event that is exceptionally dangerous and catastrophic and would most likely deeply agitate anyone. According to the corresponding definition in Pesso Boyden psychomotor therapy, which is determining here, it is a physical and emotional reaction to dangerous stimuli that trigger undesirable consequences irresolvable by one’s coping strategies. The concept of experienced intrusion is shared across both definitions. In the context of transgenerational trauma, the claim of van der Kolk ( 1997) is important that victims of trauma experience these feelings without understanding the connection to their causes.
Transgenerational trauma is approached from the PBSP angle as this method allows for a symbolic processing of trauma in a scenic symbolic space of a structure, in which trauma is experimentally integrated on cognitive, emotional and behavioural levels.
The Pesso Boyden psychomotor therapy originated in the USA; it gradually emerged in dance context as the method’s late founders Albert Pesso and Diane Boyden-Pesso previously worked as dancers and dance pedagogues. ( Perquin, 1997; Pesso, 1984; Pesso, Boyden-Pesso, & Vrtbovská, 2009) Initially, PBSP focused on non-verbal techniques and expression through movement and sounds. ( Pesso, Boyden-Pesso, & Vrtbovská, 2009) Over the course of the method’s formation, basic developmental needs of place, protection, nurturance, support and limits were identified. These requirements have to be fulfilled adequately by parent figures. The need of limits is considered framing, and is equally important for the present research; it provides a child with a so-called limited environment, within which it is in an ideal scenario aware of limits and experiences neither helplessness nor omnipotence. (Lebedová in Šamánková, 2012; Perquin, 1997; Pesso, Boyden-Pesso, & Vrtbovská, 2009) In the 1970s, a concept was developed of a so-called map, which according to Pesso and Boyden emerged over every individual’s life and provided a set of behavioural patterns available throughout one’s lifetime ( Pesso, Boyden-Pesso, & Vrtbovská, 2009). In the context of transgenerational trauma, this map is transmitted between generations. Pesso, Boyden-Pesso and Vrtbovská ( 2009) claim that if this “old” map is formed by negative experiences, especially in childhood, in therapy it is possible to create, using a symbolic ideal parent, an alternative “new” map which fulfils the abovementioned needs in time, quality, degree and manner required by a particular client. The PBSP method has been relatively actively developed; since the 1980s, new elements and concepts have been introduced – possibility sphere, fragment figures, pilot. ( Pesso, Boyden-Pesso, & Vrtbovská, 2009) PBSP is practiced in both individual and group therapy.
The effect of PBSP in traumatised clients, specifically the existence of neurobiological changes of brain activity precipitated by PBSP was measured and confirmed using functional magnetic resonance imaging by Horáček et al. ( 2005). The present study acknowledges these results, and while recognising the limitations of qualitative research, perceives them as an impulse to contribute by findings collected in monitored psychotherapeutic process pertaining to a small number of clients in whom traumas occur repeatedly over several generations and constitute a part of personal and family history.
Problem Statement
Given the abovementioned possibility, the processing of intergenerational trauma using the Pesso Boyden Psychomotor System represents the research problem of the present study.
Research Questions
Which changes occur in persons with a genetically transmitted trauma over the course of the PBSP on a cognitive, emotional and behavioural level? What are the clients’ experiences of these changes?
Purpose of the Study
To describe and analyse uncovering and awareness of transgenerational trauma in client, and to identify cognitive, emotional and behavioural changes over the course of the PBSP therapy. From the point of view of helping professions, to point out the possibilities and competencies of social pedagogues regarding the use of elements and techniques of PBSP (in the context of intergenerational transmission of trauma).
Besides transgenerational recurrence of trauma, the criterion for research participants was reaching the age of young adulthood in which the ability to reflect the experiences of three generations of one family line is presupposed; Vágnerová ( 2000) gives the range of 20–35 years of age.
One of the aims is to highlight the potential and limitations of PBSP for a social pedagogue in direct contact with a traumatised client. It was specified in advance the study will identify those PBSP principles and techniques that can be used by a social pedagogue without a long-term self-experience PBSP training. This decision was made on the following basis: social pedagogues tend to work in non-profit institutions, low-threshold facilities for children and youth, surrogate parental care, mental health care centres, psychosocial help etc. There they encounter clients in difficult situations. It is therefore possible to assume meeting traumatised clients is not uncommon for them. Likewise it is expected they are able to work with such clients, at least as regards crisis intervention and counselling, and direct them towards further follow-up care.
Research Methods
Data processing is based on interpretative phenomenological analysis (IPA), as it allows a more creative approach and greater freedom of research process in comparison to other methods ( Willig, 2001). It is considered especially useful for analysis of deep experience in therapy as well as of in-depth narrative interviews. Employment of elements of IPA allows for a description and interpretation of the way in which an experiencing subject ascribes meaning to experience. The purpose is to understand client’s lived experience as described in detail in Larkin, Watts and Clifton ( 2006). The approach is based on three primary pillars of IPA. The focus is on particular clients’ unique experiences of specific people in specific context and time. Following Smith ( 2004), the present study examines clients’ understanding of their own experiences of phenomenon in question as well the way in which this understanding is formed. The problem is approached from an ideographical angle, therefore only one case at a time is investigated in detail ( Smith, Flowers & Larkin, 2009).
The present study made use of audio recordings, a limited number of video recordings, and numerous transcripts of therapeutic sessions. A following method was used. Data gained from the first client were transcribed, read and re-read; all attention was focused on one client. The text was searched for the important and remarkable aspects and annotated. The following stage concentrated on notes and developed emerging topics in order to arrive at an essential quality of respondent’s experience. Psychological terminology, PBSP terminology, respondents’ metaphors and quotations were used. This was followed by an investigation of connections and relations between individual topics; these were marked using numerical identifiers and pagination. Certain topics in one sphere were assigned a shared name and a list of broader topics with constituent topics was assembled. Only then analysis of another case using the same procedure began. In the final stage, patterns recurring across individual cases were examined. Throughout the research there was an emphasis on the issue of connections between the respondents’ experiences and the possibility of a case explaining another one. The study also examined the possible presence of a principal shared topic that could provide a basis for a more theoretical analysis.
The primary intention of analysing a sample of 20 respondents (10 male, 10 female) was abandoned in spite of Fade’s claim (2004) it is possible, as it would not be as important in this type of paper; it was in fact beneficial to examine only a few cases in detail. Given the rich and extensive materials from psychotherapeutic sessions, 3 males and 3 females were included in a detailed research.
Findings
Re-reading materials from the first case (story and records of therapy of client Ella) provided a general notion of type of traumatisation, traumatising father figure, and manner of trauma transmission across generations. The consequences of genetically transmitted trauma for the client’s personal and professional life as well as for her relationships were identified. Cognitive, emotional and behavioural changes manifested certain typology. In this stage, the researcher attempted to adopt the client’s perspective in order to understand the quality of her experience.
Subsequently, the materials were provided with annotations and comments (examples in the left column of the table), out of which specific significances the client assigned to recurrent events in her lived experience emerged. These were the source of the so-called emerging topics (examples in the right column). In the middle column there are quotations of Ella’s testimony. Given the present study’s scope it is not possible to introduce the entire procedure in detail, therefore the table below only presents the quotations, comments and topics illustrating transgenerational trauma.
Table 1 -
Other themes and their connections were identified. In the following stage, principal topics emerged.
Key topics were established below with regards to analysed cases of Marie and Alice. As a reference, their personal experiences are given here in short. Both Alice and Marie and a traumatising mother. Intrusion had a form of frequent beating in childhood, later, as they started attending school, traumatisation became verbal (criticism, disparaging, verbal abuse, restrictions etc.). Manners of traumatisation by Ella’s father and Alice and Marie’s mothers were roughly identical. Mothers’ behaviour repeated the patterns inherited from their mothers. Ella’s father copied the behaviour of his father with whom he was no longer in contact. Ella, Alice and Marie invented strategies of survival in the form of attempts to become a good person, partner, and employee. While this strategy proved successful in their professional careers and they held prestigious positions, they lacked confidence in personal life and they repeatedly encountered partners who were critical of them and disparaged their personality, profession, and job. The women either suffered in the relationships despite their best efforts to satisfy the partners or were left by their partners. Ella, Marie and Alice underwent therapy not because they were aware of transgenerational trauma but due to relationship problems in the present.
Names of principal topics reflect the respondents’ essential experiences of transgenerational trauma and cognitive, emotional and behavioural changes: relationship problems as a motivation for change; family heritage; changes in relationship to significant others and oneself; experience of beneficial limits as a source of confidence of one’s ability to control one’s own life; freedom and creativity in behaviour.
Analysis of male respondents (Jan, Martin and Tomáš) suggested different experiences in terms of source of traumatisation and consequences in life. Given the exclusive occurrence of fathers as primary sources of traumatisation, trauma was transmitted in paternal family line only. The manner of traumatisation was identical but the consequences differed. While the women selected partners with similar personality traits as their traumatising mothers or fathers, the men tended towards partners representing the opposite of traumatising fathers. The male clients underwent therapy not because of relationship problems but due to a social anxiety manifested especially in professional and social spheres. While the women showed a significant, even unlimited desire to make efforts in the relationship, the men were afraid of the requirements associated e.g. with performance in professional life, their efforts were blocked by anxiety and they tended towards avoidance and somatisation (especially in digestive system). This led to an increase in anxiety in the long term, associated especially with the fear of loss of employment and social prestige.
For this reason, the first principal topic bears a different name: social anxiety as a motivation for change.
Conclusion
To summarise the research’s preliminary conclusions, respondents did not differ significantly regarding sources of traumatisation. The women in the sample in question traumatised by mothers had weak and submissive fathers. In case of Ella, the mother was submissive. These clients preferred critical, traumatising male partners later in their life. Subconsciously they may have desired a strong and kind partner. The men were traumatised by their fathers and tended towards female partners representing an opposite of intrusion. Their trauma was reactivated at work and in their social lives; they also suffered from social anxiety.
During the PBSP process, both male and female respondents understood quickly the theory of trauma as well as the mechanisms of transgenerational transmission of behavioural patterns. Out of general information, they selected the details relevant for themselves and gradually gained understanding of their family story, the context and the sources of problems. This cognitive foundation provided a significant emotional relief and a decrease in uncertainty related to the perception that the repeated events will be further replicated regardless of their decision and awareness. They acknowledged changes in relationship with themselves and others, especially the traumatising persons, and rediscovered their worth; a potential they undertook to develop. They started to feel protected, and regained the notion of beneficial limits for themselves and in the context of their surroundings. They became able to decide and to act upon this decision.
In case of the small sample of the present study, it is possible to confirm that during scenic symbolic work using PBSP, uncovering and bringing repetition of trauma to consciousness occurs. Clients gradually become able to acknowledge they are active agents of cognitive, emotional and behavioural changes. As a result they are able to disrupt the unconscious repetition of family traumatisation. A social pedagogue is competent to participate in cognitive changes, primarily using education in PBSP theory, micro tracking and local placeholders. Instead of movies, which require therapeutic skills, it is possible to use genogram and help a client to understand family lines and recurring topics.
Acknowledgments
This article reports results of the project Specific research No. 2111/2017 realized at the Faculty of Education, University of Hradec Králové.
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Cite this article as:
Slaninova,
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Kucerova,
Z.
(2017). Trangenerational Trauma – Context And Reflection Of Changes In Scenic Symbolic Work. In
Z.
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Economies | Free Full-Text | Gender Inequality in European Football: Evidence from Competitive Balance and Competitive Intensity in the UEFA Men’s and Women’s Champions League
Competitiveness of sporting contests is key to attract fan interest. However, limited research compared levels of competitiveness in men’s and women’s sports. This study focuses on the evolution of intra-match competitive balance (IMCB) and competitive intensity (IMCI) in the UEFA Men’s and Women’s Champions League (UMCL and UWCL). Data were initially collected for 3299 games over 2001–2019 (2314 in UMCL; 985 in UWCL) to analyse the evolution within and between each tournament. In addition, 989 matches played in UMCL over 1955–1973 were added to compare both competitions in their early stages. Results show a deterioration in IMCB and IMCI between 2001–2009 and 2009–2019 for the UMCL. Conversely, the UWCL benefitted from an increase in IMCB but not in IMCI, except for the final. The UWCL is still less competitive than the UMCL. This result holds true even when comparing the early stages of both competitions, i.e., replacing 2001–2019 by 1955–1973 for the UMCL. However, the UWCL has become closer to the UMCL in terms of IMCB and IMCI over time, a result linked to the development of women’s football. From a theoretical perspective, this article advances knowledge of IMCB and IMCI, appropriate for competitions with knockout stages. It underlines the role of the pool of players as an explanatory factor for the gap in competitiveness between European men’s and women’s football.
Background:
Gender Inequality in European Football: Evidence from Competitive Balance and Competitive Intensity in the UEFA Men’s and Women’s Champions League
by Aurélien François 1,* , Nicolas Scelles 2 and Maurizio Valenti 2
1
Centre d’Etudes des Transformations des Activités Physiques et Sportives, University of Rouen, Boulevard Siegfried, 76821 Mont-Saint-Aignan, France
2
Institute of Sport and Business School, Manchester Metropolitan University, All Saints Campus, Oxford Road, Manchester M15 6BH, UK
*
Author to whom correspondence should be addressed.
Economies 2022 , 10 (12), 315; https://doi.org/10.3390/economies10120315
Received: 9 November 2022 / Revised: 2 December 2022 / Accepted: 5 December 2022 / Published: 11 December 2022
Abstract
Competitiveness of sporting contests is key to attract fan interest. However, limited research compared levels of competitiveness in men’s and women’s sports. This study focuses on the evolution of intra-match competitive balance (IMCB) and competitive intensity (IMCI) in the UEFA Men’s and Women’s Champions League (UMCL and UWCL). Data were initially collected for 3299 games over 2001–2019 (2314 in UMCL; 985 in UWCL) to analyse the evolution within and between each tournament. In addition, 989 matches played in UMCL over 1955–1973 were added to compare both competitions in their early stages. Results show a deterioration in IMCB and IMCI between 2001–2009 and 2009–2019 for the UMCL. Conversely, the UWCL benefitted from an increase in IMCB but not in IMCI, except for the final. The UWCL is still less competitive than the UMCL. This result holds true even when comparing the early stages of both competitions, i.e., replacing 2001–2019 by 1955–1973 for the UMCL. However, the UWCL has become closer to the UMCL in terms of IMCB and IMCI over time, a result linked to the development of women’s football. From a theoretical perspective, this article advances knowledge of IMCB and IMCI, appropriate for competitions with knockout stages. It underlines the role of the pool of players as an explanatory factor for the gap in competitiveness between European men’s and women’s football.
;
women’s football
;
competitiveness
;
uncertainty of outcome
;
competition format
1. Introduction
Competitiveness in sport is key to attract teams, players and fans ( Scelles et al. 2021 ) as part of a broader marketing strategy ( Zsigmond et al. 2020 ). Past academic studies highlighted differences in competitiveness between men’s and women’s sports, including men’s and women’s football ( Kringstad 2021 ; Zambom-Ferraresi et al. 2018 ). In its strategy document for the period 2019–2024, the European governing body of football, Union of European Football Associations UEFA ( 2019, p. 13 ), identifies competitiveness as one of the five pillars for the future of the sport and emphasises that competitiveness is needed to make its men’s and women’s tournaments “ dynamic, entertaining and effective ”. Since its inception, UEFA has a long tradition of organising a wide range of football events. Within the club continental competitions held by the European football institution, the most prestigious is the UEFA Champions League. The ‘Champions League’ is the flagship tournament for both men’s and women’s elite football in the continent as it gathers under the same umbrella the top-ranked men’s and women’s clubs in two distinct competitions, namely the UEFA Men’s Champions League (UMCL) and the UEFA Women’s Champions League (UWCL). Both tournaments are considered as the most important club football competitions in elite men’s and women’s football, and therefore represent relevant terms of comparison to analyse the competitiveness of the sport. Taking these two competitions into account, the present paper aims to evaluate how the competitiveness of football has evolved and compared over time across genders.
The concepts of competitive balance (CB) and competitive intensity (CI) are employed to assist evaluation of competitiveness in the UMCL and the UWCL. In line with the seminal articles in sports economics ( Neale 1964 ; Rottenberg 1956 ), CB can be defined as “ a league structure which has relatively equal playing strength between league members ” ( Forrest and Simmons 2002, p. 229 ). This is supposed to lead to a close championship race within a season ( Szymanski 2003 ), as well as league championships divided as equally as possible between teams over time ( Powell 2003 ). Following the idea of game (championship or relegation) significance introduced by Jennett ( 1984 ), Kringstad and Gerrard ( 2004 ) suggested and defined CI as “ the degree of competition within the league/tournament with regards to its prize structure ” ( Kringstad and Gerrard 2004, p. 120 ). CI is concerned with the different sporting prizes in a league or tournament, the number of teams competing for each of them, and the intensity of the competition depending on how close the different teams are from each other for each prize. A limited number of studies focused on CB and CI in the UMCL and UWCL. Exceptions include articles having explored either the UMCL ( Scelles and Durand 2010 ; Wills et al. 2022 ) or the UWCL ( Valenti et al. 2020 ). However, the literature has not compared CB and CI between the UMCL and the UWCL yet. Such comparison is useful to assess whether any differences exist between men’s and women’s football and to evaluate whether both tournaments are competitive.
This study contributes to the advancement of the line of research concerned with gender comparison in sport. Moreover, the results of this research provide practitioners and stakeholders with original insights on the competitiveness of two of the most prestigious elite men’s and women’s tournaments worldwide. Data on indicators of CB and CI were collected over the 2001–2019 period, i.e., from the beginning of the UWCL. Attention was drawn on the impact that the format changes implemented by UEFA in 2009–2010 have had on indicators of CB and CI in both competitions. Data were also collected over the 1955–1973 period for the UMCL–i.e., from its beginning—and compared to the 2001—2019 period for the UWCL. The rationale is to control for the two competitions having started at different times, which may make the comparison over the same period biased in favour of the UMCL since it had more time to develop its competitiveness. Overall, the study aims to answer two research questions:
How has the competitiveness of the UMCL and UWCL evolved over time following the format changes in 2009–2010?
How has the competitiveness compared between the UMCL and UWCL over time?
2. Literature Review and Background Context
2.1. Determinants of Competitive Balance
The concept of CB is well documented in the sports economics literature (see e.g., Rodriguez et al. 2020 ; Scelles et al. 2022 ). One of the key issues identified is how to reach a sporting equilibrium between teams in a competition, i.e., what determines CB. Its primary determinant is the underlying population of talent. This is consistent with evolutionary biology and the so-called Gould hypothesis ( Gould 1983 , 1986 , 1996 ). Applied to the context of sport, it predicts a positive relationship between available playing talent and CB ( Schmidt and Berri 2003 ). Assuming that the underlying populations of talent for the UMCL and the UWCL are a function of the number of registered male and female players worldwide, respectively, a better CB is expected in the UMCL compared to the UWCL. This is because the number of registered female players worldwide was estimated between 4 and 5 million in the FIFA Women’s Football Survey in 2014 and 2019 ( FIFA 2014 , 2019 ); while the number of registered male players worldwide already reached 11.6 million in 1975 and grew to 38.3 million in 2013 ( Arcioni et al. 2018 ). The Gould hypothesis and its impact on CB are consistent with academic works having pointed out differences in the pool of female and male athletes resulting in differences in competitiveness between genders ( Frick 2011a , 2011b ; Frick and Moser 2021 ).
In addition to the underlying population of talent, its distribution between countries and teams also impacts CB (
Scelles et al. 2022
). Countries and teams generating the highest revenue have access to the best players supposed to be close in sporting ability, while the other countries and teams have access to the next best players supposed to be of lower sporting ability than the best players. As such, a high CB is expected if the competition includes a large proportion of countries and teams generating the highest revenue and thus a large proportion of the best players who are close in sporting ability. By contrast, a lower CB is expected if the competition aims for a better representativeness of the different countries and teams. This is because, compared to the previous situation, fewer teams with the best players face more teams with the next best players who are of lower sporting ability than the best players. This refers to the following determinants of CB developed here, namely the number and identity of the teams in the competition.
A high number of teams should be avoided when this induces the presence of teams with lower sporting ability than others. In other words, a league organiser should set an optimal number of teams to ensure CB (
Szymanski 2003
). In the cases of the UMCL and the UWCL, this optimal number is impacted by the number of slots offered to champions and non-champions from the different countries. The UMCL was first introduced in 1955–1956 as the European Champion Clubs’ Cup and only 16 teams took part in the competition, these teams being invited for this first edition and mainly but not only domestic champions. For 41 seasons from the second edition, only domestic champions and the current title holder took part in the competition. The number of teams in the UMCL gradually reached 31 then 32 teams in the main rounds in 1963–1964 and 1967–1968, respectively. In 1997–1998, UEFA opened participation in the UMCL to non-champions, with up to four clubs from the best nations from 1999–2000 (even five later). This resulted in better CB, appeal, and increased revenue over 1999–2008 than previously (
Scelles and Durand 2010
). In 2009–2010, separate routes were created for champions of smaller domestic leagues and (some) non-champions of bigger domestic leagues in the UMCL preliminary round. This change was consistent with the then President of UEFA Michel Platini aiming for returning the balance in favour of national champions and enabling more nations to take part (
Scott 2006
). However, this format change may have decreased CB in the latter stage if champions of smaller domestic leagues from 2009 onwards were not as close in ability to champions of bigger domestic leagues as non-champions of bigger domestic leagues before 2009.
The UWCL was incepted much later, reflecting the obstacles faced by women’s football historically ( Williams 2011 ). Initially launched under the name UEFA Women’s Cup in 2001–2002, the UWCL was only opened to domestic champions in its first seasons. In 2009–2010, the UWCL adopted a new format including runners up from the top 8 nations (extended to 12 in 2016–2017) and was renamed as ‘UEFA Women’s Champions League’ ( UEFA 2008 ). This change aimed at increasing the competitiveness, appeal and revenue of women’s football at the European level.
2.2. Competitive Balance and Gender Studies
CB has been originally studied in men’s competitions. Nevertheless, women’s competitions in Europe have gained increasing attention from scholars over the last years. This has led to cross-gender comparisons of CB indicators between men’s and women’s competitions. In a seminal contribution, Kringstad ( 2018 ) found lower CB in women’s football leagues based on end-of-season tables in Norway, Sweden and Denmark. The author indicated that similar structural rules (e.g., physical structure of the game such as size of the field and goals or length of the games) for both genders may be a reason for his finding, arguing that the rules in women’s football follow the ones of men’s football instead of being specifically designed for the women’s game. Zambom-Ferraresi et al. ( 2018 ) used the Herfindahl-Hirschman Index at the seasonal and championship levels in Spain, and found that top-tier men’s football league is more balanced than its women’s counterpart. This was explained as one of the consequences of the synergies established between professional men’s clubs and women’s teams, with women’s teams from professional men’s clubs dominating independent women’s teams due to the former benefitting from the infrastructure and staff of the male professional section. Moreover, Haugen and Guvag ( 2018 ) found a similar result using a win dispersion indicator to assess men’s and women’s European football and handball leagues.
More recently,
Kringstad
(
2021
) compared the level of CB (measured through win dispersion, performance persistence and championship concentration) between genders in the football and handball championships from three European countries (England, France and Germany), while extending the scope of his study to North American basketball, i.e., the men’s National Basketball Association (NBA) and its women’s counterpart (WNBA). Results show significantly lower CB for women than men in football and, to a lesser extent, in handball, consistent with the previous literature. To explain differences in CB, the attention was directed towards the Gould hypothesis. Importantly, the participation of girls and women in football has been constrained historically by socio-cultural attitudes. Therefore, as the available playing talent in the women’s game is smaller compared to the men’s game, weaker CB is expected in women’s football. By contrast, the WNBA seems to be more balanced than the NBA, despite more males playing basketball than females in North America.
Kringstad
(
2021
) suggested that this is due to the lower number of teams in WNBA (12 vs. 30 in NBA), consistent with the need for an optimal number of teams to ensure CB.
2.3. Competitive Intensity and the Champions League
While providing interesting insights, the aforementioned studies focused solely on CB and did not tackle CI. CI assumes that, apart from the degree of equality between team playing strengths, audiences are also interested in the prizes that may be distributed in the league or tournament (
Kringstad and Gerrard 2004
). For example, the current UMCL group stage includes the following prizes: teams that end 1st qualify to the round of 16 and gain the possibility to play at home during the return leg of the match; teams that end 2nd qualify to the round of 16; and teams that end 3rd rather than 4th and last qualify to the next round of the UEFA Europa League. The knockout phase of both the UMCL and the UWCL are played over two legs (except the final, which has always been played as a single leg in the UMCL while this has been the case for the UWCL in 2001–2002 and since 2009), with the prize being the qualification for the next round. Hence, the outcome of the first leg affects the level of CI before the start of the second leg: it is high if the first leg ends with a draw, while much lower if the first leg ends with a large margin in favour of one of the competing teams. With a single leg, CI is automatically optimal at the start of the game. These examples highlight the importance of competition format to generate CI, suggesting that a high number of prizes during the group stage (as opposed to only the teams ranked first in groups of four qualifying for the next round in the UWCL over 2001–2004) and one leg over two legs in the knockout phase favour CI.
By contrast, two games against each team instead of only one may favour CI in the group stage. As an illustration, let us consider the games between the two weakest teams in a group of four teams, with only the top two qualifying for the next round. If the two weakest teams lost their first two games against the two strongest teams before playing against each other, they are already eliminated if there are no return games, i.e., there is no CI in the game between them. If there are return games and they play against each other in the third and fourth games, they are not eliminated, i.e., there is CI in both games between them. This is an important consideration, as there were no return games in the group stage in the UWCL over 2001–2009, as opposed to return games in the group stage in the UMCL over 2001–2019. Another important consideration is that a group stage without return games (UWCL over 2001–2009) may still be better than knockout games with two legs (UWCL over 2009–2019). This is because the two weakest teams in our example are still in contention at the start of the second of their three games in a group stage, as opposed to being already out of contention very early in the first of the two legs in a knockout game (e.g., after only 10 out of the 180 min) if they face the strongest teams.
To the best of the authors’ knowledge, there is no research that compared CI between genders in football. However, a few studies investigated CI in either the UMCL or the UWCL separately. In the UMCL, Scelles and Durand ( 2010 ) found an improvement in both CB and CI at the intra-match level (i.e., within a game) over the 1955–2008 period. The authors interpreted it as the consequence of the development and professionalisation of men’s football over time, higher number of teams from the most competitive nations accessing the competition, as well as the changes in rules. For example, the introduction of a group stage in 1991 led to a higher percentage of game time with CI compared to the two-legged knockout games used at similar stages of the competition before 1991, as teams were found to be in contention for longer. This suggests that the CI of the UWCL may have suffered from the move to a group stage to two-legged knockout games only (except in final) from 2009. Moreover, in the UMCL, Wills et al. ( 2022 ) tested the impact of CI on TV audience demand over the 2013–2019 period. These authors focused on six markets: France, Germany, Italy, the Netherlands, Spain and the UK. While no significant impact of CI was found in knockout stages (measured as the possibility of score reversals after the first leg game), either a positive impact or no impact of CI in group stages (measured through a dummy variable capturing whether at least one team had something to compete for) was evidenced in some of the markets considered. In the UWCL, Valenti et al. ( 2020 ) found a significant positive impact of CI (measured as the possibility of score reversals after the first leg game) on stadium attendance over the 2009–2018 period.
3. Methodology
3.1. Hypotheses
From the two research questions provided in introduction (evolution within and between competitions), as well as the literature review and background context, seven hypotheses are derived:
H1.1.
Competitive balance and competitive intensity decreased in the UEFA men’s Champions League between 2001–2009 and 2009–2019.
It is expected that the champions of weaker domestic leagues that replaced some non-champions of stronger domestic leagues are less close in ability to champions and other non-champions of stronger domestic leagues.
H1.2.
Competitive balance increased in the UEFA women’s Champions League between 2001–2009 and 2009–2019.
It is expected that the non-champions of stronger domestic leagues that replaced some champions of weaker domestic leagues are closer in ability to champions of stronger domestic leagues. H1.1 and H1.2 relate to the determinant of CB and CI ‘identity of the teams in the competition’.
H1.3.
Competitive intensity did not increase in the UEFA women’s Champions League between 2001–2009 and 2009–2019.
It is expected that moving from a group stage to two-legged knockout stages only (except in final) negatively impacted CI, counterbalancing the positive impact expected from H1.2. H1.3 relates to the determinant of CI ‘competition format’.
H2.1.
Competitive balance and competitive intensity were lower in the UEFA women’s Champions League than in the UEFA men’s Champions League over 2001–2019.
This is because of the lower available playing talent in women’s football compared to men’s football, in line with the Gould hypothesis. It is also consistent with academic works having pointed out differences in the pool of female and male athletes resulting in differences in competitiveness between genders ( Frick 2011a , 2011b ; Frick and Moser 2021 ). H2.1 relates to the determinant of CB and CI ‘underlying population of talent’.
H2.2.
The competitive balance and competitive intensity of the UEFA women’s Champions League became closer to the competitive balance and competitive intensity of the UEFA men’s Champions League over 2009–2019 compared to 2001–2009.
This is in line with H1.1, H1.2 and H1.3.
H2.3.
Competitive balance and competitive intensity were lower in the UEFA women’s Champions League over 2001–2009 than in the UEFA men’s Champions League over 1955–1963.
This is because a higher number of teams or countries took part in the UWCL over 2001–2009 than in the UMCL over 1955–1963, which is expected to lead to more teams with lower sporting ability than others, supposed to be close in such ability. It is assumed that the number of registered players was equivalent or slightly higher for males over 1955–1963 than females over 2001–2009. Moreover, it is assumed that the presence of a group stage in the UWCL over 2001–2009 did not affect positively CI and might even have affected it negatively due to only the teams ending 1st in groups of four qualifying for the next round in the UWCL over 2001–2004.
H2.4.
Competitive balance and competitive intensity were similar in the UEFA women’s Champions League over 2009–2019 and the UEFA men’s Champions League over 1963–1973.
This is because of the similarities in the number of teams (31 or 32) and format (only two-legged knockout stages except one-legged final), while it is expected that runners up from the bigger domestic leagues entering the UWCL from 2009 (positive impact) compensated the number of registered female players over 2009–2019 (4 to 5 million in 2014 and 2019) assumed to be lower than the number of registered male players over 1963–1973 (11.6 million in 1975). H2.3 and H2.4 relate to the determinants of CB and CI ‘number of teams in the competition’, ‘underlying population of talent’ and ‘competition format’.
3.2. Definition and Measurement of Intra-Match Competitive Balance and Intensity
In the literature, indicators of CB and CI are usually calculated at a national league level. Most studies have applied seasonal measures of CB and CI to domestic leagues, calculated from the league tables ( Bond and Adessa 2020 ; Scelles et al. 2022 ; Wagner et al. 2020 ). However, such indicators are inappropriate when analysing CB and CI in competitions such as the UEFA Champions League as it includes only a small number of games in the group stage(s), if any. In addition, the tournament includes a knockout stage, making usual measures at seasonal level irrelevant. Instead, intra-match measures are more appropriate for competitions that include knockout stages. If they can be applied to a domestic league ( Scelles et al. 2011 ), they seem particularly suitable to a tournament including knockout stages, as recently done in studies on the FIFA women’s World Cups ( Scelles 2021a ) and UEFA men’s national team competitions ( Scelles 2021b ), and earlier in an article on the UMCL ( Scelles and Durand 2010 ). Thus, the present research relies on intra-match CB (IMCB) and intra-match CI (IMCI) measures.
IMCB and IMCI capture the excitement of fans during the game. This is assumed to derive from close and uncertain score lines. Accordingly, IMCB is defined as a relatively balanced score that generates high uncertainty about the possible winner until the end (e.g., a score enabling a team to take the lead or equalise if this is to score the next goal). IMCB is high when a team either scores an equaliser (e.g., from 0–1 to 1–1) or takes the lead with only one goal difference (e.g., from 0–0 to 0–1). In line with this, we consider that there is uncertainty when the difference between competing teams is no more than one goal.
Falter and Pérignon
(
2000
) found that the probability of winning becomes far higher and, subsequently, outcome uncertainty far lower when a team leads by at least two goals. Moreover, fluctuations in the ‘state’ of score need to be considered for a better assessment of how exciting a game is for fans. To illustrate, a game with a score of 3–3 with six fluctuations is likely to be more exciting than a game with a score of 0–0 with no fluctuation. Importantly,
Alavy et al.
(
2010
) showed that 0–0 or a sustained game-time without fluctuation is associated with lower TV viewership in football. However, because fluctuations cannot occur when there is no uncertainty (i.e., at least a two goals difference between teams), the latter is considered of prime importance over the former.
In addition to IMCB, at least one team needs to have a prize to compete for to make the game meaningful and, as such, competitively intense. Accordingly, IMCI is defined as a score where the next goal can change the situation of at least one team in relation to a prize (e.g., qualification to the next round). Like IMCB, fluctuations need to be considered for IMCI. However, for IMCI, fluctuations are related to the changes in the context of the competition that are determined by a change in match score (e.g., the team that scores a goal moves from being eliminated to being qualified). There is some evidence in the literature that CI may be more important than CB in explaining stadium attendance (
Andreff and Scelles 2015
) and TV audience (
Scelles 2017
), although the indicators chosen did not measure the intra-match level.
1
IMCB and IMCI measures used here follow the methods applied in previous literature. For IMCB, we calculated both the intra-match uncertainty (IMU) and the intra-match fluctuations (IMF) defined as follows:
IMU refers to the percentage of game-time with a score difference of no more than one goal between the competing teams. For example, if the score moves from 0–0 to 1–0, 1–1, 2–1, then 3–1 at the 81st minute of the game (a football game lasting 90 min), there is uncertainty during 81 min and IMU is 90% (= 81/90). Values can range from 0% to 100%. However, 0% is theoretical since even if team A scores within seconds after the kick-off, there is still uncertainty as team B is only one goal away from equalising.
IMF refers to the number of times a goal determines a change on the ‘state’ of the score. Values are expressed in absolute terms. Adopting the example described above for IMU, the value of IMF would be equal to 3: 1 from 0–0 (draw) to 1–0 (team A leading); 1 from 1–0 to 1–1 (draw); and 1 from 1–1 to 2–1 (team A leading again). No additional fluctuation is considered from 2–1 to 3–1 since team A would remain the leading one.
The same indicators were selected for IMCI, renamed as IMU’ and IMF’. Definitions of these indicators are equivalent to those of IMU and IMF, but contextualised with regard to the prize(s) the two teams compete for. In the previous example, if both teams have nothing to compete for (e.g., team A is sure to end first in its group and team B is already eliminated) or the game is the return game of a two-legged tie and team A won the first leg 3–0, IMU’ = 0% and IMF’ = 0. By contrast, if team A needs to win with a two goals margin and team B needs a draw, IMU’ = 100%, since, even at 3–1, team A is under the threat of not having a two goals margin anymore in the case of team B scoring a goal. IMF’ would be equal to 4: 1 from 0–0 to 1–0 (no draw anymore for team B); 1 from 1–0 to 1–1 (draw again for team B); 1 from 1–1 to 2–1 (no draw anymore for team B); and 1 from 2–1 to 3–1 (two goals margin for team A).
3.3. Data Collection and Analysis
To test the first five hypotheses, data were collected at match level both for the UMCL and the UWCL over the 2001–2019 period. As important changes occurred in 2009 in the formats of both competitions, the data were split into two sub-periods, 2001–2009 and 2009–2019. Over this period, 3299 matches were analysed: 2314 in UMCL, respectively 1064 between 2001 and 2009 and 1250 between 2009 and 2019; and 985 in UWCL, respectively 375 between 2001 and 2009 and 610 between 2009 and 2019.
To test the last two hypotheses, 989 UMCL matches analysed between 1955 and 1973 were added and also divided in two sub-periods—1955–1963 (393 matches) and 1963–1973 (596 matches)—to make possible the comparison with the 2001–2009 and 2009–2019 sub-periods in UWCL. In total, 4288 matches are included in the dataset. Table 1 provides information for each sub-period analysed on the total number of matches analysed, the average numbers of clubs and associations involved in the competition, the stages selected and the number of matches for each stage.
Table 1. Dataset for UEFA Men’s and Women’s Champions Leagues.
To verify whether the hypotheses are valid or not, the evolution of IMCB and IMCI in each tournament separately over 2001–2019 was first analysed by considering the two sub-periods identified (2001–2009 vs. 2009–2019) within the two competitions. Then, cross-comparisons on the level of IMCB and IMCI between both genders over the same period were undertaken. Additionally, a similar comparison between men and women was applied, but based on the first 18 years of the competition in UMCL (i.e., 1955–1973) and UWCL (i.e., 2001–2019) under the rationale that it is necessary to control for the two competitions having started at different times.
The different analyses were conducted both for the overall competition and specific rounds. As an example, over the 2001–2019 period, the analysis not only overall but also from the quarter-finals allowed to test not only the impact of the format changes implemented in 2009 but also examine the evolution of both IMCB and IMCI between the best eight teams. For the UMCL, the impact of the introduction of the champions and non-champions paths in the qualifying rounds was tested. For the UWCL, the impact of the transition from a group stage to home-and-away knockout games in the round of 32 with more teams from the highest ranked associations was tested. The evolution of IMCB and IMCI of both competitions for both sub-periods analysed was also compared to assess whether any differences existed between the men’s and women’s competitions and how these evolved before and after the format changes under consideration.
A last important methodological consideration is that, to conduct relevant calculations from a longitudinal and comparative perspective, it was chosen to consider games from the round the best teams enter the competitions over 2001–2019. In the UWCL, the focus was on the 16 teams that participated in the second qualifying round over 2001–2009, and the 32 teams that entered the round of 32 over 2009–2019. In the UMCL, the 32 teams that took part in the group stage were selected for the 2001–2019 period. Over 1955–1973, most of the time, many teams took part in the preliminary round when there was one, if not all except the previous winner. Thus, it was decided to include the preliminary round in the analysis, except in 1996–1967 (only four teams involved). All 16 teams were covered in the first edition of the competition in 1955–1956, extending to 22 teams in 1956–1957 and gradually a few more the following years, until reaching 32 teams in 1967–1968.
Comparisons were undertaken through one-paired or two-paired
t
-tests, depending on whether a specific direction (one-paired) was expected (i.e., H1.1, H1.2, H2.1 and H2.3) or not (i.e., H1.3, H2.2 and H2.4).
4. Results
4.1. UMCL 2001–2019
IMCB results in the UMCL are displayed in
Table 2
. IMU significantly deteriorated between 2001–2009 and 2009–2019, with a drop in the percentage of game-time with a difference of no more than one goal from 84.5% to 80.9% overall. This is consistent with the assumption that champions of smaller domestic leagues from 2009 onwards did not perform as well as non-champions of bigger domestic leagues before 2009. However, the decrease is also significant from the quarter-finals, indicating a decreasing IMU even between the best teams. The deterioration for uncertainty did not translate into a decrease in the number of fluctuations. IMF went from 1.58 to 1.64 fluctuations overall, although this increase is not statistically significant.
Table 2. Intra-match competitive balance and intensity–UEFA Men’s Champions League 2001–2019.
IMCI results considering the prizes in the UMCL are also shown in
Table 2
. Like IMU, IMU’ decreased between 2001–2009 and 2009–2019. Overall, this deterioration was even more prominent, from 80.1% to 74.7%. Like IMCB, IMCI suffered from a significant decrease in IMU’ not only overall but also from the quarter-finals. However, IMF’ for IMCI did not follow the same path as IMF for IMCB. There was a significant decrease in IMF’ overall, from 1.49 to 1.41 fluctuations, aligning this result with the significant decrease in IMU’. Overall, both IMCB and IMCI significantly decreased in the UMCL between 2001–2009 and 2009–2019. This result is in support of H1.1.
4.2. UWCL 2001–2019
IMCB results in the UWCL are shown in
Table 3
. Overall, there was a significant improvement in IMU, with the indicator going from 64.3% of game-time with a score difference of no more than one goal over 2001–2009 to 71.1% over 2009–2019. This result is in support of H1.2. However, there was no significant improvement when looking at IMU from the quarter-finals. These results are consistent with the assumption that the runners up from top nations included from 2009 onwards are better than the champions from lower ranked nations, rather than an overall development of women’s football over time that would also translate in better CB between the best teams. Although the UWCL became more balanced overall from 2009, IMF followed the opposite direction. IMF showed a significant decrease from 1.59 to 1.46.
Table 3. Intra-match competitive balance and intensity–UEFA Women’s Champions League 2001–2019.
Looking at the IMCI results in the UWCL, it can be observed that IMU’ deteriorated from 50.9% to 49.9% overall between 2001–2009 and 2009–2019. However, the difference is not statistically significant. This is consistent with the assumption that moving from a group stage to two-legged knockout stages only (except in final) negatively impacted CI, counterbalancing the positive impact related to the significant increase in CB. This result is in support of H1.3. The only significant difference between both periods is for the final, which shows a significant improvement in IMU’ from 52.4% to 82.2%. This result can be directly linked to the change in the format of the final, played as a single leg since 2009. A single leg avoids a return match potentially without IMCI after an unbalanced first leg, as this was often the case over 2001–2009. The statistical tests conducted for IMF’ are all significant. They show a decrease in the number of fluctuations since 2009, except for the final that benefitted from a significant increase, with the indicator going from 0.73 to 1.4 fluctuations. This confirms the positive impact of the format change implemented for the UWCL final since 2009.
Overall, the fact that the significant increase in IMU did not translate in a significant increase in IMU’ casts doubt about the overall relevance of the format change, with in particular a move from a group stage to knockout rounds only. This suggests the need to include a group stage, consistent with Scelles and Durand ( 2010 ).
4.3. UWCL vs. UMCL 2001–2019
By adopting a cross-analysis perspective, indicators of IMCB and IMCI were compared for each stage in the UWCL and UMCL. IMCB results are presented in
Table 4
and
Table 5
for the overall competitions and from the quarter-finals, respectively. Over each of the two sub-periods studied, the differences in IMU between women and men were statistically significant overall, with IMU being lower for women than men. This is consistent with the lower available playing talent in women’s football compared to men’s football, in line with the Gould hypothesis. However, the improvement of IMU for women and its deterioration for men between 2001–2009 and 2009–2019 led to a reduction in the gap between the UWCL and the UMCL. The overall difference between the two competitions reduced from 20.2 percentage points (64.3% in the UWCL and 84.5% in the UMCL) to 9.8 percentage points (71.1% in the UWCL and 80.9% in the UMCL) across the two sub-periods. The same applies to the difference between the two competitions from the quarters-finals, which reduced from 14.8 percentage points (73.6% in the UWCL and 88.4% in the UMCL) to 6.5% (75.5% in the UWCL and 82.0% in the UMCL). The difference between the two competitions from the quarter-finals over 2009–2019 is significant at the 5% level instead of the 1% level over 2001–2009. This is with a one-tailed test; if the assumption would have been that IMU for women and men from the quarter-finals over 2009–2019 should not have been different (two-tailed test), the difference would have been significant at the 10% level only.
Table 4. Intra-match competitive balance and intensity–UEFA Women’s vs. Men’s Champions Leagues 2001–2019–Overall.
Table 5. Intra-match competitive balance and intensity–UEFA Women’s vs. Men’s Champions Leagues 2001–2019–From the quarter-finals.
Overall IMF was slightly higher for the UWCL than for the UMCL over 2001–2009 (1.59 vs. 1.58, difference not significant), before this was reversed over 2009–2019 (1.46 vs. 1.64, significant difference).
IMCI results are also presented in
Table 4
and
Table 5
. They are similar to IMU for IMU’ over both 2001–2009 and 2009–2019, and both overall and from the quarter-finals, i.e., IMU’ was significantly lower in the UWCL than the UMCL but the difference reduced. These results are in support of H2.1 and H2.2. The overall difference between the two competitions reduced from 29.2 percentage points (50.9% in the UWCL and 80.1% in the UMCL) to 24.8 percentage points (49.9% in the UWCL and 74.7% in the UMCL) across the two sub-periods. The same applies to the difference between the two competitions from the quarters-finals, which reduced from 23.9 percentage points (52.7% in the UWCL and 76.6% in the UMCL) to 10.3% (53.5% in the UWCL and 63.8% in the UMCL).
Over 2001–2009, both differences between women and men overall and from the quarter-finals are significant for IMF’ (lower IMF’ for women than men) while they were not significant for IMF. This indicates that the format was less suitable to generate IMF’ in the UWCL than in the UMCL over 2001–2009. This format included a group stage with only one game against each of the other teams in the group and only the top teams over 2001–2004 (top two teams over 2004–2009) qualifying for the next round (vs. two games against each of the other teams in the group and the third ranked team qualifying for the UEFA Cup in the UMCL), as well as a two-legged final. The format being less suitable in the UWCL than the UMCL was also true over 2009–2019. Indeed, IMF’ displays similar results to IMF over 2009–2019, i.e., significantly lower IMF’ for women than men, with a larger overall difference for IMF’ (0.51; 0.90 in the UWCL and 1.41 in the UMCL) than for IMF (0.18; 1.46 in the UWCL and 1.64 in the UMCL). This result is consistent with the need to include a group stage in the UWCL. However, the result over 2001–2009 suggests that this is not enough. The group stage must include enough prizes, i.e., at least two teams qualifying with an incentive to be ranked first rather than second; and enough games, i.e., two games against each of the other teams in the group rather than one.
4.4. UWCL 2001–2019 vs. UMCL 1955–1973
Table 6
presents IMCB and IMCI in the UWCL over 2001–2019 and the UMCL over 1955–1973. IMCB and IMCI were lower in the UWCL over 2001–2009 than in the UMCL over 1955–1963. This result is in support of H2.3. IMCB and IMCI were also lower in the UWCL over 2009–2019 than in the UMCL over 1963–1973 (not significant for FIM). This result does not support H2.4. This may mean that runners up from the bigger domestic leagues entering the UWCL from 2009 did not compensate the number of registered female players over 2009–2019 assumed to be lower than the number of registered male players over 1963–1973. However, it must be noted that the differences between the UWCL over 2001–2019 and the UMCL over 1955–1973, i.e., when considering their first 18 seasons, are far lower than when both competitions are considered over 2001–2019. This comparison seems fairer for the UWCL since the competition had not the same opportunity to develop its competitiveness over time as the UMCL. Moreover, IMU was 71.1% in the UWCL over 2009–2019 vs. 73.9% in the UMCL over 1963–1973. Although significant at the 10% level, the difference corresponds to less than three minutes: does it really make a difference in terms of perceived uncertainty by fans?
Table 6. Intra-match competitive balance and intensity–UEFA Champions Leagues–Women 2001–2019 vs. Men 1955–1973.
5. Discussion
The present study aimed to answer two research questions:
How has the competitiveness of the UMCL and UWCL evolved over time following the format changes in 2009–2010?
How has the competitiveness compared between the UMCL and UWCL over time?
From these two research questions, as well as the literature review and background context, seven hypotheses were tested. The first six hypotheses were supported by the results:
H1.1.
CB and CI decreased in the UMCL between 2001–2009 and 2009–2019.
H1.2.
CB increased in the UWCL between 2001–2009 and 2009–2019.
H1.3.
CI did not increase in the UWCL between 2001–2009 and 2009–2019.
H2.1.
CB and CI were lower in the UWCL than in the UMCL over 2001–2019.
H2.2.
The CB and CI of the UWCL became closer to the CB and CI of the UMCL over 2009–2019 compared to 2001–2009.
H2.3.
CB and CI were lower in the UWCL over 2001–2009 than in the UMCL over 1955–1963.
By contrast, H2.4 was not supported by the results, i.e., CB and CI were
not
similar in the UWCL over 2009–2019 and the UMCL over 1963–1973. Instead, CB and CI were lower in UWCL, although the difference in CB (IMU) was significant only at the 10% level and corresponded to less than three minutes.
5.1. More Balanced European Women’s Football: The Consequence of an Increased Professionalisation?
Results show an overall improvement in CB measured through IMU in the UWCL between 2001–2009 and 2009–2019. The first sub-period comprised 16 teams from 15 to 16 countries, while the second sub-period relied on 32 teams with two teams from up to the 12 best countries (even three teams for Germany in 2009–2010) based on the UEFA coefficients. The improvement in CB (IMU) can be interpreted as a positive consequence of allowing more than one team from the best UEFA countries. This suggests that the second-best teams in these countries are better than the best teams in the countries with lower UEFA coefficients. A similar result would likely be found if extended to the third-best teams in the best countries, consistent with the new UWCL format implemented in 2021–2022 that includes three teams for each of the six best-ranked countries (
UEFA 2019
). Nevertheless, the improvement does not hold anymore when looking at CI measured through IMU’. Findings show that a group stage is more appropriate than a knockout stage with two legs. This is logical as a group stage is supposed to keep most teams in contention until late, especially if most positions are associated with a prize (as in the UMCL with three positions out of four being in contention for a prize). In contrast, a two-legged knockout stage game may be decided early (e.g., in the first leg of the game), thus leading to reduced fan interest towards the second leg. The new UWCL format, implemented in 2021–2022, includes a group stage qualifying 50% of the teams to the next round. This is a format change that is directly supported by our findings.
If the move from a group stage to a round of 32 was not the best choice in terms of CI (IMU’), the move from a two-legged to a one-legged final was wise, as confirmed by the significant improvement in CI (IMU’ and IMF’). The significant improvement in IMF’ for the final is in contrast with the significant decreases in IMF and IMF’ overall and from the quarter-finals.
When comparing the UWCL and the UMCL, it appears that the former still lags behind the latter in terms of CB and CI. Following the so-called Gould hypothesis, this was expected due to the relatively limited amount of available playing talent in the women’s game as compared to the men’s, despite its increase over time ( Scelles 2021a ). Yet, the gap between the UWCL and the UMCL was reduced, in particular from the quarter-finals, i.e., when it comes to the eight best teams. This reduced gap between women and men may be partly explained by the progressively larger involvement of professional men’s clubs in women’s football. The collaboration between men’s and women’s clubs enables a scenario in which players can benefit from the infrastructure of the male counterparts and dedicate full-time to training and football activities thanks to professionalisation and associated payments ( Valenti 2019 ). As demonstrated by Frick ( 2011a , 2011b ), gender differences in competitiveness of professional distance running considerably narrowed over the years following larger financial incentives for the women’s races. Remarkably, the composition of the UWCL started to see an increasing number of women’s teams that are associated with a men’s club following the introduction of prize money in 2010 ( Valenti et al. 2019 ). Thus, findings of the present research do not support the hypothesis that differences in CB between the UWCL and the UMCL reflect different physical capabilities between the two genders ( Kringstad 2018 ). Instead, they show that gradual improvements in CB and CI in the UWCL are in line with the increasing returns to success and the professionalisation it has favoured, suggesting that UEFA should pursue its efforts and investments in this area.
However, given the still low available playing talent in women’s football, the integration of women’s teams with men’s clubs also risks creating imbalances in the concentration of talent (
Zambom-Ferraresi et al. 2018
), thus potentially undermining the chances of both independent clubs and clubs based in smaller market leagues to reach sporting success. Under the new format, the UWCL rights are centralised from the group stage onwards instead of the final only (
UEFA 2019
), with at least 11 associations represented in the group stage. If coupled with a strong solidarity in revenue sharing, this centralisation may favour CB and CI between more clubs and countries in the UWCL, although the potential consequences on CB and CI in domestic leagues would need to be considered.
5.2. Less Balanced European Men’s Football: A Super League Is Not the Panacea?
Given recent events that occurred in European football with the announcement of the European Super League (
The Super League 2021
), further considerations relating to the future of the game can be derived from the findings of this study. If there is some evidence of improvement in CB and CI in the UWCL, there is instead some evidence of deterioration in the UMCL. Interestingly, this holds true not only overall—i.e., including when the best teams play against lower teams—but also at the later stages of the competition, i.e., when the best teams play each other. This finding can help assess the opportunity of a European Super League in men’s football. The rationale usually provided for its organisation is the ever-increasing gap between the best teams and the other teams, leading to a deterioration of CB in European men’s football. Yet, our results show that CB between the best teams is not as strong as it used to be. This questions the idea that a European Super League would solve the issue of a deteriorating CB in European men’s football. Moreover, a European Super League may struggle to generate a high CI if structured as a closed competition without promotions and relegations, i.e., without the prize of avoiding relegation. In other words, it appears as a potential move without clear benefits for fans and football in general, consistent with recent research (
Brannagan et al. 2022
;
Wagner et al. 2021
); by contrast, it raises a clear threat on the sustainability of European men’s football as it has been organised since the late 19th century.
The threat of a European Super League in men’s football can be considered as well in women’s football. This may lead to the same format and be played by the same clubs as in its men’s counterpart. This underlines the moves that may happen in both European women’s and men’s football, and their potential synergies. Although a broader economic approach combined with more managerial and socio-cultural perspectives would be necessary to explore this research direction further, this avenue may still be usefully informed by a reflection on the potential impact on CB and CI in European women’s and men’s football.
5.3. Limitations and Future Research Directions
In addition to the last suggestion, other future research directions can be identified following the limitations of the present research. A first limitation is identified in the lack of longitudinal data to account for the differences in available playing talent between women’s and men’s football and their evolution in European football over 2001–2019. Official figures over the entire period are not available. However, with this information now being collected more regularly by UEFA, it is suggested that future research investigate further the impact of these differences and their evolution on CB and CI. A second limitation is that a regression model was not tested to confirm the results while controlling for the different explanatory variables at the same time. Testing a regression model with the data available in the dataset collected would not allow to include an explanatory variable enabling to make a distinction between the different games played during the same leg or matchday of the same round for the same competition during the same season. Yet, the data show that there can be important differences between such games in terms of CB and CI. For this reason, it was decided not to include a regression model. Future research could address this limitation by identifying additional data that enable to test a regression model with at least one explanatory variable (e.g., differences in UEFA coefficients between clubs/countries) that distinguishes between the different games. A third limitation is that the impact of CB and CI on fan demand has not been tested. The reason is that the focus was on the analysis of CB and CI rather than their impact on fan demand. Future research could explore the latter, extending from
Valenti et al.
(
2020
) in the UWCL. This could also help identify differences in terms of how fans perceive CB and CI for similar levels between men’s and women’s football, while the present research assumed that they are equivalent (e.g., a game with 80% of uncertainty is considered as exciting for both men’s and women’s football). A fourth limitation is that the perceptions of key European football stakeholders have not been included in the analysis. Yet, such perceptions based on interviews and surveys may help understand further the reasons behind the past evolution of CB and CI, as well as better anticipate their future evolution in the context of the European football model.
No potential conflict of interest was reported by the authors.
Note
1 IMCB and IMCI can be equivalent in some situations (e.g., single leg or early games in a group stage, when all teams can still qualify for the next round), while they differ in others (e.g., in a second leg after 5–0 in the first leg or when both teams have nothing to compete for anymore in the group stage), depending on the competition format.
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Table 1. Dataset for UEFA Men’s and Women’s Champions Leagues.
Matches Analysed Average Number of Clubs Represented Average Number of Associations Represented Stages Selected Number of Matches Analysed Per Stage UMCL 1955–1963 393 28 27 Preliminary (when there was one) and knockout stages Preliminary rounds: 148 Round of 16: 136 Quarter-finals: 67 Semi-finals: 34 Final: 8 1963–1973 596 31 30 Preliminary (when there was one, except 1966–1967) and knockout stages Preliminary rounds: 126 Round of 32: 179 Round of 16: 157 Quarter-finals: 83 Semi-finals: 41 Final: 10 2001–2009 1064 73 49 Group and knockout stages Group stage: 864 Round of 16: 96 Quarter-finals: 64 Semi-finals: 32 Final: 8 2009–2019 1250 77 53 Group and knockout stages Group stage: 960 Round of 16: 160 Quarter-finals: 80 Semi-finals: 40 Final: 10 UWCL 2001–2009 375 41 40 2nd qualifying round and knockout stages 2nd qualifying round: 264 Quarter-finals: 64 Semi-finals: 32 Final: 15 2009–2019 610 56 46 Knockout stages Round of 32: 320 Round of 16: 160 Quarter-finals: 80 Semi-finals: 40 Final: 10
Table 2. Intra-match competitive balance and intensity–UEFA Men’s Champions League 2001–2019.
Overall From Quarter-Finals 2001–2009 2009–2019 p -Value 2001–2009 2009–2019 p -Value Intra-match competitive balance (IMCB) Intra-match uncertainty (IMU) 84.5% 80.9% <0.001 *** 88.4% 82.0% 0.018 ** Intra-match fluctuations (IMF) 1.58 1.64 0.119 1.81 1.72 0.294 Intra-match competitive intensity (IMCI) Intra-match uncertainty (IMU’) 80.1% 74.7% <0.001 *** 76.6% 63.8% 0.004 *** Intra-match fluctuations (IMF’) 1.49 1.41 0.055 * 1.42 1.24 0.126
*, ** and *** mean significant at 10%, 5% and 1%, respectively; p -values based on one-tailed t -tests (direction specified).
Table 3. Intra-match competitive balance and intensity–UEFA Women’s Champions League 2001–2019.
Overall From Quarter-Finals Finals 2001–2009 2009–2019 p -Value 2001–2009 2009–2019 p -Value 2001–2009 2009–2019 p -Value Intra-match competitive balance (IMCB) Intra-match uncertainty (IMU) 64.3% 71.1% <0.001 *** 73.6% 75.5% 0.313 72.7% 82.2% 0.214 Intra-match fluctuations (IMF) 1.59 1.46 0.043 ** 1.66 1.31 0.008 *** 1.47 1.4 0.453 Intra-match competitive intensity (IMCI) Intra-match uncertainty (IMU’) 50.9% 49.9% 0.687 52.7% 53.5% 0.444 52.4% 82.2% 0.033 ** Intra-match fluctuations (IMF’) 1.13 0.90 0.001 *** 1.14 0.87 0.038 ** 0.73 1.4 0.094 *
*, ** and *** mean significant at 10%, 5% and 1%, respectively; p -values based on one-tailed t -tests (direction specified) for IMCB; two-tailed t -tests (direction not specified) for IMCI.
Table 4. Intra-match competitive balance and intensity–UEFA Women’s vs. Men’s Champions Leagues 2001–2019–Overall.
2001–2009 2009–2019 Women Men p -Value Women Men p -Value Intra-match competitive balance (IMCB) Intra-match uncertainty (IMU) 64.3% 84.5% <0.001 *** 71.1% 80.9% <0.001 *** Intra-match fluctuations (IMF) 1.59 1.58 0.481 1.46 1.64 <0.001 *** Intra-match competitive intensity (IMCI) Intra-match uncertainty (IMU’) 50.9% 80.1% <0.001 *** 49.9% 74.7% <0.001 *** Intra-match fluctuations (IMF’) 1.13 1.49 <0.001 *** 0.90 1.41 <0.001 ***
*** means significant at 1%; p -values based on one-tailed t -tests (direction specified).
Table 5. Intra-match competitive balance and intensity–UEFA Women’s vs. Men’s Champions Leagues 2001–2019–From the quarter-finals.
2001–2009 2009–2019 Women Men p -Value Women Men p -Value Intra-match competitive balance (IMCB) Intra-match uncertainty (IMU) 73.6% 88.4% <0.001 *** 75.5% 82.0% 0.028 ** Intra-match fluctuations (IMF) 1.66 1.81 0.199 1.31 1.72 0.002 *** Intra-match competitive intensity (IMCI) Intra-match uncertainty (IMU’) 52.7% 76.6% <0.001 *** 53.5% 63.8% 0.017 ** Intra-match fluctuations (IMF’) 1.14 1.42 0.052 * 0.87 1.24 0.004 ***
*, ** and *** mean significant at 10%, 5% and 1%, respectively; p -values based on one-tailed t -tests (direction specified).
Table 6. Intra-match competitive balance and intensity–UEFA Champions Leagues–Women 2001–2019 vs. Men 1955–1973.
Women 2001–2009 Men 1955–1963 p -Value Women 2009–2019 Men 1963–1973 p -Value Intra-match competitive balance (IMCB) Intra-match uncertainty (IMU) 64.3% 72.0% <0.001 *** 71.1% 73.9% 0.093 * Intra-match fluctuations (IMF) 1.59 1.79 <0.001 *** 1.46 1.50 0.515 Intra-match competitive intensity (IMCI) Intra-match uncertainty (IMU’) 50.9% 56.4% 0.023 ** 49.9% 57.8% <0.001 *** Intra-match fluctuations (IMF’) 1.13 1.41 0.002 *** 0.90 1.12 <0.001 ***
*, ** and *** mean significant at 10%, 5% and 1%, respectively; p -values based on one-tailed t -tests (direction specified) for UWCL 2001–2009 vs. UMCL 1955–1963; two-tailed t -tests (direction not specified) for UWCL 2009–2019 vs. UMCL 1963–1973.
© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( https://creativecommons.org/licenses/by/4.0/ ).
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François, A.; Scelles, N.; Valenti, M. Gender Inequality in European Football: Evidence from Competitive Balance and Competitive Intensity in the UEFA Men’s and Women’s Champions League. Economies 2022, 10, 315.
https://doi.org/10.3390/economies10120315
AMA Style
François A, Scelles N, Valenti M. Gender Inequality in European Football: Evidence from Competitive Balance and Competitive Intensity in the UEFA Men’s and Women’s Champions League. Economies. 2022; 10(12):315.
https://doi.org/10.3390/economies10120315
Chicago/Turabian Style
François, Aurélien, Nicolas Scelles, and Maurizio Valenti. 2022. "Gender Inequality in European Football: Evidence from Competitive Balance and Competitive Intensity in the UEFA Men’s and Women’s Champions League" Economies10, no. 12: 315.
https://doi.org/10.3390/economies10120315
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Environments | Free Full-Text | Adapting to Climate Change: Lessons from Farmers and Peri-Urban Fringe Residents in South Australia
This paper reports on results from two major research projects conducted in South Australia. The first investigates adaptation to climate change in two of the state’s major grain and sheep farming regions, using semi-structured interviews and focus groups. The second uses a postal questionnaire and an internet-based survey of residents in the peri-urban fringes of Adelaide, the state capital, to examine knowledge of and attitudes to climate change and resulting adaptations, especially in the context of increasing risk of wildfires. The research on adaptation to climate change in agriculture focused on formal institutions (e.g., government agencies) and communities of practice (e.g., farm systems groups). Both groups noted that farmers autonomously adapt to various risks, including those induced by climate variability. The types and levels of adaptation varied among individuals partly because of barriers to adaptation, which included limited communication and engagement processes established between formal institutions and communities of practice. The paper discusses possibilities for more effective transfers of knowledge and information on climate change among formal institutions, communities of practice, trusted individual advisors and farmers. Research in the peri-urban fringe revealed that actions taken by individuals to mitigate and/or adapt to climate change were linked to the nature of environmental values held (or ecological worldview) and place attachment. Individuals with a strong place attachment to the study area (the Adelaide Hills) who possessed knowledge of and/or beliefs in climate change were most likely to take mitigating actions. This was also linked to previous experience of major risk from wildfires. The paper concludes by discussing prospects for developing co-management for reducing the impact of climate change across multiple groups in rural and peri-urban areas.
Background:
Adapting to Climate Change: Lessons from Farmers and Peri-Urban Fringe Residents in South Australia
Douglas K. Bardsley 1 ,
Christopher M. Raymond 2 ,
1
Department of Geography, Environment & Population, School of Social Sciences, University of Adelaide, Adelaide, South Australia 5005, Australia
2
Department of Landscape Architecture, Planning and Management, Swedish University of Agricultural Sciences, 230 53 Alnarp, Sweden
3
School of Natural and Built Environments, University of South Australia, Mawson Lakes, South Australia 5095, Australia
Office of Education Research, National Institute of Education, Nanyang Technological University, 1 Nanyang Walk, Singapore 637616, Singapore
Environments 2018 , 5 (3), 40; https://doi.org/10.3390/environments5030040
Received: 16 January 2018 / Revised: 22 February 2018 / Accepted: 6 March 2018 / Published: 8 March 2018
(This article belongs to the Special Issue Agriculture and Climate Change )
Abstract
:
This paper reports on results from two major research projects conducted in South Australia. The first investigates adaptation to climate change in two of the state’s major grain and sheep farming regions, using semi-structured interviews and focus groups. The second uses a postal questionnaire and an internet-based survey of residents in the peri-urban fringes of Adelaide, the state capital, to examine knowledge of and attitudes to climate change and resulting adaptations, especially in the context of increasing risk of wildfires. The research on adaptation to climate change in agriculture focused on formal institutions (e.g., government agencies) and communities of practice (e.g., farm systems groups). Both groups noted that farmers autonomously adapt to various risks, including those induced by climate variability. The types and levels of adaptation varied among individuals partly because of barriers to adaptation, which included limited communication and engagement processes established between formal institutions and communities of practice. The paper discusses possibilities for more effective transfers of knowledge and information on climate change among formal institutions, communities of practice, trusted individual advisors and farmers. Research in the peri-urban fringe revealed that actions taken by individuals to mitigate and/or adapt to climate change were linked to the nature of environmental values held (or ecological worldview) and place attachment. Individuals with a strong place attachment to the study area (the Adelaide Hills) who possessed knowledge of and/or beliefs in climate change were most likely to take mitigating actions. This was also linked to previous experience of major risk from wildfires. The paper concludes by discussing prospects for developing co-management for reducing the impact of climate change across multiple groups in rural and peri-urban areas.
Keywords:
climate change
;
adaptation
;
mitigation
;
wildfires
;
risk
;
farmers
;
peri-urban
;
South Australia
Graphical Abstract
1. Introduction
This paper reports on results from two major research projects conducted in South Australia: one on ‘Regional communities adapting to climate change’ and the other on ‘Bushfires and biodiversity: Optimising conservation outcomes in peri-urban areas at risk.’ The latter used a postal questionnaire and an internet-based survey of residents in the peri-urban fringes of Adelaide, the state capital, to examine knowledge of and attitudes to climate change and resulting mitigation/adaptation, especially in the context of increasing risk of wildfires (termed locally as bushfires). The first project focused on adaptation to climate change in two of the state’s major grain and sheep farming regions, using semi-structured interviews and focus groups.
The paper first addresses current understandings about barriers that may restrict adaptations to climate change. Consideration of these barriers is then reported with respect to the two different scenarios represented by the research projects. One relates specifically to decisions taken by farmers with respect to their farm operations whilst the second reports on attitudes and actions of householders in the peri-urban fringe. In both cases emphasis is placed on responses to available information and what might constitute improved communication strategies to overcome barriers to adaptation.
The background to this research is a climatic record in which there has been a pronounced warming trend for South Australia in the last one hundred years, featuring a series of positive anomalies since 1980 compared with the one hundred-year mean annual temperature from 1915 to 2015 [ 1 ]. In addition, there have been a series of notable recent dry spells, with widespread rain deficiencies for prolonged periods, such as that occurring in spring and summer 2012/13 [ 2 ]. This trend towards hotter and drier weather is forecast to continue through the 21st century, with mean annual temperatures across the state possibly rising by more than 2 °C by 2100 [ 3 ]. This combination of greater heat and drought is likely to promote increased risk of wildfires [ 4 ] as well as more incidences of weather-related illness [ 5 , 6 , 7 ] and general inconvenience [ 8 ]. The extent of the projected changes is likely to have far-reaching consequences for agricultural activity [ 9 , 10 ], including the possibility of decreases in median grain yield across the state from between 13.5 to 32% under the most likely climate change scenarios [ 11 , 12 ].
2. Barriers to Climate Change Adaptation
The paper focuses on adaptations to climate change, defining adaptation as “adjustments in natural or human systems in response to actual or expected climatic stimuli or their effects, which moderate harm or exploit beneficial opportunities” [ 13 , 14 ]. Adaptations may be incremental, involving short-term and small-scale actions to reduce losses or enhance the benefits of variations in climate. Alternatively, they may be transformational, where actions are adopted at a much larger scale or intensity than current actions, and/or comprise those that are new to a region. Transformations may be based upon technological innovation, institutional reforms, behavioural shifts and cultural changes [ 15 ]. Climate change mitigation addresses the reduction of the causes of global warming: increased atmospheric carbon dioxide (CO 2 ), methane and other gasses resulting from a range of human activities such as burning fossil fuels, land use change and deforestation. Adaptation recognizes that currently higher than ‘normal’ levels of greenhouse gases already exist and even if they levelled off today they would produce significant changes to the climate. Hence, we need to adapt to these changes. “Many adaptations to climate change will be spontaneous actions to perceived and actual risks in the environment” [ 16 ]. Households use risk management strategies that are either ex-ante (risk prevention, reduction and mitigation), such as emissions reduction, actions to reduce household exposure to given risks and taking out insurance cover or ex-post (coping) actions, which are often ad hoc [ 17 ].
People’s engagement with climate change adaptation and mitigation may be limited by “objective constraints that intervene between individuals’ desire to become engaged (affective engagement) and their ability to take relevant actions” [
18
]. Further investigation of this with respect to adaptive actions for Australia’s Great Barrier Reef revealed constraints reflecting individuals’ lack of knowledge about actions they could take, lack of time and possessing different priorities, all of which were influenced by individuals’ age, gender, education level, income and place of residence. In general, these constraints and barriers “arise from uncertainties of future climate and socio-economic conditions, as well as financial, technologic, institutional, social capital and individual cognitive limits” [
19
]. Moreover, climate change may well be frequently regarded as being ‘somebody else’s problem’ and not something an individual, a household or even a community can tackle. There is also a tendency for individuals to assess risks arising from climate change as being minimal [
20
].
In further elaboration on ‘barriers,’ Gibson et al. identify issues pertaining to both consumption and sustainability within households [ 21 ]. There is a complex set of relationships between everyday household practices, cultural processes and climate change but strong environmental beliefs are not necessarily correlated with mitigating actions [ 22 , 23 , 24 ]. Grothmann and Patt argue that two key psychological factors, namely risk perception and perceived adaptive capacity, are major restrictions on individuals taking adaptive action. Social barriers are generally malleable and can be overcome but only with greater understanding of how they operate [ 25 ].
Previous research on household decision making, especially amongst farm families, suggests that practical initiatives representing adaptations to risk often do not consider climate as a separate risk but rather combine it with other environmental and social stresses [ 26 , 27 ]. This means that adaptations are integrated into actions linked to sustainable development, resource management and disaster preparedness [ 28 ]. However, much of this work on adaptation refers to farm families where risks from climate change may be a direct threat to their livelihood [ 29 , 30 , 31 ]. Less work has been concentrated on adaptation and, more particularly, mitigation by households in urban and suburban locations involving specific actions by householders as opposed to supporting higher taxes for energy and fuel. Yet it is acknowledged that actions taken by individuals and households to mitigate climate change, when considered as an aggregate, are significant. Hence mobilizing individuals to act is complementary to any national climate change strategy [ 32 ], with suggestions for greater government encouragement of altered adoption and use of available technologies in homes and for non-business travel [ 33 ].
In examining barriers to climate change adaptation, the investigations reported in this paper used grounded theory, in which the research seeks to generate theory from a systematic approach, rather than basing it on a specific pre-determined theory [ 34 ]. This acknowledges the need to develop theory about factors which discourage or encourage adaptation to climate change. Theory generation is based primarily on recognizing important themes that emerge from interviews, observations and focus groups. However, there is also the opportunity to build on the previous work referred to above.
3. Farmers Adapting to Climate Change in the Eyre and Yorke Peninsulas, South Australia
3.1. Study Areas
Research into farm-based adaptation to climate change took place in two areas in South Australia: the Eyre Peninsula and the Yorke Peninsula. The Eyre Peninsula in the west of the state covers an area of over 80,000 km
2
with a population of approximately 55,000 people. The economy is dominated by agriculture (broadacre cropping and sheep), mining, mineral processing, tourism, aquaculture and fishing. Around 45% of native vegetation cover remains. Climate change may produce shorter, hotter, drier and/or more unreliable growing periods [
35
]. Research has shown the desirability of developing farming systems more responsive to increased seasonal variability, including modifications to the range of crop types, enterprise mixes, input types and levels of water use [
36
].
The Northern and Yorke region (see Figure 1 ) covers an area of 34,500 km 2 and includes the Yorke Peninsula, the Northern Mount Lofty Ranges and the Southern Flinders Ranges. The region has a population of 89,000 people. Dryland farming (mixed crops and livestock) is the dominant land-use. Only 26% of remnant native vegetation remains in the agricultural areas but the proportion is 94% in the pastoral zone in the north of the area [ 37 , 38 ].
3.2. Methods
Interviews were conducted with a sample of 30 farmers: 15 in the Eyre Peninsula and 15 in the Yorke Peninsula (
Figure 1
), using a semi-structured interview guide. Participants were selected by using nominations received from the general managers of local Natural Resource Management (NRM) Boards. The number of interviews was determined with reference to the concept of data saturation [
40
,
41
], in which a point is reached in the sampling when no new themes or thematic information are attained or add to the overall experiences described by the interviewees. This occurred around
n
= 15 in each area. In addition, focus groups were held involving in total 50 farm advisors, members of primary industry organisations (including employees in State Government departments), members of NRM Boards
,
representatives of conservation organisations
,
members of farm systems groups (including the South Australian Farmers Federation, the Australian Bureau of Agriculture and the South Australian No-Till Farmers Association) and employees of financial organisations providing advice to farmers (e.g., Rabobank, Elders, Landmark). So, in total 80 individuals participated in the interviews and focus groups.
The interviews and focus group proceedings were transcribed, after which open coding was applied. This comprised becoming familiar with the content through close reading of the transcript and noting down initial ideas, before generating categories of those factors which encourage or discourage adaptation to climate change [
42
]. The next step was searching for themes by selecting text from the interview transcripts and assigning it to the categories. As core themes became apparent, a second level of coding, selective coding, was employed, which involved defining and refining the specifics of each theme. This generated clear information for each theme based on the overall dataset. The final stage involved theoretical coding; namely, identifying relationships between responses from two key groups to the different themes and relating them to the literature.
3.3. Results
In terms of providing farmers with information about climate change, it was possible to differentiate between two sets of organisations, namely formal institutions and communities of practice [
30
]. The former are groups which follow rules and procedures that are created, communicated and enforced through channels widely accepted as official, such as courts, legislatures and bureaucracies. One example of a formal institution in this context is the government agency responsible for regulating natural resource management: NRM Boards, one for each of the two regions studied. Another is the Department of Primary Industries and Regions South Australia (PIRSA), a key economic development agency in the Government of South Australia, with responsibility for the prosperity of the state’s primary industries and regions. Communities of practice are informal structures or groups brought together through the social construction of knowledge, in which members share a similar set of interests, expertise, roles and goals. Opportunities exist for members to interact with one another through both formal and informal spaces and groups share a common practice or set of practices. Farm systems groups are exemplars of communities of practice.
Interview responses from farmers indicated they are capable of autonomously adjusting to on-farm risks associated both with short-term variability in physical conditions and also variations in the market for their produce. However, they are more likely to respond to short-term risks which have a direct impact on their farm operations rather than longer-term risks such as those related to climate change. There was a strongly expressed view from farmers that the communities of practice, notably the farm systems groups, generally tailored their trial programmes and communication techniques to address short-term risks to the farming system. Knowledge and information about adaptation to climate change is gathered and absorbed by the farmers’ trusted individual advisors in the communities of practice who then pass it on to the farmers.
In contrast, the information provided by the formal institutions tends to be regarded by farmers as quite complex and focused more on long-term climate change rather than considering direct and immediate risk. Farmers do not regard statements such as ‘a prediction of 3 to 4 °C warming this century’ as presenting information of practical value. They deal in much shorter-term risk and so require warnings of an impending heat wave or of a serious rainstorm in the next week. Much information from government sources may not be location specific whereas farmers desire something that pertains to their own farm and immediate locality.
An added complication may be the fact that two-thirds of the farmers interviewed and 40% of farm advisors in the focus groups did not believe in human-induced climate change and so they are quite sceptical about information being presented on the stated topic of climate change. This may be a significant barrier to making climate change-related adaptations as strength of belief in climate change has been found to be a key factor in explaining differences in adaptation actions. For example, this was the case in work by Wheeler et al. [
43
] with respect to irrigators in Australia’s Murray-Darling Basin and among Swedish forest owners by Blennow et al. [
44
]. In the Murray-Darling farmers convinced that climate change is occurring were more likely to plan accommodating, but not expansive, adaptation strategies.
Farmers generally (75%) did not consider extreme heat or drought to be a major threat to their livelihood because they were able to take measures to adapt to these extreme weather events. For example, they referred to the fact that their crops and livestock were bred to suit the conditions.
“I can recall from 30–40 years ago that we would often get heat waves come, with hot north winds coming much too early, like in late August/September which affect the crops. You know, it might hit them at flowering time, affect the yield, knock them about; it means we need more rain. If you have a kind spring then they can cope with less rain, etc. So, we need more varieties bred that are drought tolerant/heat tolerant.”
(grain producer, Eyre Peninsula)
Nevertheless, they acknowledged that spells of extreme (or ‘exceptional’) heat in combination with reduced rainfall could be problematic. They supported this view by providing accounts of crops being ‘wiped out’ by unseasonal heat combined with dry conditions.
“One day in 2004 in October we had a very, very high… the temperature went up to about 43 or 44, really high for one day but it happened when crops were just towards the end of their ripening cycle ... it just finished it. One really hot day would have taken hundreds of thousands [of dollars] off the value of those cereal crops through the mid-North.”
(grain producer, Yorke Peninsula)
Overwhelmingly (>80%), farmers referred to adopting moisture conservation practices that addressed excessive heat and/or drought. They tended to adopt measures similar to those employed by their predecessors on the farm (usually parents or grandparents) to cope with ‘exceptional’ circumstances. A variety of measures was involved, for example, clay spreading and delving on sandy soils, raising the pH of acidic soils through liming, containing saline seepage by planting salt tolerant perennial species such as alkali grass (
Puccinellia
), tall wheatgrass (
Thinopyrum ponticum)
and saltbush (
Atriplex
species). Adopting different pasture species [
45
] and planting of shorter season wheat varieties to combat shorter growing seasons were other common strategies. In addition, there were instances of some long-term adaptations, such as large-scale changes to the farming type, e.g., moving from cropping to sheep [
46
], though economic motives might also be involved, such as responding to low grain prices [
47
].
Information gained from the interviews and focus groups suggests that the nature of the communications between government and farmers needs to be changed to enable a stronger two-way flow of information and knowledge. At present, there is often a marked top-down approach from government/formal institutions, which largely fails to acknowledge the key role played by communities of practice. Based on the data assembled in this research, this current situation is portrayed in
Table 1
. It is one that produces relatively little policy debate, with the communities of practice in the two study areas having relatively few opportunities to inform government decision making. The was summarized by one farm advisor in a focus group discussion:
“Farmers tend to feel that policy makers do not stray far from Adelaide. The farmers have a view that they are ‘out of sight, out of mind’ in respect to policy making.”
(farm advisor, Eyre Peninsula)
In one of the interviews with farmers, this sentiment was reiterated:
“We don’t have much contact with the people who provide information on climate change. They are in Adelaide and we are a long way away! They don’t seem very interested in what we might know about weather patterns and how to deal with it all.”
(grain producer, Eyre Peninsula)
In general, government seems to under-utilize the knowledge and expertise of the farmers. A stronger two-way flow of information would require greater interaction not only between government agencies and communities of practice but also more directly with individual farmers as illustrated in
Table 2
. This might help overcome some of the farmers’ antipathy to messages being promulgated by government. More so if the short-term consideration of risk by farmers was given more acknowledgement by government and vice-versa a recognition by farmers that a longer-term horizon for consideration of climate change requires some immediate on-farm actions.
4. Peri-Urban Residents Adapting to Climate Change in the Adelaide Hills, South Australia
4.1. Study Area
The Mount Lofty Ranges are located immediately to the east of South Australia’s state capital, Adelaide. Rising to a height of 936 m, they extend north-south for around 300 km, with the area closest to Adelaide generally known as the Adelaide Hills, which is also an administrative district. It was one of the first areas of South Australia to be settled by European settlers and now has a population of around 60,000 in a mixture of farming communities, rural hamlets and townships, larger service centres and suburban commuter developments. It has a Mediterranean-type climate, with moderate rainfall (mostly < 800 mm pa) brought by south-westerly winds, hot summers (mean daily January maxima = 27.8 °C) and cool winters (mean daily July maxima = 14.9 °C) [
48
]. This supports apple, pear and cherry orchards as well as a major high quality, cool-climate wine region.
As described above for the Eyre and Yorke Peninsulas, drier and hotter conditions are predicted in addition to more extreme weather events, which will increase the likelihood of wildfires (termed locally ‘bushfires’) [
49
]. The last wildfire in the region to cause loss of human life occurred in 1983 when 160,000 ha burnt and 28 deaths were recorded (though immediately to the north, a fire in November 2015 burnt over 85,000 ha and caused two deaths). More recently, in 2015 across the northern part of the Hills over 20,000 ha burnt, destroying 26 homes but with no human fatalities. So, many residents should be aware of the risk of wildfires in the area, though the link between increased risk and climate change may be less widely recognised.
4.2. Methods
A postal questionnaire comprising 55 questions was distributed to 2650 households in the Adelaide Hills (see
Figure 2
). This yielded 797 responses or a 30.1% rate of return and was supplemented with information obtained from an internet-based survey (
n
= 308) conducted by Underwood [
50
] representing a subset of questionnaire respondents who volunteered to provide additional data. This survey elicited a 44.1% response rate and contained 23 questions largely focusing on climate change, using a combination of Likert scale [
51
], multiple fixed-choice answers and open-ended questions, allowing participants to express their beliefs and perceptions. It also used a series of attitude-based statements towards the environment to determine whether residents hold pro-, mid-, or anti-ecological views. Respondents were asked whether they believed that a changing climate is altering the risk of wildfire on their property. If the response was yes, they were asked if they had made any conscious changes in terms of their Bushfire Survival Plans (BSP) as a result (each household is encouraged to prepare such a plan).
4.3. Results
Our recent review of climate change interactions with wildfire management in peri-urban South Australia [
52
] showed that two-thirds of respondents to the postal questionnaire agreed with the statement that climate change was a general risk to the region. A similar proportion agreed that climate change was altering wildfire risk on their properties. From the internet-based survey, it was apparent that actions taken by individuals to adapt to climate change in the peri-urban fringe were closely linked to the nature of the environmental values they hold (or their ecological worldview) and to place attachment. Individuals with a strong place attachment to the Adelaide Hills who possessed knowledge of and/or beliefs in climate change were most likely to take action. The respondents who recognized that climate change is increasing the risk of wildfires ranked natural values highly and were supportive of ecological conservation goals.
Another important factor was previous experience of major risk from wildfires (defined as living in a property damaged or threatened by a wildfire event), which also prompted a greater likelihood of actions to lessen the effects from a wildfire. The latter varied from removal of major trees, bushes and undergrowth within the vicinity of the house to installing irrigation systems to keeping gutters free from leaves and debris. Tree removal close to buildings has been encouraged by recent relaxations to the state’s Native Vegetation Act and in 2012, amendments were made to the Development Act 2003 to allow landowners to clear vegetation within 20 m surrounding their home without having to undergo approval from the Native Vegetation Council. Further changes were also made to the process involved in gaining permission to clear beyond 20 m (again relaxing the approval process), with the purpose of such changes being to facilitate so-called ‘fire-smart communities’ [
53
].
Householders’ actions were primarily a response to reducing wildfire risk and some of these actions could be problematic in terms of reducing local biodiversity, e.g., removing trees near houses. But there were also increases in ‘green’ lifestyles e.g., installing solar panels, increasing the use of recycling, practising ‘eat local’ (i.e., consumption of food with short as opposed to long food-miles) where possible and consciously adopting more sustainable travel practices. Clearing leaves, twigs and long grass immediately adjacent to the house was practised by 89% of respondents to the postal survey, whilst 85% cleared gutters of leaves. Three-quarters watered their gardens frequently during the wildfire season (officially from 1 December to 30 April) and a similar proportion cleared undergrowth at least to 20 m from the house. Two-thirds claimed they had a BSP (as recommended by the Country Fire Service), though this did not always refer to a formal written plan, merely an informal intention of what to do in the event of a major fire. In such an emergency, 62% had obtained and prepared equipment such as ladders, buckets and mops to put out spot fires and 61% stated they would move combustible materials such as firewood and wooden garden furniture away from the house. One-third of residents had removed large trees from within 20 m of their house and 15% up to 40 m from the house.
In terms of self-assessed knowledge about climate change, the respondents to the larger survey divided equally between high, medium and low knowledge whilst two-thirds felt that changing climate was altering the risk of wildfire on their property [
52
]. Yet, there was no significant relationship between recognition of risks posed by climate change and the perceived likelihood of wildfire within the next five years. Just under 90% felt that climate change was occurring both in the region and globally, primarily supported by observable changes to the seasons and more severe weather events. For example, in the words of different residents:
‘The seasons now are different to what they were 20 years ago’;
‘I believe the scientists and weather observation records show that the climate is changing’;
‘Changes in climatic conditions in the 30+ years we have lived in our current house have affected the plant and animal biodiversity around us.’
However, some respondents thought this was a natural phenomenon:
‘Climate change occurred before Man and will continue regardless of our efforts’;
‘I strongly believe we are in a warming cycle but don’t think the science is settled enough to say it’s a one off irreversible Man-induced change.’
Of the respondents to the online survey, 44% believed they could take no or hardly any personal actions that could help mitigate climate change whilst just 14.2% believed there was a lot they could do [ 50 ]. This contrasts with the finding from a state-wide survey in which 65% of respondents reported that they ‘agreed’ or ‘strongly agreed’ with the proposition that risks associated with a changing climate could be ‘reduced by their own actions’ [ 54 ]. Our online survey suggests there are major constraints to individual engagement with climate change, reflecting the presence of various psychological barriers [ 55 ], referred to by Gifford [ 56 ] as ‘the dragons of inaction.’ These barriers are related to “a muddle over causes, consequences and appropriate policy measures for mitigation” [ 57 ]. At the centre of this is a widespread view that the consequences of possible behavioural shifts arising from the need to implement mitigation measures are daunting and hence the creation of socio-psychological denial mechanisms. Consequently, the public is largely ignoring actions promoted by government to mitigate climate change, such as using less household energy. Indeed, where individuals are using less energy it is often primarily as a money saving measure rather than to mitigate climate change [ 58 , 59 ]. Nevertheless, 16.5% of sample respondents stated that some of their everyday behaviour was influenced by concern about climate change and only 24% had made no or little attempt to change their behaviour in response to climate change. However, when identifying specific behaviours, recycling (17.5% of all responses) was the most popular single behaviour and ‘reducing waste and pollution’ accounted for a further 9.9%. More direct actions, such as reducing energy use and using renewable energy (principally domestic solar power) accounted for 11.1% ( Table 3 ).
There was no correlation between self-assessed climate change knowledge and climate change beliefs. However, a Kruskal-Wallis test between knowledge of climate change and climate change behaviours was significant at the 0.05 level (H
6
= 13.27,
p
< 0.05). The same test run on climate change behaviours and climate change beliefs (globally) showed no significant relationship (H
6
= 7.68,
p
> 0.05) but for climate change beliefs with respect to South Australia, a significant relationship was found at the 0.05 level (H
6
= 13.52,
p
< 0.05).
Based on the relationships between respondents’ perceptions of climate change and wildfire risk, key differences emerged between three distinct groups, as reported in the detailed analysis by Bardsley et al. [
52
]. The first of these comprised 38.4% of respondents who recognise an increased wildfire risk in response to climate change and have changed their BSPs in response. These respondents tend to live on rural blocks of land which possess native or wildlife gardens; they are typically aged in their 40s and 50s; are more likely to have experienced wildfire damage; possess strong ties to place; are more actively preparing for the emerging risk; and have a pro-environment outlook. This group also indicated they possessed the capacity to activate their BSPs and they showed greater place attachment than other respondents. They were more likely than other respondents to thin vegetation and to prune large trees but less likely to remove large trees from within 40 m around their house. Indeed, they placed greater value overall on maintaining the wooded environment and biodiversity of the Hills despite the wildfire risk.
The second group comprised 26.5% who recognised an increased wildfire risk due to climate change but were neither altering their household plans and actions, nor supportive of collective action to mitigate wildfire risk. These are largely aged between 18 and 44; with a graduate education; and live on residential-size blocks. Members of this group typify the gap between perceptions (of risk) and taking actions (to mitigate that risk) because whilst they recognize a growing risk, they are not planning for the likely changes that will arise. It is possible that members of this group prefer to let others take actions that will reduce risks. Alternatively, they may value their ‘pleasant green environment’ above other considerations and do not wish to see it changed to reduce risk of wildfire.
In the third group (35.1% of all respondents) many did not recognise that climate change alters wildfire risk. This group was typified by older male residents who may not believe in climate change; work in non-professional employment; and have a low educational attainment. However, they are similarly supportive of risk mitigation actions as the first group. This implies that climate change is only one of several factors that can influence individuals to act or to support collective actions. Group three appears more supportive of prescribed burning and vegetation clearance to mitigate risk and they themselves are exploiting the opportunity of a weakening of the SA Native Vegetation Act to clear trees in their gardens.
5. Discussion and Conclusions
A common thread that links the two studies reported above is the various responses made by farmers in the Eyre and Yorke Peninsulas and householders in the Adelaide Hills to changes in climate. They respond in different ways: from some householders making little attempt to adapt to greater heat and/or drought to some farmers making substantial modifications to their farming systems in attempts to withstand drier and hotter conditions. For farmers and householders alike, there was a spectrum of adaptive decision-making, with the research on householders revealing different groups based on perceptions of climate change and wildfire risk. Differentiation of the survey respondents into three groups raises important questions about whether different messages need to be delivered to them to overcome barriers that might prevent some residents from taking desirable adaptive or mitigation actions. Similarly, with the farmers, focus groups and interviews highlighted how different communication and engagement strategies can be at the heart of transmitting important information about climate change and on-farm adaptation.
Irrespective of whether the farmers regarded human-created climate change as the main factor in episodes of greater heat and drought, they adjusted their farming systems in response to the changing conditions. In this respect, they can be regarded as autonomous adapters, treating climate change as one of several risk factors that they experience. This supports the findings of work by Head et al. [
29
] whose assessment for farmers facing drought in eastern Australia is apposite: “These farmers are not adapting to future conditions but are in continuous interplay among multiple temporalities, including memories of the past… Capacities to deal with risk and uncertainty vary with a range of social and locational factors, tending to coalesce into patterns of vulnerability and resilience that offer strong predictors as to which households are most likely to be sustainable in the longer term.” They took measures to drought-proof their operations as much as possible but their adaptations, which were largely directed at short time-scale changes in the farming environment, may be of relatively limited effect because of constraints imposed by broad changes in the soil/water base and economic environment occurring over longer time scales [
60
]. So, farmers’ short-term responses may not be very effective measures to combat ongoing climate change. One financial advisor in a focus group likened it to “attempting to put a sticking plaster over a gaping and ever-growing wound.”
Many of the farmers and their advisors expressed scepticism regarding human causality in climate change. However, there was no significant correlation between scepticism and on-farm responses. This contrasted to the Adelaide Hills residents surveyed where a distinct group of respondents who were more sceptical than their neighbours tended to have different views about the relationship between climate change and wildfires. They either took no related actions or removed trees around their property as a precaution against threat from wildfires. Moreover, recognition of a relationship between climate change and wildfire risk amongst all respondents did not necessarily translate into mitigation efforts, as also noted by other studies [
61
].
For the farmers, the nature of actions taken in response to increased heat and severe drought closely reflected the advice received via communities of practice as opposed to that from formal institutions. There was much discussion about the relationship between the farmers and these two sources of information. Farmers relied greatly on the views expressed within the communities of practice and on the advice from their trusted advisors who were often members of the latter. In contrast, the formal institutions were widely regarded as being distant and unable to supply the type of information that farmers felt they needed. From the focus groups, a general agreement was reached regarding the importance of maintaining networks and information flows to provide support to farmers and the wider rural community, in part to counter sensational media reports debunking climate change. On all sides, there was an emphasis on the need for more investment into research and development on low-rainfall agriculture so that farmers could be better placed to adapt their farming systems.
In terms of promoting practices that are likely to bring greater and more cohesive responses to climate change, adoption of a simple co-management model for the farming community could be considered as an improvement upon current arrangements. In this, there should be encouragement for groups of actors to reach a shared understanding of issues and identification of their vision for the future. The vision of each group can then be translated into action plans, with multiple cycles of joint and collaborative action supported so that individuals and groups can contribute fully to policies shaping decision making within individual households and on individual farms [
62
]. This process needs to involve different levels of government, the commercial private sector, civil society and local communities.
With respect to the wider community, co-management is harder to achieve, in part because appropriate and effective adaptation may not be regarded by individuals as achievable or sustainable as messages from government may imply [
63
,
64
]. Knowing exactly what to adapt to is problematic not only given the limits of scientific knowledge regarding projections of likely environmental changes but also people’s understanding of the phenomenon [
65
]. Attempts at persuading individuals to act in a certain way often assume that everyone is receptive to a given message and then will behave in the desired fashion. The differences between the three groups distinguished in this paper, suggest that this not the case. Different messages may need to be produced for different segments of society but for this to be effective better means of conveying information to the public need to be formulated.
One factor that emerges from this analysis is that the majority of the respondents in the Adelaide Hills recognize a risk posed by climate change and link it to the likelihood of greater risk of wildfires. However, they tend to conceive of this risk as something that will produce a wildfire event at some unspecified time well into the future. This may be related to the lack of a major fire event in much of the Adelaide Hills since 1983, which has instilled a complacency in the residents. Many of these residents have no previous experience of a wildfire and some have migrated from urban areas where threat of wildfire is low.
A major concern is whether actions to reduce risk of wildfires can be implemented without producing major reverses to biodiversity. The extent of native vegetation in the Hills is diminishing and some green space is being lost to urban development [
66
] but will actions to offset risk of wildfire further reduce natural and semi-natural habitats? Bardsley et al. [
52
] concluded that those Hills’ residents who recognized climate change and its influence over risk of wildfire were less likely to support vegetation management that undermines local ecological values. They may be taking some minor mitigating actions (e.g., clearing scrubland) but not in ways that could significantly diminish habitat values, such as via the more dramatic intervention of clearing large trees. Indeed, the majority of those surveyed highly valued their local environment and did not wish adaptations to compromise the ‘clean and green’ feel of the Hills. Such attitudes and their link to actions will need to be better recognized in future planning for reducing risk from wildfires.
This recognition could be carried into new communication strategies aimed at residents. The experience with the farmers, namely that key messages about adaptation need to be tailored to the specific audience and presented by people/organizations that are trusted, could be utilized in a different setting. For example, it seems sensible to pursue further research on what messages to present to householders about both adapting to and mitigating against climate change. The differentiation of the community into different segments also needs further investigation as does the most appropriate media and sources for information. As with the farmers, more thought should be given to how individuals and groups can be more active participants in shaping policy and co-managing responses to climate change.
Acknowledgments
This paper draws upon research conducted in two separate research projects. ‘Regional communities adapting to climate change’ was funded by the NRM Alliance and Department of Water, Land & Biodiversity Conservation South Australia. We are grateful to assistance from Karen Cosgrove who conducted interviews and focus groups for this project. ‘Bushfires and biodiversity: optimising conservation outcomes in peri-urban areas at risk’ was funded by the Australian Research Council (LP130100406) with additional funding from the Eyre Peninsula NRM Board and the Adelaide Mount Lofty Ranges NRM Board.
Author Contributions
Guy M. Robinson—principal investigator for both projects; main writer of the paper; Douglas K. Bardsley—co-investigator on project 2: produced the grouping of residents featured as a major result plus providing general arguments in the paper; Christopher M. Raymond—principal research assistant on project 1: produced analysis of farmers featured as a major result plus providing general arguments in the paper; Tegan Underwood—honours student on project 2: produced online survey and its analysis featured in results; Emily Moskwa—postdoctoral research fellow in project 2: contributed re- context, statistical and general analysis; Delene Weber—co-investigator on project 2: contributed re- context and general analysis; Nicolette Waschl—research assistant on project 2: contributed statistical analysis; Annette M. Bardsley—postgraduate working on project 2: contributed context and general analysis.
Conflicts of Interest
The authors declare no conflict of interest.
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Figure 1. Location map (source of base map [ 39 ]).
Figure 1. Location map (source of base map [ 39 ]).
Figure 2. Areas where questionnaire survey distributed (medium blue) and residential location of participants (red dots). NB. This paper only focuses on responses from the Adelaide Hills.
Figure 2. Areas where questionnaire survey distributed (medium blue) and residential location of participants (red dots). NB. This paper only focuses on responses from the Adelaide Hills.
Table 1. Characteristics of key linkages between formal institutions, communities of practice, independent trusted advisors and rural farmers with respect to current transfer of knowledge about adaptation to climate change.
Table 1. Characteristics of key linkages between formal institutions, communities of practice, independent trusted advisors and rural farmers with respect to current transfer of knowledge about adaptation to climate change.
Actors Formal Institutions (FIs) Communities of Practice (CoPs) Independent Trusted Advisors (ITAs) Farmers Formal Institutions (FIs) Set policy with traditional top-down approach Relatively weak links. Little opportunity for CoPs to influence policy Relatively weak links Policy enacted ‘on the ground’ but policy debate missing. Communities of Practice (CoPs) FIs are increasingly recognizing importance of the need to engage CoPs Hugely important in provision of information in rural communities ITAs are often part of CoPs Risk management knowledge and other information from multiple CoPs inform farmers Independent Trusted Advisors (ITAs) May have some informal links to FIs but little influence on policy Often embedded in CoPs; sometimes a leader of a CoP Often have agronomy or financial background ITAs are main vehicle or channel for exchange of knowledge and information on the management of risks, which in turn addresses risks from climate change and climate change adaptation Farmers Complain that FIs do not consult. One-way, top-down flow of information about climate change High value placed on on-farm meetings, e.g., trialling new techniques, equipment, best practice ITAs have partly replaced traditional extension service workers Autonomous adjusters to risk
Table 2. Characteristics of key linkages between formal institutions, communities of practice, independent trusted advisors and rural farmers with respect to current transfer of knowledge about adaptation to climate change.
Table 2. Characteristics of key linkages between formal institutions, communities of practice, independent trusted advisors and rural farmers with respect to current transfer of knowledge about adaptation to climate change.
Actors Formal Institutions (FIs) Communities of Practice (CoPs) Independent Trusted Advisors (ITAs) Farmers Formal Institutions (FIs) Set policy with traditional top-down approach Relatively weak links. Little opportunity for CoPs to influence policy Relatively weak links Policy enacted ‘on the ground’ but policy debate missing. Communities of Practice (CoPs) FIs are increasingly recognizing importance of the need to engage CoPs Hugely important in provision of information in rural communities ITAs are often part of CoPs Risk management knowledge and other information from multiple CoPs inform farmers Independent Trusted Advisors (ITAs) May have some informal links to FIs but little influence on policy Often embedded in CoPs; sometimes a leader of a CoP Often have agronomy or financial background ITAs are main vehicle or channel for exchange of knowledge and information on the management of risks, which in turn addresses risks from climate change and climate change adaptation Farmers Complain that FIs do not consult. One-way, top-down flow of information about climate change High value placed on on-farm meetings, e.g., trialling new techniques, equipment, best practice ITAs have partly replaced traditional extension service workers Autonomous adjusters to risk
Table 3. Actions taken out of concern for climate change.
Table 3. Actions taken out of concern for climate change.
Actions Taken Frequency of Response ( n ) Recycle 44 Reduce energy usage around the home 32 Reduce car usage/use public transport more 32 Use renewable energy sources 28 Reducing waste and pollution 25 Conserve natural resources 20 Sourcing local/sustainable products 20 Planting more vegetation 18 Consuming less meat/sustainable resources 14 General support/volunteering/communication about climate change 14 Use rain water instead of mains supply 5 * Total 252
* The total equals more than the n = 136 who responded to the internet survey as respondents could identify more than one action. Source: Underwood [ 50 ].
MDPI and ACS Style
Robinson, G.M.; Bardsley, D.K.; Raymond, C.M.; Underwood, T.; Moskwa, E.; Weber, D.; Waschl, N.; Bardsley, A.M. Adapting to Climate Change: Lessons from Farmers and Peri-Urban Fringe Residents in South Australia. Environments 2018, 5, 40.
https://doi.org/10.3390/environments5030040
AMA Style
Robinson GM, Bardsley DK, Raymond CM, Underwood T, Moskwa E, Weber D, Waschl N, Bardsley AM. Adapting to Climate Change: Lessons from Farmers and Peri-Urban Fringe Residents in South Australia. Environments. 2018; 5(3):40.
https://doi.org/10.3390/environments5030040
Chicago/Turabian Style
Robinson, Guy M., Douglas K. Bardsley, Christopher M. Raymond, Tegan Underwood, Emily Moskwa, Delene Weber, Nicolette Waschl, and Annette M. Bardsley. 2018. "Adapting to Climate Change: Lessons from Farmers and Peri-Urban Fringe Residents in South Australia" Environments5, no. 3: 40.
https://doi.org/10.3390/environments5030040
Robinson GM, Bardsley DK, Raymond CM, Underwood T, Moskwa E, Weber D, Waschl N, Bardsley AM. Adapting to Climate Change: Lessons from Farmers and Peri-Urban Fringe Residents in South Australia. Environments. 2018; 5(3):40.
https://doi.org/10.3390/environments5030040
Chicago/Turabian Style
Robinson, Guy M., Douglas K. Bardsley, Christopher M. Raymond, Tegan Underwood, Emily Moskwa, Delene Weber, Nicolette Waschl, and Annette M. Bardsley. 2018. "Adapting to Climate Change: Lessons from Farmers and Peri-Urban Fringe Residents in South Australia" Environments5, no. 3: 40.
https://doi.org/10.3390/environments5030040
| https://www.mdpi.com/2076-3298/5/3/40/htm |
Zebra Technologies IAPWR63000902 Digital Spread Spectrum Device User Manual MEA Setup and Deployment User s Guide
User manual instruction guide for Digital Spread Spectrum Device IAPWR63000902 Zebra Technologies Corporation. Setup instructions, pairing guide, and how to reset.
Zebra Technologies IAPWR63000902 Digital Spread Spectrum Device User Manual MEA Setup and Deployment User s Guide
Zebra Technologies Corporation Digital Spread Spectrum Device MEA Setup and Deployment User s Guide
Contents
1. users manual
2. users manual statements
users manual
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Date Submitted 2002-11-08 00:00:00
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Document Title MEA Setup and Deployment User’s Guide
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Document Author: MeshNetworks, Inc. Copyright 2002, All Right Reserved
Setup and Deployment
User’s Guide
Copyright 2002, MeshNetworks, Inc. All Rights Reserved
Setup and Deployment Guide
Foreword
This document describes in detail the confidential and proprietary technology of MeshNetworks’
™ Architecture. MeshNetworks products and technology are protected by US and
international patent and patent pending technology. MeshNetworks provides both the
Architecture as well as the MeshLAN 802.11b product. MeshLAN provides a mobile internet
solution intended for interior office and small campus deployments with pedestrian speeds. The
solution uses a proprietary technology to extend the mobile internet to wide area networks
and permits highway speed mobility.
OEM Evaluation Package, the contents are subject
This document represents the current
to change at any time at the discretion of MeshNetworks, Inc. This document is a deliverable
associated with the OEM license package. This document is confidential and for the sole use of
the licensee and is not for general distribution. All provisions of the Non-Disclosure Agreement
associated with the license package apply to this document.
, MeshLAN, MeshManager, MeshTray, MeshView, and MeshNetworks’ logo are
trademarks or registered trademarks of MeshNetworks, Inc. Microsoft, Windows, Windows
2000 and Windows CE are registered trademarks of Microsoft Corporation. All other product
names and services identified throughout this publication are trademarks or registered
trademarks of their respective companies. No such uses or the use of any trade name is
intended to convey endorsement or other affiliation with this publication. Copyright 2002,
MeshNetworks, Inc. All Rights Reserved.
iii
Setup and Deployment Guide
Table of Contents
OVERVIEW.............................................................................................................. 1
1.1
Product Kit Overview .............................................................................................1
1.2
Document Overview...........................................................................................................1
1.3
Acronyms ............................................................................................................................1
1.4
Related Documentation .....................................................................................................1
1.5
Overview of the
1.5.1
1.6
Introduction...................................................................................................................2
Operational View of the
1.6.1
System...........................................................................................2
System.............................................................................4
Network Architecture ...................................................................................................5
SUBSCRIBER DEVICE (SD)................................................................................... 7
2.1
Equipment ..........................................................................................................................7
2.2
Loading and Verifying Software ......................................................................................7
2.2.1
2.3
Windows 2000 Installation ...........................................................................................7
Testing.................................................................................................................................7
INTELLIGENT ACCESS POINT (IAP) .................................................................... 8
3.1
Equipment ..........................................................................................................................8
3.2
IAP Assembly .....................................................................................................................9
3.3
Deployment.........................................................................................................................9
3.4
Initial IAP Configuration ................................................................................................10
3.5
Testing...............................................................................................................................11
WIRELESS ROUTER (WR) ................................................................................... 12
4.1
Equipment ........................................................................................................................12
4.2
WR Assembly ...................................................................................................................13
4.3
Deployment.......................................................................................................................13
4.4
Initial Configuration........................................................................................................13
4.5
Testing...............................................................................................................................14
iv
Setup and Deployment Guide
Table of Contents - Continued
MOBILE INTERNET SWITCHING CONTROLLER (MISC)................................... 15
5.1
Equipment ........................................................................................................................15
5.2
Network Setup Description .............................................................................................15
5.3
MiSC Assembly ................................................................................................................17
5.4
Onsite Configuration of Routers ....................................................................................17
5.4.1
EdgeRTR Configuration.............................................................................................17
5.4.2
EdgeRTR TEST..........................................................................................................18
5.4.3
CoreRTR Configuration .............................................................................................18
5.4.4
CoreRTR Test.............................................................................................................20
5.5
Network Configuration ...................................................................................................20
5.6
Testing...............................................................................................................................21
5.6.1
Basic MiSC Tests .......................................................................................................21
5.6.2
Wireless System Tests ................................................................................................21
5.6.3
Internet Test ................................................................................................................21
APPENDIX A SITE SELECTION/DEPLOYMENT GUIDELINES.............................. 22
A.1
General Guidelines...........................................................................................................22
A.2
Antenna Guidelines..........................................................................................................22
APPENDIX B NOTES ............................................................................................... 24
B.1
DNS Server .......................................................................................................................24
B.2
Tera Term Pro..................................................................................................................24
APPENDIX C LICENSE AND WARRANTY INFORMATION ................................... 25
C.1
IMPORTANT NOTICE..................................................................................................25
APPENDIX D FCC REGULATORY INFORMATION ................................................ 28
D.1
FCC Information .............................................................................................................28
D.2
FCC RF Radiation Exposure Statement........................................................................28
D.3
Safety Information for the
...................................................................................29
Setup and Deployment Guide
List of Figures
Figure 1.
Elements of the
System.......................................................................................2
Figure 2.
Operational View of the
System .........................................................................5
Figure 3.
Network Architecture..........................................................................................6
Figure 4.
IAP Connection Points.................................................................................................9
Figure 5.
Optional Mounting Brackets........................................................................................9
Figure 6.
IAP Enclosure Illustration..........................................................................................10
Figure 7.
WR Connection Points...............................................................................................13
Figure 8.
Basic MiSC Configuration.........................................................................................16
Figure 9.
Antenna Mounting .....................................................................................................22
vi
Setup and Deployment Guide
1 Overview
1.1
Product Kit Overview
The
Product Kit allows a network operator to deploy a wireless, multi-hopping ad hoc
network. The product kit supports up to 25 Subscriber Devices, allows mobility between IAPs,
and provides enhanced system management capabilities.
It is recommended that the Network Operator receive setup and deployment training at
MeshNetworks’ facility prior to deploying the
network. MeshNetworks may provide the
Network Operator, as an option, assistance with site surveys and deployment.
1.2 Document Overview
This document describes how to setup, configure, and deploy a
kit. The
MWR6300
(Wireless Router) and IAP6300 (Intelligent Access Point) require “professional installation” to
ensure the installation is performed in accordance with FCC licensing regulations.
system are provided with a preinstalled “standard configuration”
The components of a
provided by MeshNetworks. The configuration items described in this document allow the
system to be customized with site-specific information.
The document presents information on the current
evolve, the document will be updated.
components.
As the components
1.3 Acronyms
HAS
Hardware Authentication Server
IAP
Intelligent Access Point
Mesh Enabled Architecture
MiSC
Mobile Internet Switching Controller
SD
Subscriber Device (a host device with a WMC6300 installed and operational)
WMC
Wireless Modem Card
WR
Wireless Router
1.4 Related Documentation
WMC6300 Wireless Router User’s Guide
MeshView User’s Guide
MeshManager User’s Guide
Location Analyzer User’s Guide
Setup and Deployment Guide
1.5 Overview of the
System
1.5.1 Introduction
MeshNetworks develops Mobile Broadband communications systems with “meshed”
architectures. That is, each node can connect directly, or indirectly (by hopping through other
nodes), with any other node in the network. The peer-to-peer nature of the mesh architecture
combined with data rate control in each subscriber and infrastructure node in the network
insures reliable delivery while providing increased network capacity through geographic reuse of
the frequency spectrum.
The network comprises four distinct elements:
•
Subscriber Devices (SDs)
•
Wireless Routers (WRs)
•
Intelligent Access Points (IAPs)
•
Mobile Internet Switching Controllers (MiSCs)
The overwhelming portion of the value that MeshNetworks provides is in the Wireless Modem
Card (WMC). The WMC is used in Subscriber Devices as well as in the Wireless Router and
Intelligent Access Point (IAP), both of which are types of infrastructure equipment.
MeshNetworks provides a Mobile Internet Switching Controller (MiSC) which is assembled from
industry standard equipment and conform to industry standards. MeshNetworks also provides
the network applications which are required for proper operation and value extraction from the
mobile internet system.
Figure 1.
Elements of the
System
All network elements are designed to support mobile applications. Subscriber Devices can be
either mobile or fixed, while the remaining components are typically fixed. Wireless Routers and
Setup and Deployment Guide
IAPs can be mounted on utility poles, light poles, traffic apparatus, billboards, and buildings.
Their fixed positions allow the Subscriber Device to pinpoint its location within one second.
WRs and IAPs can also be mobile, attached to emergency vehicles, utility vehicles, or fleet
vehicles. It is important to note that the WMC technology within a Subscriber Device is identical
to the WMC technology in Wireless Routers and IAPs.
The
system was designed to minimize the cost associated with deploying a mobile Internet
with end user data access rates on the order of DSL or Cable Modem. The chosen metric of
network efficiency for a data centric network is bits per second per Hertz per square kilometer
per dollar (bps/hz/km /$). This metric balances the user data rates, allocated bandwidth,
coverage area, and cost. One of the most important factors in optimizing this metric is the
choice of network architecture.
1.5.1.1
Subscriber Devices (SDs)
The MeshNetworks’ Wireless Modem Card (WMC) is
provided as a PCMCIA form factor device. The WMC is
used with an off-the-shelf IP-enabled laptop, handheld
computer, PDA, or entertainment device. These two devices
together make up a Subscriber Device (SD).
The WMC provides access to the fixed infrastructure network
and other networks, such as the Internet, and it can also
function as a Wireless Router and repeater for other SDs.
SDs can therefore be a key part of the network
infrastructure. Adding subscribers can effectively increase the number of Wireless Routers in
the network, which increases the number of alternative paths that subscribers may utilize. This
can reduce both the time and cost to deploy network infrastructure, while also increasing the
spectral efficiency and therefore the capacity of the network. And because SDs can also
operate in an ad hoc peer-to-peer mode, two or more SDs can form a network without the need
for any fixed infrastructure.
1.5.1.2
Wireless Routers (WRs)
The Wireless Router (WR) is a low-cost small-sized wireless device
that is primarily deployed to seed a geographical area, extending
the range between IAPs and subscribers, and to simultaneously
increase the network’s spectral efficiency. Wireless Routers provide
a number of functions in the network, such as:
•
Range extension for Subscriber Devices and IAPs
•
Hopping points for subscriber peer-to-peer networking
•
Automatic load balancing
•
Route selection
•
Network capacity optimization through small packet consolidation
•
Fixed reference for geo-location services
The Wireless Router's small size and light weight allow it to be mounted almost anywhere. No
towers are required.
Setup and Deployment Guide
1.5.1.3
Intelligent Access Points (IAPs)
The Intelligent Access Point (IAP) is a low-cost shoebox-sized
device that acts as the transition point from the wireless network
to the wired core network and from there, through media
gateways, out to the Internet. Each IAP offers up to 6 Mbps burst
of data capacity to subscribers. IAPs support the 10/100 base-T
Ethernet interface. Other interfaces are supported through
commercially available media translation devices. If additional
network capacity is required, more IAPs can be easily deployed without the need for extensive RF or site planning. The location
of an IAP is non-critical due to the self-forming, self-balancing
nature of MeshNetworks’ technology. IAPs provide functions
such as:
•
Local mobility management of SDs
•
Fixed reference for geo-location services
•
Hopping points for subscriber peer-to-peer networking
•
Transition point from the wireless to the wired portions of the network
•
Route selection
The IAP’s small size and light weight allow it to be mounted anywhere power and network
connectivity are available. No towers are required. IAP software can be updated via over-thewire downloads.
1.5.1.4
Mobile Internet Switching Controller (MiSC)
The Mobile Internet Switching Controller (MiSC) provides
connectivity between the IAPs and wired world, and hosts the
network’s management and provisioning functions. The MiSC is
composed of off-the-shelf hardware components, such as LAN
routers and application servers. MiSC software consists of both
off-the-shelf
and
MeshNetworks’
proprietary
software,
MeshManager. The MeshManager software provides functions for
the network such as:
•
Subscriber provisioning, management, and authentication
•
Configuration and fault management
•
Network monitoring and reporting
1.6 Operational View of the
System
Figure 2 shows the different ways in which a subscriber can reach an IAP. It can connect
directly, or hop through any number or combination of WRs and SDs. Additionally, if the
subscriber wishes to execute a peer-to-peer application such as a file transfer, the subscriber
can communicate directly, or through any combination of SDs, WRs, and IAPs.
The ability to use ad hoc routing to forward traffic improves the scalability of the mobile wireless
Internet. In particular, the ability for the user to accomplish a peer-to-peer application without
the use of infrastructure has tremendous advantages. A significant problem in every mobile
wireless network is backhaul. The
architecture provides the ability to route traffic from
Setup and Deployment Guide
applications through SDs and WRs without ever reaching an IAP or the wired Internet. This
reduces the amount of backhaul required by enabling the SDs to accomplish the backhaul
whenever the opportunity arises. This results in lower deployment costs, reduced backhaul,
and lower operating expenditures. The service provider can provide the same level of service
with less equipment by empowering the SDs with ad hoc networking capability.
MiSC
IAP
WR
SD
Global
Internet
Mobile Inte rne tSw itching Ce nter
Inte lligentAccessPoint
W ire lessRouter
SubscriberDevice
SD 1
T1
T1
SD 1
SD 2
...
T1
MiSC
SD 2
...
...
IAP 2
IAP 1
SD 3
IAP N
SD 1
WR 2
WR 1
...
...
. . . W R k1
Handoff
SD 1
SD 2
WR 2
WR 1
...
SD 2
W R k2
...
SD 1
SD 2
...
Router Mesh
Handoff
SD 4
Figure 2.
Operational View of the
System
1.6.1 Network Architecture
The mea network utilizes two subnets, one for the
wireless elements and one for the
server elements. All of the
wireless elements must be in a single subnet. The subnets are
connected together by the core router, and the edge router provides Internet connectivity.
deployment.
Figure 3 shows the logical network layout of a
Setup and Deployment Guide
Internet
other
edge
servers
router
server
sw itch
MeshManager
server
server sub net
core router
w ireless
sw itch
WR
IAP1
...
wireless
sub net
SD
m ēa
w ireless
domain
IAPn
SD
Figure 3.
Network Architecture
Setup and Deployment Guide
2 Subscriber Device (SD)
A Subscriber Device consists of both a Wireless Modem Card (WMC6300) and a customer
provided host device such as a notebook computer.
2.1 Equipment
The following list defines the
hardware components required to setup the WMC6300:
•
WMC6300 Card
•
2.4 GHz Antenna with a MMCX connector
•
Antenna Clip with adhesive backing
Equipment that must be supplied by the Subscriber includes the following:
•
Notebook PCs running Microsoft Windows 2000™ Operating System
Optional Equipment
•
External 2.4 GHz Automobile Antenna
2.2 Loading and Verifying Software
Refer to the WMC6300 User’s Guide for step-by-step details on the setup procedures.
A CD will be supplied with the software to load on the Subscriber’s equipment. It contains the
following files:
Windows 2000
Setupmeaclient.exe – installs the
drivers and MeshTray
Setupmv.exe – installs MeshView
2.2.1 Windows 2000 Installation
To install the drivers for the first time on a notebook PC running Microsoft Windows 2000, run
the Setupmeaclient.exe from the CD-ROM. Note: The drivers must be installed before
inserting the wireless modem card).
If MeshView is desired on a Win2000 subscriber device, run the setupmv.exe from the CDROM.
2.3 Testing
When the WMC6300 is inserted, you may receive an audible indicator that the device has been
recognized. (If there is a problem with the drivers, Windows will prompt you for a new device
installation.)
Click on the Windows “Start” button and select “Run” from the popup menu. Enter the
command “ipconfig“ in the text box and click on the “OK” button to check your IP address. If an
IP address in the range of 10.0.x.1 is displayed, the transceiver is working properly.
Setup and Deployment Guide
3 Intelligent Access Point (IAP)
The IAP is an infrastructure device that is positioned at a fixed location such as a building
rooftop. The IAP6300 requires “professional installation” to ensure the installation is performed
in accordance with FCC licensing regulations.
The antenna(s) used for this transmitter must be fixed-mounted on outdoor permanent
structures with a separation distance of at least 2 meters from all persons and must not be colocated or operating in conjunction with any other antenna or transmitter. Users and installers
must be provided with antenna installation and transmitter operating conditions for satisfying RF
exposure compliance.
The principle function of the IAP is to provide access for Subscriber Devices in the coverage
area of the IAP to wired services. The IAP also provides a fixed location reference for GeoLocation (optional feature), provides wireless routing for units in the IAPs coverage area, and is
the principal network management interface to transceivers within Wireless Routers and
Subscriber Devices.
All
IAPs have mounting points for an optional mounting bracket. For a
permanent AC power source for each IAP must be provided.
3.1 Equipment
The following list defines the standard
hardware components for the IAP:
•
IAP Box with N-type Male Antenna Connector
•
A/C Power Cable with standard 3 prong plug
•
7.5 dBi Antenna with N-type Female Antenna Connector
The Network Operator must supply the following:
•
Mounting Location
•
A/C Power Source
•
Ethernet connection between the IAP and the MiSC
Optional Equipment
•
Mounting Bracket
•
Pelco AB-3009-96 for attaching to poles up to 4” in diameter
•
Pelco AB-3010 for poles greater than 4” in diameter
•
Universal Mounting Bracket
•
Net-to-net boxes for T1 deployment
•
Power Cords terminating in PE cell connector
•
Serial Cable with DB9 Male Connectors (for PC to IAP transceiver debug)
deployment, a
Setup and Deployment Guide
3.2 IAP Assembly
The Figure 4 shows the connection points on an IAP box.
Antenna
Power Out (3 pin)
Power In (4 pin)
RJ45 (Data) Port
Serial Port
Figure 4.
IAP Connection Points
Assemble the IAP with the following steps:
1. Insert the antenna into the N-type Connector on the top of the box, and rotate to close.
2. Insert the IAP Power Plug into the 4-pin connector.
3. Insert the Ethernet Cable into the RJ45 connector.
4. If used, insert the Net-to-Net Power Cable into the 3-pin connector.
5. The Serial Port should remain unconnected; it is used for maintenance/debug purposes.
6. The transceiver number and the SBC number are recorded on the back of the IAP.
Record these numbers, as they will be required to configure and test the device.
3.3 Deployment
The IAP may be mounted on either a flat surface or a pole, depending on which optional bracket
is chosen. The antenna must also be fixed-mounted on outdoor permanent structures with a
separation distance of at least 2 meters from all persons and must not be co-located or
operating in conjunction with any other antenna or transmitter. Users and installers must be
provided with antenna installation and transmitter operating conditions for satisfying RF
exposure compliance.
See Figure 5 for an illustration of the optional brackets; Astro-brac Tenon Mount kit, Part
Number AB-3010 and Astro-brac Cable Mount Kit, Part Number AB-3009L, respectively.
Figure 5.
Optional Mounting Brackets
When deploying the IAP, the antenna should be a minimum of 30 inches from any nearby metal
poles to avoid interference in the RF pattern.
Setup and Deployment Guide
The IAP must have an Ethernet connection to the MiSC. If the distance between the IAP and
the MiSC is greater than 100 meters, the Network Operator may utilize a T1 with Net-to-Net
boxes. The IAP has a 5V, 3-pin, power out connection on the side of the box to power the Netto-Net boxes.
The installation location must have AC power available for the IAP.
It is the responsibility of the Network Operator to ensure that the installation complies with any
local building codes.
Figure 6.
IAP Enclosure Illustration
3.4 Initial IAP Configuration
Geo-location may be entered into an infrastructure device via the Device Manager tool (refer to
the MiSC section of this document). Complete the following procedure to enter GPS data into
the device:
1. Click on the “DevMan” shortcut icon located on the desktop.
2. If the device is not listed in the Device Tree (the left window), then perform the following:
a. Select “File/New Device”
b. Enter the device information (address type, device address, autoconfiguration button
selected, device type, and template name).
c. Click on the “Add” button.
3. Select the device in the Device Tree. This causes the device information to be displayed
in the Detail Pane.
4. Click on the “Configuration” tab.
5. Enter the latitude, longitude and altitude information in the Geo-location box.
Note: 5 digits following the decimal point is recommended.
6. Click on the “Save” button. The status bar will indicate if the save was successful or
failed.
7. Click on the “Status” tab.
8. Click the “Refresh” button.
9. Verify that the geo data displayed in the position box has been updated
10
Setup and Deployment Guide
3.5 Testing
Once deployed, verify the health of the IAP with the following procedure:
1. The transceiver number and the SBC number are recorded on the back of the IAP.
Record these numbers, as they will be required in Step 3.
2. Apply power to the IAP.
3. Obtain the transceiver number from the IAP box. Substitute the number for the “x” in the
following commands:
4. From a Subscriber Device, issue the ping command for the transceiver: ping 10.0.x.2.
5. Next ping the SBC: ping 10.0.x.1
This verifies that both the transceiver and SBC are alive.
11
Setup and Deployment Guide
4 Wireless Router (WR)
The MWR6300 (Wireless Router) is an infrastructure device positioned in a fixed location, such
as on a pole, wall, or rooftop. The MWR6300 requires “professional installation” to ensure the
installation is performed in accordance with FCC licensing regulations.
The antenna(s) used for this transmitter must be fixed-mounted on outdoor permanent
structures with a separation distance of at least 2 meters from all persons and must not be colocated or operating in conjunction with any other antenna or transmitter. Users and installers
must be provided with antenna installation and transmitter operating conditions for satisfying RF
exposure compliance.
The Wireless Routers primary function is to provide range extension, but it also provides a
means to route around obstructions, and it provides a fixed and known location reference for
use in Geo-Location (optional feature).
WRs have mounting points for an optional mounting bracket. For a
All
permanent AC power source for each WR must be provided.
4.1 Equipment
The following list defines the
hardware components needed to setup a WR:
•
WR Box with N-type Antenna Connector
•
A/C Power Cable with standard 3 prong plug
•
7.5 dBi Antenna with N-type Female Antenna Connector
The Network Operator must supply the following:
•
Mounting Location
•
A/C Power Source
Optional Configurations:
•
Mounting Bracket
•
Pelco AB-3009-96 for attaching to poles up to 4” in diameter
•
Pelco AB-3010 for poles greater than 4” in diameter
•
Power Cable to connect to a Fisher-Pierce 7570B photoelectric cell
•
Serial Cable with DB9 Male Connectors (for PC to WR debug)
12
deployment, a
Setup and Deployment Guide
4.2 WR Assembly
Figure 7 shows the connection points on a WR box.
Antenna
Power In (4 pin)
Serial Port
Figure 7.
WR Connection Points
Assemble the WR using the following procedure:
1. Insert the Antenna into the N-type Connector on the top of the box, and rotate to close.
2. Insert the Power Plug into the 4-pin Connector.
3. The Serial Port should remain unconnected; it is used for maintenance/debug purposes.
4. The transceiver number is recorded on the back of the WR. Record this number, as it
will be required to configure and test the device.
4.3 Deployment
The WR may be mounted on either a flat surface or a pole, depending on which optional bracket
is selected.
When deploying the WR, the antenna should be a minimum of 30 inches from any nearby metal
poles to avoid interference in the RF pattern. The antenna must also be fixed-mounted on
outdoor permanent structures with a separation distance of at least 2 meters from all persons
and must not be co-located or operating in conjunction with any other antenna or transmitter.
Users and installers must be provided with antenna installation and transmitter operating
conditions for satisfying RF exposure compliance.
The installation sight must have AC power available for the WR.
It is the responsibility of the Network Operator to ensure that the installation complies with any
local building codes.
4.4 Initial Configuration
The configuration process for Geo-Location is the same as for the IAP. Refer to Section 3.4.
13
Setup and Deployment Guide
4.5 Testing
Verify the operation of the WR with the following procedure:
1. The transceiver number is recorded on the back of the WR. Record this number, as it
will be required in Step 3.
2. Apply power to the WR.
3. Obtain the transceiver number from the WR box. Substitute the number for the “x” in the
following commands:
4. From a Subscriber Device, issue the ping command for the transceiver: ping 10.0.x.2.
14
Setup and Deployment Guide
5 Mobile Internet Switching Controller (MiSC)
The MiSC provides routing, switching and management functions for the wireless network, and
the connection to the wired world.
5.1 Equipment
The following list defines the standard
•
SMC 24 Port Switch
•
Cisco 1720 – Edge Router
•
Cisco 1720 – Core Router
•
MeshManager Server
•
Monitor
•
5 Ethernet Cables
•
2 Ethernet Crossover Cables
components needed for the MiSC:
The Network Operator must supply the following:
•
Physical location and AC power, for routers, switch, server, monitor, keyboard, mouse,
etc.
•
Ethernet connection(s) from switch to IAP(s)
•
Ethernet connection to Internet or to Network Operator’s private network (Custom IP
network configuration may be required depending on Network Operator’s network
configuration)
•
Public address for Edge Router, DNS resolver address
•
PC running Windows 2000 with an Ethernet Port for MiSC Configuration and MeshView
Optional Equipment:
•
Geo Server
•
T1 Network Extenders
5.2 Network Setup Description
The basic MiSC hardware configuration is shown in Figure 8.
15
Setup and Deployment Guide
internet
Geo server
CISCOSYSTEMS
edge
router
MeshManager server
server subnet
CISCOS YSTEMS
wireless subnet
switch
core
router
IAP1
IAP2
Figure 8.
Basic MiSC Configuration
The following describes the parameters for setting up the network:
•
All
wireless devices must be within the same subnet.
•
currently uses the non-routable 10.x.x.x (8 bit) subnet as defined in RFC 1918.
•
The IAP will use DHCP to obtain an address, and it must be returned a 10.x.x.x address.
•
All MeshNetworks devices (other than the IAP) currently have fixed addresses of
10.0.x.x with a default gateway of 10.0.0.1.
•
All Mesh devices (other than the IAP) currently expect a DNS server at the IP address
192.168.50.20. If a DNS server is not available at this address, subscriber device hosts
will be unable to resolve web URLs. (This can be overcome by manually setting a DNS
server address in the TCP/IP configuration for the subscriber device host. See Notes in
Appendix B.)
•
A VPN needs to be set up between the Network Operator and MeshNetworks’ Support
group.
16
Setup and Deployment Guide
5.3 MiSC Assembly
The MiSC hardware consists of commercial off-the-shelf components. The components are
pre-configured with a basic configuration which requires minimal site-specific changes.
The SMC switch arrives configured as two virtual LANs. The upper row of Ethernet ports is for
the server subnet; the lower row of ports is for the wireless subnet.
Unpack the SMC switch and mount as desired (either in a rack or on a table top). Connect the
switch to a power source.
Unpack the Cisco router labeled “EdgeRTR” and connect to a power source. Plug interface
labeled “10BT Ethernet” into the ISP router using a crossover Ethernet cable. Plug interface
labeled “10/100 Ethernet” into the SMC switch on port 1.
Unpack the Cisco router labeled “CoreRTR” and connect to a power source. Plug interface
labeled “10BT Ethernet” into switch port 12. Plug interface labeled “10/100 Ethernet” into the
SMC switch on port 24.
Unpack the SunBlade/MeshManager server and monitor and connect to a power source. Plug
the network interface into any of the ports 2-11 on the SMC Switch.
Connect Network Operator supplied computer running Window 2000.
interface into any of the ports 2-11 on the SMC Switch.
Plug the network
Apply power to each of the devices.
5.4 Onsite Configuration of Routers
5.4.1 EdgeRTR Configuration
The EdgeRTR must have on-site configuration done in order to connect to the Internet. Prior to
performing the following steps, obtain the IP address, netmask, and default gateway for the public
interface from the Internet Service Provider. These are shown as ip.ip.ip.ip, nm.nm.nm.nm, and
gw.gw.gw.gw, respectively, in the instructions below. Also, obtain the IP address of the edgeRTR, it will
be in the form of 172.xx.0.1.
Telnet into the EdgeRTR from a computer connected to the server subnet. Use the address 172.xx.0.1 to
connect to the EdgeRTR.
Update the public IP information using the commands below
Password:g0ld1.
EdgeRTR>enable
password:g0ld1.
EdgeRTR#configure terminal
Enter configuration commands, one per line. End with CNTL/Z.
EdgeRTR(config)#interface Ethernet0
EdgeRTR(config-if)#ip address ip.ip.ip.ip mm.nm.nm.nm
EdgeRTR(config-if)#exit
EdgeRTR(config)#no ip route 0.0.0.0 0.0.0.0
EdgeRTR(config)#ip route 0.0.0.0 0.0.0.0 gw.gw.gw.gw
EdgeRTR(config)#exit
EdgeRTR#write memory
17
Setup and Deployment Guide
Building configuration...
!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!![OK]
EdgeRTR#copy running-config startup-config
Destination filename [startup-config]?
Building configuration...
!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!![OK]
EdgeRTR#exit
Connect the IAPs to any of the ports 13-23.
5.4.2 EdgeRTR TEST
Use a computer connected to the switch (in either the server or wireless subnet) to ping to the
ISP gateway IP. Next, test access to the Internet using a web browser. If this fails troubleshoot
and retry.
Obtain the VPN peer address and the appropriate pre-shared key for the VPN.
5.4.3 CoreRTR Configuration
The CoreRTR must have on-site configuration performed to allow remote management of the
wireless devices. During this exercise, the wireless subnet address of each of the wireless
devices is mapped to a server subnet address.
The wireless address is of the form 10.0.x.y. The value of “x” is obtained from the ID number
found on the WMC, IAP or WR. The value of “y” is either 1 or 2; 1 indicates the host device
and 2 indicates the transceiver. Note that a SD and IAP have both a host device and an
transceiver, however a WR has a transceiver but not a host device.
The server subnet address is of the form 172.a.b.c. The value of ‘a’ is supplied by
MeshNetworks as part of the VPN setup. The default value is 31. The value of ‘b’ is the same
as the ‘x’ in the wireless address. Likewise, the value of ‘c’ is the same as the ‘y’ in the wireless
address.
For example, if there is an IAP with an id number of 69, the wireless subnet addresses for it will
be 10.0.69.1 and 10.0.69.2. MeshNetworks supplies the second value in the server subnet
access; this example will use the value of 22. The server subnet address corresponding to the
wireless subnet address will be 172.22.69.1 and 172.22.69.2, respectively. The table below
shows the address mapping which must be done for each IAP, WR and SD. A generic “xx” is
used in the server subnet address since it is a site-dependent value.
Telnet to the CoreRTR from a computer connected to the server subnet. Use the address
172.xx.0.2 to connect to the CoreRTR. Update the NAT information using the commands
below:
CoreRTR>
CoreRTR>enable
Password:
CoreRTR#configure terminal
18
Setup and Deployment Guide
Table 1.
Static NAT Mapping for an IAP, WR and SD
Wireless Subnet Address
Server Subnet Address
Device Type
10.0.201.1
172.xx.201.1
SD #1 Host
10.0.201.2
172.xx.201.2
SD #1 XCVR
10.0.100.2
172.xx.100.2
WR #1 XCVR
10.0.69.1
172.xx.69.1
IAP #1 Host
10.0.69.2
172.xx.69.2
IAP #1 XCVR
The following commands show how the example mapping is done. The commands must be
repeated for each device in the network. The actual address values will be based on the
equipment which is shipped in the kit.
CoreRTR#configure terminal
Enter configuration commands, one per line.
End with CNTL/Z
CoreRTR(config)#ip nat inside source static 10.0.201.1 172.xx.201.1 ;#SD Host
CoreRTR(config)#ip nat inside source static 10.0.201.2 172.xx.201.2 ;#SD XCVR
CoreRTR(config)#ip nat inside source static 10.0.100.2 172.xx.100.2 ;#WR XCVR
CoreRTR(config)#ip nat inside source static 10.0.69.1 172.xx.69.1
CoreRTR(config)#ip nat inside source static 10.0.69.2 172.xx.69.2
;#IAP HOST
;#IAP XCVR
CoreRTR(config)#exit
CoreRTR#write memory
3d01h: %SYS-5-CONFIG_I: Configured from console by console
Building configuration...
!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!
!![OK]
CoreRTR#copy running-config startup-config
Destination filename [startup-config]?
Building configuration...
!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!
!![OK]
CoreRTR#
19
Setup and Deployment Guide
5.4.4 CoreRTR Test
Test the configuration with MeshNetworks to verify operation of the VPN connection.
should be able to ping specific addresses on MeshNetworks management network.
You
5.5 Network Configuration
The “Device Manager” is a utility located on the MeshManager server. It is used to configure
and monitor the deployed network. The following provides a basic overview for using the
Device Manager to perform network setup, refer to the Device Manager User’s Guide for
additional information on using this utility.
1. Start Device Manager by clicking on the shortcut key on the desktop
2. Perform initial device discovery:
a. Select “Tools/Network Discovery”
b. Inside the Wired Range box select the “Wildcard” button, and enter the address
10.0.x.1
c. Inside the Wireless Range box, select the Wildcard button, and enter the address
10.0.x.2
d. Inside the Discovery Timeout box, use the default 3 second SNMP timeout
e. Inside the Configuration Template box, select “Autoconfigure”. Select the desired
templates for the IAP, WR and SD.
f.
Click the “Start” button.
3. The devices should now show up in the Device Tree pane on the left side of the window.
4. For each IAP and WR device in the Device Tree pane, double click on the address. This
brings up the status in the detailed window.
a. Click on the “Configuration” tab.
b. Enter the appropriate data in the General box (Contact, Location, Host Name, Node
Name)
5. If the geo location has not previously been entered, enter the latitude, longitude, and
altitude in the Geo Location box.
6. Enter the IP address to send traps to in the SNMP box
7. For each SD device in the Device Tree pane, double click on the address. This brings
up the status in the detailed window.
a. Click on the “Configuration” tab.
b. Enter the appropriate data in the General box. (Contact, Location, Host Name,
Node Name, and Default IAP MAC Address).
20
Setup and Deployment Guide
c. If Geo-location is to be demonstrated, then in the Geo Location box, select “Enable
Position Calculations”, and select the default interval of 10 seconds. Select
“Enable Position Reporting”, select the default interval of 10 seconds. Enter the
map server’s IP address.
Note: If Geo-location will not be demonstrated, ensure that both “Enable Position
Calculations” and “Enable Position Reporting” are not checked.
d. Enter the IP address to send traps to in the SNMP box.
8. Close the Device Manager utility.
Once the system components have been installed, there are two basic tests to verify correct
operation the system. The first test is to perform ping tests to each device and the second test
is to verify access the Internet.
5.6 Testing
5.6.1 Basic MiSC Tests
To verify the basic connectivity of the MiSC, conduct the following from the MeshManager
server:
•
Ping an IAP
•
Ping the NAT Router
•
Ping the Edge Router
5.6.2 Wireless System Tests
From Device Manager, complete the following to verify correct operation of the system:
1. Ping the transceiver of the deployed IAPs (10.0.x.2)
•
From the Device Manager drop down menu, select Preferences/Use Transceiver
Address
•
For each IAP in the device tree, right click and select Ping Device
2. Ping the transceiver of the deployed WRs (10.0.x.2)
•
From the Device Manager drop down menu, select Preferences/Use SBC Address
•
For each WR in the device tree, right click and select Ping Device
3. Ping the transceiver of each Subscriber Devices (10.0.x.2)
•
From the Device Manager drop down menu, select Preferences/Use Transceiver
Address
•
For each SD in the device tree, right click and select Ping Device
5.6.3 Internet Test
If the
system has been configured to access the Internet, complete the following to verify
correct network setup:
1. From a SD, start the web browser and enter a URL such as
http://www.MeshNetworks.com.
21
Setup and Deployment Guide
Appendix A Site Selection/Deployment Guidelines
A.1
General Guidelines
The IAP location(s) should be selected first since they have the additional requirement of routing
information back to the MiSC. This may be done via an Ethernet cable if the IAP and MiSC are
located within 100 meters (the max length permitted for standard Ethernet) of each other. If the
distance is greater than 100 meters, a mechanism for extending the Ethernet connection will be
required, e.g., using fiber or T1. (MeshNetworks recommends T1 backhaul equipment from Netto-Net Technologies.)
Once the IAPs have been placed, then the location of the WRs can be determined. Optimally,
the devices should be distributed such that a SD has no more than 3 hops to an IAP.
AC power must be available for both IAPs and WRs.
Lastly, any local building/structure codes must be adhered to, as well as proper permits for
placing devices on structures that are not owned by the Network Operator (e.g., light poles).
MeshNetworks has developed the “Location Analyzer” tool to assist in the placement of
infrastructure. This tool runs on a Win2000 SD. The tool collects and analyzes data, ultimately
resulting in a deployment quality indication. Refer to the Location Analyzer documentation for
information on configuring and using this tool.
A.2
Antenna Guidelines
The location of fixed infrastructure antennas must address proper antenna orientation, selection
of elevation pattern for the specific locale, the avoidance of pattern distortion, and the impact of
obscuration and non-line-of-sight paths.
Polarization - Most of the antennas used in deployment will be vertically polarized. To maximize
line-of-sight signal reception, both the transmit and receive antenna should be vertically oriented
to avoid signal loss due to polarization mismatch. This applies to mobile and stationary
antennas. For example, placing a magnetically mounted vehicle antenna on a curved portion of
the vehicle roof so that its axis is not vertical risks a measure of signal loss at range, dependent
upon the specific elevation pattern details, as discussed above.
Local obstructions - Antennas should be mounted either above or below the plane of
obstructions as shown in Figure 9.
antenna
obstruction
antenna
obstruction
Figure 9.
Antenna Mounting
22
Setup and Deployment Guide
Low gain “rubber duck” antennas that are mounted directly to Mesh transceivers are designed
for transmitting and receiving vertically polarized radiation. Hence, care must be taken to insure
close-to-vertical orientation of these antennas to avoid substantial signal loss due to polarization
mismatch. Additionally, attenuation sustained by use of these antennas inside vehicles can be
as high as 10 dB. Typically, losses are in the 4 to 7 dB range if the antenna is above the “metal
can” of the vehicle so that radiation and reception occur at window level.
23
Setup and Deployment Guide
Appendix B Notes
DNS Server
B.1
The Wireless Modem Card returns a fixed IP address (192.168.50.20) to the SD host for the
DNS server. If there is no DNS server in the wired network at this address, the SD host will
be unable to resolve web URLs such as www.meshnetworks.com. To resolve this, the SD
host must be manually configured with a DNS server IP address.
Instructions to setup a Windows 2000 Host:
a. Start/Settings/Network and Dial-up Connections/Local Area Connection
(choose the Local Area Connection Corresponding to the Wireless Modem Card)
b. Click on the “Properties” button.
c. Highlight “Internet Protocol (TCP/IP)” in the Components window.
d. Click on the “Properties” button.
e. Click on the “Advanced” button.
f.
Click on the “DNS” tab
g. Click on the DNS “Add” button.
h. Enter the “DNS Server IP Address” provided by the local network administrator and
then click the “Add” button.
i.
Click the “OK” button to close the Advanced TCP/IP Settings windows.
j.
Click the “OK” button to close the Internet Protocol (TCP/IP) Properties windows.
k. Click the “OK” button to close the Local Area Connection Properties windows.
l.
Click the “Close” button to close the Local Area Connection Status window.
This configuration should remain in the Windows 2000 host.
B.2
Tera Term Pro
Tera Term Pro is a free-ware software emulation program that has more capabilities than HyperTerminal
(which is provided with the standard Windows suite of applications). It is recommended that Tera Term
be obtained so that in the event that MeshNetworks needs to assist the Network Operator with advanced
debugging, there is a common utility in place.
24
Setup and Deployment Guide
Appendix C License and Warranty Information
C.1
IMPORTANT NOTICE
PLEASE READ THE FOLLOWING CAREFULLY BEFORE INSTALLING OR USING THE PRODUCT. IF
YOU AGREE WITH ALL OF THE TERMS OF THIS LICENSE AGREEMENT & LIMITED WARRANTY,
PROCEED WITH THE INSTALLATION OF THE PRODUCT FOLLOWING THE ONSCREEN
INSTRUCTIONS. IF YOU DO NOT AGREE, DO NOT INSTALL OR USE THE PRODUCT. BY
INSTALLING OR USING THE PRODUCT, YOU ARE AGREEING TO BE BOUND BY ALL OF THE
TERMS OF THIS LICENSE AGREEMENT & LIMITED WARRANTY. IF YOU DO NOT AGREE TO THE
TERMS OF THIS LICENSE AGREEMENT & LIMITED WARRANTY, PROMPTLY RETURN THE
UNUSED PRODUCT AND DOCUMENTATION TO MESHNETWORKS, INC. FOR A FULL REFUND OF
THE PURCHASE PRICE.
LICENSE AGREEMENT & LIMITED WARRANTY
Intelligent Access Point – IAP6300
Wireless Router – MWR6300
Wireless Modem Card – WMC6300
LICENSE GRANT
MeshNetworks, Inc. ("MeshNetworks") hereby licenses to the end-user (“You”) the software
accompanying this license ("Software"), regardless of the media on which it is distributed. You own the
medium on which the Software is recorded, but MeshNetworks retains title to the Software and related
documentation. The license is non-exclusive, non-transferable, non-sublicensable and confers a right to
use only the machine-readable, object code form of the Software for its normal and intended purpose by
a single-user. You may:
•
•
make one copy of the Software in machine-readable form for backup purposes only. You must reproduce
on such copy the MeshNetworks’ copyright notice and any other proprietary legends that were on the
original copy of the Software.
transfer all your license rights in the Software, the backup copy of the Software, the related documentation
and a copy of this License to another party, provided the other party reads and agrees to accept the terms
and conditions of this License.
RESTRICTIONS
You acknowledge that the product contains copyrighted material, trade secrets and other proprietary
material owned by MeshNetworks, and that unauthorized use of such material may cause serious loss or
damage to MeshNetworks. You agree that you will not:
•
•
•
•
•
decompile, reverse engineer, disassemble, translate or reduce the Software to a human-perceivable form.
modify, adapt, network, pledge, lease, rent, share, lend, distribute, disclose or create derivative works based
upon the Software in whole or in part.
use the Software in a client-server environment or electronically transmit the Software from one computer to
another or over a network.
transfer any of your rights in the Software, the backup copy of the Software, the media, the documentation,
or this License Agreement to another party.
use the Software for any unlawful or harmful purpose.
TERMINATION
This license is effective until terminated. You may terminate this license at any time by destroying the
Software, related documentation and all copies thereof. This license will terminate immediately without
notice from MeshNetworks if you fail to comply with any provision of this License Agreement & Limited
Warranty. Upon termination you must destroy the Software, related documentation and all copies
thereof.
25
Setup and Deployment Guide
HARDWARE WARRANTY
MeshNetworks warrants to You that this hardware product will be substantially free from material defects
in workmanship and materials, under normal use and service, for a period of one (1) year from the date of
purchase from MeshNetworks or its authorized reseller.
MeshNetworks’ sole obligation under this express warranty will be, at MeshNetworks’ option and
expense, (1) to repair the defective product or part, (2) deliver to You an equivalent product or part to
replace the defective item, or (3) if neither of the two foregoing options is reasonably available, refund to
You the purchase price paid for the defective product. All products that are replaced will become the
property of MeshNetworks. Replacement products or parts may be new or reconditioned. MeshNetworks
warrants any replaced or repaired product or part for the greater of ninety (90) days from shipment, or the
remainder of the initial warranty period.
SOFTWARE WARRANTY
MeshNetworks warrants to You that the Software, except as noted below, will perform in substantial
conformance to its published program specifications, for a period of ninety (90) days from the date of
purchase from MeshNetworks or its authorized reseller. MeshNetworks warrants the media containing
software against failure during the warranty period. No updates are provided under this warranty.
MeshNetworks’ sole obligation under this express warranty will be, at MeshNetworks’ option and
expense, to refund the purchase price paid by You for any defective software product, or to replace any
defective media with software which substantially conforms to applicable MeshNetworks’ published
program specifications. You assume responsibility for the selection of the appropriate applications
program and associated reference materials.
MeshNetworks makes no warranty or representation that the Software will meet your requirements or
work in combination with any hardware or applications software products provided by third parties, that
the operation of the Software will be uninterrupted or error free, or that all defects in the Software will be
corrected.
WARRANTY SERVICE
You must contact the MeshNetworks’ Customer Service Center within the applicable warranty period to
obtain warranty service authorization. Dated proof of purchase from MeshNetworks or its authorized
reseller may be required. A Return Material Authorization (RMA) number will be issued. This number
must be marked on the outside of the package. The product must be packaged appropriately for safe
shipment and sent prepaid. It is recommended that returned products be insured or sent by a method
that provides for tracking of the package. Responsibility for loss or damage does not transfer to
MeshNetworks until the returned item is received by MeshNetworks. MeshNetworks will make
commercially reasonable efforts to ship the repaired or replaced item to You, at MeshNetworks’ expense,
not later than thirty (30) days after MeshNetworks receives the defective product. MeshNetworks will
retain risk of loss or damage until the item is delivered to You.
MeshNetworks will not be responsible for any software, firmware, information, or memory data belonging
to You contained in, stored on, or integrated with any products returned to MeshNetworks for repair,
whether under warranty or not.
Technical support via telephone is available for an additional charge. To obtain information regarding this
option, send an email to [email protected]. During the warranty period stated above, You
may also obtain technical support by sending an email to
[email protected].
The MeshNetworks’ website (www.meshnetworks.com) is available at no charge, and provides a bug list,
and technical information about MeshNetworks’ products.
WARRANTIES EXCLUSIVE, WARRANTY DISCLAIMER
TO THE FULL EXTENT ALLOWED BY LAW, THE FOREGOING WARRANTIES AND REMEDIES ARE
EXCLUSIVE AND ARE IN LIEU OF ALL OTHER WARRANTIES, TERMS, OR CONDITIONS, EXPRESS
OR IMPLIED, EITHER IN FACT OR BY OPERATION OF LAW, STATUTORY OR OTHERWISE,
INCLUDING, WITHOUT LIMITATION, WARRANTIES OF MERCHANTABILITY, FITNESS FOR A
PARTICULAR PURPOSE, SATISFACTORY QUALITY, CORRESPONDENCE WITH DESCRIPTION,
INFORMATIONAL CONTENT, ACCURACY, SYSTEM INTEGRATION, NON-INFRINGEMENT AND
26
Setup and Deployment Guide
QUIET ENJOYMENT, ALL OF WHICH ARE EXPRESSLY DISCLAIMED. . MESHNETWORKS DOES
NOT WARRANT THAT THE FUNCTIONS CONTAINED IN THE PRODUCT WILL MEET YOUR
REQUIREMENTS, THAT THE PRODUCT WILL BE COMPATIBLE WITH ANY OTHER SOFTWARE,
HARDWARE OR OPERATING SYSTEM, THAT THE OPERATION OF THE SOFTWARE WILL BE
UNINTERRUPTED OR ERROR-FREE. MESHNETWORKS NEITHER ASSUMES NOR AUTHORIZES
ANY OTHER PERSON TO ASSUME FOR IT ANY OTHER LIABILITY IN CONNECTION WITH THE
SALE, INSTALLATION, MAINTENANCE OR USE OF THIS PRODUCT.
MESHNETWORKS WILL NOT BE LIABLE UNDER THIS WARRANTY IF ITS TESTING AND
EXAMINATION DISCLOSE THAT THE ALLEGED DEFECT OR MALFUNCTION IN THE PRODUCT
DOES NOT EXIST OR WAS CAUSED BY YOUR OR ANY THIRD PERSON’S MISUSE, NEGLECT,
IMPROPER INSTALLATION OR TESTING, UNAUTHORIZED ATTEMPTS TO OPEN, REPAIR OR
MODIFY THE PRODUCT, OR ANY OTHER CAUSE BEYOND THE RANGE OF THE INTENDED USE,
OR BY ACCIDENT, FIRE, LIGHTNING, POWER CUTS OR OUTAGES, OTHER HAZARDS, OR ACTS
OF GOD.
LIMITATION OF LIABILITY
TO THE FULL EXTENT ALLOWED BY LAW, MESHNETWORKS EXCLUDES FOR ITSELF AND ITS
DIRECTORS, OFFICERS, EMPLOYEES, OR AGENTS, ANY LIABILITY, WHETHER BASED IN
CONTRACT OR TORT (INCLUDING NEGLIGENCE), FOR INCIDENTAL, CONSEQUENTIAL,
INDIRECT, SPECIAL, OR PUNITIVE DAMAGES OF ANY KIND, OR FOR LOSS OF REVENUE OR
PROFITS, LOSS OF BUSINESS, LOSS OF INFORMATION OR DATA, OR OTHER FINANCIAL LOSS
ARISING OUT OF OR IN CONNECTION WITH THE SALE, INSTALLATION, MAINTENANCE, USE,
PERFORMANCE, FAILURE, OR INTERRUPTION OF ITS PRODUCTS, EVEN IF MESHNETWORKS
OR ITS AUTHORIZED REPRESENTATIVE HAS BEEN ADVISED OF THE POSSIBILITY OF SUCH
DAMAGES, AND LIMITS ITS LIABILITY TO REPAIR, REPLACEMENT, OR REFUND OF THE
PURCHASE PRICE PAID, AT MESHNETWORKS’ OPTION. THIS DISCLAIMER OF LIABILITY FOR
DAMAGES WILL NOT BE AFFECTED IF ANY REMEDY PROVIDED HEREIN WILL FAIL OF ITS
ESSENTIAL PURPOSE.
Some jurisdictions do not allow the exclusion or limitation of implied warranties or the limitation of
incidental or consequential damages for certain products supplied to consumers, or the limitation of
liability for death or personal injury, so the above limitations and exclusions may be limited in their
application to you. When the implied warranties are not allowed to be excluded in their entirety, they will
be limited to the duration of the applicable written warranty. This warranty gives you specific legal rights
which may vary depending on local law.
EXPORT COMPLIANCE
The export laws and regulations of the United States control the Software and documentation provided by
MeshNetworks. You represent and agree that You will remain fully cognizant of and in compliance with
all export laws and regulations that may be or become applicable to your import, use, resale, export, or
re-export of the Software and technical data. In addition, the Software and technical data may not be
exported or re-exported to any country or person to which the United States prohibits the export of goods,
technology or services, or to any country that the United States government has deemed to be a terroristsupporting country. You represent and warrant that You are not a national of any country to which the
United States prohibits the export or re-export of goods, services or technology and that You are not a
person specially designated as ineligible to export, or otherwise receive or deal in, U.S.-origin goods,
services or technology. In addition, the Software and technical data may be subject to the export or
import laws and regulations of other countries. You agree to comply fully with all such laws and
regulations.
GOVERNING LAW
This License Agreement & Limited Warranty will be governed by the laws of the state of Florida, U.S.A.,
and by the laws of the United States, excluding their conflicts of laws principles. Both the Uniform
Computer Information Transactions Act and the United Nations Convention on Contracts for the
International Sale of Goods are hereby excluded in their entirety from application to this License
Agreement & Limited Warranty.
27
Setup and Deployment Guide
Appendix D FCC Regulatory Information
D.1
FCC Information
This device complies with Part 15 of the FCC Rules. Operation is subject to the following two
conditions: (1) this device may not cause harmful interference, and (2) this device must accept
any interference received; including interference that may cause undesired operation.
Federal Communications Commission (FCC) Statement:
This Equipment has been tested and found to comply with the limits for a Class A digital device,
pursuant to Part 15 of the FCC rules. These limits are designed to provide reasonable
protection against harmful interference in a commercial installation. This equipment generates,
uses and can radiate radio frequency energy and, if not installed and used in accordance with
the instructions, may cause harmful interference to radio communications. However, there is no
guarantee that interference will not occur in a particular installation. If this equipment does
cause harmful interference to radio or television reception, which can be determined by turning
the equipment off and on, the user is encouraged to try to correct the interference by one or
more of the following measures:
•
Reorient or relocate the receiving antenna.
•
Increase the separation between the equipment and receiver.
•
Connect the equipment into an outlet on a circuit different from that to which the receiver
is connected.
•
Consult the dealer or an experienced radio/TV technician for help.
D.2
1.
FCC RF Radiation Exposure Statement
CAUTION: This equipment complies with FCC RF radiation exposure limits set forth for
an uncontrolled environment. This equipment should be installed and operated with a
minimum distance of 2 meters between the antenna and your body.
2. This Transmitter must not be co-located or operating in conjunction with any other
antenna or transmitter.
28
Setup and Deployment Guide
D.3
Safety Information for the
The Federal Communications Commission (FCC) with its action in ET Docket 96-8 has adopted
a safety standard for human exposure to radio frequency (RF) electromagnetic energy emitted
by FCC certified equipment.
MeshNetworks’
products meet the uncontrolled
environmental limits found in OET-65 and ANSI C95.1, 1991. Proper operation of this radio
according to the instructions found in this manual and the hardware and software guides on the
CD will result in user exposure that is substantially below the FCC recommended limits.
•
Do not touch or move the antenna(s) while the unit is transmitting or receiving.
•
Do not hold any component containing a radio such that the antenna is very close to or
touching any exposed parts of the body, especially the face or eyes, while transmitting.
•
Do not operate a portable transmitter near unshielded blasting caps or in an explosive
environment unless it is a type especially qualified for such use.
•
Do not operate the radio or attempt to transmit data unless the antenna is connected;
otherwise, the radio may be damaged.
•
Antenna use:
•
In order to comply with FCC RF exposure limits, dipole antennas should be located
at a minimum distance of 2 meters or more from the body of all persons.
29
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Full article: The effect of tax risk on audit report delay: Empirical evidence from Indonesia
Tax risk has the potential to have far-reaching economic consequences, including the effect on late audit reports. This study aims to empirically investigate the effect of tax risk on audit report ...
The effect of tax risk on audit report delay: Empirical evidence from Indonesia
Eko Suwardi 1 Department of Accounting, Faculty of Economics and Business, Universitas Gadjah Mada, Yogyakarta, Indonesia Correspondence [email protected] https://orcid.org/0000-0002-6083-0095 View further author information& Arfah Habib Saragih 1 Department of Accounting, Faculty of Economics and Business, Universitas Gadjah Mada, Yogyakarta, Indonesia;2 Department of Fiscal Administration, Faculty of Administrative Sciences, Universitas Indonesia https://orcid.org/0000-0003-4190-3196 View further author information
Abstract
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Abstract
Tax risk has the potential to have far-reaching economic consequences, including the effect on late audit reports. This study aims to empirically investigate the effect of tax risk on audit report lag. This study took a quantitative approach. Companies listed on the Indonesia Stock Exchange (IDX) between 2012 and 2017 were used as samples. Our final observations consist of 1,813 firm-years. We find that the tax risk has no effect on audit report lag. This finding holds up when one alternative measure of tax risk and several additional control variables are considered. The result of this study has clear implications not only for company management but also for tax authority. Company management is required to always implement good tax risk management practices because this can result in a relatively low corporate tax risk. A relatively minor tax risk will have no effect on auditors’ performance in completing audit work so that companies can submit their financial reports on time. Furthermore, the tax authority benefits because the finalization of tax collection settlement is improved. Tax authority is encouraged to always maintain tax regulations that are not overly complex, complicated, or change too frequently.
Keywords:
Tax risk
tax uncertainty
audit report lag
timeliness of financial reporting
emerging country
JEL Classifications:
H20
H26
M41
M10
M00
1. Introduction
The phenomenon associated with audit report lag is a global phenomenon that occurs in companies in many countries, including both developed and developing countries. Delays in submitting the auditor’s opinion on the correctness and fairness of the company’s financial statements have the potential to increase uncertainty in decision making by various interested parties. Furthermore, timeliness is recognized as one of the fundamental characteristics of financial information that makes it useful. The important objective of accounting information is to aid the users of financial reporting to generate an accurate decision (Al-Ebel et al., Citation 2020 Al-Ebel, A., Baatwah, S., Al-Musali, M., & Ntim, C. G.( 2020). Religiosity, accounting expertise, and audit report lag: Empirical evidence from the individual level. Cogent Business & Management, 7(1), 1823587. https://doi.org/10.1080/23311975.2020.1823587[Taylor & Francis Online], [Web of Science ®] , [Google Scholar]; Alsmady, Citation 2022 Alsmady, A. A.( 2022). Accounting information quality and tax avoidance effect on investment opportunities evidence from Gulf Cooperation Council GCC. Cogent Business & Management, 9(1). https://doi.org/10.1080/23311975.2022.2143020[Taylor & Francis Online], [Web of Science ®] , [Google Scholar]). Given the importance of timely financial reporting to investors and other stakeholders, determining the causes of the recent audit report delay is critical. The purpose of this research is to re-examine the impact of tax risk on audit report lag.
Several previous studies have identified a variety of determinants of audit report lag (Abernathy et al., Citation 2017 Abernathy, J. L., Barnes, M., Stefaniak, C., & Weisbarth, A.( 2017). An International Perspective on Audit Report Lag: A Synthesis of the Literature and Opportunities for Future Research. International Journal of Auditing, 21(1), 100– 19. https://doi.org/10.1111/ijau.12083[Crossref], [Web of Science ®] , [Google Scholar]; Durand, Citation 2019 Durand, G.( 2019). The determinants of audit report lag: A meta-analysis. Managerial Auditing Journal, 34(1), 44– 75. https://doi.org/10.1108/MAJ-06-2017-1572[Crossref], [Web of Science ®] , [Google Scholar]; Habib et al., Citation 2019 Habib, A., Bhuiyan, M. B. U., Huang, H. J., & Miah, M. S.( 2019). Determinants of audit report lag: A meta-analysis. International Journal of Auditing, 23(1), 20– 44. https://doi.org/10.1111/ijau.12136[Crossref], [Web of Science ®] , [Google Scholar]). These factors include corporate governance characteristics (Afify, Citation 2009 Afify, H. A. E.( 2009). Determinants of audit report lag: Does implementing corporate governance have any impact? Empirical evidence from Egypt. Journal of Applied Accounting Research, 10(1), 56– 86. https://doi.org/10.1108/09675420910963397 [Crossref] , [Google Scholar]; Lajmi & Yab, Citation 2021 Lajmi, A., & Yab, M.( 2021). The impact of internal corporate governance mechanisms on audit report lag: Evidence from Tunisian listed companies. EuroMed Journal of Business, 17(4), 619– 633. https://doi.org/10.1108/EMJB-05-2021-0070[Crossref], [Web of Science ®] , [Google Scholar]), audit committees (Oussii & Boulila Taktak, Citation 2018 Oussii, A. A., & Boulila Taktak, N.( 2018). Audit committee effectiveness and financial reporting timeliness: The case of Tunisian listed companies. African Journal of Economic and Management Studies, 9(1), 34– 55. https://doi.org/10.1108/AJEMS-11-2016-0163[Crossref], [Web of Science ®] , [Google Scholar]; Raweh et al., Citation 2021 Raweh, N. A. M., Abdullah, A. A. H., Kamardin, H., Malek, M., & Ntim, C. G.( 2021). Industry expertise on audit committee and audit report timeliness. Cogent Business & Management, 8(1). https://doi.org/10.1080/23311975.2021.1920113[Taylor & Francis Online], [Web of Science ®] , [Google Scholar]; Sultana et al., Citation 2015 Sultana, N., Singh, H., & Van der Zahn, J. L. W. M.( 2015). Audit Committee Characteristics and Audit Report Lag. International Journal of Auditing, 19(2), 72– 87. https://doi.org/10.1111/ijau.12033[Crossref], [Web of Science ®] , [Google Scholar]), chief accounting officers (Hsu & Khan, Citation 2019 Hsu, H. T., & Khan, S.( 2019). Chief accounting officers and audit efficiency. Asian Review of Accounting, 27(4), 614– 638. https://doi.org/10.1108/ARA-09-2018-0171[Crossref], [Web of Science ®] , [Google Scholar]), and internal control systems (Belina, Citation 2022 Belina, H.( 2022). “Surprise” material weakness disclosures: Effects on audit fees and audit report lags. Journal of Accounting and Public Policy, 404(6), 106979. https://doi.org/10.1016/j.jaccpubpol.2022.106979 [Crossref] , [Google Scholar]; Gontara et al., Citation 2022 Gontara, H., Khelil, I., & Khlif, H.( 2022). The association between internal control quality and audit report lag in the French setting: The moderating effect of family directors. Journal of Family Business Management. https://doi.org/10.1108/JFBM-11-2021-0139[Crossref], [Web of Science ®] , [Google Scholar]; Munsif et al., Citation 2012 Munsif, V., Raghunandan, K., & Rama, D. V.( 2012). Internal control reporting and audit report lags: Further evidence. AUDITING: A Journal of Practice & Theory, 31(3), 203– 218. https://doi.org/10.2308/ajpt-50190[Crossref], [Web of Science ®] , [Google Scholar]). Other determinants also include accounting standards (Cho & Krishnan, Citation 2021 Cho, M., & Krishnan, G. V.( 2021). Principles-based accounting standards and audit outcomes: Empirical evidence. Review of Accounting Studies. https://doi.org/10.2139/ssrn.3821688 [Web of Science ®] , [Google Scholar]; Habib, Citation 2015 Habib, A.( 2015). The new Chinese accounting standards and audit report lag. International Journal of Auditing, 19(1), 1– 14. https://doi.org/10.1111/ijau.12030 [Crossref] , [Google Scholar]; Khlif & Achek, Citation 2016 Khlif, H., & Achek, I.( 2016). IFRS adoption and auditing: A review. Asian Review of Accounting, 24(3), 338– 361. https://doi.org/10.1108/ARA-12-2014-0126 [Crossref] , [Google Scholar]; Zhou et al., Citation 2022 Zhou, Y., Liu, J., & Lei, D.( 2022). The effect of financial reporting regimes on audit report lags and audit fees: Evidence from firms cross-listed in the USA. Journal of Financial Reporting and Accounting. https://doi.org/10.1108/JFRA-09-2021-0261[Crossref], [Web of Science ®] , [Google Scholar]), earnings volatility (Bryan & Mason, Citation 2020 Bryan, D. B., & Mason, T. W.( 2020). Earnings volatility and audit report lag. Advances in Accounting, 51(xxxx), 100496. https://doi.org/10.1016/j.adiac.2020.100496 [Crossref] , [Google Scholar]), firm-level political risk (Hossain & Mitra, Citation 2022 Hossain, M., & Mitra, S.( 2022, August). Do auditors account for firm-level political risk? International Journal of Auditing, 26(4), 534– 552. https://doi.org/10.1111/ijau.12294[Crossref], [Web of Science ®] , [Google Scholar]), litigation against clients (Liu et al., Citation 2021 Liu, H., Cullinan, C., & Zhang, J.( 2021). Litigation against clients and audit report lag: An examination of the role of state ownership and regional legal development in China. Managerial Auditing Journal, 36(5), 744– 769. https://doi.org/10.1108/MAJ-02-2020-2557[Crossref], [Web of Science ®] , [Google Scholar]), audit firm industry specialization (Yeboah et al., Citation 2023 Yeboah, E. N., Addai, B., & Appiah, K. O.( 2023). Audit pricing puzzle: Do audit firm industry specialization and audit report lag matter? Cogent Business & Management, 10(1). https://doi.org/10.1080/23311975.2023.2172013[Taylor & Francis Online], [Web of Science ®] , [Google Scholar]), the COVID-19 pandemic (Bajary et al., Citation 2023 Bajary, A. R., Shafie, R., & Ali, A.( 2023). COVID-19 Pandemic, Internal Audit Function and Audit Report Lag: Evidence from Emerging economy COVID-19 Pandemic, Internal Audit Function and Audit Report Lag: Evidence from Emerging economy. Cogent Business & Management, 10(1). https://doi.org/10.1080/23311975.2023.2178360[Taylor & Francis Online], [Web of Science ®] , [Google Scholar]), and tax avoidance (Gontara & Khlif, Citation 2020 Gontara, H., & Khlif, H.( 2020). Tax avoidance and audit report lag in South Africa: The moderating effect of auditor type. Journal of Financial Crime, 28(3), 732– 740. https://doi.org/10.1108/JFC-09-2020-0197 [Crossref] , [Google Scholar]). Studies discussing the impact of tax avoidance on audit report lag have indeed been carried out (Asiriuwa et al., Citation 2021 Asiriuwa, O., Adeyemi, S. B., Uwuigbe, O. R., Uwuugbe, U., & Ozordi, E.( 2021). Tax Aggressiveness and Timeliness of Financial Reporting in Nigeria Financial Sector. Academy of Accounting and Financial Studies Journal, 25(6), 1– 11. [Google Scholar]; Crabtree & Kubick, Citation 2014 Crabtree, A. D., & Kubick, T. R.( 2014). Corporate tax avoidance and the timeliness of annual earnings announcements. Review of Quantitative Finance and Accounting, 42(1), 51– 67. https://doi.org/10.1007/s11156-012-0333-9 [Crossref] , [Google Scholar]; Gontara & Khlif, Citation 2020 Gontara, H., & Khlif, H.( 2020). Tax avoidance and audit report lag in South Africa: The moderating effect of auditor type. Journal of Financial Crime, 28(3), 732– 740. https://doi.org/10.1108/JFC-09-2020-0197 [Crossref] , [Google Scholar]). However, it is important to understand that tax avoidance and tax risk are two different constructs (Gallemore & Labro, Citation 2015 Gallemore, J., & Labro, E.( 2015). The importance of the internal information environment for tax avoidance. Journal of Accounting and Economics, 60(1), 149– 167. https://doi.org/10.1016/j.jacceco.2014.09.005[Crossref], [Web of Science ®] , [Google Scholar]; Drake et al., Citation 2017 Drake, K. D., Lusch, S. J., & Stekelberg, J.( 2019). Does Tax Risk Affect Investor Valuation of Tax Avoidance?. Journal of Accounting, Auditing & Finance, 34(1), 151– 176. https://doi.org/10.1177/0148558x17692674[Crossref], [Web of Science ®] , [Google Scholar]; Hamilton & Stekelberg, Citation 2017 Hamilton, R., & Stekelberg, J.( 2017). The effect of high-quality information technology on corporate tax avoidance and tax risk. Journal of Information Systems, 31(2), 83– 106. https://doi.org/10.2308/isys-51482[Crossref], [Web of Science ®] , [Google Scholar]; Lin et al., Citation 2019 Lin, X., Liu, M., So, S., & Yuen, D.( 2019). Corporate social responsibility, firm performance and tax risk. Managerial Auditing Journal, 34(9), 1101– 1130. https://doi.org/10.1108/MAJ-04-2018-1868[Crossref], [Web of Science ®] , [Google Scholar]; Neuman et al., Citation 2020 Neuman, S. S., Omer, T. C., & Schmidt, A. P.( 2020). Assessing Tax Risk: Practitioner Perspectives. Contemporary Accounting Research, 37(3), 1788– 1827. https://doi.org/10.1111/1911-3846.12556[Crossref], [Web of Science ®] , [Google Scholar]; Saragih & Ali, Citation 2021 Saragih, A. H., & Ali, S.( 2021). Corporate tax risk: A literature review and future research directions. Management Review Quarterly. https://doi.org/10.1007/s11301-021-00251-8 [Crossref] , [Google Scholar]).
Despite the well-established determinants of audit report lag, very few studies appear to have looked into the impact of tax risk on audit report lag (see the literature review presented by Saragih & Ali, Citation 2021 Saragih, A. H., & Ali, S.( 2021). Corporate tax risk: A literature review and future research directions. Management Review Quarterly. https://doi.org/10.1007/s11301-021-00251-8 [Crossref] , [Google Scholar]). Knechel and Payne ( Citation 2001 Knechel, W. R., & Payne, J. L.( 2001). Additional evidence on audit report lag. AUDITING: A Journal of Practice & Theory, 20(1), 137– 146. https://doi.org/10.2308/aud.2001.20.1.137[Crossref], [Web of Science ®] , [Google Scholar]) contend that the presence of a contentious corporate tax issue causes a longer audit report lag. Knechel and Payne’s ( Citation 2001 Knechel, W. R., & Payne, J. L.( 2001). Additional evidence on audit report lag. AUDITING: A Journal of Practice & Theory, 20(1), 137– 146. https://doi.org/10.2308/aud.2001.20.1.137[Crossref], [Web of Science ®] , [Google Scholar]) study, on the other hand, does not explicitly focus the discussion on the concept of tax risk (tax uncertainty). Abernathy et al. ( Citation 2019 Abernathy, J. L., Finley, A. R., Rapley, E. T., & Stekelberg, J.( 2019). External Auditor Responses to Tax Risk. Journal of Accounting, Auditing & Finance, 36(3), 489– 516. https://doi.org/10.1177/0148558X19867821[Crossref], [Web of Science ®] , [Google Scholar]) state unequivocally that tax risks increase late audit reports. However, their research is limited to listed firms in the developed country (the United States) from 2003 to 2015.
Abernathy et al. ( Citation 2019 Abernathy, J. L., Finley, A. R., Rapley, E. T., & Stekelberg, J.( 2019). External Auditor Responses to Tax Risk. Journal of Accounting, Auditing & Finance, 36(3), 489– 516. https://doi.org/10.1177/0148558X19867821[Crossref], [Web of Science ®] , [Google Scholar]) study encourages researchers to investigate whether similar findings apply in Indonesia. We contend that the findings of these studies cannot be extrapolated to publicly traded companies in developing countries. We believe that this study is significant, feasible, and worthy of replication. Re-examination will be useful for synthesizing, combining, and expanding knowledge of specific phenomena (J. H. Block et al., Citation 2022 Block, J. H., Fisch, C., Kanwal, N., Lorenzen, S., & Schulze, A.( 2022). Replication studies in top management journals: An empirical investigation of prevalence, types, outcomes, and impact. Management Review Quarterly. https://doi.org/10.1007/s11301-022-00269-6 [Crossref] , [Google Scholar]), which will ultimately help to place academic discussions on a solid foundation because it is supported by a variety of empirical evidence (J. Block & Kuckertz, Citation 2018 Block, J., & Kuckertz, A.( 2018). Seven principles of effective replication studies: Strengthening the evidence base of management research. Management Review Quarterly, 68(4), 355– 359. https://doi.org/10.1007/s11301-018-0149-3 [Crossref] , [Google Scholar]). Re-examination is still required for disciplines to develop more meaningfully and to bridge the gap between practice and theory (J. Block & Kuckertz, Citation 2018 Block, J., & Kuckertz, A.( 2018). Seven principles of effective replication studies: Strengthening the evidence base of management research. Management Review Quarterly, 68(4), 355– 359. https://doi.org/10.1007/s11301-018-0149-3 [Crossref] , [Google Scholar]).
The purpose of this study is to broaden our understanding of the factors that influence audit report lag by focusing on tax risk as the primary predictor and utilizing the context of a growing country. On the one hand, in Indonesia, there has been an issue of reducing the corporate income tax rate (from 25% to 22%) released by the government. The issue of declining corporate tax rates has the potential to create tax uncertainty (tax risk). Previous studies have found that institutional factors influence the firm’s tax risks. Tax rules and regulations are examples of institutional factors (Towery, Citation 2017 Towery, E. M.( 2017). Unintended consequences of linking tax return disclosures to financial reporting for income taxes: Evidence from schedule UTP. The Accounting Review, 92(5), 201– 226. https://doi.org/10.2308/accr-51660[Crossref], [Web of Science ®] , [Google Scholar]). This potential tax risk could result in a longer audit report lag (Abernathy et al., Citation 2019 Abernathy, J. L., Finley, A. R., Rapley, E. T., & Stekelberg, J.( 2019). External Auditor Responses to Tax Risk. Journal of Accounting, Auditing & Finance, 36(3), 489– 516. https://doi.org/10.1177/0148558X19867821[Crossref], [Web of Science ®] , [Google Scholar]). On the other hand, there is a possibility that the tax risk of companies in Indonesia (as a developing country) is also relatively smaller so that it does not have an impact on audit report lag. Prior study states that firms in developing countries are less likely to engage in tax avoidance than firms in developed countries (Zeng, Citation 2019 Zeng, T.( 2019). Country-level governance, accounting standards, and tax avoidance: A cross-country study. Asian Review of Accounting, 27(3), 401– 424. https://doi.org/10.1108/ARA-09-2018-0179[Crossref], [Web of Science ®] , [Google Scholar]). Firms that are less aggressive in their tax avoidance face less tax risk, and vice versa (Dyreng et al., Citation 2019 Dyreng, S. D., Hanlon, M., & Maydew, E. L.( 2019). When does tax avoidance result in tax uncertainty? The Accounting Review, 94(2), 179– 203. https://doi.org/10.2308/accr-52198[Crossref], [Web of Science ®] , [Google Scholar]). Therefore, whether the tax risk drives longer audit report lag in Indonesia is an important open empirical question that we address in our study.
Furthermore, the significance of this study stems from the fact that there has not been a significant amount of research done on the relationship between tax risk and audit report lag (Saragih & Ali, Citation 2021 Saragih, A. H., & Ali, S.( 2021). Corporate tax risk: A literature review and future research directions. Management Review Quarterly. https://doi.org/10.1007/s11301-021-00251-8 [Crossref] , [Google Scholar]). We argue that it is critical to understand the causes of audit lag in order to mitigate it as much as possible and thus produce timely information. There is no clear link between tax risk and audit report lag in listed firms from developing countries, according to existing research (Saragih & Ali, Citation 2021 Saragih, A. H., & Ali, S.( 2021). Corporate tax risk: A literature review and future research directions. Management Review Quarterly. https://doi.org/10.1007/s11301-021-00251-8 [Crossref] , [Google Scholar]). We attempt to fill this gap by investigating the effect of tax risk on audit report lag in a developing country. This is something new that can be provided in this study.
We used a sample of companies listed on the Indonesia Stock Exchange (IDX) from 2012 to 2017 to put our research question to the test. The total number of observations is 1,813 firm-years. From our study, we found that tax risk has no effect on audit report lag. One possible explanation is that corporate tax risk is relatively low in Indonesia. Some factors can contribute to this relatively low tax risk. Companies may have well-implemented tax management and tax risk management. In addition, there is a possibility that the complexity of corporate tax planning in Indonesia is low enough that the amount of effort expended by the auditor to investigate the client’s tax accounts, including potential tax risk, is not increased. Finally, there is a possibility that the complexity of tax regulations set by the Indonesian tax regulator is low.
This study makes several contributions. Our study adds to the existing literature by documenting a finding that contradicts previous research (see Abernathy et al., Citation 2019 Abernathy, J. L., Finley, A. R., Rapley, E. T., & Stekelberg, J.( 2019). External Auditor Responses to Tax Risk. Journal of Accounting, Auditing & Finance, 36(3), 489– 516. https://doi.org/10.1177/0148558X19867821[Crossref], [Web of Science ®] , [Google Scholar]). Our finding also adds to the growing body of knowledge on the intersection of corporate tax risk and auditing. From a practical standpoint, this study shows that well-implemented corporate tax risk management practices have the potential to result in lower tax risk, which benefits both the company and the tax authority.
The remainder of this paper is organized as follows. Section2examines the literature on audit report lag, tax risk, and developing research hypothesis. Section3describes the research methods. Section4includes descriptive statistics, correlation matrices, and details on the study’s main finding. This section also goes over the study’s finding and implications. Section5discusses robustness checks. Section6contains the study’s conclusions, limitations, and suggestions for future research.
2. Literature review and hypothesis development
2.1. Audit report lag
The distance between the company’s fiscal year-end period and the date of the audit report is defined as audit report lag. Many previous studies have documented the factors that contribute to audit report lag (Abernathy et al., Citation 2017 Abernathy, J. L., Barnes, M., Stefaniak, C., & Weisbarth, A.( 2017). An International Perspective on Audit Report Lag: A Synthesis of the Literature and Opportunities for Future Research. International Journal of Auditing, 21(1), 100– 19. https://doi.org/10.1111/ijau.12083[Crossref], [Web of Science ®] , [Google Scholar]; Durand, Citation 2019 Durand, G.( 2019). The determinants of audit report lag: A meta-analysis. Managerial Auditing Journal, 34(1), 44– 75. https://doi.org/10.1108/MAJ-06-2017-1572[Crossref], [Web of Science ®] , [Google Scholar]; Habib et al., Citation 2019 Habib, A., Bhuiyan, M. B. U., Huang, H. J., & Miah, M. S.( 2019). Determinants of audit report lag: A meta-analysis. International Journal of Auditing, 23(1), 20– 44. https://doi.org/10.1111/ijau.12136[Crossref], [Web of Science ®] , [Google Scholar]). Aspects of good corporate governance play critical roles in reducing audit report lag (Fakhfakh Sakka et al., Citation 2016 Fakhfakh Sakka, I., Jarboui, A., & Bisogno, M.( 2016). Audit reports timeliness: Empirical evidence from Tunisia. Cogent Business & Management, 3(1), 1195680. https://doi.org/10.1080/23311975.2016.1195680[Taylor & Francis Online], [Web of Science ®] , [Google Scholar]; Waris & Haji Din, Citation 2023 Waris, M., & Haji Din, B.( 2023). Impact of corporate governance and ownership concentrations on timelines of financial reporting in Pakistan. Cogent Business & Management, 10(1). https://doi.org/10.1080/23311975.2023.2164995[Taylor & Francis Online], [Web of Science ®] , [Google Scholar]). According to Knechel and Payne’s ( Citation 2001 Knechel, W. R., & Payne, J. L.( 2001). Additional evidence on audit report lag. AUDITING: A Journal of Practice & Theory, 20(1), 137– 146. https://doi.org/10.2308/aud.2001.20.1.137[Crossref], [Web of Science ®] , [Google Scholar]), one of the main determinants of audit report delay is additional audit effort (e.g. audit hours). Singh et al. ( Citation 2022 Singh, H., Sultana, N., Islam, A., & Singh, A.( 2022). Busy auditors, financial reporting timeliness and quality. The British Accounting Review, 54(3), 101080. https://doi.org/10.1016/j.bar.2022.101080[Crossref], [Web of Science ®] , [Google Scholar]) found that companies with overburdened auditors take longer to complete audits and have lower levels of financial reporting quality. Waris and Haji Din ( Citation 2023 Waris, M., & Haji Din, B.( 2023). Impact of corporate governance and ownership concentrations on timelines of financial reporting in Pakistan. Cogent Business & Management, 10(1). https://doi.org/10.1080/23311975.2023.2164995[Taylor & Francis Online], [Web of Science ®] , [Google Scholar]) reported that auditor brand name decreases audit report lag. Habib et al. ( Citation 2019 Habib, A., Bhuiyan, M. B. U., Huang, H. J., & Miah, M. S.( 2019). Determinants of audit report lag: A meta-analysis. International Journal of Auditing, 23(1), 20– 44. https://doi.org/10.1111/ijau.12136[Crossref], [Web of Science ®] , [Google Scholar]) classified meta-analysis studies on the factors influencing audit report lag into three categories: audit and audit-related factors, corporate governance-related factors, and firm-specific determinants. Meanwhile, Durand ( Citation 2019 Durand, G.( 2019). The determinants of audit report lag: A meta-analysis. Managerial Auditing Journal, 34(1), 44– 75. https://doi.org/10.1108/MAJ-06-2017-1572[Crossref], [Web of Science ®] , [Google Scholar]) stated in his literature review that audit report lag is related to various factors such as audit complexity, types of audit opinions, factors related to other audit work, various auditor characteristics, and auditor business risk measures. Auditor business risk is the risk that audit firms will incur losses as a result of the engagement, including potential litigation (Durand, Citation 2019 Durand, G.( 2019). The determinants of audit report lag: A meta-analysis. Managerial Auditing Journal, 34(1), 44– 75. https://doi.org/10.1108/MAJ-06-2017-1572[Crossref], [Web of Science ®] , [Google Scholar]). In relation to the auditor’s business risk, it appears that the company’s tax risk may also play a role.
According to Knechel and Payne’s ( Citation 2001 Knechel, W. R., & Payne, J. L.( 2001). Additional evidence on audit report lag. AUDITING: A Journal of Practice & Theory, 20(1), 137– 146. https://doi.org/10.2308/aud.2001.20.1.137[Crossref], [Web of Science ®] , [Google Scholar]), companies with contentious tax issues have a longer audit report lag. This is possible because complex and complicated tax situations can have a direct impact on financial statements and must be resolved prior to issuing an audit opinion (Knechel & Payne, Citation 2001 Knechel, W. R., & Payne, J. L.( 2001). Additional evidence on audit report lag. AUDITING: A Journal of Practice & Theory, 20(1), 137– 146. https://doi.org/10.2308/aud.2001.20.1.137[Crossref], [Web of Science ®] , [Google Scholar]). Then, Abernathy et al. ( Citation 2019 Abernathy, J. L., Finley, A. R., Rapley, E. T., & Stekelberg, J.( 2019). External Auditor Responses to Tax Risk. Journal of Accounting, Auditing & Finance, 36(3), 489– 516. https://doi.org/10.1177/0148558X19867821[Crossref], [Web of Science ®] , [Google Scholar]) found that tax risk is positively related to audit report delays at publicly listed companies in the United States. Tax risk is viewed by the auditor as an additional risk component for tax avoidance activities, which has the potential to exacerbate audit report lag. This is also related to the fact that auditors are required by auditing standards to perform risk assessments for their clients as part of the audit planning process (Abernathy et al., Citation 2019 Abernathy, J. L., Finley, A. R., Rapley, E. T., & Stekelberg, J.( 2019). External Auditor Responses to Tax Risk. Journal of Accounting, Auditing & Finance, 36(3), 489– 516. https://doi.org/10.1177/0148558X19867821[Crossref], [Web of Science ®] , [Google Scholar]). To summarize, while there has been a substantial amount of research into the causes of audit report lag, there is very little empirical evidence examining the relationship between tax risk and audit report lag (see Saragih & Ali, Citation 2021 Saragih, A. H., & Ali, S.( 2021). Corporate tax risk: A literature review and future research directions. Management Review Quarterly. https://doi.org/10.1007/s11301-021-00251-8 [Crossref] , [Google Scholar]).
2.2. Tax risks
Deloitte ( Citation 2017 Deloitte. ( 2017). Tax and the CTO or CIO(pp. 1–2). pp. 1– 2. Retrieved from https://www2.deloitte.com/content/dam/Deloitte/global/Documents/Tax/dttl-tax-and-the-cto-or-cio.pdf [Google Scholar]) the issue of corporate taxation is increasingly becoming the focus of regulatory, media, and public scrutiny. Corporate tax management, while capable of producing results in the form of tax savings, can also result in tax risks (tax uncertainty). On the one hand, risk-taking is a topic that has been researched for many years (Almustafa et al., Citation 2023 Almustafa, H., Kijkasiwat, P., Jreisat, A., Al-Mohamad, S., & Khaki, A. R.( 2023). Corporate risk-taking and national governance quality: Empirical evidence from MENA emerging markets. Cogent Business & Management, 10(1). https://doi.org/10.1080/23311975.2022.2156141[Taylor & Francis Online], [Web of Science ®] , [Google Scholar]; Thi Pham & Thi Dao, Citation 2022 Thi Pham, P. M., & Thi Dao, B. T.( 2022). A meta-analysis of risk taking and corporate performance. Cogent Business & Management, 9(1). https://doi.org/10.1080/23311975.2022.2064263[Taylor & Francis Online], [Web of Science ®] , [Google Scholar]). On the other hand, the concept of corporate tax risk (tax uncertainty) is relatively new and has not grown significantly in comparison to previous research on tax avoidance (Abernathy et al., Citation 2019 Abernathy, J. L., Finley, A. R., Rapley, E. T., & Stekelberg, J.( 2019). External Auditor Responses to Tax Risk. Journal of Accounting, Auditing & Finance, 36(3), 489– 516. https://doi.org/10.1177/0148558X19867821[Crossref], [Web of Science ®] , [Google Scholar]; Saragih & Ali, Citation 2021 Saragih, A. H., & Ali, S.( 2021). Corporate tax risk: A literature review and future research directions. Management Review Quarterly. https://doi.org/10.1007/s11301-021-00251-8 [Crossref] , [Google Scholar]).
Arlinghaus ( Citation 1998 Arlinghaus, B. P.( 1998). Goal setting and performance measures. Tax Executive, 50(6), 434– 441. Retrieved from. https://www.proquest.com/trade-journals/goal-setting-performance-measures/docview/212263485/se-2?accountid=17242 [Google Scholar]) defines tax risk as the possibility that tax outcomes differ from those expected for a variety of reasons, including judicial proceedings, changes in laws, changes in business assumptions, increased audit intensity, uncertainty in the interpretation of laws, and any actions taken by the tax function that expose the company to negative publicity. Several previous studies have reported on the determinants of tax risk, such as internal governance (Beasley et al., Citation 2021 Beasley, M. S., Goldman, N. C., Lewellen, C. M., & McAllister, M.( 2021). Board risk oversight and corporate tax-planning practices. Journal of Management Accounting Research, 33(1), 7– 32. https://doi.org/10.2308/JMAR-19-056[Crossref], [Web of Science ®] , [Google Scholar]; H. Chen et al., Citation 2020 Chen, H., Yang, D., Zhang, X., & Zhou, N.( 2020). The moderating role of internal control in tax avoidance: Evidence from a COSO-Based internal control index in China. Journal of the American Taxation Association, 42(1), 23– 55. https://doi.org/10.2308/atax-52408 [Crossref] , [Google Scholar]), managerial ability (Saragih & Ali, Citation 2023 Saragih, A. H., & Ali, S.( 2023). The impact of managerial ability on corporate tax risk and long-run tax avoidance: Empirical evidence from a developing country. Corporate Governance the International Journal of Business in Society. https://doi.org/10.1108/CG-08-2022-0346[Crossref], [Web of Science ®] , [Google Scholar]), in-house tax department (X. Chen et al., Citation 2021 Chen, X., Cheng, Q., Chow, T., & Liu, Y.( 2021). Corporate in-house tax departments. Contemporary Accounting Research, 38(1), 443– 482. https://doi.org/10.1111/1911-3846.12637[Crossref], [Web of Science ®] , [Google Scholar]), and auditors providing tax services (Watrin et al., Citation 2019 Watrin, C., Burggraef, S., & Weiss, F.( 2019). Auditor-provided tax services and accounting for tax uncertainty. The International Journal of Accounting, 54(3), 1950011. https://doi.org/10.1142/S1094406019500112[Crossref], [Web of Science ®] , [Google Scholar]), in accordance with this definition. The company’s tax risk is also determined by institutional factors. The institutional environment and tax supervision (W. Chen, Citation 2020 Chen, W.( 2020). Tax risks control and sustainable development: Evidence from China. Meditari Accountancy Research, 29(6), 1381– 1400. https://doi.org/10.1108/MEDAR-05-2020-0884[Crossref], [Web of Science ®] , [Google Scholar]), as well as tax rules and regulations (Towery, Citation 2017 Towery, E. M.( 2017). Unintended consequences of linking tax return disclosures to financial reporting for income taxes: Evidence from schedule UTP. The Accounting Review, 92(5), 201– 226. https://doi.org/10.2308/accr-51660[Crossref], [Web of Science ®] , [Google Scholar]), are among these institutional factors.
Tax risks can have far-reaching consequences for businesses (see Saragih & Ali, Citation 2021 Saragih, A. H., & Ali, S.( 2021). Corporate tax risk: A literature review and future research directions. Management Review Quarterly. https://doi.org/10.1007/s11301-021-00251-8 [Crossref] , [Google Scholar]). Tax risk is an important factor in investors’ evaluation of tax avoidance; if tax risk is low, the market reaction to tax avoidance will be positive (Drake et al., 2017). In addition, in the context of the debt market, tax risk raises the cost of debt, and the impact of tax avoidance on the cost of debt is also affected by the level of tax risk (Kovermann, Citation 2018 Kovermann, J. H.( 2018). Tax avoidance, tax risk and the cost of debt in a bank-dominated economy. Managerial Auditing Journal, 33(8–9), 683– 699. https://doi.org/10.1108/MAJ-12-2017-1734[Crossref], [Web of Science ®] , [Google Scholar]). Tax risk influences business investment (W. Chen, Citation 2021 Chen, W.( 2021). Too far east is west: Tax risk, tax reform and investment timing. International Journal of Managerial Finance, 17(2), 303– 326. https://doi.org/10.1108/IJMF-03-2020-0132[Crossref], [Web of Science ®] , [Google Scholar]), stock prices (Campbell et al., Citation 2019 Campbell, J. L., Cecchini, M., Cianci, A. M., Ehinger, A. C., & Werner, E. M.( 2019). Tax-related mandatory risk factor disclosures, future profitability, and stock returns. Review of Accounting Studies, 24(1), 264– 308. https://doi.org/10.1007/s11142-018-9474-y[Crossref], [Web of Science ®] , [Google Scholar]), general company risk (Lin et al., Citation 2019 Lin, X., Liu, M., So, S., & Yuen, D.( 2019). Corporate social responsibility, firm performance and tax risk. Managerial Auditing Journal, 34(9), 1101– 1130. https://doi.org/10.1108/MAJ-04-2018-1868[Crossref], [Web of Science ®] , [Google Scholar]), and overall company value (Jacob & Schütt, Citation 2020 Jacob, M., & Schütt, H. H.( 2020). Firm Valuation and the Uncertainty of Future Tax Avoidance. European Accounting Review, 29(3), 409– 435. https://doi.org/10.1080/09638180.2019.1642775[Taylor & Francis Online], [Web of Science ®] , [Google Scholar]; Moore, Citation 2021 Moore, R. D.( 2021). The concave association between tax reserves and equity value. Journal of the American Taxation Association, 43(1), 107– 124. https://doi.org/10.2308/JATA-17-109[Crossref], [Web of Science ®] , [Google Scholar]). Tax risk has an impact on the quality (Alsadoun et al., Citation 2018 Alsadoun, N., Naiker, V., Navissi, F., & Sharma, D. S.( 2018). Auditor-provided tax nonaudit services and the implied cost of equity capital. AUDITING: A Journal of Practice & Theory, 37(3), 1– 24. https://doi.org/10.2308/ajpt-51866[Crossref], [Web of Science ®] , [Google Scholar]) and readability of financial reports (Nguyen, Citation 2020 Nguyen, J. H.( 2020). Tax Avoidance and financial statement readability. European Accounting Review, 30(5), 1043– 1066. https://doi.org/10.1080/09638180.2020.1811745[Taylor & Francis Online], [Web of Science ®] , [Google Scholar]). As previously stated, tax risk is also closely related to audit report lag (Abernathy et al., Citation 2019 Abernathy, J. L., Finley, A. R., Rapley, E. T., & Stekelberg, J.( 2019). External Auditor Responses to Tax Risk. Journal of Accounting, Auditing & Finance, 36(3), 489– 516. https://doi.org/10.1177/0148558X19867821[Crossref], [Web of Science ®] , [Google Scholar]).
2.3. Hypothesis development
Companies’ timely release of financial information is an important aspect of financial reporting that plays a critical role in facilitating decision making by various parties, particularly investors. However, the presence of various tax risks may result in audit report delays (Abernathy et al., Citation 2019 Abernathy, J. L., Finley, A. R., Rapley, E. T., & Stekelberg, J.( 2019). External Auditor Responses to Tax Risk. Journal of Accounting, Auditing & Finance, 36(3), 489– 516. https://doi.org/10.1177/0148558X19867821[Crossref], [Web of Science ®] , [Google Scholar]). Auditors are required to identify, confirm, and assess various potential tax risks associated with the company as a client as part of a financial statement audit. If this is not done, the corporate tax risk may expose the auditor to negative publicity, causing the auditor’s reputation to suffer. As a result, auditors must evaluate the fairness of various transactions as well as the potential tax risks that may result. The possibility of auditors reporting material tax-related weaknesses in the client’s internal control is related to tax risk (Abernathy et al., Citation 2019 Abernathy, J. L., Finley, A. R., Rapley, E. T., & Stekelberg, J.( 2019). External Auditor Responses to Tax Risk. Journal of Accounting, Auditing & Finance, 36(3), 489– 516. https://doi.org/10.1177/0148558X19867821[Crossref], [Web of Science ®] , [Google Scholar]). Complex and complicated corporate tax activities raise the risk of financial reporting, resulting in higher audit fees and audit effort (Donohoe & Knechel, Citation 2014 Donohoe, M. P., & Knechel, W. R.( 2014). Does corporate tax aggressiveness influence audit pricing? Contemporary Accounting Research, 31(1), 284– 308. https://doi.org/10.1111/1911-3846.12027[Crossref], [Web of Science ®] , [Google Scholar]). Because of the additional risks, it is estimated that auditors’ legal liability would be increased due to the increased likelihood of errors and/or fraud in financial reports (Bajary et al., Citation 2023 Bajary, A. R., Shafie, R., & Ali, A.( 2023). COVID-19 Pandemic, Internal Audit Function and Audit Report Lag: Evidence from Emerging economy COVID-19 Pandemic, Internal Audit Function and Audit Report Lag: Evidence from Emerging economy. Cogent Business & Management, 10(1). https://doi.org/10.1080/23311975.2023.2178360[Taylor & Francis Online], [Web of Science ®] , [Google Scholar]). In addition, the likelihood of auditors failing to detect material misstatements may be increased (Bajary et al., Citation 2023 Bajary, A. R., Shafie, R., & Ali, A.( 2023). COVID-19 Pandemic, Internal Audit Function and Audit Report Lag: Evidence from Emerging economy COVID-19 Pandemic, Internal Audit Function and Audit Report Lag: Evidence from Emerging economy. Cogent Business & Management, 10(1). https://doi.org/10.1080/23311975.2023.2178360[Taylor & Francis Online], [Web of Science ®] , [Google Scholar]).
Auditors tailor their responses to potential tax risks based on the risk profile of the client. The greater the potential tax risk, the longer the audit takes to complete (Abernathy et al., Citation 2019 Abernathy, J. L., Finley, A. R., Rapley, E. T., & Stekelberg, J.( 2019). External Auditor Responses to Tax Risk. Journal of Accounting, Auditing & Finance, 36(3), 489– 516. https://doi.org/10.1177/0148558X19867821[Crossref], [Web of Science ®] , [Google Scholar]). This is possible because auditors must confirm and resolve any issues related to the presentation of tax-related accounts and estimates of corporate tax risk with management through discussions and negotiations. These critical steps will necessitate additional audit effort and time, resulting in longer audit delays for companies with high tax risk than for companies with low tax risk.
During an audit, the process of identifying various tax risks may also include investigations to management and company advisors. Management inquiries may not provide sufficient evidence (Liu et al., Citation 2021 Liu, H., Cullinan, C., & Zhang, J.( 2021). Litigation against clients and audit report lag: An examination of the role of state ownership and regional legal development in China. Managerial Auditing Journal, 36(5), 744– 769. https://doi.org/10.1108/MAJ-02-2020-2557[Crossref], [Web of Science ®] , [Google Scholar]). Furthermore, given the audit team’s limited access to information and knowledge, the audit team may find it difficult to develop their own estimate of the client’s tax risk. Auditors must also read the minutes of board meetings to determine whether the company’s potential tax risks are material. Furthermore, auditors will modify their response to pending litigation based on the risk profile of the client (Liu et al., Citation 2021 Liu, H., Cullinan, C., & Zhang, J.( 2021). Litigation against clients and audit report lag: An examination of the role of state ownership and regional legal development in China. Managerial Auditing Journal, 36(5), 744– 769. https://doi.org/10.1108/MAJ-02-2020-2557[Crossref], [Web of Science ®] , [Google Scholar]).
Previous research has found that the presence of contentious tax issues is positively related to late audit reports (Knechel & Payne, Citation 2001 Knechel, W. R., & Payne, J. L.( 2001). Additional evidence on audit report lag. AUDITING: A Journal of Practice & Theory, 20(1), 137– 146. https://doi.org/10.2308/aud.2001.20.1.137[Crossref], [Web of Science ®] , [Google Scholar]). Due to the increased potential risks, audit firms will be more cautious and stringent in their audit execution, increasing the audit scope and time allotted to their work (Bajary et al., Citation 2023 Bajary, A. R., Shafie, R., & Ali, A.( 2023). COVID-19 Pandemic, Internal Audit Function and Audit Report Lag: Evidence from Emerging economy COVID-19 Pandemic, Internal Audit Function and Audit Report Lag: Evidence from Emerging economy. Cogent Business & Management, 10(1). https://doi.org/10.1080/23311975.2023.2178360[Taylor & Francis Online], [Web of Science ®] , [Google Scholar]). Higher audit risk necessitates more audit effort in the form of additional procedural tests (Gontara & Khlif, Citation 2020 Gontara, H., & Khlif, H.( 2020). Tax avoidance and audit report lag in South Africa: The moderating effect of auditor type. Journal of Financial Crime, 28(3), 732– 740. https://doi.org/10.1108/JFC-09-2020-0197 [Crossref] , [Google Scholar]) and unfavorable audit outcomes (Rasheed et al., Citation 2021 Rasheed, P. C., Hawaldar, A., T, I., T, M., & Ntim, C. G.( 2021). Related party transactions and audit risk. Cogent Business & Management, 8(1). https://doi.org/10.1080/23311975.2021.1888669[Taylor & Francis Online], [Web of Science ®] , [Google Scholar]). Auditors responded by conducting more audit tests in order to reduce the tax risk, implying a longer audit delay. Auditors may spend additional hours completing audits to combat increased business risk, thus increasing audit report lag. Previous research indicates that auditors devote more audit resources to clients who face higher tax risks (Abernathy et al., Citation 2019 Abernathy, J. L., Finley, A. R., Rapley, E. T., & Stekelberg, J.( 2019). External Auditor Responses to Tax Risk. Journal of Accounting, Auditing & Finance, 36(3), 489– 516. https://doi.org/10.1177/0148558X19867821[Crossref], [Web of Science ®] , [Google Scholar]; Knechel & Payne, Citation 2001 Knechel, W. R., & Payne, J. L.( 2001). Additional evidence on audit report lag. AUDITING: A Journal of Practice & Theory, 20(1), 137– 146. https://doi.org/10.2308/aud.2001.20.1.137[Crossref], [Web of Science ®] , [Google Scholar]). In this study, the hypothesis is thus stated formally as follows.
H 1Tax risk has a positive effect on audit report lag
3. Research method
3.1. Sample and data sources
To test the hypothesis, a quantitative approach was used in this study. The sample was restricted to Indonesia Stock Exchange (IDX) companies. In Indonesia, the obligations for the listed companies to convey their financial reports are regulated by the IDX (Saragih & Ali, Citation 2022a Saragih, A. H., & Ali, S.( 2022a). The effect of XBRL adoption on corporate tax avoidance: Empirical evidence from an emerging country. Journal of Financial Reporting and Accounting, Ahead-Of-P(ahead-Of-Print). https://doi.org/10.1108/jfra-09-2021-0281 [Crossref] , [Google Scholar]). Furthermore, purposive sampling was used, which meant that only companies meeting certain criteria could be included in the sample (see Table 1). The study lasted from 2012 to 2017. The observation data for this study was obtained from the Thomson Reuters and Osiris databases.
The effect of tax risk on audit report delay: Empirical evidence from Indonesia
Table 1.Sample selection procedure
The Indonesian context makes for an intriguing study setting. There are three reasons why to use data from Indonesia. First, based on information from the World Bank Open Data, Indonesia is currently in the top 20 of the world’s economic growth (measured as Gross Domestic Product-GDP), and in the last ten years (from 2010–2019), it has become the highest GDP contributor in ASEAN (Association of Southeast Asian Nations). Second, in terms of taxation, according to publicly available data released by the Tax Justice Network in 2020, most emerging countries, including several ASEAN countries, have a relatively high tax revenue loss. Based on the data, Indonesia has a corporate effective tax rate of roughly 21.18% (despite the statutory corporate tax rate of 25%), and is a country with the highest tax loss in ASEAN (see, e.g., Cobham et al., Citation 2020 Cobham, A., Bernardo, J. G., Palansky, M., & Mansour, M. B.( 2020). The State of Tax Justice 2020: Tax Justice in the time of COVID-19. Tax Justice Network, ( November), 1– 83. Retrieved from https://www.taxjustice.net/reports/the-state-of-tax-justice-2020/ [Google Scholar]). In other words, it is a fact that Indonesia is among the countries with high levels of tax avoidance in ASEAN (see, e.g., Cobham et al., Citation 2020 Cobham, A., Bernardo, J. G., Palansky, M., & Mansour, M. B.( 2020). The State of Tax Justice 2020: Tax Justice in the time of COVID-19. Tax Justice Network, ( November), 1– 83. Retrieved from https://www.taxjustice.net/reports/the-state-of-tax-justice-2020/ [Google Scholar]). Nevertheless, there is a possibility that the tax uncertainty of firms in Indonesia (as a developing country) is also relatively low. Zeng ( Citation 2019 Zeng, T.( 2019). Country-level governance, accounting standards, and tax avoidance: A cross-country study. Asian Review of Accounting, 27(3), 401– 424. https://doi.org/10.1108/ARA-09-2018-0179[Crossref], [Web of Science ®] , [Google Scholar]) states that companies in emerging countries are less likely to engage in tax avoidance than companies in emerged countries. Companies that are less aggressive in their tax avoidance face less tax uncertainty, and vice versa (Dyreng et al., Citation 2019 Dyreng, S. D., Hanlon, M., & Maydew, E. L.( 2019). When does tax avoidance result in tax uncertainty? The Accounting Review, 94(2), 179– 203. https://doi.org/10.2308/accr-52198[Crossref], [Web of Science ®] , [Google Scholar]).
Third, the corporate tax rate applicable in Indonesia until 2019 is relatively high in ASEAN, at around 25%, which remains in effect until March 2020 (from then onward, the tax rate applied will be 22%). The relatively high corporate tax rate set by the tax regulator may encourage tax avoidance practices, potentially increasing the firm’s tax risks. Previous studies have shown that a specific level of tax avoidance is possible with a wide range of risks (Drake et al., Citation 2019 Drake, K. D., Lusch, S. J., & Stekelberg, J.( 2019). Does Tax Risk Affect Investor Valuation of Tax Avoidance? Journal of Accounting, Auditing & Finance, 34(1), 151– 176. https://doi.org/10.1177/0148558X17692674[Crossref], [Web of Science ®] , [Google Scholar]; Guenther et al., Citation 2017 Guenther, D. A., Matsunaga, S. R., & Williams, B. M.( 2017). Is tax avoidance related to firm risk? The Accounting Review, 92(1), 115– 136. https://doi.org/10.2308/accr-51408[Crossref], [Web of Science ®] , [Google Scholar]; Hamilton & Stekelberg, Citation 2017 Hamilton, R., & Stekelberg, J.( 2017). The effect of high-quality information technology on corporate tax avoidance and tax risk. Journal of Information Systems, 31(2), 83– 106. https://doi.org/10.2308/isys-51482[Crossref], [Web of Science ®] , [Google Scholar]), including tax risks. In addition, in the last five years, Indonesia has experienced an issue regarding a change in the corporate income tax rate from 25% to 22%. It also has an element of tax uncertainty (tax risk). The regulator’s announcement of a lower corporate tax rate may have an impact on the company’s tax position. As is well known, when the government announced its plan to reduce the statutory tax rate, many businesses began to prepare to manage profits in this manner. The company will shift income or expenses to more favorable figures in the future (so that the aggregate tax savings obtained are still optimal). A reduction in tax rates has the potential to create tax uncertainty (tax risk). Such uncertainty includes the potential for a company not to be successful in defending its tax position when challenged by the tax authority. Tax uncertainty (tax risk) can also arise when the tax authority has not fully confirmed the tax position figures submitted by the taxpayer. Defining or interpreting proper tax position management is a major point of contention between taxpayers and tax authority (Bame-Aldred et al. Citation 2013 Bame-Aldred, C. W., Cullen, J. B., Martin, K. D., & Parboteeah, K. P.( 2013). National culture and firm-level tax evasion. Journal of Business Research, 66(3), 390– 396. https://doi.org/10.1016/j.jbusres.2011.08.020[Crossref], [Web of Science ®] , [Google Scholar]).
3.2. Model specification and variable definitions
This study examined whether tax risk has a positive impact on audit report lag. We estimated the following regression model to test the hypothesis.
A R L i t = β 0 + β 1 B T D V i t + β 2 C A E Q i t + β 3 D E R i t + β 4 E P S i t + β 5 A G E i t + β 6 S I Z E i t + β 7 S A L E S i t + β 8 R O A i t + β 9 L O S S i t + β 10 B I G F i t + ε i tTo estimate the dependent variable, audit report lag (ARL) was calculated as the logarithm of the number of days between the fiscal year’s end and the date of the audit report. Our primary focus was on corporate tax risk by using book-tax-differences volatility (BTDV). We used a volatility basis for tax risk proxies as the main independent variable, as Hamilton and Stekelberg ( Citation 2017 Hamilton, R., & Stekelberg, J.( 2017). The effect of high-quality information technology on corporate tax avoidance and tax risk. Journal of Information Systems, 31(2), 83– 106. https://doi.org/10.2308/isys-51482[Crossref], [Web of Science ®] , [Google Scholar]) and Lin et al. ( Citation 2019 Lin, X., Liu, M., So, S., & Yuen, D.( 2019). Corporate social responsibility, firm performance and tax risk. Managerial Auditing Journal, 34(9), 1101– 1130. https://doi.org/10.1108/MAJ-04-2018-1868[Crossref], [Web of Science ®] , [Google Scholar]) did. Volatility was frequently used as a risk indicator (Mathew et al., Citation 2018 Mathew, S., Ibrahim, S., & Archbold, S.( 2018). Corporate governance and firm risk. Corporate Governance (Bingley), 18(1), 52– 67. https://doi.org/10.1108/CG-02-2017-0024[Crossref], [Web of Science ®] , [Google Scholar]). The tax risk reflected the degree to which tax avoidance was volatile (Hamilton & Stekelberg, Citation 2017 Hamilton, R., & Stekelberg, J.( 2017). The effect of high-quality information technology on corporate tax avoidance and tax risk. Journal of Information Systems, 31(2), 83– 106. https://doi.org/10.2308/isys-51482[Crossref], [Web of Science ®] , [Google Scholar]). In this regard, we used volatility based on book-tax differences as a basis. BTD is the difference between pre-tax and taxable income. Taxable income was calculated by dividing income tax expenses by the statutory tax rate. Specifically, we used the three-year (year t-1 to t + 1) standard deviation of BTD/total assets to quantify the corporate tax risk (see Saragih & Ali, Citation 2022b Saragih, A. H., & Ali, S.( 2022b). The role of XBRL adoption on the association between managerial ability and corporate tax outcomes: Empirical evidence from Indonesia. Journal of Applied Accounting Research, 24(2), 217– 234. https://doi.org/10.1108/JAAR-10-2021-0267[Crossref], [Web of Science ®] , [Google Scholar], Citation 2023 Saragih, A. H., & Ali, S.( 2023). The impact of managerial ability on corporate tax risk and long-run tax avoidance: Empirical evidence from a developing country. Corporate Governance the International Journal of Business in Society. https://doi.org/10.1108/CG-08-2022-0346[Crossref], [Web of Science ®] , [Google Scholar]). Greater volatility values indicate higher levels of tax risk (Hamilton & Stekelberg, Citation 2017 Hamilton, R., & Stekelberg, J.( 2017). The effect of high-quality information technology on corporate tax avoidance and tax risk. Journal of Information Systems, 31(2), 83– 106. https://doi.org/10.2308/isys-51482[Crossref], [Web of Science ®] , [Google Scholar]). In this model, a positive and significant β 1suggested that tax risk positively impacted the corporate tax risk.
In addition, we included a common set of control variables in our models to see if they could account for economies of scale, macro-level factors, and firm complexity. Previous studies on audit reports documented other variables such as firm cash and equivalent (CAEQ), firm debt (DER), firm market performance (EPS), firm age (AGE), firm size (SIZE), firm sales (SALES), firm profitability (ROA), a dummy variable for loss-making companies (LOSS), and a dummy variable for companies audited by the Big 4 (BIGF). Big 4 audit firms are known for employing higher-quality staff, superior technology, and more efficient audit planning and resources, and they are expected to provide a better and faster audit process than non-Big 4 firms (Gontara & Khlif, Citation 2020 Gontara, H., & Khlif, H.( 2020). Tax avoidance and audit report lag in South Africa: The moderating effect of auditor type. Journal of Financial Crime, 28(3), 732– 740. https://doi.org/10.1108/JFC-09-2020-0197 [Crossref] , [Google Scholar]).Appendix Acontains a summary of variable definitions.
3.3. Data analysis
The Winsorizing procedure was used as the first step in data analysis. This step was applied to all continuous variables in order to validate observations containing extreme outlier data (Gallemore & Labro, Citation 2015 Gallemore, J., & Labro, E.( 2015). The importance of the internal information environment for tax avoidance. Journal of Accounting and Economics, 60(1), 149– 167. https://doi.org/10.1016/j.jacceco.2014.09.005[Crossref], [Web of Science ®] , [Google Scholar]). The Winsorizing procedure was used to replace the extreme data values of a variable with data values at the specified percentiles, with limits set at the 5th and 95th percentiles. To process the data, we used Stata statistical software. Several statistical analyses were presented, including descriptive statistics to describe data patterns and correlation matrices to identify potential multicollinearity problems.
Then, to gain more meaningful insights, we ran a regression analysis using the model described above. We use the fixed effect method in particular (seeAppendix B). Furthermore, because there is evidence that the residual model is non-normal, heteroscedastic (seeAppendix C), and autocorrelative (seeAppendix D), our study employs a robust standard error for regression analysis (Koester et al., Citation 2016 Koester, A., Shevlin, T., & Wangerin, D.( 2016). The role of managerial ability in corporate tax avoidance. Management Science, 63(10), 1– 27. https://doi.org/10.1287/mnsc.2016.2510 [Web of Science ®] , [Google Scholar]). Finally, this research includes additional tests to ensure that our findings are consistent and reliable.
4. Result, discussion, and implications
4.1. Descriptive statistics and correlation analysis
Table 2shows descriptive statistics for the variables in the research model. Audit report lag (ARL) has a minimum value of 1.69, a mean value of 1.88, and a maximum value of 2.05, with a standard deviation of around 0.08. Furthermore, tax risk (BTDV) has a minimum value of 0.00, a mean value of 0.05, and a maximum value of 0.26, with a relatively small standard deviation of around 0.06. ARL and BTDV have low standard deviation values. This demonstrates that our sample companies have relatively low cross-company variations in terms of audit report lag and tax risk.
The effect of tax risk on audit report delay: Empirical evidence from Indonesia
Table 2.Descriptive statistics
The correlation matrix for this study is shown in Table 3. The correlation coefficients are all less than 0.8 (see Gujarati & Porter, Citation 2009 Gujarati, D. N., & Porter, D. C.( 2009). Basic Econometrics( fifthed.). McGraw-Hill. [Google Scholar]). Furthermore, we report the statistics of Variance Inflation Factor (VIF) and Tolerance, which are all less than 10 and 1, respectively (see Gujarati & Porter, Citation 2009 Gujarati, D. N., & Porter, D. C.( 2009). Basic Econometrics( fifthed.). McGraw-Hill. [Google Scholar]). These results show that our model has no multicollinearity issues (see Gujarati & Porter, Citation 2009 Gujarati, D. N., & Porter, D. C.( 2009). Basic Econometrics( fifthed.). McGraw-Hill. [Google Scholar]).
Table 3.Correlation matrix, variance inflation factor, and tolerance
4.2. Regression result
Table 4displays the research model’s estimation results. The coefficient value of the tax risk variable in this model is not significant ( p= 0.285). This implies that the impact of tax risk on audit report lag is nil. As a result, the hypothesis is not supported. This finding contradicts previous research findings that show that companies with a high tax risk have a longer audit report lag (see Abernathy et al., Citation 2019 Abernathy, J. L., Finley, A. R., Rapley, E. T., & Stekelberg, J.( 2019). External Auditor Responses to Tax Risk. Journal of Accounting, Auditing & Finance, 36(3), 489– 516. https://doi.org/10.1177/0148558X19867821[Crossref], [Web of Science ®] , [Google Scholar]). Meanwhile, only the control variables ROA and BIGF have a significant impact on audit report lag. The audit report lag has a negative relationship with company profitability (ROA). Companies audited by the Big 4 (BIGF), on the other hand, have a positive relationship with audit report lag.
The effect of tax risk on audit report delay: Empirical evidence from Indonesia
All authors
Eko Suwardi& Arfah Habib Saragih
Table 4.Primary regression results a
4.3. Discussion and implications
As with the regression results, we show that tax risk has no effect on audit report lag for Indonesian listed firms. The reason for this is that there is a possibility that corporate tax risk in Indonesia is relatively low. Several factors can contribute to the relatively low tax risk. First, it is possible that businesses have well-implemented tax management and tax risk management. Companies can save money on taxes while minimizing their tax liabilities. This low tax risk can also be attributed to tax avoidance activities, which can also be regarded as relatively safe and not overly aggressive (see descriptive statistical data from the study of Kanagaretnam et al., Citation 2016 Kanagaretnam, K., Lee, J., Lim, C. Y., & Lobo, G. J.( 2016). Relation between auditor quality and tax aggressiveness: Implications of cross-country institutional differences. AUDITING: A Journal of Practice & Theory, 35(4), 105– 135. https://doi.org/10.2308/ajpt-51417[Crossref], [Web of Science ®] , [Google Scholar], Citation 2018 Kanagaretnam, K., Lee, J., Lim, C. Y., & Lobo, G. J.( 2018). Cross-Country Evidence on the Role of Independent Media in Constraining Corporate Tax Aggressiveness. Journal of Business Ethics, 150(3), 879– 902. https://doi.org/10.1007/s10551-016-3168-9[Crossref], [Web of Science ®] , [Google Scholar]; Zeng, Citation 2019 Zeng, T.( 2019). Country-level governance, accounting standards, and tax avoidance: A cross-country study. Asian Review of Accounting, 27(3), 401– 424. https://doi.org/10.1108/ARA-09-2018-0179[Crossref], [Web of Science ®] , [Google Scholar]; Hasan et al., Citation 2022 Hasan, I., Kim, I., Teng, H., & Wu, Q.( 2022). The effect of foreign institutional ownership on corporate tax avoidance: International evidence. Journal of International Accounting, Auditing and Taxation, 46, 100440. https://doi.org/10.1016/j.intaccaudtax.2021.100440 [Crossref] , [Google Scholar]dan Li et al., Citation 2022 Li, Q., Maydew, E. L., Willis, R. H., & Xu, L.( 2022). Taxes and director independence: Evidence from board reforms worldwide. Review of Accounting Studies. https://doi.org/10.1007/s11142-021-09660-2[Crossref], [Web of Science ®] , [Google Scholar]). Companies that are less aggressive in their tax avoidance face less tax uncertainty, and vice versa (Dyreng et al., Citation 2019 Dyreng, S. D., Hanlon, M., & Maydew, E. L.( 2019). When does tax avoidance result in tax uncertainty? The Accounting Review, 94(2), 179– 203. https://doi.org/10.2308/accr-52198[Crossref], [Web of Science ®] , [Google Scholar]). The Indonesian tax authority requires a corporate income tax rate of 25% (from 2010 to 2019). According to the 2020 National Tax Justice report, Indonesia has a high corporate effective tax rate of around 21.18% (Cobham et al., Citation 2020 Cobham, A., Bernardo, J. G., Palansky, M., & Mansour, M. B.( 2020). The State of Tax Justice 2020: Tax Justice in the time of COVID-19. Tax Justice Network, ( November), 1– 83. Retrieved from https://www.taxjustice.net/reports/the-state-of-tax-justice-2020/ [Google Scholar]). This indicates that there is only a small amount of tax avoidance, which is approximately 3.82% (25%-21.18%).
A certain level of tax avoidance is possible with a wide range of risks (Drake et al., Citation 2019 Drake, K. D., Lusch, S. J., & Stekelberg, J.( 2019). Does Tax Risk Affect Investor Valuation of Tax Avoidance? Journal of Accounting, Auditing & Finance, 34(1), 151– 176. https://doi.org/10.1177/0148558X17692674[Crossref], [Web of Science ®] , [Google Scholar]; Guenther et al., Citation 2017 Guenther, D. A., Matsunaga, S. R., & Williams, B. M.( 2017). Is tax avoidance related to firm risk? The Accounting Review, 92(1), 115– 136. https://doi.org/10.2308/accr-51408[Crossref], [Web of Science ®] , [Google Scholar]; Hamilton & Stekelberg, Citation 2017 Hamilton, R., & Stekelberg, J.( 2017). The effect of high-quality information technology on corporate tax avoidance and tax risk. Journal of Information Systems, 31(2), 83– 106. https://doi.org/10.2308/isys-51482[Crossref], [Web of Science ®] , [Google Scholar]). Furthermore, creditors seem to associate tax avoidance to risk-generating practices (Khuong et al., Citation 2020 Khuong, N. V., Liem, N. T., Thu, P. A., Khanh, T. H. T., & Ntim, C. G.( 2020). Does corporate tax avoidance explain firm performance? Evidence from an emerging economy. Cogent Business & Management, 7(1), 1780101. https://doi.org/10.1080/23311975.2020.1780101[Taylor & Francis Online], [Web of Science ®] , [Google Scholar]). Aggressive tax avoidance by businesses has the potential to increase corporate risk (Guenther et al., Citation 2017 Guenther, D. A., Matsunaga, S. R., & Williams, B. M.( 2017). Is tax avoidance related to firm risk? The Accounting Review, 92(1), 115– 136. https://doi.org/10.2308/accr-51408[Crossref], [Web of Science ®] , [Google Scholar]), including the implications for accounting and auditing, as well as audit risk (Mills & Sansing, Citation 2000 Mills, L. F., & Sansing, R. C.( 2000). Strategic Tax and Financial Reporting Decisions: Theory and Evidence. Contemporary Accounting Research, 17(1), 85– 106. https://doi.org/10.1111/j.1911-3846.2000.tb00912.x [Crossref] , [Google Scholar]). Aggressive tax avoidance has the potential to increase tax risk, such as increasing the risk of being investigated more thoroughly and intensively by tax authority. As risks become more visible, managers’ proclivity for risk avoidance makes them accountable for managing them in a better manner (Jankensgård, Citation 2019 Jankensgård, H.( 2019). A theory of enterprise risk management. Corporate Governance (Bingley), 19(3), 565– 579. https://doi.org/10.1108/CG-02-2018-0092[Crossref], [Web of Science ®] , [Google Scholar]). Executives will attempt and plan to maximize corporate tax savings while minimizing tax risk (e.g., Lin et al., Citation 2019 Lin, X., Liu, M., So, S., & Yuen, D.( 2019). Corporate social responsibility, firm performance and tax risk. Managerial Auditing Journal, 34(9), 1101– 1130. https://doi.org/10.1108/MAJ-04-2018-1868[Crossref], [Web of Science ®] , [Google Scholar]).
Second, it is possible that the complexity of corporate tax planning in Indonesia is low enough that it does not affect the complexity of the audit and the amount of effort expended by the auditor to examine the client’s tax accounts, including potential tax risk. Due to the low complexity of corporate tax planning, matters relating to various corporate transactions and associated taxation aspects are relatively easier to track accountability.
Third, it is possible that the complexity of tax regulations stipulated by the Indonesian tax authority is low. Thus, it does not drive large tax risks on the corporate side. The most common source of tax risk is systematic changes in tax laws (e.g., tax rates, tax benefits, calculation procedures and timing of tax payments). In Indonesia, corporate tax regulations are dominated by one major central tax, namely the corporate income tax. Tax regulations tend to be easier for companies as taxpayers to implement. This makes it easier for managers to enforce tax account accountability more precisely and mitigate tax risks better. This in turn facilitates the auditors to be able to carry out and complete their audit work in a more-timely manner.
This study has a number of implications. The following are the implications for the company’s management. Companies are encouraged to improve the effectiveness of their corporate governance on a continuous basis. Good corporate governance has a crucial role in enhancing the quality of timeliness of financial reports (Fakhfakh Sakka et al., Citation 2016 Fakhfakh Sakka, I., Jarboui, A., & Bisogno, M.( 2016). Audit reports timeliness: Empirical evidence from Tunisia. Cogent Business & Management, 3(1), 1195680. https://doi.org/10.1080/23311975.2016.1195680[Taylor & Francis Online], [Web of Science ®] , [Google Scholar]). Good corporate governance entails how the board of directors and management operate and demonstrate their commitment to an adequate internal control and risk management system (Kassem, Citation 2022 Kassem, R.( 2022). Elucidating corporate governance’s impact and role in countering fraud. Corporate Governance (Bingley), 22(7), 1523– 1546. https://doi.org/10.1108/CG-08-2021-0279[Crossref], [Web of Science ®] , [Google Scholar]). The understanding of risk by board members is heavily reliant on their experience and knowledge of their environment (Światowiec-Szczepańska & Stępień, Citation 2022 Światowiec-Szczepańska, J., & Stępień, B.( 2022). Impact of corporate network position on strategic risk and company’s performance – evidence from Poland. Corporate Governance (Bingley), 22(5), 947– 978. https://doi.org/10.1108/CG-02-2021-0061[Crossref], [Web of Science ®] , [Google Scholar]). Members of the supervisory board are made aware of the company’s risk position through regular reports on the risk appetite and risk profile (Światowiec-Szczepańska & Stępień, Citation 2022 Światowiec-Szczepańska, J., & Stępień, B.( 2022). Impact of corporate network position on strategic risk and company’s performance – evidence from Poland. Corporate Governance (Bingley), 22(5), 947– 978. https://doi.org/10.1108/CG-02-2021-0061[Crossref], [Web of Science ®] , [Google Scholar]). The overall risk exposure of a business entity is a significant result of executive investment decisions and actions (Al-Shammari & Akram, Citation 2021 Al-Shammari, H. A., & Akram, U.( 2021). CEO compensation and firm performance: The mediating effects of CEO risk taking behaviour. Cogent Business & Management, 8(1). https://doi.org/10.1080/23311975.2021.1894893[Taylor & Francis Online], [Web of Science ®] , [Google Scholar]).
Appropriate corporate risk management practices are important (Kabuye et al., Citation 2019 Kabuye, F., Bugambiro, N., Akugizibwe, I., Nuwasiima, S., Naigaga, S., & Ntim, C. G.( 2019). The influence of tone at the top management level and internal audit quality on the effectiveness of risk management practices in the financial services sector. Cogent Business & Management, 6(1). https://doi.org/10.1080/23311975.2019.1704609[Taylor & Francis Online], [Web of Science ®] , [Google Scholar]; Kiptoo et al., Citation 2021 Kiptoo, I. K., Kariuki, S. N., Ocharo, K. N., & McMillan, D.( 2021). Risk management and financial performance of insurance firms in Kenya. Cogent Business & Management, 8(1). https://doi.org/10.1080/23311975.2021.1997246 [Web of Science ®] , [Google Scholar]), and should be encouraged to ensure compliance (Kafidipe et al., Citation 2021 Kafidipe, A., Uwalomwa, U., Dahunsi, O., Okeme, F. O., & Ntim, C. G.( 2021). Corporate governance, risk management and financial performance of listed deposit money bank in Nigeria. Cogent Business & Management, 8(1). https://doi.org/10.1080/23311975.2021.1888679[Taylor & Francis Online], [Web of Science ®] , [Google Scholar]), including tax compliance. Improved tax compliance necessitates a thorough understanding of the tax risk dynamics (Boateng et al., Citation 2022 Boateng, K., Omane-Antwi, K. B., & Ndori Queku, Y.( 2022). Tax risk assessment, financial constraints and tax compliance: A bibliometric analysis. Cogent Business & Management, 9(1). https://doi.org/10.1080/23311975.2022.2150117[Taylor & Francis Online], [Web of Science ®] , [Google Scholar]). In a two-tier model, the supervisory board is critical in understanding risk management and audit issues (Światowiec-Szczepańska & Stępień, Citation 2022 Światowiec-Szczepańska, J., & Stępień, B.( 2022). Impact of corporate network position on strategic risk and company’s performance – evidence from Poland. Corporate Governance (Bingley), 22(5), 947– 978. https://doi.org/10.1108/CG-02-2021-0061[Crossref], [Web of Science ®] , [Google Scholar]), such as tax risk and audit report lag. Internal control and risk management are important in reducing company risk, including tax risk. Furthermore, to mitigate differences in financial accounting standards and tax regulations, it is necessary to strengthen internal controls and information systems for tax harmonization and reconciliation.
As is well known, the calculation of corporate income tax refers to the self-assessment system that is governed by law. Companies, as taxpayers, are responsible for calculating, depositing, and reporting taxes in accordance with existing regulations. Tax risks associated with compliance risk are fully entrusted to taxpayers before tax authority discovers that there are different data through the data matching process. Tax risk mitigation is typically performed prior to filing a tax return by a business entity based on the interpretation of the taxpayer filing the tax return. Tax risks arising from different legal interpretations and tax disputes occur after taxpayers file tax returns and the tax authority conducts material compliance monitoring to identify potential tax risks arising from different interpretation points of view. Companies, as taxpayers, are encouraged to carry out routine tax risk mitigation on various transactions. Its form is to investigate tax issues that may arise from the transaction scheme in accordance with the draft contract that the parties to the agreement will agree on. Companies are also encouraged to conduct tax reviews and tax control on tax obligations that have been implemented using a data matching approach on a regular basis.
The finding of this study may have implications for tax authority as well. The finding of this study is actually a good sign for the tax authority. Companies that have a low tax risk complete and submit their financial reports more quickly. As a result, the finalization of corporate tax obligations with tax authority is also expedited. Thus, tax collection performance on the tax regulator side has improved. Consequently, tax authority is strongly encouraged to keep tax regulations simple, not complicated, and not changing too frequently. The more complex and complicated the tax system becomes, the greater the cost of compliance (Musimenta & Ntim, Citation 2020 Musimenta, D., & Ntim, C. G.( 2020). Knowledge requirements, tax complexity, compliance costs and tax compliance in Uganda. Cogent Business & Management, 7(1), 1812220. https://doi.org/10.1080/23311975.2020.1812220[Taylor & Francis Online], [Web of Science ®] , [Google Scholar]). As a result, the company faces little tax risk as a potential taxpayer. Various tax-related transactions involving the acquisition of income and expenses in the company have become clearer. Accounts related to corporate taxes are also easily clarified by auditors who work to audit.
Furthermore, it is critical for tax authority to continuously improve the effectiveness of the tax audit and monitoring function in order to keep future corporate tax risks to a minimum. Moreover, as a measure to mitigate the growing corporate tax risks in the future, tax authority may require minimum disclosure regarding corporate tax risks. Risk disclosure is becoming increasingly important for all users of corporate financial statements and annual reports in general (Saggar & Singh, Citation 2017 Saggar, R., & Singh, B.( 2017). Corporate governance and risk reporting: Indian evidence. Managerial Auditing Journal, 32(4–5), 378– 405. https://doi.org/10.1108/MAJ-03-2016-1341[Crossref], [Web of Science ®] , [Google Scholar]). The importance of risk disclosure has piqued the interest of policymakers and standard setters all over the world (Raimo et al., Citation 2022 Raimo, N., NIcolò, G., Tartaglia Polcini, P., & Vitolla, F.( 2022). Corporate governance and risk disclosure: Evidence from integrated reporting adopters. Corporate Governance (Bingley), 22(7), 1462– 1490. https://doi.org/10.1108/CG-07-2021-0260[Crossref], [Web of Science ®] , [Google Scholar]).
5. Robustness checks
We ran two robustness tests on both models. This robustness test was required to determine the stability of our conclusions and to validate the main finding (Beasley et al., Citation 2021 Beasley, M. S., Goldman, N. C., Lewellen, C. M., & McAllister, M.( 2021). Board risk oversight and corporate tax-planning practices. Journal of Management Accounting Research, 33(1), 7– 32. https://doi.org/10.2308/JMAR-19-056[Crossref], [Web of Science ®] , [Google Scholar]; Hamilton & Stekelberg, Citation 2017 Hamilton, R., & Stekelberg, J.( 2017). The effect of high-quality information technology on corporate tax avoidance and tax risk. Journal of Information Systems, 31(2), 83– 106. https://doi.org/10.2308/isys-51482[Crossref], [Web of Science ®] , [Google Scholar]). First, we examine the robustness of the main finding using another proxy for tax risk, namely effective tax risk volatility (ETRV). Second, we test the robustness of the main results by including three control variables (market-to-book; net property, plant, and equipment; and free cash flows). AppendixAcontains information on the definition and measurement of these extra variables. Based on the results in Table 5, the series of robustness examination results are consistent with our main finding in Table 4.
The effect of tax risk on audit report delay: Empirical evidence from Indonesia
Table 5.Robustness checks regression results a
6. Conclusion, limitations, and suggestions for future research
This study investigates whether tax risk influences audit report delays in Indonesian public companies. According to the finding of this study, tax risk is not a significant predictor of audit report lag. We present detailed evidence that the economically significant consequence of tax risk does not exist in listed firms in a developing country such as Indonesia. The research finding is significant from the standpoint of corporate risk management, which is defined as decision making and implementation of actions that result in a relatively low level of tax risk and are controllable by the company.
The authors recognize that this work should be interpreted with one major caveat in mind. We only use one metric to evaluate audit outcomes, namely audit report lag. The audit fees construct cannot be used in conjunction with the audit report lag construct. This is due to the fact that audit fees are rarely disclosed in annual reports in Indonesia. If we insist on using audit fees, the number of observations will be drastically reduced. Then, this study only included a sample of publicly traded companies from a single developing country (Indonesia).
We recommend several future research directions. As is well known, the finding of our study differ from those of Abernathy et al. ( Citation 2019 Abernathy, J. L., Finley, A. R., Rapley, E. T., & Stekelberg, J.( 2019). External Auditor Responses to Tax Risk. Journal of Accounting, Auditing & Finance, 36(3), 489– 516. https://doi.org/10.1177/0148558X19867821[Crossref], [Web of Science ®] , [Google Scholar]). Abernathy et al. ( Citation 2019 Abernathy, J. L., Finley, A. R., Rapley, E. T., & Stekelberg, J.( 2019). External Auditor Responses to Tax Risk. Journal of Accounting, Auditing & Finance, 36(3), 489– 516. https://doi.org/10.1177/0148558X19867821[Crossref], [Web of Science ®] , [Google Scholar]) found a link between tax risk and audit report delays in a developed country. Meanwhile, our finding shows that there is no link between tax risk and audit report lag in a developing country. These inconsistencies are worth further investigation. There are several moderating variables that could be used to clarify the relationship between the two constructs. Several aspects of corporate governance, in our opinion, can mitigate the impact of tax risk on audit report lag. For example, the effectiveness of board oversight and audit committees is expected to improve the relationship between tax risk and audit report lag. Finally, future research can also replicate and expand our study by involving the effect of COVID-19 (see Bajary et al., Citation 2023 Bajary, A. R., Shafie, R., & Ali, A.( 2023). COVID-19 Pandemic, Internal Audit Function and Audit Report Lag: Evidence from Emerging economy COVID-19 Pandemic, Internal Audit Function and Audit Report Lag: Evidence from Emerging economy. Cogent Business & Management, 10(1). https://doi.org/10.1080/23311975.2023.2178360[Taylor & Francis Online], [Web of Science ®] , [Google Scholar]).
Table 1.Sample selection procedure
<table><tr><th> Selection procedure</th><th> Firm-year</th></tr><tbody><tr><td> Initial observation, companies with complete financial reports and annual reports, period 2012 to 2017</td><td> 2,094</td></tr><tr><td> Less: observations with missing data for audit report lag</td><td> (39)</td></tr><tr><td> Less: observations with missing data for tax risk</td><td> (242)</td></tr><tr><td> Number of final observations (period 2012 to 2017), firm-year</td><td> 1,813</td></tr></tbody></table>
Table 2.Descriptive statistics
<table><tr><th> Variable</th><th> Obs.</th><th> Mean</th><th> Std. dev.</th><th> Min</th><th> Max</th></tr><tbody><tr><td> ARL</td><td> 1,813</td><td> 1.8844</td><td> 0.0867</td><td> 1.6990</td><td> 2.0569</td></tr><tr><td> BTDV</td><td> 1,813</td><td> 0.0511</td><td> 0.0675</td><td> 0.0038</td><td> 0.2633</td></tr><tr><td> CAEQ</td><td> 1,813</td><td> 0.0886</td><td> 0.0871</td><td> 0.0038</td><td> 0.3077</td></tr><tr><td> DER</td><td> 1,813</td><td> 1.2787</td><td> 1.2480</td><td> 0.0085</td><td> 5.0229</td></tr><tr><td> EPS</td><td> 1,813</td><td> 55.5980</td><td> 117.3895</td><td> −67.7090</td><td> 450.1130</td></tr><tr><td> AGE</td><td> 1,813</td><td> 2.7690</td><td> 0.4858</td><td> 1.7918</td><td> 3.3322</td></tr><tr><td> SIZE</td><td> 1,813</td><td> 19.8522</td><td> 3.5972</td><td> 12.0142</td><td> 24.0322</td></tr><tr><td> SALES</td><td> 1,813</td><td> 0.8265</td><td> 0.6351</td><td> 0.0679</td><td> 2.3827</td></tr><tr><td> ROA</td><td> 1,813</td><td> 0.0462</td><td> 0.0849</td><td> −0.1220</td><td> 0.2278</td></tr><tr><td> LOSS</td><td> 1,813</td><td> 0.2642</td><td> 0.4410</td><td> 0</td><td> 1</td></tr><tr><td> BIGF</td><td> 1,813</td><td> 0.4054</td><td> 0.4911</td><td> 0</td><td> 1</td></tr></tbody></table>
Table 3.Correlation matrix, variance inflation factor, and tolerance
<table><tr><th colspan=13> Panel A. Correlation matrix</th></tr><tr><th> BTDV</th><th> CAEQ</th><th> DER</th><th colspan=2> EPS</th><th> AGE</th><th colspan=2> SIZE</th><th> SALES</th><th> ROA</th><th> LOSS</th><th> BIGF</th></tr><tbody><tr><td> BTDV</td><td> 1.000</td></tr><tr><td> CAEQ</td><td> −0.168</td><td> 1.000</td></tr><tr><td> DER</td><td> −0.003</td><td> −0.201</td><td> 1.000</td></tr><tr><td> EPS</td><td> −0.190</td><td> 0.281</td><td> −0.133</td><td colspan=2> 1.000</td></tr><tr><td> AGE</td><td> 0.027</td><td> −0.034</td><td> −0.073</td><td colspan=2> 0.170</td><td> 1.000</td></tr><tr><td> SIZE</td><td> −0.177</td><td> 0.087</td><td> −0.050</td><td colspan=2> 0.338</td><td> 0.088</td><td colspan=2> 1.000</td></tr><tr><td> SALES</td><td> −0.153</td><td> 0.089</td><td> 0.151</td><td colspan=2> 0.115</td><td> 0.151</td><td colspan=2> −0.058</td><td> 1.000</td></tr><tr><td> ROA</td><td> −0.321</td><td> 0.403</td><td> −0.210</td><td colspan=2> 0.553</td><td> 0.065</td><td colspan=2> 0.216</td><td> 0.307</td><td> 1.000</td></tr><tr><td> LOSS</td><td> 0.352</td><td> −0.245</td><td> 0.115</td><td colspan=2> −0.395</td><td> −0.046</td><td colspan=2> −0.226</td><td> −0.206</td><td> −0.699</td><td> 1.000</td></tr><tr><td> BIGF</td><td> −0.153</td><td> 0.121</td><td> 0.014</td><td colspan=2> 0.184</td><td> 0.112</td><td colspan=2> 0.012</td><td> 0.187</td><td> 0.252</td><td> −0.099</td><td> 1.000</td></tr><tr><td colspan=13> Panel B. Variance inflation factor (VIF) and Tolerance</td></tr><tr><td> Mean</td><td> CAEQ</td><td colspan=2> DER</td><td> EPS</td><td> AGE</td><td> SIZE</td><td colspan=2> SALES</td><td> ROA</td><td> LOSS</td><td> BIGF</td></tr><tr><td> VIF</td><td> 1.50</td><td> 1.24</td><td colspan=2> 1.15</td><td> 1.61</td><td> 1.08</td><td> 1.17</td><td colspan=2> 1.24</td><td> 2.92</td><td> 2.01</td><td> 1.11</td></tr><tr><td> Tolerance</td><td> 0.67</td><td> 0.81</td><td colspan=2> 0.87</td><td> 0.62</td><td> 0.92</td><td> 0.86</td><td colspan=2> 0.81</td><td> 0.34</td><td> 0.50</td><td> 0.90</td></tr></tbody></table>
Table 4.Primary regression results a
Note: aRobust standard error is used due to the non-normality and heteroscedasticity of residuals.
bPanel regression using fixed-effect method.
***represent significance at level 0.01
Table 5.Robustness checks regression results a
Note: aRobust standard error is used due to the non-normality and heteroscedasticity of residuals.
bPanel regression using the fixed effect method.
**and *** represent significance at levels 0.10, 0.05, and 0.01
Additional information
Notes on contributors
EkoSuwardiEko Suwardi is an Associate Professor with the Department of Accounting, Faculty of Economics and Business, Universitas Gadjah Mada, Indonesia. He earned a Doctor of Philosophy from Queensland University of Technology, Australia, and a Master of Science from California State University, Fresno, United States of America, and a Bachelor of Accounting from the Accounting Department, Faculty of Economics and Business Universitas Gadjah Mada. His research interests include taxation, financial accounting, auditing, public sector accounting, corporate governance, and business ethics.
Arfah HabibSaragihArfah Habib Saragih is currently pursuing a doctoral degree with the Doctoral Program, Faculty of Economics and Business, Universitas Gadjah Mada, Indonesia. She received a Master of Accounting Science degree in 2014 and a Bachelor of Accounting in 2010 from the Accounting Department, Faculty of Economics and Business, Universitas Indonesia. She is currently an Assistant Professor with the Department of Fiscal Administration, Faculty of Administrative Sciences, Universitas Indonesia. Her research interests centre on tax administration, corporate tax, information technology governance, accounting information systems, and corporate governance.
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Appendices
The effect of tax risk on audit report delay: Empirical evidence from Indonesia
Appendix B. Model selection for main regression model
The effect of tax risk on audit report delay: Empirical evidence from Indonesia
Appendix C. Heteroscedasticity test for main regression model
The effect of tax risk on audit report delay: Empirical evidence from Indonesia
Appendix D. Autocorrelation test for main regression model
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SS Charter | IEEE CASS
1. Preamble
The Sensory Systems Technical Committee (SSTC or the Committee or the TC) is a Technical Committee of the IEEE Circuits and Systems Society (CASS or the Society). As a subsidiary committee of IEEE CASS, the SSTC is governed by the rules and regulations of the IEEE and by the Constitution and Bylaws of CASS, which take precedence over this Charter in case of conflict.
TCs are established by IEEE CASS in significant fields of interest of the Society, through its Technical Activities Division (TAD), to advance the state of knowledge and educate Society members and the general IEEE membership. To these ends, the SSTC plays a major role in creating a high quality technical program for the Society’s flagship conference, the International Symposium on Circuits and Systems (ISCAS). TCs also may organize or contribute to other workshops and conferences, special sessions at conferences, and tutorial programs, and undertake other activities to help better achieve their purpose.
Further, the SSTC may act as a bridge between CASS and related IEEE Societies and Councils, and other institutions in the general area of the TC.
2. Purpose
The purpose of the SSTC is to foster research, development, education and dissemination of knowledge relating to the field of sensors and associated processing systems. The activity is multidisciplinary, drawing upon knowledge and expertise from fields such as biology, physics, mechanics and chemistry, in addition to areas more traditionally associated with the IEEE such as electrical and computer engineering, computer science and information technology.
3. Activities
The SSTC activities include:
Organizing that part of the technical program of ISCAS related to the SSTC field; this includes review of all papers submitted to ISCAS in tracks on topics in the field of Sensory Systems (appointing TPC Track Chairs, Review Committee Members [RCMs] and paper reviewers), and arranging Tutorials, Special Sessions, Workshops and other sessions
Nominating individuals for (1) Society Awards, (2) Editorial appointments, (3) Distinguished Lecturer appointments, and (4) roles as CASS representatives for Steering and other Committees arising from joint efforts with other Societies and Councils
Nominating papers for CASS journal Best Paper awards
Preparing the TC Annual Report
Preparing information for periodic Review of the TC by the Society
Maintaining the TC website
Reviewing and, if needed, updating the TC Vision & Mission statements at least every 5 years
Assessing the quality and helping to maintain/raise the quality of any CASS-sponsored conferences in the field
Other activities to help achieve the Purpose
4. Membership
4.1 Any CASS or IEEE member of good standing and willing to perform the duties of membership may seek to join the SSTC. Membership requires nomination by a current member and is approved by a majority of voting members either present at the Committee's Annual Meeting or by internet ballot of the membership. All new member nominees should attend the TC meeting at ISCAS and express their interest to be active members.
4.2 A member is said to be active if they participate at least once every two years in one of the following: (i) attending the TC meeting; (ii) serving as Review Committee Member or Best Paper judge for ISCAS paper submissions in the SSTC tracks; (iii) actively contribute to another activity carried out by the TC, as listed in Clause 3 Activities (a) to (i) of this Charter.
4.3 A member is said to be inactive if they have not participated in one of the aforementioned activities for two consecutive years. The Chair-Elect will email all members that appear to be inactive to verify their status and encourage them to become active. Members who do not respond or who give sufficient cause for a 2 year lack of activity yet fail to contribute for a 3rd consecutive year will automatically be removed from the Committee.
4.4 The TC will maintain and publish annually the TC Roll of Members, including email addresses, a record of attendance at the Annual Meeting and participation in activities.
5. Duties and Election of Officers
5.1 The Committee shall have five officers: Chair, Chair-Elect, Past Chair, Secretary and Secretary-Elect. Each will serve a two-year term.
5.2 The Chair, supported by the Chair-Elect, is responsible for:(a) ensuring that the purpose of the TC is well achieved through timely and diligent execution of the activities,(b) ensuring that the TC operates according to all other aspects of its Charter, and(c) establishing the TC Chair as a well-known channel of communication between the TC and the CASS Board of Governors.
5.3 The Chair will preside over Committee meetings and will be responsible for all interactions with the Society. They will report on Committee activities to the CASS Board of Governors, through the CASS Vice President for Technical Activities, at least once a year, before ISCAS.
5.4 The Chair is a member of the CASS Technical Activities Division (TAD) and will attend the Annual Meeting of the TAD, normally held at the ISCAS site during or shortly before the symposium.
5.5 The Chair will oversee all activities of the TC, calling on assistance from the Chair-Elect and other members as necessary, and will be responsible in particular for: chairing the ISCAS Sensory Systems Track; soliciting and making the TC’s nominations of individuals for awards, editorial appointments, Distinguished Lecturer and CASS representative roles; soliciting and making the TC’s nominations for Best Paper Awards; preparing the TC Annual Report; preparing material for and participating in periodic TC Reviews; and maintaining the TC vision and mission; i.e. for aforementioned Clause 3 Activities (a), (b), (c), (d), (e) and (g).
5.6 The Chair-Elect will assist the Chair as necessary in conducting the business of the Committee. They will participate in the TC Review meeting, and co-chair the ISCAS Sensory Systems Track. They will be responsible in particular for: maintaining/raising the quality of CASS-sponsored conferences in the TC field, and other activities undertaken by the TC; i.e. for aforementioned Clause 3 Activities (h) and (i).
5.7 The Secretary will be responsible for recording meeting minutes and their expeditious posting on the TC website. The Secretary will assist the Chair in the preparation of the TC Annual Report and will attend to membership issues including maintaining the member roll of the TC. They will be responsible for ensuring the TC web site is maintained, i.e. for aforementioned Clause 3 Activity (f).
5.8 The Secretary-Elect will assist the Secretary in their duties.
5.9 The Past Chair will advise the Chair in transacting the business of the committee. The Past Chair assumes his/her position immediately after the ISCAS following their two-year term as Chair.
5.10 The Chair is normally not directly elected and is filled by transition of the Chair-Elect at the end of their two-year term. An out-of-sequence election for the Chair can be held should the Chair-Elect be unable to assume the role of Chair.
5.11 The Chair-Elect is elected by the Committee members and must be a member of the Committee. They will serve a two-year term as Chair-Elect commencing immediately after the ISCAS of their election. At the end of their term the Chair-Elect will become the Chair.
5.12 Chair-Elect nominations can be made by any Member of the TC. Any nominations must be received by the Chair three weeks before the general TC meeting.
5.13 The Secretary is normally not directly elected and is filled by transition of the Secretary-Elect at the end of their two-year term. An out-of-sequence election for the Secretary can be held should the Secretary-Elect be unable to assume the role of Secretary.
5.14 The Secretary-Elect is elected by the Committee members and must be a member of the Committee. They will serve a two-year term as Secretary-Elect commencing immediately after the ISCAS of their election. At the end of their term the Secretary-Elect will become the Secretary. The nominations for Secretary-Elect can be made by any Member of the TC and must be received by the Chair two weeks before the general TC meeting.
6. Meetings and Conduct of Business
6.1 Business relevant to this Charter may be conducted at meetings or by ballot via the internet. Meetings may be held in-person, typically at a conference, or by electronic means.
A meeting quorum is Ceiling function of one third of the TC members attending the meeting.
A minimum of two weeks notice of any Motions shall be provided to voting members prior to the close of voting to allow members to consider the issues, except for matters arising at or immediately before the TC meeting, or as otherwise provided in Clause 7 of this Charter.
A majority of the legal votes cast by the TC members attending a meeting with a quorum is necessary to approve a Motion, except as otherwise provided in Clause 7 of this Charter.
For internet ballots, voting by a minimum of one-half of the TC members is a valid ballot.
If a quorum is not reached, tentative actions may be taken which will become effective after subsequent ratification, either by internet ballot or at a subsequent meeting.
6.3 The Committee Annual Meeting shall be held at ISCAS. Any CASS or IEEE member is allowed to attend this Annual Meeting as an observer; the Chair may invite other observers to attend and speak.
6.4 At the Annual Meeting,
An agenda is circulated prior to the meeting
The Chair will present an annual report on membership, activities, and progress on achieving the TC vision and mission
TC members will vote to elect new Members and new Officers if any
The members may discuss any other business relevant to the TC Charter
The members may vote on Motions provided the required notice periods are met; a quorum is needed to resolve any Motions at the meeting
6.5 Outside of the meetings, the Officers can, upon a majority vote (provided that at least one of the Officers has to be the Chair or Chair-Elect), undertake unplanned business on behalf of the TC, provided that these activities do not require formal committee approval and that they be reported to the TC at the next meeting.
7. Charter Amendments
7.1 Any charter amendment, including closing the SSTC, can be considered at a meeting provided that the Chair and Chair-Elect have been notified at least one month prior to the Meeting. Approval by the Officers is not necessary, but notification is required. An approved amendment will take effect the day following the conclusion of the ISCAS meeting when it has been approved.
7.2 Motions to Amend the Charter and to Close (i.e. shut down) the TC have special conditions to be consistent with CASS and IEEE rules. The conditions for such ballots at a meeting and by internet ballot differ:
(a) Internet Ballot: voting by a minimum of one half of the TC members is a valid ballot; a two-thirds majority is required to pass the Motion
(b) Ballot at TC Meeting: a Special Quorum of the Ceiling function of one-half of the TC members at the meeting is required; a two-thirds majority is required to pass the Motion.
Approved by SSTC members on 24.05.2016
| https://ieee-cas.org/technical-committee/SS/ss-charter |
Long-Term Impact of Neonatal Breastfeeding on Childhood Adiposity and Fat Distribution Among Children Exposed to Diabetes In Utero | Diabetes Care | American Diabetes Association
OBJECTIVE. To evaluate whether breastfeeding attenuates increased childhood adiposity associated with exposure to diabetes in utero.RESEARCH DESIGN AND METHODS.
Long-Term Impact of Neonatal Breastfeeding on Childhood Adiposity and Fat Distribution Among Children Exposed to Diabetes In Utero
Tessa L. Crume, PHD
1 Department of Epidemiology, Colorado School of Public Health, University of Colorado Denver, Aurora, Colorado
Lorraine Ogden, PHD
Lorraine Ogden, PHD
1 Department of Epidemiology, Colorado School of Public Health, University of Colorado Denver, Aurora, Colorado
MaryBeth Maligie, BS
MaryBeth Maligie, BS
1 Department of Epidemiology, Colorado School of Public Health, University of Colorado Denver, Aurora, Colorado
;
Shelly Sheffield, MS
1 Department of Epidemiology, Colorado School of Public Health, University of Colorado Denver, Aurora, Colorado
Kimberly J. Bischoff, MSHA
;
Kimberly J. Bischoff, MSHA
2 Health Services and Behavioral Research, Kaiser Permanente of Colorado, Denver, Colorado
Robert McDuffie, MD
;
Robert McDuffie, MD
2 Health Services and Behavioral Research, Kaiser Permanente of Colorado, Denver, Colorado
Stephen Daniels, MD
;
Stephen Daniels, MD
3 Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado
Richard F. Hamman, MD
;
Richard F. Hamman, MD
1 Department of Epidemiology, Colorado School of Public Health, University of Colorado Denver, Aurora, Colorado
Jill M. Norris, PHD
;
Jill M. Norris, PHD
1 Department of Epidemiology, Colorado School of Public Health, University of Colorado Denver, Aurora, Colorado
Google Scholar
Dana Dabelea, MD
Dana Dabelea, MD
1 Department of Epidemiology, Colorado School of Public Health, University of Colorado Denver, Aurora, Colorado
Corresponding author: Dana Dabelea, [email protected] .
Corresponding author: Dana Dabelea, [email protected] .
Diabetes Care 2011;34(3):641–645
https://doi.org/10.2337/dc10-1716
Article history
Received:
September 03 2010
Accepted:
October 31 2010
PubMed:
21357361
Connected Content
Tessa L. Crume ,Lorraine Ogden ,MaryBeth Maligie ,Shelly Sheffield ,Kimberly J. Bischoff ,Robert McDuffie ,Stephen Daniels ,Richard F. Hamman ,Jill M. Norris ,Dana Dabelea; Long-Term Impact of Neonatal Breastfeeding on Childhood Adiposity and Fat Distribution Among Children Exposed to Diabetes In Utero. Diabetes Care1 March 2011; 34 (3): 641–645.https://doi.org/10.2337/dc10-1716
OBJECTIVE
To evaluate whether breastfeeding attenuates increased childhood adiposity associated with exposure to diabetes in utero.
RESEARCH DESIGN AND METHODS
Retrospective cohort study of 89 children exposed to diabetes in utero and 379 unexposed youth with measured BMI, waist circumference, skinfolds, visceral (VAT) and subcutaneous (SAT) abdominal fat. A measure of breast milk–months was derived from maternal self-report and used to categorize breastfeeding status as low (<6) and adequate (≥6 breast milk–months). Multiple linear regression was used to model the relationship between exposure to diabetes in utero and offspring adiposity outcomes among youth stratified according to breastfeeding status.
RESULTS
Adequate (vs. low) breastfeeding status was associated with significantly lower BMI, waist circumference, SAT, and VAT at ages 6–13 years. Among youth in the low breastfeeding category, exposure to diabetes in utero was associated with a 1.7 kg/m 2higher BMI ( P= 0.03), 5.8 cm higher waist circumference ( P= 0.008), 6.1 cm 2higher VAT ( P= 0.06), 44.6 cm 2higher SAT ( P= 0.03), and 0.11 higher ratio of subscapular-to-triceps skinfold ratio ( P= 0.008). Among those with adequate breastfeeding in infancy, the effect of prenatal exposure to diabetes on childhood adiposity outcomes was not significant.
CONCLUSIONS
Adequate breastfeeding protects against childhood adiposity and reduces the increased adiposity levels associated with exposure to diabetes in utero. These data provide support for mothers with diabetes during pregnancy to breastfeed their infants in order to reduce the risk of childhood obesity.
Children born to mothers with diabetes during pregnancy have been shown to have a greater prevalence of obesity in childhood, both among populations at high risk for obesity and type 2 diabetes, such as American Indian youth (1,2), as well as among multiethnic populations (3,4). These youth may be “programmed” in utero for later development of obesity by exposure to excess maternal glucose (and other fuels) at a critical period of development (i.e., the fetal over-nutrition hypothesis) (5). Infancy has been suggested as another critical period for future obesity risk. Large epidemiologic studies suggest that the early postnatal weeks of life are a critical period for determining levels and distribution of adiposity, a time when breast-fed infants often lose weight and formula-fed infants tend to gain weight (6,7). The relationship between breastfeeding and long-term obesity risk has been extensively studied, and breastfeeding is now promoted as an important prevention strategy with considerable public health benefits. Meta-analyses have estimated an effect size of 13–22% reduced odds for overweight or obesity in childhood and later in life associated with having been breast-fed (8). A dose-response effect was reported by Harder et al. (9) describing a 4% reduction in childhood obesity risk for each additional month of breastfeeding (95% CI [−0.06 to −0.02]). A systematic review and meta-analysis (10) quantified a protective effect on risk for type 2 diabetes in later life for subjects who were breast-fed compared with those formula-fed (7 studies; 76,744 subjects; odds ratio [OR] 0.61 [95% CI 0.44–0.85]; P =0.003). However, the question of whether breastfeeding may actually reduce the risk of future obesity conferred by fetal overnutrition, as marked by exposure to diabetes in utero, is inconclusive. The objective of this study was to evaluate if breastfeeding is protective against childhood obesity and whether it attenuates the association between exposure to diabetes in utero and adiposity parameters in a multiethnic cohort of youth from Colorado.
RESEARCH DESIGN AND METHODS
Study design and eligibility criteria
This article uses data from a retrospective cohort study, Exploring Perinatal Outcomes among Children (EPOCH), which was conducted in Colorado. Participants were 6–13 years of age; the multiethnic offspring of singleton pregnancies; born at a single hospital in Denver, Colorado, between 1992 and 2002; whose biological mothers were members of the Kaiser Permanente of Colorado Health Plan (KPCO); and who were still KPCO members and living in Colorado over the study period (2006–2009).
For this analysis, eligible participants were children exposed to diabetes in utero (exposed group) and a random sample of children not exposed to diabetes in utero without intrauterine growth restriction (defined as birth weight for gestational age score < the 10th percentile) (unexposed group). Children and their biological mothers were invited for a research visit between January 2006 and October 2009. The study was approved both by the Colorado Multiple Institutional Review Board and Human Participant Protection Program. All participants provided written informed consent, and youth provided written assent.
Exposure definition
Physician-diagnosed maternal diabetes status was ascertained from the KPCO Perinatal database, an electronic database linking the neonatal and perinatal medical records, as described previously. The database contains data that define delivery events for each woman. Gestational diabetes mellitus (GDM) is coded as present if diagnosed through the standard KPCO screening protocol (described below) and absent if screening was negative. At 24–28 weeks, all pregnant women are offered screening with a 1-h 50-g oral glucose tolerance test (OGTT). A value ≥140 mg/dL identifies patients who undergo a 3-h 100-g diagnostic OGTT. GDM is diagnosed when two or more glucose values during the diagnostic OGTT meet or exceed the criteria for a positive test as recommended by the National Diabetes Data Group (11). Exposure to diabetes in utero was defined as the presence of preexistent diabetes or GDM diagnosed during the index pregnancy. In addition, birth weight, gestational age, and maternal prepregnancy weight were also obtained from the database.
Breastfeeding status
At the study visits, mothers were queried about breast- and formula-feeding, timing, and the introduction of other solid foods and beverages. Because of the high levels of reported mixed feeding, a measure of breast milk–months was developed that incorporated duration and exclusivity. For exclusively breast-fed infants, duration was equal to the age of the child (months) when breastfeeding was stopped. For infants that were ever fed formula, mothers were asked to classify their infant feeding as formula only, more formula than breast milk, equal breast milk and formula, or more breast milk than formula. Breastfeeding exclusivity was quantified using weights from 0 to 1, with exclusive breastfeeding having a weight of 1 and exclusive formula-feeding having a weight of 0. For infants fed both breast milk and formula, exclusivity was equal to 0.25 for “more formula than breast milk”; 0.50 for “formula and breast milk equally”; and 0.75 for “more breast milk than formula.” The breast milk–months measure incorporated duration and exclusivity to estimate an overall breast milk dose equivalent in months. It was the sum of months of exclusive breastfeeding and the weighted months of mixed breast milk and formula (duration of exclusive breastfeeding [months] + duration of mixed breast- and formula-feeding [months] × exclusivity weight). Breastfeeding status was categorized as low (<6 breast milk–months) and adequate (≥6 breast milk–months) based on American Academy of Pediatrics recommendations (12). Maternal recall of breastfeeding after periods of time spanning between 9 and 20 years has been found to correlate well with infant feeding data obtained from medical records ( r= 0.86) (13) or collected prospectively ( r= 0.95) (14).
Measures of childhood adiposity and fat distribution
Childhood height and weight were measured in light clothing and without shoes. Weight was measured to the nearest 0.1 kg using an electronic scale. Height was measured to the nearest 0.1 cm using a portable stadiometer. BMI was calculated as kg/m 2. Waist circumference was measured to the nearest 1 mm at the midpoint between the lower ribs and the pelvic bone with a metal or fiberglass nonspring-loaded tape measure. Skinfolds were measured in triplicate using Holtain calipers (average: subscapular, ∼20 mm below the tip of the scapula; triceps, halfway between the acromion process and the olecranon process). The subscapular-to-triceps skinfold ratio (STR) was calculated to assess regional differences in subcutaneous fat distribution. Magnetic resonance imaging of the abdominal region was used to quantify visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) with a 3T HDx imager (General Electric, Waukashau, WI) by a trained technician. Each study participant was placed supine and a series of T1-weighted coronal images were taken to locate the L4/L5 plane. One axial, 10-mm, T1-weighted image at the umbilicus or L4/L5 vertebra was analyzed to determine SAT and VAT content. The analysis technique used was a modification of the technique of Engelson, where adipose tissue regions were differentiated by their signal intensity and location (i.e., not internal contents of bowel). Images were analyzed by a single reader, blinded to exposure status.
Other measurements
Race/ethnicity was self-reported using 2000 U.S. Census-based questions and categorized as Hispanic (any race), non-Hispanic white, or non-Hispanic African American. Pubertal development was assessed by child self-report with a diagrammatic representation of Tanner staging adapted from Marshall and Tanner (15). Youth were categorized as Tanner <2 (prepubertal) and ≥2 (pubertal). Maternal level of education and total household income were self-reported during the research office visit.
Statistical analysis
All analyses were conducted using SAS v.9.2 (SAS Institute, Cary, NC). Results are presented as means ± SD. Group differences were analyzed using χ 2test. Multiple linear regression was conducted to examine the association between exposure to maternal diabetes in utero and measures of offspring adiposity (BMI, waist circumference, VAT, SAT, and STR), controlling for potential confounders. In determining the best model for the relationship between adiposity outcomes and in utero diabetes exposure, a significant interaction between age and Tanner stage on VAT was noted ( P= 0.0008), suggesting that the effect of age on childhood adiposity depends on pubertal development. Because such an effect was reported previously in the literature (16,17), an interaction term between age and Tanner stage was included in our model for all outcomes of interest.
Stratified analyses were conducted to explore the association between exposure to diabetes in utero and childhood adiposity outcomes in offspring with low versus adequate breastfeeding. A formal test for heterogeneity was used to assess whether associations were significantly different.
RESULTS
A total of 89 youth exposed to diabetes in utero (91% with GDM) and 379 unexposed youth participated in the study and had complete data on variables of interest. The mean ± SD age of exposed youth was 9.6 ± 1.7 years and 10.6 ± 1.3 for unexposed youth ( P< 0.0001) at the study visit. Exposed youth were more likely to be non-Hispanic white or Hispanic ( P= 0.04), and a larger proportion of exposed youth self-reported a Tanner stage <2, indicating they were prepubertal (71.1 vs. 50.8%, P= 0.0005). Mothers with diabetes during pregnancy were, on average, older ( P< 0.0001) than mothers whose pregnancies were not complicated by diabetes. Exposed and unexposed offspring were not significantly different in terms of intrauterine growth and socio-economic factors or infant feeding practices (Table 1).
Table 2shows the association between breastfeeding status (low vs. adequate) and adiposity outcomes among offspring exposed and unexposed to diabetes in utero. Both exposed and unexposed youth who had adequate breastfeeding (≥6 breast milk–months) had significantly lower BMI, waist circumference, SAT, and VAT at ages 6–13 years than those with <6 breast milk–months. The only adiposity parameter that did not show a statistically significant relationship with breastfeeding was STR ( P= 0.26 and P= 0.72, respectively, in exposed and unexposed participants), though the pattern was similar.
Figure 1shows the associations between exposure to diabetes in utero and adiposity outcomes stratified by breastfeeding status and adjusted for age, sex, Tanner stage, and Tanner by age interaction. Among adolescents with low breastfeeding status (<6 breast milk–months), exposure to diabetes in utero was associated with a 1.7 kg/m 2higher BMI ( P= 0.03); 5.8 cm higher waist circumference ( P= 0.008); 6.1 cm 2higher VAT ( P= 0.06); 44.6 cm 2higher SAT ( P= 0.03); and 0.11 higher STR ( P= 0.008). The association between exposure to diabetes in utero and the adiposity parameters was substantially reduced and not significant for adolescents with adequate breastfeeding in infancy (≥6 breast milk–months) with a 0.7 kg/m 2lower BMI ( P= 0.4); 2.7 cm higher waist circumference ( P= 0.1); 2.1 cm 2higher VAT ( P= 0.4); 23.4 cm 2higher SAT ( P= 0.11); and 0.05 higher STR ( P= 0.14) among exposed versus unexposed children.
CONCLUSIONS
We found that adequate breastfeeding (≥6 breast milk–months) was associated with lower BMI, waist circumference, and SAT levels in a multiethnic population of youth 6–13 years of age from Colorado. Moreover, our study provides novel evidence that the effect of exposure to diabetes in utero on childhood adiposity parameters is substantially attenuated by breastfeeding, such that the obesity outcomes in exposed youth who were adequately breast-fed were similar to those of unexposed youth. Our data suggest that breastfeeding promotion may be an effective strategy for reducing the increased risk of childhood obesity in the offspring of mothers with diabetes during pregnancy.
The current literature on the impact of breastfeeding for the offspring of diabetic women is inconclusive. Plagemann et al. (18) suggested an adverse effect of breastfeeding during the first 7 days of life on relative weight at 2 years of age among offspring of women with type 1 diabetes and GDM. However, a follow-up of this study was conducted by Rodekamp et al. (19) with an extended assessment of breastfeeding exposure beyond the first week of life. The researchers found that neither dose of breast milk nor duration of breastfeeding among offspring of type 1 diabetic women was associated with increased risk of overweight or impaired glucose tolerance at 2 years of age. In another study, Kerssen et al. (20) showed no effect of breast milk, formula, or mixed feeding on the weight or BMI of offspring exposed to type 1 diabetes during pregnancy at 1 year of age. In contrast, among 15,253 offspring of the 1989 Nurses’ Health Study II, Mayer-Davis et al. (21) reported a protective OR of 0.63 (95% CI 0.50–0.78) for overweight at 12 years of age for breastfeeding duration of ≥9 versus <9 months. OR for overweight among offspring exposed to GDM in utero who were exclusively breast-fed compared with those exclusively formula-fed was 0.62 (0.24–1.60). Among Pima Indians, Pettitt and Knowler (22) found a substantial reduction (30.1 vs. 43.6%) in type 2 diabetes among the offspring exposed to diabetes in utero if they were breast-fed for at least 2 months compared with those who were bottle-fed. A similar reduction was observed among Pima offspring not exposed to in utero diabetes (6.9 and 11.9% among offspring of nondiabetic women who were breast-fed and bottle-fed, respectively).
The early postnatal period may represent a critical period for the future obesity risk in childhood (23) and adult life (6). The macronutrient composition of breast milk (i.e., protein, fat, carbohydrate) and bioactive substances not present in formula may influence metabolic programming and regulation of body fatness and growth rate. Higher insulin levels (24) and lower leptin levels (25) have been reported in formula-fed infants compared with breast-fed babies. The effect of breastfeeding on infant growth may be an important determinant of early life programming for future obesity and chronic disease, especially for the offspring of diabetic pregnancies.
Our study adds to the limited body of evidence by suggesting that breastfeeding attenuates the unfavorable effects on childhood adiposity parameters conferred by exposure to maternal diabetes. Importantly, all measures of adiposity were influenced including the more sensitive VAT and SAT. The mechanisms that trigger adipose tissue deposition in specific locations at different periods of fetal development or in childhood remain unclear. Identification of strategies to alter the long-term development of fat deposition and accumulation are necessary to minimize the significant increased morbidity risk associated with childhood obesity. Fetal life and early infancy both represent critical periods when obesity begins and may be effectively minimized by targeted prevention strategies.
Our study had some limitations. An a priori power calculation suggested that, with 100 exposed individuals, our study had 80% power to detect a difference in the effect of exposure to diabetes in utero on childhood BMI according to breastfeeding status (an interaction) of 0.4 BMI units. The observed difference in our study was 0.5 BMI units; however, the difference was not statistically significant, possibly because of the slightly smaller achieved sample of exposed individuals. This suggests that we had limited power to detect a statistically significant effect of breastfeeding in modifying the association between exposure to diabetes in utero and childhood adiposity. Nevertheless, our findings of an attenuation of the effect of in utero exposure on childhood adiposity by breastfeeding was robust and consistent across various measures of adiposity including BMI, waist circumference, SAT, VAT, and fat distribution. Similar effects were noted regardless of how our breastfeeding variable was defined (i.e., breastfeeding yes/no, duration in months, etc.; data not shown). Moreover, our study had several important strengths including state-of-the-art assessment of childhood adiposity and fat distribution, a validated exposure assessment, and an assessment of breast milk dose that incorporated breastfeeding exclusivity and duration.
In conclusion, our study found no deleterious effects of breastfeeding among a diverse group of children exposed to diabetes in utero. In contrast, we suggest that breastfeeding may be protective against the increased childhood adiposity associated with intrauterine diabetes exposure. Further work is needed to confirm this finding in larger populations, and to determine if the reductions in adiposity continue into adulthood.
See accompanying editorial, p. 779.
Acknowledgments
This work was supported by National Institutes of Health Grant R01-DK068001 (principal investigator D.D.). The study sponsor had no role in the study.
No potential conflicts of interest relevant to this article were reported.
T.L.C. researched data and wrote the manuscript. L.O. reviewed and edited the manuscript and advised on analysis. M.M. researched data. S.S. researched data. K.J.B. researched data. R.M. reviewed the manuscript. S.D. reviewed and edited the manuscript. R.F.H. reviewed and edited the manuscript. J.M.N. reviewed and edited the manuscript. D.D. contributed to discussion and reviewed and edited the manuscript.
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Data & Figures
Figure 1
A– E: Effect of exposure to diabetes in utero on mean levels of childhood adiposity parameters. Stratified by breastfeeding (BF) status, data are adjusted for age, sex, race/ethnicity, Tanner stage, and age × Tanner stage interaction. A: BMI: P= 0.03 for youth with low breastfeeding; P= 0.4 for youth with adequate breastfeeding. B: Waist circumference (WC): P= 0.008 for youth with low breastfeeding; P= 0.10 for youth with adequate breastfeeding. C: VAT: P= 0.06 for youth with low breastfeeding; P= 0.40 for youth with adequate breastfeeding. D: SAT: P= 0.03 for youth with low breastfeeding; P= 0.11 for youth with adequate breastfeeding. E: STR: P= 0.008 for youth with low breastfeeding; P= 0.14 for youth with adequate breastfeeding.
Figure 1
A– E: Effect of exposure to diabetes in utero on mean levels of childhood adiposity parameters. Stratified by breastfeeding (BF) status, data are adjusted for age, sex, race/ethnicity, Tanner stage, and age × Tanner stage interaction. A: BMI: P= 0.03 for youth with low breastfeeding; P= 0.4 for youth with adequate breastfeeding. B: Waist circumference (WC): P= 0.008 for youth with low breastfeeding; P= 0.10 for youth with adequate breastfeeding. C: VAT: P= 0.06 for youth with low breastfeeding; P= 0.40 for youth with adequate breastfeeding. D: SAT: P= 0.03 for youth with low breastfeeding; P= 0.11 for youth with adequate breastfeeding. E: STR: P= 0.008 for youth with low breastfeeding; P= 0.14 for youth with adequate breastfeeding.
Table 1
Infant feeding and characteristics of EPOCH subjects according to exposure to maternal diabetes in utero
. Unexposed to diabetes in utero . Exposed to diabetes in utero . P . n 379 89 Infant feeding . . . . Any breastfeeding (% yes) 88.0 83.2 0.2 Any formula-feeding (% yes) 73.7 77.0 0.5 Average duration of breastfeeding £ 7.51 ± 7.35 6.79 ± 5.97 0.3 Breastfeeding exclusivity (%) Exclusively formula-fed (weight = 0) ‡ 120 (32.2) 24 (27.9) 0.9 More formula than breast milk (weight = 0.25) ‡ 22 (5.9) 4 (4.7) Equal formula and breast milk (weight = 0.50) ‡ 40 (10.7) 12 (13.9) More breast milk than formula (weight = 0.75) ‡ 47 (12.6) 11 (12.8) Exclusively breast-fed (weight = 1) 99 (26.5) 20 (23.3) Breast milk–months ¥ Low (<6 months, n = 253) 54.1 53.9 1.0 Adequate (≥6 months, n = 215) 45.9 46.1 Offspring characteristics Current age (years) 10.6 ± 1.3 9.6 ± 1.7 <0.0001 Sex (% males) 48.8 55.6 0.3 Tanner stage (% <2) 50.8 71.1 0.0005 Race/ethnicity (%) NHW 45.7 60.0 0.04 Hispanic 45.1 34.4 AA 9.2 5.6 Birth weight (g) 3,286 ± 526 3,366 ± 489 0.2 Gestational age (weeks) 38.9 ± 2.1 38.7 ± 1.6 0.2 Maternal characteristics Age at delivery (years) 30.0 ± 5.4 33.0 ± 5.3 <0.0001 Education (%) < High school 0.7 3.3 0.1 High school 11.4 7.8 Any college 87.9 88.9 Total household income (% <$50,000/year) 20.9 15.6 0.3
. Unexposed to diabetes in utero . Exposed to diabetes in utero . P . n 379 89 Infant feeding . . . . Any breastfeeding (% yes) 88.0 83.2 0.2 Any formula-feeding (% yes) 73.7 77.0 0.5 Average duration of breastfeeding £ 7.51 ± 7.35 6.79 ± 5.97 0.3 Breastfeeding exclusivity (%) Exclusively formula-fed (weight = 0) ‡ 120 (32.2) 24 (27.9) 0.9 More formula than breast milk (weight = 0.25) ‡ 22 (5.9) 4 (4.7) Equal formula and breast milk (weight = 0.50) ‡ 40 (10.7) 12 (13.9) More breast milk than formula (weight = 0.75) ‡ 47 (12.6) 11 (12.8) Exclusively breast-fed (weight = 1) 99 (26.5) 20 (23.3) Breast milk–months ¥ Low (<6 months, n = 253) 54.1 53.9 1.0 Adequate (≥6 months, n = 215) 45.9 46.1 Offspring characteristics Current age (years) 10.6 ± 1.3 9.6 ± 1.7 <0.0001 Sex (% males) 48.8 55.6 0.3 Tanner stage (% <2) 50.8 71.1 0.0005 Race/ethnicity (%) NHW 45.7 60.0 0.04 Hispanic 45.1 34.4 AA 9.2 5.6 Birth weight (g) 3,286 ± 526 3,366 ± 489 0.2 Gestational age (weeks) 38.9 ± 2.1 38.7 ± 1.6 0.2 Maternal characteristics Age at delivery (years) 30.0 ± 5.4 33.0 ± 5.3 <0.0001 Education (%) < High school 0.7 3.3 0.1 High school 11.4 7.8 Any college 87.9 88.9 Total household income (% <$50,000/year) 20.9 15.6 0.3
Data are n(%) or means ± SD unless otherwise indicated.
£Includes mixed breast- and formula-feeding.
¥Weighted months of mixed breast milk and formula (duration of exclusive breastfeeding [months] + duration mixed breast- and formula-feeding [months] × exclusivity weight).
AA, non-Hispanic African American; NHW, non-Hispanic white.
Table 2
Association between breast milk–months (<6 and ≥6 breast milk–months) and adiposity parameters at age 6–13 years for youth exposed and not exposed to maternal diabetes in utero
. Unexposed to diabetes in utero . Exposed to diabetes in utero . Breast milk–months . ≥6 m . <6 m . P . ≥6 m . <6 m . P . n 174 205 41 48 BMI (kg/m 2 ) 18.6 19.6 0.02 18.0 20.1 0.05 Waist circumference (cm) 64.9 67.2 0.05 62.4 68.4 0.03 SAT (cm 2 ) 114.7 137.9 0.03 97.9 152.3 0.02 VAT (cm 2 ) 22.4 26.3 0.03 21.5 29.2 0.09 STR 0.76 0.77 0.72 0.76 0.83 0.26
. Unexposed to diabetes in utero . Exposed to diabetes in utero . Breast milk–months . ≥6 m . <6 m . P . ≥6 m . <6 m . P . n 174 205 41 48 BMI (kg/m 2 ) 18.6 19.6 0.02 18.0 20.1 0.05 Waist circumference (cm) 64.9 67.2 0.05 62.4 68.4 0.03 SAT (cm 2 ) 114.7 137.9 0.03 97.9 152.3 0.02 VAT (cm 2 ) 22.4 26.3 0.03 21.5 29.2 0.09 STR 0.76 0.77 0.72 0.76 0.83 0.26
Means from multiple linear regression model adjusted for age, sex, race/ethnicity, Tanner stage, and age × Tanner stage interaction.
m, months.
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Sickle cell disease: Ischemia and seizures | Request PDF
Request PDF | Sickle cell disease: Ischemia and seizures | Although the prevalence of seizures in children with sickle cell disease (SCD) is 10 times that of the general population, there are few... | Find, read and cite all the research you need on ResearchGate
Sickle cell disease: Ischemia and seizures
July 2005
Annals of Neurology58(2):290 - 302
DOI: 10.1002/ana.20556
Authors:
<here is a image f2f62089ad6ff61c-d19572ff1996375a>
PhD Mara Prengler MD
PhD Mara Prengler MD
<here is a image f2f62089ad6ff61c-d19572ff1996375a>
Steven G. Pavlakis MD
Steven G. Pavlakis MD
<here is a image b6cdceaf8e01fcda-fee8e328f38a5c35>
Stewart G Boyd
Great Ormond Street Hospital for Children NHS Foundation Trust
<here is a image 1937ee36a50dd27a-fa33d150fae83bfe>
Alan Connelly
The Florey Institute of Neuroscience and Mental Health
Abstract
Although the prevalence of seizures in children with sickle cell disease (SCD) is 10 times that of the general population, there are few prospectively collected data on mechanism. With transcranial Doppler and magnetic resonance imaging (MRI) and angiography, we evaluated 76 patients with sickle cell disease, 29 asymptomatic and 47 with neurological complications (seizures, stroke, transient ischemic attack, learning difficulty, headaches, or abnormal transcranial Doppler), who also underwent bolus-tracking perfusion MRI. The six patients with recent seizures also had electroencephalography. Group comparisons (seizure, nonseizure, and asymptomatic) indicated that abnormal transcranial Doppler was more common in the seizure (4/6; 67%) and nonseizure (26/41; 63%) groups than in the asymptomatic (10/29; 34%) group (χ2; p = 0.045), but abnormal structural MRI (χ2; p = 0.7) or magnetic resonance angiography (χ2; p = 0.2) were not. Relative decreased cerebral perfusion was found in all seizure patients and in 16 of 32 of the remaining patients with successful perfusion MRI (p = 0.03). In the seizure patients, the perfusion abnormalities in five were ipsilateral to electroencephalographic abnormalities; one had normal electroencephalogram results. These findings suggest that vasculopathy and focal hypoperfusion may be factors in the development of sickle cell disease–associated seizures. Ann Neurol 2005;58:290–302
<here is a image 175d1bd4b7439d95-754927124da715c1>
... Epilepsy occurs in SCD at a risk two to three times higher than the general population [12]. In addition, epilepsy in SCD is harder to treat and is associated with increased mortality and earlier age of death [12]
[13]
[14]. Although seizures are common in SCD, the likelihood of a patient providing information regarding seizure may vary by site. ...
... Regarding the diagnostic tests, transcranial doppler ultrasound was shown to be abnormal in seizure patients compared to non-symptomatic sickle patients. In seizure patients, perfusion abnormalities were shown to be ipsilateral to electroencephalogram (EEG) abnormalities suggesting a focal hypoperfusion as result of vasculopathy
[13]
. ...
... On the other hand, neuronal, glial, and inflammatory changes as well as genetic factors were implicated in the late phase [26]. Prengler et al. using transcranial Doppler ultrasonography, magnetic resonance angiography, and perfusion imaging studied 76 SCD patients and suggested that a relative decrease in cerebral blood flow in addition to large and small vessel disease might contribute to seizures in SCD patients
[13]
. The increase in utilizing brain imaging in SCD patients will lead to a better understanding of the link between strokes and seizures in SCD patients by correlating its data with EEG and the clinical context [27]. ...
Seizures Risk Factors in Sickle Cell Disease. The Cooperative Study of Sickle Cell Disease
Article
May 2021
SEIZURE-EUR J EPILEP
<here is a image f0be8444c69e9d64-716c88f8c6ad24ac> Mohammed Nawaiseh
<here is a image 08d69a6c748a2953-28576547418bbe06> Ala E. Shaban
Mohammad Abualia
<here is a image 7321eb64cac04e34-77a4bbb511e4af65> Iyad Sultan
Introduction
Although evidence suggests that neurological complications, including seizures and epilepsy, are more common among sickle cell disease (SCD) patients, few studies have assessed the risk factors of developing seizures among SCD patients
Methods
We used a nested case–control study design to compare pediatric and adult SCD patients who experienced seizures with patients who did not experience any seizure regarding clinical and laboratory parameters. We conducted a secondary analysis using the data from the Cooperative Study of Sickle Cell Disease in this study
Results
There were 153 out of 2804 (5.5%) pediatric patients who had seizures with a median age of 8.5 (Interquartile range [IQR] = 10.1) years at first seizure and 115 out of 1281 (9.0%) adult patients who had seizures with a median age of 28.0 (IQR = 10.6) years at first seizure. Cerebrovascular accident ([CVA], OR: 5.7, 95% CI: 2.9-11.0), meningitis (OR: 3.6, 95% CI: 1.8-7.2), and eye disease (OR: 3.4, 95% CI: 1.5-8.0) were associated with increased risk of developing seizures among pediatric patients. While CVA (OR = 7.5, 95% CI = 3.5-16.0), meningitis (OR = 5.6, 95% CI = 1.5-20.0), nephrotic syndrome (OR = 3.0, 95% CI = 1.2-7.9), spleen sequestration (OR = 2.7, 95% CI = 1.1-6.3), and pneumonia (OR = 2.1, 95% CI = 1.0-4.4) were associated with increased risk of developing seizures among adult patients
Conclusion
These findings suggest the need for treatment optimization and regular neurological follow up for SCD patients with these identified risk factors to prevent the development of seizures.
... Melek et al. observed that in over 95% of SCD patients with silent infarcts, at least one soft sign was present [60]. In addition, seizures (20-48%) [62,
63]
, decreased levels of consciousness [64], and headache (6.9%) [65,66] are also indicators of stroke and CVA in children with SCD. Altered mental status-with or without reduced level of consciousness, headache, seizures, visual loss, or focal signs-can occur in numerous contexts, including infection, shunted hydrocephalus [67], acute chest syndrome (ACS) [68,69], aplastic anemia secondary to parvovirus [70], after surgery [65], transfusion [71], or immunosuppression [72,73], and apparently spontaneously [74]. ...
... In one large series of 538 patients with ACS, 3% of children had neurological symptoms at presentation, and such symptoms developed in a further 7-10% in association with ACS [68]. These patients are classified clinically as having had a CVA [47], although there is a wide differential of focal and generalized vascular and nonvascular pathologies-often distinguished using acute magnetic resonance techniques [74]-with important management implications
[63,
67,71,[75][76][77][78]. Sixtyseven percent of those who have had an initial stroke and are not transfused will develop another, most likely within 36 months [79]. ...
Evidence-Based Emergency Neuroimaging in Children and Adults with Sickle Cell Disease and Symptoms of Stroke
Chapter
Full-text available
Mar 2018
<here is a image bbf7575d6db67863-e3d90c4fdac4e28a> Jaroslaw Krejza
<here is a image 2d906317166726e4-595bdbdac932e0fa> Michal Arkuszewski
Elias R Melhem
Stroke is a major cause of morbidity in children with sickle cell disease. There is a broad spectrum of acute presentations of both ischemic and hemorrhagic strokes. The optimal medical management of patients with acute ischemic stroke is not yet determined based on randomized clinical trials. Non-contrast computed tomography (CT) remains the initial test of choice for emergency brain assessment of patients with acute stroke. Magnetic resonance imaging (MRI) may be as accurate as CT for the detection of acute hemorrhage in patients presenting with acute stroke symptoms and is more accurate than CT for the detection of ischemic stroke and chronic intracerebral hemorrhage. CT angiography, CT perfusion, MR angiography, and MR venography can be added to emergency CT to detect large arterial vasculopathy, perfusion defects, and cerebral venous thrombosis; however, there is no sufficient evidence to justify their emergency use.
... 3. Seizures: the prevalence of seizures in children with SCD is 10 times that of the general population.
18,
19 Prengler et al found in a cohort of individuals with SCD, that those with seizures had increased perfusion and electroencephalographic abnormalities, suggesting that vasculopathy and focal hypoperfusion may be factors in the development of SCD-associated seizures. 18 In case 1, an electroencephalogram was done, which revealed generalized nonspecific cerebral dysfunction and no ictal or interictal epileptiform discharges were recorded. ...
... 18,19 Prengler et al found in a cohort of individuals with SCD, that those with seizures had increased perfusion and electroencephalographic abnormalities, suggesting that vasculopathy and focal hypoperfusion may be factors in the development of SCD-associated seizures.
18
In case 1, an electroencephalogram was done, which revealed generalized nonspecific cerebral dysfunction and no ictal or interictal epileptiform discharges were recorded. ...
How I treat and manage strokes in sickle cell disease
Article
Mar 2015
BLOOD
Adetola A. Kassim
<here is a image 5a4d00df80d8012c-a5e960b8252e53f7> Najibah A. Galadanci
Sumit Pruthi
<here is a image cc5ca26b70599073-3a8cd83b21d6ebf8> Michael R DeBaun
Neurological complications are a major cause of morbidity and mortality in sickle cell disease. In children with sickle cell anemia, routine use of transcranial Doppler screening coupled with regular blood transfusion therapy has decreased the prevalence of overt stroke from approximately 11% to 1%. Limited evidence is available to guide acute and chronic management of individuals with sickle cell disease and strokes. Current management strategies are based primarily on single arm clinical trials and observational studies, coupled with principles of neurology and hematology. Initial management of a focal neurological deficit includes evaluation by a multi-disciplinary team (a hematologist, neurologist, neuroradiologist and transfusion medicine specialist); prompt neuro-imaging, and an initial blood transfusion (simple followed immediately by an exchange transfusion or only exchange transfusion), is recommended if the hemoglobin is > 4 gm/dL and < 10 gm/dL. Standard therapy for secondary prevention of strokes and silent cerebral infarcts includes regular blood transfusion therapy and in selected cases, hematopoietic stem cell transplantation. A critical component of the medical care following an infarct is cognitive and physical rehabilitation. We will discuss our strategy of acute and long-term management of strokes in sickle cell disease.
Copyright © 2015 American Society of Hematology.
... There was strong evidence (ps < 0.001, adjusted using the Bonferroni correction) of a [715]. Finally, SCD patients are ten times more likely to suffer from seizures than the general population and Zarontin or ethosuximide is commonly prescribed to treat absence seizures
[716]
. ...
Callahan Dissertation V2.2 October2021
Thesis
Full-text available
Aug 2022
<here is a image f9839e14b9fc9093-7075884df4478990> Tiffany J Callahan
Traditional computational phenotypes (CPs) identify patient cohorts without consideration of underlying pathophysiological mechanisms. Deeper patient-level characterizations are necessary for personalized medicine and while advanced methods exist, their application in clinical settings remains largely unrealized. This thesis advances deep CPs through several experiments designed to address four requirements.
Stability was examined through three experiments. First, a multiphase study was performed and identified resources and remediation plans as barriers preventing data quality (DQ) assessment. Then, through two experiments, the Harmonized DQ Framework was used to characterize DQ checks from six clinical organizations and 12 biomedical ontologies finding Atemporal Plausibility and Completeness and Value Conformance as the most common clinical checks and Value and Relation Conformance as the most common biomedical ontology checks.
Scalability was examined through three experiments. First, a novel composite patient similarity algorithm was developed that demonstrated that information from clinical terminology hierarchies improved patient representations when applied to small populations. Then, ablation studies were performed and showed that the combination of data type, sampling window, and clinical domain used to characterize rare disease patients differed by disease. Finally, an algorithm that losslessly transforms complex knowledge graphs (KGs) into representations more suitable for inductive inference was developed and validated through the generation of expert-verified plausible novel drug candidates.
Interoperability was examined through two experiments. First, 36 strategies to align five eMERGE CPs to standard clinical terminologies were examined and revealed lower false negative and positive counts in adults than in pediatric patient populations. Then, hospital-scale mappings between clinical terminologies and biomedical ontologies were developed and found to be accurate, generalizable, and logically consistent.
Multimodality was examined through two experiments. A novel ecosystem for constructing ontologically-grounded KGs under alternative knowledge models using different relation strategies and abstraction strategies was created. The resulting KGs were validated through successfully enriching portions of the preeclampsia molecular signature with no previously known literature associations.
These experiments were used to develop a joint learning framework for inferring molecular characterizations of patients from clinical data. The utility of this framework was demonstrated through the accurate inference of EHR-derived rare disease patient genotypes/phenotypes from publicly available molecular data.
... Also, in some younger populations, most patients with epilepsy were found to have a prior history of stroke [12]. According to the observations in a study, it is believed that vasculopathy and localized hypoperfusion may play a role in the progression of seizures in sickle cell disease
[13]
. However, the cause of febrile seizures in children with sickle cell disease is not fully understood yet. ...
Association of Anemia With Epilepsy and Antiepileptic Drugs
Full-text available
Nov 2021
Jaskamal Padda
Khizer Khalid
<here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Mohammad Syam
Gutteridge Jean-Charles
Epilepsy is a disorder that causes unprovoked seizures regularly. It affects between 1% and 3% of the population. After the first seizure, the chances of having another one are almost 40%-52%. The etiology of febrile seizures in children with sickle cell disease is still unknown. In some groups, iron deficiency anemia has been linked to an increased risk of seizures. Although the reason and process are uncertain, some people believe that taking iron supplements can help prevent seizures. This literature covers haptene, non-haptene immune-related hemolysis, and oxidative processes activated by anti-seizure medications (ASMs). In epileptic patients, ASMs can cause anemia. Folic acid can be given to carbamazepine-treated anemic patients. There is growing evidence that it improves hemoglobin and leukocytes in individuals who take it. Therefore, one of the most efficient strategies to avoid future seizures is to take ASMs daily to maintain an even level of anticonvulsant in the body. To prevent further seizures, lifestyle changes are essential. Further studies and clinical trials are warranted to prove a clear association between epilepsy and hematologic disease, which will improve quality of life in the future.
... There are clinical descriptions of myopathy [172], myelopathy and neuropathy [160,166,[173][174][175]
[176]
[177] but access to a neurological opinion and investigation with electromyography and nerve conduction and/or muscle biopsy may not have been available. There are few populationbased studies of prevalence but one case-control study in Nigeria found a high prevalence of sensory neuropathy [46]. ...
Epidemiology of Stroke in Sickle Cell Disease
Full-text available
Sep 2021
Ikeoluwa A. Lagunju
<here is a image 89d64e7b4f5fc680-ee7363292291b486> Fenella J Kirkham
Sickle cell disease is the most common cause of stroke in childhood, both ischaemic and haemorrhagic, and it also affects adults with the condition. Without any screening or preventative treatment, the incidence appears to fall within the range 0.5 to 0.9 per 100 patient years of observation. Newborn screening with Penicillin prophylaxis and vaccination leading to reduced bacterial infection may have reduced the incidence, alongside increasing hydroxyurea prescription. Transcranial Doppler screening and prophylactic chronic transfusion for at least an initial year has reduced the incidence of stroke by up to 10-fold in children with time averaged mean of the maximum velocity >200 cm/s. Hydroxyurea also appears to reduce the incidence of first stroke to a similar extent in the same group but the optimal dose remains controversial. The prevention of haemorrhagic stroke at all ages and ischaemic stroke in adults has not yet received the same degree of attention. Although there are fewer studies, silent cerebral infarction on magnetic resonance imaging (MRI), and other neurological conditions, including headache, epilepsy and cognitive dysfunction, are also more prevalent in sickle cell disease compared with age matched controls. Clinical, neuropsychological and quantitative MRI screening may prove useful for understanding epidemiology and aetiology.
... Todd's palsy in patients with SCD with the prevalence of seizures, especially in the younger age-groups, is extremely highly compared with the general population. In addition, patients presenting with post-ictal weakness can be mistaken as a case of stroke
[11]
. Cerebral venous thrombosis can occur in SCD patients, and sometimes an acute CVST can mimic strokes [12]. ...
Educational Corner -Case Report Acute Ischemic Stroke in Sickle Cell Disease Challenges for Thrombolysis Keywords Blood · Hematology · Neurology · Sickle cell disease · Hemoglobinopathy · Acute ischemic stroke · Management · Thrombolysis · Tissue type plasminogen activator · Stroke mimics · Oman · Treatment · Vascular
Oct 2020
<here is a image 59b509fe40fd43b1-8de90cc8ce9eac9b> Amal Al Hashmi
<here is a image 59ef6a9c3400d4bb-6dcd3ce3bfccfb24> Sanjith Aaron
Sickle cell disease (SCD) is a hemoglobinopathy disorder that was recognized in 1949. Stroke is one of the most devastating complications of this disorder. The risk of stroke in SCD patients varies with the genotype; the highest rate has been reported with hemoglobin S. Tissue type plasminogen acti-vator (t PA) is class I recommended therapy for acute isch-emic stroke (AIS) since 1996. Although it is unclear if SCD patients were included in the t PA trail, SCD has never been identified as contraindication. The debate of offering t PA for adult SCD patient presenting with AIS continued for at least 2 decades. It is not up and until 2 years ago when the Amer-ican Heart Association and American stroke association (AHA/ASA) announced that intravenous (IV) t PA can be offered to adult SCD patients presenting with AIS. Here, we report a case where successful IV thrombolytic therapy was offered to an adult SCD patient presenting with AIS with excellent outcome.
... Forty percent of the patients presented with headache, 20% with limb weakness, and 20% presented with convulsions that are of high prevalence in children with SCA (10 times more that of general population)
[17]
. One patient presented with hypertension and posterior reversible encephalopathy syndrome which is very rare association in pediatric patients with SCA. ...
Prevalence of Stroke in Patients with Sickle Cell Anemia, a Single Center’s Experience
<here is a image ff93cc738f1a066c-5f33318a521e5dff> Ehab Hanafy
Nazim Faisal
Gihan Mahmoud
<here is a image 87fdab757f42b536-d2f17248827f4a42> Osama Mukhtar
INTRODUCTION: Stroke is a common complication occurring in approximately 10% of children with sickle cell anemia. A major breakthrough in sickle cell anemia is the use of hydroxyurea for prevention of stroke and the advances in trans-cranial doppler for early detection of stroke coupled with blood transfusion program as primary prevention. Different risk factors are associated with stroke development and identifying the modifiable risk factors might improve the quality of life of these patients.
METHODS: This is a retrospective review of patients with sickle cell anemia who developed stroke over the last 5 years in King Salman Armed Forces Hospital. The target population was children with sickle cell anemia 1 to 14 years of age. All data was entered into SPSS v.20. Frequencies and percentages of the descriptive analysis of the data are presented in tabulated and graphical form.
RESULTS: We reviewed 237 patients under active follow up, 10 patients (4.2%) have stroke and 5 patients (2.1%) have been detected to have abnormal cerebral blood velocities by trans-cranial doppler, all 15 patients (6.3%) are on chronic blood transfusion program. Trans-cranial doppler was performed in 75 patients (32%). Magnetic resonance imaging of brain was done for all 15 patients with internal carotid artery being the most common artery affected. Sixty percent of the patients had ischemic stroke. Forty percent of the patients presented with headache and 20% with convulsions. Neurologic deficit occurred in 4 patients (26.6%), hemiplegia and epilepsy were the most common deficits 26.6% and 20% respectively. Leukocytosis was the most frequent risk factor 66.6% followed by recurrent acute chest syndrome 46.6%.
CONCLUSION: Due to paucity of data, prevalence of stroke in patients with sickle cell anemia is not accurately known in Saudi Arabia. The prevalence of stroke in children at King Salman Armed Forces Hospital in Tabuk is 4.2% which is comparable with other studies. This can be attributed to the regular use of hydroxyurea as early as 2 years of age, and to the introduction of trans-cranial doppler as the most essential screening tool for stroke in patients with sickle cell anemia.
... Seizures were more common in children with elevated/ absent/low CBFv, consistent with previous UK data.
26
In our study, children with elevated/low/absent CBFv and a history of seizure had a higher proportion of infarcts than children who did not have a history of seizure. The CSSCD study (Cooperative Study of Sickle Cell Disease) of American children also found that seizures were associated with stroke and SCI, 27 but did not report TCD or MRA. ...
Transcranial Doppler and Magnetic Resonance in Tanzanian Children With Sickle Cell Disease
Edward Kija
<here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Dawn E Saunders
Angela Darekar
<here is a image b28c6112428f8722-268116f61a24259e> Charles Newton
Background and Purpose—
We determined prevalences of neurological complications, vascular abnormality, and infarction in Tanzanian children with sickle cell disease.
Methods—
Children with sickle cell disease were consecutively enrolled for transcranial Doppler; those with slightly elevated (>150 cm/s), low (<50 cm/s) or absent cerebral blood flow velocity (CBFv) were invited for brain magnetic resonance imaging and magnetic resonance angiography.
Results—
Of 200 children (median age 9; range 6–13 years; 105 [2.5%] boys), 21 (11%) and 15 (8%) had previous seizures and unilateral weakness, respectively. Twenty-eight (14%) had elevated and 39 (20%) had low/absent CBFv, all associated with lower hemoglobin level, but not higher indirect bilirubin level. On multivariable analysis, CBFv>150 cm/s was associated with frequent painful crises and low hemoglobin level. Absent/low CBFv was associated with low hemoglobin level and history of unilateral weakness. In 49 out of 67 children with low/absent/elevated transcranial Doppler undergoing magnetic resonance imaging, 43% had infarction, whereas 24 out of 48 (50%) magnetic resonance angiographies were abnormal. One had hemorrhagic infarction; none had microbleeds. Posterior circulation infarcts occurred in 14%. Of 11 children with previous seizure undergoing magnetic resonance imaging, 10 (91%) had infarction (5 silent) compared with 11 out of 38 (29%) of the remainder ( P =0.003). Of 7 children with clinical stroke, 2 had recurrent stroke and 3 died; 4 out of 5 had absent CBFv. Of 193 without stroke, 1 died and 1 had a stroke; both had absent CBFv.
Conclusions—
In one-third of Tanzanian children with sickle cell disease, CBFv is outside the normal range, associated with frequent painful crises and low hemoglobin level, but not hemolysis. Half have abnormal magnetic resonance angiography. African children with sickle cell disease should be evaluated with transcranial Doppler; those with low/absent/elevated CBFv should undergo magnetic resonance imaging/magnetic resonance angiography.
... Seizure was included as a new neurological event because seizures may reflect new cerebral ischemia in children with SCA. [12]
[13]
[14][15] Definitions of cerebrovascular events: ...
Children with sickle cell anemia with normal TCD and without silent infarcts have a low incidence of new strokes
<here is a image 41b350df23a66ef8-ea37f157a7a4e42c> Lori Chaffin Jordan
Dionna O. Roberts Williams
<here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Mark Rodeghier
<here is a image cc5ca26b70599073-3a8cd83b21d6ebf8> Michael R DeBaun
In a prospective cohort study, we tested the hypothesis that children with sickle cell anemia (SCA) with normal transcranial Doppler ultrasound (TCD) velocities and without silent cerebral infarcts (SCIs) would have a lower incidence rate of new neurological events (strokes, seizures or transient ischemic attacks) compared to children with normal TCD measurements and SCIs, not receiving regular blood transfusions. Non-randomized participants from the Silent Cerebral Infarct Transfusion (SIT) Trial who had screening magnetic resonance imaging (MRI) of the brain and normal TCD measurements were included. Follow-up ended at the time of first neurological event, start of regular blood transfusion, or loss to follow-up, whichever came first. The primary endpoint was a new neurological event. Of 421 participants included, 68 had suspected SCIs. Mean follow-up was 3.6 years. Incidence rates of new neurological events in non-transfused participants with normal TCD values with SCIs and without SCIs were 1.71 and 0.47 neurological events per 100 patient-years, respectively, p=0.065. The absence of SCI(s) at baseline was associated with a decreased risk of a new neurological event (hazard ratio 0.231, 95% CI 0.062 - 0.858; p=0.029). Local pediatric neurologists examined 67 of 68 participants with suspected SCIs and identified 2 with overt strokes classified as SCIs by local hematologists; subsequently one had a seizure and the other an ischemic stroke. Children with SCA, without SCIs, and normal TCD measurements have a significantly lower rate of new neurological events when compared to those with SCIs and normal TCD measurements. Pediatric neurology assessment may assist risk stratification. This article is protected by copyright. All rights reserved.
... 58,60 The majority of patients have focal abnormality on neuroimaging or electroencephalography 61 and cerebrovascular disease (see supplemental Figure 3A-D).
62
Given the high rate of moyamoya in individuals with SCD, we do not recommend hyperventilation during electroencephalography because of the risk of ischemia. 63 ...
Central nervous system complications and management in sickle cell disease
Article
Feb 2016
BLOOD
<here is a image cc5ca26b70599073-3a8cd83b21d6ebf8> Michael R DeBaun
<here is a image 89d64e7b4f5fc680-ee7363292291b486> Fenella J Kirkham
With advances in brain imaging and completion of randomized clinical trials (RCTs) for primary and secondary stroke prevention, the natural history of central nervous system (CNS) complications in sickle cell disease (SCD) is evolving. In order of current prevalence, the primary CNS complications include silent cerebral infarcts (39% by 18 years), headache (both acute and chronic: 36% in children with sickle cell anemia [SCA]), ischemic stroke (as low as 1% in children with SCA with effective screening and prophylaxis, but ∼11% in children with SCA without screening), and hemorrhagic stroke in children and adults with SCA (3% and 10%, respectively). In high-income countries, RCTs (Stroke Prevention in Sickle Cell Anemia [STOP], STOP II) have demonstrated that regular blood transfusion therapy (typically monthly) achieves primary stroke prevention in children with SCA and high transcranial Doppler (TCD) velocities; after at least a year, hydroxycarbamide may be substituted (TCD With Transfusions Changing to Hydroxyurea [TWiTCH]). Also in high-income countries, RCTs have demonstrated that regular blood transfusion is the optimal current therapy for secondary prevention of infarcts for children with SCA and strokes (Stroke With Transfusions Changing to Hydroxyurea [SWiTCH]) or silent cerebral infarcts (Silent Infarct Transfusion [SIT] Trial). For adults with SCD, CNS complications continue to be a major cause of morbidity and mortality, with no evidence-based strategy for prevention.
... 58,60 The majority of patients have focal abnormality on neuroimaging or electroencephalography 61 and cerebrovascular disease (see supplemental Figure 3A-D).
62
Given the high rate of moyamoya in individuals with SCD, we do not recommend hyperventilation during electroencephalography because of the risk of ischemia. 63 ...
Central nervous system complications and management in sickle cell disease: a review
Article
Jan 2016
BLOOD
<here is a image cc5ca26b70599073-3a8cd83b21d6ebf8> Michael R DeBaun
<here is a image 89d64e7b4f5fc680-ee7363292291b486> Fenella J Kirkham
With advances in brain imaging and completion of randomized clinical trials (RCTs) for primary and secondary stroke prevention, the natural history of central nervous system (CNS) complications in sickle cell disease (SCD) is evolving. In order of current prevalence the primary CNS complications include silent cerebral infarcts (39% by 18 years), headache (both acute and chronic: 36% in children with sickle cell anemia (SCA), ischemic stroke (as low as 1% in children with SCA with effective screening and prophylaxis, but ~11% in children with SCA without screening) and hemorrhagic stroke in children and adults with SCA, 3% and 10%, respectively. In high income countries RCTs (STOP, STOP II) have demonstrated that regular blood transfusion therapy (typically monthly) achieves primary stroke prevention in children with SCA and high transcranial Doppler (TCD) velocities; after at least a year, hydroxycarbamide may be substituted (TWiTCH). Also in high income countries, RCTs have demonstrated that regular blood transfusion is the optimal current therapy for secondary prevention of infarcts for children with SCA and strokes (SWiTCH), or silent cerebral infarcts (SIT). For adults with SCD, CNS complications continue to be a major cause of morbidity and mortality, with no evidence-based strategy for prevention.
... SCD could rather lead to a vascular damage in the brain, which could be a risk factor for subsequent epilepsy. Recent findings suggest that vasculopathy and focal hypoperfusion may be factors in the development of SCD-associated seizures
(Prengler et al., 2005)
. But, to our knowledge, no study has been conducted to specifically quantify a possible relationship between SCD and epilepsy, taking into account the confusing role of malaria. ...
Relationship between cerebral Malaria and Epilepsy : a case-control study in Libreville, Gabon.
Article
Full-text available
Aug 2005
Edgard Brice Ngoungou
<here is a image 4da8366d56af8faf-599e48a52150e188> Jean Koko
Yvonne Assengone-Zeh-Nguema
<here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Michel Druet-Cabanac
Purpose: Cerebral malaria (CM) is suspected to be a potential cause of epilepsy in tropical areas. The purpose of this article was to evaluate the relationship between CM and epilepsy in Gabon. Methods: A matched case–control study was carried out on a sample of subjects aged six months to 25 years and hospitalized between 1990 and 2004 in three hospitals in Libreville, Gabon. Cases were defined as patients suffering from epilepsy and confirmed by a neurologist. Controls were defined as patients without epilepsy. The exposure of interest was CM according to WHO criteria. Results: In total, 296 cases and 296 controls were included. Of these, 36 (26 cases and 10 controls) had a CM history. The adjusted odds ratio (aOR) to develop epilepsy after CM was 3.9 [95% CI: 1.7–8.9], p < 0.001. Additional risk factors were identified: family history of epilepsy: aOR = 6.0 [95% CI: 2.6– 14.1], p < 0.0001, and febrile convulsions: aOR = 9.2 [95% CI 4.0–21.1], p < 0.0001. Conclusions: This first case–control study on that issue suggests that epilepsy-related CM is an underrecognized problem. It emphasizes the need for further studies to better evaluate the role of convulsions during CM.
... Specific neurological complications such as stroke, SCI, abnormal TCD velocities, seizures, headaches or developmental complications, such as intellectual disability and ADHD, were all considered. Seizures and headaches are quite common in the pediatric sickle cell disease population as are intellectual disability and ADHD [5,20,
21]
. ...
Proteomic and Biomarker Studies and Neurological Complications of Pediatric Sickle Cell Disease
Article
Dec 2014
PROTEOM CLIN APPL
<here is a image 28d67d3bd7474fb5-05fbf12f1bd509a1> Eboni Lance
James F. Casella
Allen D. Everett
Emily Barron-Casella
Biomarker analysis and proteomic discovery in pediatric sickle cell disease has the potential to lead to important discoveries and improve care. The aim of this review article is to describe proteomic and biomarker articles involving neurological and developmental complications in this population. A systematic review was conducted to identify relevant research publications. Articles were selected for children under the age of 21 years with the most common subtypes of sickle cell disease. Included articles were focused on growth factors (platelet-derived growth factor), intra and extracellular brain proteins (glial fibrillary acidic protein, brain-derived neurotrophic factor), and inflammatory and coagulation markers (interleukin-1β, L-selectin, thrombospondin-1, erythrocyte and platelet-derived microparticles). Positive findings include increases in plasma brain-derived neurotrophic factor and platelet-derived growth factor with elevated transcranial Dopplers velocities, increases in platelet-derived growth factor isoform AA with overt stroke, and increases in glial fibrillary acidic protein with acute brain injury. These promising potential neuro-biomarkers provide insight into pathophysiologic processes and clinical events, but their clinical utility is yet to be established. Additional proteomics research is needed, including broad-based proteomic discovery of plasma constituents and blood cell proteins, as well as urine and cerebrospinal fluid components, before, during and after neurological and developmental complications.This article is protected by copyright. All rights reserved
... That specific type of multiple ischemias is likely caused by a combination of hemodynamic mechanisms and microvascular processes associated with SCD [18][19][20]. Even though the stenosis appears fixed, the microvascular processes could continue to progress during adulthood, leading to symptomatic and recurrent strokes in adults
[21]
[22][23]. This possibility seems to indicate lower brain tolerance of reduced perfusion due to stenosis in SCD patients and could explain specific triggering factor-associated stroke in adults. ...
Sickle-cell disease stroke throughout life: A retrospective study in an adult referral center
Article
Mar 2014
AM J HEMATOL
<here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Antoine Guéguen
Matthieu Mahévas
Ruben Nzouakou
<here is a image 12ab4fe6f9f02fc8-0f02732f8d0aea27> Pablo Bartolucci
Strokes are one of the most severe complications of sickle-cell disease. Most studies have been restricted to children with sickle-cell disease. To better understand the characteristics and follow-up of strokes occurring from childhood to adulthood, we undertook a retrospective cohort study of 69 stroke patients among the 2,875 patients consulting at the French Adult Sickle-Cell Disease Referral Center. Between 1970 and 2008, they had experienced 104 strokes: 80 ischemic, 22 hemorrhagic, and 2 intracranial sinus thromboses. Coma and/or fatal outcomes underscored the severity of strokes in sickle-cell disease patients.Hemorrhagic strokes occurred mostly in adults and carried a higher risk of death than ischemic stroke. The mechanisms underlying sickle-cell disease associated strokes were reevaluated and etiologies were determined for first stroke and recurrences, in childhood and adulthood. Sickle-cell disease vasculopathy concerned only SS patients and remains their most frequent stroke etiology. Cardioembolism, vaso-occlusive crisis and triggering factors were other etiologies identified in adults. Recurrences occurred in 19 SS patients only after a first ischemic stroke. SC patients' strokes occurred in adulthood and were associated with cardiovascular risk factors. Our findings provide novel information about cerebrovascular pathologies throughout the lives of sickle-cell disease patients and suggest the need for different diagnostic and therapeutic management approaches in those different settings.
... The risk is substantially reduced by chronic blood transfusion (Adams et al, 1998). Elevated CBFv is also associated with increased risk of other neurological complications, including seizures
(Prengler et al, 2005)
, neurocognitive deficits (Kral et al, 2003;Strouse et al, 2006) and silent infarcts (Pegelow et al, 2001). Low velocities may also be seen in patients with cerebrovascular disease, consistent with proximal vascular stenosis (Kirkham et al, 1986) or occlusion (Lee et al, 2004) and appears to be associated with cerebrovascular accidents (Buchanan et al, 2012). ...
Haptoglobin, alpha‐thalassaemia and glucose‐6‐phosphate dehydrogenase polymorphisms and risk of abnormal transcranial Doppler among patients with sickle cell anaemia in Tanzania
Full-text available
Feb 2014
BRIT J HAEMATOL
<here is a image 72c91d87aa9c6fdb-65f5c862328429aa> Sharon E Cox
<here is a image 1992897f41ff84f4-d70e3831d1973753> Julie Makani
Deogratias Soka
<here is a image 89d64e7b4f5fc680-ee7363292291b486> Fenella J Kirkham
Transcranial Doppler ultrasonography measures cerebral blood flow velocity (CBFv) of basal intracranial vessels and is used clinically to detect stroke risk in children with sickle cell anaemia (SCA). Co-inheritance in SCA of alpha-thalassaemia and glucose-6-phosphate dehydrogenase (G6PD) polymorphisms is reported to associate with high CBFv and/or risk of stroke. The effect of a common functional polymorphism of haptoglobin (HP) is unknown. We investigated the effect of co-inheritance of these polymorphisms on CBFv in 601 stroke-free Tanzanian SCA patients aged <24 years. Homozygosity for alpha-thalassaemia 3·7 deletion was significantly associated with reduced mean CBFv compared to wild-type (β-coefficient -16·1 cm/s, P = 0·002) adjusted for age and survey year. Inheritance of 1 or 2 alpha-thalassaemia deletions was associated with decreased risk of abnormally high CBFv, compared to published data from Kenyan healthy control children (Relative risk ratio [RRR] = 0·53 [95% confidence interval (CI):0·35-0·8] & RRR = 0·43 [95% CI:0·23-0·78]), and reduced risk of abnormally low CBFv for 1 deletion only (RRR = 0·38 [95% CI:0·17-0·83]). No effects were observed for G6PD or HP polymorphisms. This is the first report of the effects of co-inheritance of common polymorphisms, including the HP polymorphism, on CBFv in SCA patients resident in Africa and confirms the importance of alpha-thalassaemia in reducing risk of abnormal CBFv.
... This was not the case in our study, where the extent of SCIs was not well-correlated with clinical severity. However according to other previous studies,
25
various imaging techniques reveal a more extensive and diffuse pattern of vascular involvement than the one expected from the patient's clinical presentation. This may imply the silent, insidious nature and complex pathophysiology of microvascular disease in SCD patients. ...
Extent of Silent Cerebral Infarcts in Adult Sickle-Cell Disease Patients on Magnetic Resonance Imaging: Is There a Correlation with the Clinical Severity of Disease?
Jan 2013
<here is a image 477401104c2470ce-c832c750f617880c> Ekaterini Solomou
Pantelis Kraniotis
<here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Alexandra Kourakli
<here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Theodore Petsas
The aim of this paper is to correlate the extent of silent cerebral infarcts (SCIs) on magnetic resonance imaging (MRI) with the clinical severity of sickle cell disease (SCD) in adult patients. Twenty-four consecutive adult asymptomatic SCD patients (11 male and 13 female) with a mean age of 38.4 years (range 20-59) were submitted to brain MRI on a 1 Tesla Gyroscan Intera, Philips MR scanner with a dedicated head coil. The protocol consisted of TSE T2-weighted and FLAIR images on the axial and coronal planes. MRI readings were undertaken by two radiologists and consensus readings. Patients were compound heterozygotes (HbS/β-thal). The extent of SCIs was classified from 0-2 with 0 designating no lesions. Clinical severity was graded as 0-2 by the hematologist, according to the frequency and severity of vaso-occlusive crises. There was no statistically significant correlation between the severity of clinical disease and the extent of SCIs on MR imaging. The extent of SCI lesions did not differ statistically between younger and older patients. Patients receiving hydroxyurea had no statistically significant difference in the extent of SCI lesions. The extent of SCIs in heterozygous (HbS/β-thal) SCD patients is not age related and may be quite severe even in younger (<38.4 years) patients. However the extent of SCIs is not correlated with the severity of clinical disease.
Cerebrovascular disease in sickle cell disease
Sep 2022
Vafa Alakbarzade
Chinedu Maduakor
<here is a image 5b0f08445c835137-545aa939ccffe65b> Usman Khan
<here is a image 7b65a3bc9bbb8d29-60214bfc0dc1f45c> Cicero Pereira
Sickle cell disease (SCD) is the most common type of hereditary anaemia and genetic disorder worldwide. Cerebrovascular disease is one of its most devastating complications, with consequent increased morbidity and mortality. Current guidelines suggest that children and adults with SCD who develop acute ischaemic stroke should be transfused without delay. Those with acute ischaemic stroke aged over 18 years who present within 4.5 hours of symptom onset should be considered for intravenous thrombolysis; older patients with conventional vascular risk factors are the most likely to benefit. Endovascular thrombectomy should be considered carefully in adults with SCD as there are few data to guide how the prevalence of cerebral vasculopathy may confound the expected benefits or risks of intervention. We present a practical approach to cerebrovascular disease in sickle cell patients based on the available evidence and our experience.
Non Invasive Evaluation of Hepatic Iron Concentration By Fibroscan in Transfusion-Dependent Egyptian Patients with Chronic Hemolytic Anemia
Nov 2018
BLOOD
<here is a image 2a9038d62c22fe26-c9b2bc0f20cea586> Mohamed Ahmed Abdelnaem Attaalla
<here is a image 02fb8ad9c851f72d-3d6f579737cf1bee> Amal El-Beshlawy
<here is a image c4ba4e974c8cd120-2e5b3096d86ecc53> Amina Abdel-Salam
<here is a image 27286396cdcdd2f0-391361da93dfdbc4> Mona El-Ghamrawy
Background: Transient elastography (Fibroscan®) is an ultrasound technique used to measure liver stiffness (LS), and thus assess for liver fibrosis, in patients with various chronic hepatic disorders. It can also be used to predict severity in multiple other diseases that might affect LS such as amyloidosis and possibly conditions associated with iron overload.
Objectives: To assess the frequency of liver fibrosis in patients with chronic hemolytic anemia using Transient elastography (Fibroscan®), and to determine the reliability of this tool as a non-invasive method to predict hepatic iron content as compared to liver iron concentration (LIC) measured by magnetic resonance imaging (MRI).
Patients and methods: Seventy-five transfusion dependent patients (50 β-thalassemia major;25 sickle cell disease) with a mean age of 13.4±5.2 years in addition to 75 -age and sex matched- healthy children were recruited. All subjects underwent assessment of LS in kilopascals (kPa), by Transient elastography measurement using FibroScan (Echosens, Paris, France І). Steady state serum ferritin (SF), and hepatitis B serologies (HBsAg and antiHB core antibodies) were assessed by enzyme linked immunoassay (ELISA). LIC values, within 6 months' duration, as identified by quantitative MRI of hepatic iron stores as a signal intensity ratio method based on T1 and T2* contrast imaging without gadolinium were retrieved. Informed consent was obtained from patients' legal guardians prior to enrollment in the study.
Results: The median SF was 2280 ng/ml (84% had values exceeding 1000 ng/ml). The median LIC was 13.86 mg/g dw (78.7% patients showed LIC above 7 mg/g dw). The median cardiac T2* was 30.8 ms (3 patients had values below 20). Fifty-two (69.3%) patients were categorized as F0-1 and 21 (28%) were stage F2, 2 (1.3%) were stage F3, and 2 patients had severe fibrosis. The mean and median fibroscan (FS) values were 6.19 ±1.76 kPa and 5.9 kPa (range 3 to 14.1) respectively. Patients had significantly higher mean FS compared to control group (p ˂0.001). Patients with no or mild fibrosis (F0-1) had lower FS values (5.3kPa) compared to patients with fibrosis grades 2-4 (p ˂0.001). FS values were not affected by disease type (thalassemia or sickle cell disease), age (above 12 years), or HCV sero-positivity. FS values correlated with SF (r=0.410, p˂ 0.001). Simple regression analysis of the two variables suggested that changes in SF were associated with minimal but significant changes in FS values (p=0.04) with good agreement (kappa =0.324, p=0.003). LIC did not differ in relation to grade of fibrosis (p>0.05), did not correlate with FS values (r= 0.014, p=0.908), and no changes in FS were expected with LIC changes on regression analysis (p=0.466) with low agreement between LIC and FS at cutoff value 5.3 kPa (kappa = 0.015, p=0.9). Sensitivity and specificity of FS values to predict LIC were high at cutoff values ranging between 3.2 to 3.75 kPa but decreased markedly at higher cutoff values. On comparing sensitivity and specificity of FS values in prediction of iron overload at different cutoff values by ROC curve, it could not significantly predict iron overload (p=0.7). No correlations were found between LIC and other variables including SF (r=0.2), and changes in SF were not significantly associated with changes in LIC values (p =0.089). However, sensitivity and specificity of SF in predicting LIC were good at cutoff 1003.85 ng/ml but decreased markedly at higher cutoff values. Comparing its sensitivity and specificity to that of SF in the prediction of iron overload at different cutoff values by ROC curve, FS could not predict iron overload accurately (p=0.9) and the degree of agreement between these two variables as indicators of iron overload was low (kappa=0.063, p=0.478).
Conclusion: Fibroscan could be a valuable tool to assess the degree of liver fibrosis in patients with elevated SF, but it does not appear to reliably predict LIC in such group of patients especially with severe iron overload. FS values were not affected by disease type, age above 12 years, or HCV sero-positivity.
Hemiplegia
Oct 2009
Gerald M. Fenichel
Doença Cerebrovascular: Aspectos de uma população com Doença Falciforme / Cerebrovascular Disease: Aspects of a population with sickle cell disease
<here is a image c336b543181cb093-35d70b93c3ea7c80> Nathalia Noyma Sampaio Magalhaes
Tássia Mariana Moreira da Paz
<here is a image 801ed53f1a07f368-193745da431a7238> Renato Lourenço De Medeiros
<here is a image 1dd480af63049060-2f8ad96fc82bac99> Daniela O.W. Rodrigues
Neurological Complications of Systemic Disease
Chapter
Jan 2008
Aline I. Hamati
Neurocritical Care in Children
Chapter
Jan 2011
José Pineda
Mark Wainwright
Blood Cell Disorders and the Nervous System
<here is a image b9ed5f98843ccb8f-82f46bc16c003c66> Alexander Merkler
Purpose of review:
This article discusses the epidemiology, diagnosis, treatment, and prevention of neurologic complications of common and rare blood cell disorders.
Recent findings:
A growing number of preventive treatment options are available for stroke in sickle cell disease. Paroxysmal nocturnal hemoglobinuria and immune thrombocytopenia can lead to stroke. Thrombotic thrombocytopenic purpura frequently causes neurologic symptoms and should be considered in the differential diagnosis of a patient with neurologic symptoms, thrombocytopenia, and hemolytic anemia. Polycythemia vera and essential thrombocythemia are rare causes of stroke.
Summary:
This article discusses sickle cell disease and the most recent advances in stroke preventive therapy as well as neurologic complications of paroxysmal nocturnal hemoglobinuria, immune thrombocytopenia, thrombotic thrombocytopenic purpura, polycythemia vera, and essential thrombocythemia.
Neurological Manifestations of Sickle Cell Disease and Their Impact on Allogeneic Hematopoietic Stem Cell Transplantation
Chapter
Jan 2018
Jessica L. Carpenter
<here is a image 141873d52ce11aba-b670cf5de8800cf9> Monica Hulbert
While sickle cell disease (SCD) affects all organ systems, the brain has long been recognized as a major site of SCD-related morbidity. In fact, children with sickle cell anemia (SCA) historically have had higher stroke risk than any other group of children outside of the perinatal period. Overt strokes are widely accepted as an indication for curative allogeneic hematopoietic stem cell transplantation (HSCT). As we learn more about the broad spectrum of neurological disease due to SCA, from the well-described ischemic strokes and intracranial hemorrhage to the less understood neurocognitive deficits, the indications for and outcomes of allogeneic HSCT are in flux. In this chapter, we review the spectrum of neurological disease associated with SCA and the impact of pre-existing neurological conditions on HSCT complications and outcomes. We identify knowledge gaps and highlight recent developments. We also suggest a standardized clinical approach for assessing neurological complications of SCA before, during, and after HSCT.
Current World Literature
Sickle Cell Disease and Associated Seizures
Aug 2005
<here is a image 1d59b378b22c86ed-dc4f0b2dc02446f5> J. Gordon Millichap
The prevalence of cerebral vasculopathy in 76 patients with sickle cell disease (SCD), with and without seizures, and of magnetic resonance (MR) perfusion abnormality in those with recent seizures, was determined in a study at Great Ormond Street Hospital for Children, London, UK.
Neurological Complications of Systemic Disease
Jan 2012
Aline I. Hamati
Prognosis of Cerebral Arteriopathy in Stroke
<here is a image 1d59b378b22c86ed-dc4f0b2dc02446f5> J. Gordon Millichap
The evolution of cerebral arteriopathy in 50 children with first arterial ischemic stroke (AIS) was evaluated at Great Ormond Street Hospital for Children, and Neuroscience Unit, Institute of Child Health, London.
Hemiplegia
Chapter
Dec 2013
<here is a image cae4d213425fd900-be2e147a39907154> Jesus Eric Pina Garza
Cerebral infarction and occult degenerative cerebrovascular disease
<here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Ruth E Nemire
R.E. Ramsey
Introduction Stroke is among the most frequent causes of death and disability worldwide. Evidence for the relationship between cerebrovascular disease and epilepsy is based on data from studies that ask the questions: what are the risks for developing epilepsy; what diagnostic tests might be used; and what treatments are appropriate? There are few studies, they have different methodologies and patient numbers, and they are often based on retrospective chart reviews and case histories. Based on the neurobiology and pathophysiology of cerebrovascular disease, little evidence exists to support the use of any particular one of the currently available antiepileptic medications when stroke is the cause of seizures; however, in specific populations there may be good reasons to use one drug rather than another because of issues of patient tolerance or the absence of adverse impacts on comorbid diseases. The best approach is prevention, and, in lieu of that, design of future treatments should be aimed at reducing cell death and the cascade of events which may lead to development of epilepsy. Cerebrovascular disease The World Health Organization (2004, 2009a, b) defines cerebrovascular disease (stroke) as an interruption of blood supply by hemorrhage or clot which causes a reduction in oxygen and nutrient supply resulting in damage to the brain. Risk factors include age, hypertension, and hypercholesterolemia. Hematologic disorders such as sickle-cell disease and coagulopathies also put patients at risk for stroke (Gordon 2008).
Fenichel's Clinical Pediatric Neurology: A Signs and Symptoms Approach: Seventh Edition
<here is a image cae4d213425fd900-be2e147a39907154> Jesus Eric Pina Garza
Confidently diagnose and manage primary neurologic disorders of childhood with actionable, step-by-step assistance from Fenichelâs Clinical Pediatric Neurology! A signs-and-symptoms-based approach - with consideration of each presenting symptom in terms of differential diagnosis and treatment - mirrors the way you would typically evaluate and manage a patient. A practical and well-organized introduction to pediatric neurology, this is an ideal resource for board exam preparation, office use, and reference during residency.
Clinical Pediatric Neurology
Jan 2009
Gerald M. Fenichel
Clinical Pediatric Neurology, 6th Edition, by Gerald M. Fenichel, MD, offers you highly practical assistance in diagnosing and managing the primary neurologic disorders of childhood. Simply look up the presenting symptoms, and you'll be guided step by step through evaluation and management! Thorough coverage for each neurological disease clearly defines age at onset, course of illness, clinical features, and treatment options. Differential diagnosis tables and treatment algorithms expedite clinical decision making. And now, you can also rapidly consult the book from any computer at expertconsult.com! Thorough coverage for each neurological disease clearly defines age at onset, course of illness, clinical features, and treatment options. Differential diagnosis tables and treatment algorithms lead you through the evaluation and management of even the most difficult neurodegenerative disorders, including those caused by inborn errors of metabolism. An organization by body system, together with a user-friendly, highly templated format, makes reference quick and easy. Online access at expertconsult.com allows you to rapidly and efficiently reference the complete contents of the book from any computer. Updated clinical treatment strategies throughout equip you with the most current drugs and dosages. New bulleted "Key Points" summaries present crucial information at a glance. A new two-color interior design greatly enhances the readability of differential diagnosis and treatment algorithms. Your purchase entitles you to access the web site until the next edition is published, or until the current edition is no longer offered for sale by Elsevier, whichever occurs first. Elsevier reserves the right to offer a suitable replacement product (such as a downloadable or CD-ROM-based electronic version) should access to the web site be discontinued.
Sickle Cell Disease
Chapter
Dec 2015
<here is a image 89d64e7b4f5fc680-ee7363292291b486> Fenella J Kirkham
People with sickle cell disease, a chronic hemolytic anemia, present with a wide variety of neurological syndromes, including ischemic and hemorrhagic stroke, anterior and posterior territory transient ischemic attacks (TIAs), "soft neurological signs," seizures, headache, coma, visual loss, and altered mental status. There is a peak for ischemic stroke in childhood, typically associated with stenosis or occlusion of the distal internal carotid and proximal middle cerebral arteries diagnosable using magnetic resonance angiography or transcranial Doppler ultrasound (TCD). For hemorrhagic stroke, the peak age is early adulthood, when aneurysms are common. Covert infarction may be detected on magnetic resonance imaging in around 25%. Cognitive difficulties, characteristically affecting attention, executive function, memory, arithmetic and processing speed, are also common. Indefinite transfusion is standard care for secondary prevention (and primary in those with TCD velocities. >. 200. cm per second). In addition to the possibility of cure from transplantation, hydroxyurea, aspirin and overnight respiratory support are under investigation as strategies to prevent neurological complications.
Neurologic Manifestations of Hematologic Disorders
Apr 2014
J.D. Sussman
G.A.B. Davies-Jones
Hematologic disorders can affect the central and peripheral nervous systems in a number of different ways, producing a wide range of neurologic disturbances. They result in nervous system dysfunction through a variety of mechanisms, including vascular occlusion, hemorrhage, infiltration and metabolic disturbance, which may be hereditary or acquired. Hematologic disorders are a frequent cause of certain syndromes, such as venous thrombosis, but rarer causes of a wide range of neurologic conditions. Hematologic disease should be considered as a cause of subacute multifocal disorders. Some of these neurologic complications are well described, but others are less clearly defined. In the present chapter, neurologic aspects of each of the main groups of hematologic disorders are discussed.
Sickle-Cell Disease and Stroke: Evidence-Based Neuroimaging
Chapter
Jan 2013
<here is a image bbf7575d6db67863-e3d90c4fdac4e28a> Jaroslaw Krejza
<here is a image 2d906317166726e4-595bdbdac932e0fa> Michal Arkuszewski
<here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Maciej Swiat
Elias R Melhem
SCD is the family of recessively inherited disorders of hemoglobin (Hb) [1], which have developed in response to strong evolutionary selection by malaria [2, 3]. Sickle-cell anemia (SCA), the most severe form of SCD, refers specifically to homozygosity for the HbS (βS), a variant of the HbB gene (which encodes β-globin), whereas people who inherit only one sickle gene are sickle-cell carriers [4, 5]. HbS homozygotes suffer from SCD, but heterozygotes have a tenfold reduced risk of severe malaria [6, 7]. SCD also includes other variants of the HbB gene, namely, HbC and HbE [8–11] and regulatory defects of HbA and HbB, which cause α and ß thalassemia (Sß + or Sß0) [12–14]. The evolutionary pressure has risen to high frequencies of HbS allele in malaria-exposed populations despite the fatal consequences for homozygotes (HbSS) [2]. Different populations have developed independent evolutionary responses to malaria at both the global and the local levels [15]. The most striking example is the Hb gene, in which three different coding single nucleotide points confer protection against malaria: Glu6Val (HbS), Glu6Lys (HbC), and Glu26Lys (HbE) [3]. The HbS allele is common in Africa but rare in Southeast Asia, whereas the opposite is true for the HbE allele [3, 15]. At the local level, not only frequency of the HbC and HbS allele varies [8], but the frequency of their haplotypes also varies; for instance, the HbS allele is found in four distinct haplotypes in West Africa region [16–18].
Der kindliche Schlaganfall
Article
May 2008
M Hörmann
Zusammenfassung Der Schlaganfall wird zunehmend als wichtige Erkrankung auch des Kindesalters erkannt. Die Gründe für dieses schwere und für
das weitere Leben bedeutende Ereignis sind gänzlich anders als beim Erwachsenen. Gleiches gilt daher auch für Diagnose und
Therapie. Der Artikel soll einen kurzen Überblick über die Besonderheiten des kindlichen Schlaganfalls geben und dem Radiologen
helfen, rasch und sicher die Diagnose und Ursache des Schlaganfalls zu erkennen.
12 Pediatric Sickle Cell Disease and Stroke
Article
Mar 2011
<here is a image bbf7575d6db67863-e3d90c4fdac4e28a> Jaroslaw Krejza
<here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Maciej Swiat
Maciej Tomaszewski
Elias R Melhem
Implementation of the Stroke Prevention Trial in Sickle Cell Anemia (STOP) primary prevention strategy that uses transcranial
Doppler (TCD) screening resulted in lower rates in stroke admissions in California (limited evidence). Presence of silent
infarcts on magnetic resonance (MR) scans in asymptomatic children with SCD is associated with higher risk for future stroke
(limited evidence). The risk of first stroke can be substantially reduced by chronic transfusions in asymptomatic children
with SCD and hemoglobin (Hb) SS, in whom intracranial arterial mean velocities are over 200 cm/s on TCD examination (strong
evidence). Management of children with SCD and acute stroke requires immediate non-contrast computed tomography (CT) to exclude
intracranial hemorrhage (moderate–strong evidence). Children with symptoms of stroke and negative CT for hemorrhage require
urgent MRI/diffusion-weighted imaging (DWI)/ MR angiography (MRA) to assess the degree and extent of brain structural abnormalities
and positron emission tomography (PET)/single photon emission CT (SPECT) or MRS to determine the degree of ischemia (moderate
evidence). Presence of intracranial arterial stenosis and new lesions on MR imaging in patients with stroke history is associated
with high risk for recurrent stroke (limited evidence). There are no specific neuroimaging findings which can suggest that
blood transfusions be safely halted in children with SCD (strong evidence). No data were found that evaluate the cost-effectiveness
of the different neuroimaging modalities in the evaluation of symptomatic and asymptomatic patients with SCD and suspected
stroke (limited evidence).
Adverse neurological outcomes in Nigerian children with sickle cell disease
Nov 2012
INT J HEMATOL
<here is a image beddbe551ae0924b-cf2be5053bef1914> Ikeoluwa Lagunju
<here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Biobele Brown
Sickle cell disease (SCD) is reported to be the most common genetic disorder affecting Nigerians. Children with SCD are at a high risk of neurological morbidity. The main objective of this study was to determine the pattern of adverse neurological outcomes among a cohort of Nigerian children with SCD. All children with SCD seen in the Department of Paediatrics, University College Hospital, Ibadan, Nigeria, over a period of 2 years were carefully evaluated for symptoms and signs of neurological complications, defined as clinical outcomes referable to the central nervous system. Of the 214 children evaluated, 187 were diagnosed with Hb SS disease and 27 with Hb SC disease. Neurological complications were identified in 78 (36.4 %) of the cases. The most common complications were headache (17.8 %), seizure (9.3 %) and stroke (8.4 %). Other less frequent complications included bacterial meningitis (2.8 %), spontaneous visual loss (1.4 %), paraplegia (0.9 %) and transient ischaemic attacks (0.9 %). Neurological complications occurred more frequently in children with sickle cell anaemia than in those with Hb SC disease (P = 0.002, 95 % CI 1.450-82.870). Adverse neurological events are common in Nigerian children with SCD, with a significantly higher risk in Hb SS than Hb SC disease. Stroke represents a major underlying cause of symptomatic epilepsy in SCD. Institution of primary preventive measures for stroke in SCD will significantly reduce the burden of stroke and epilepsy associated with SCD in Nigeria.
Sickle cell disease and electroencephalogram hyperventilation
ANN NEUROL
PhD Mara Prengler MD
Steven G. Pavlakis MD
<here is a image b6cdceaf8e01fcda-fee8e328f38a5c35> Stewart G Boyd
<here is a image 89d64e7b4f5fc680-ee7363292291b486> Fenella J Kirkham
Neurologic Complications of Hemoglobinopathies
<here is a image 26bb2cb97b35cf53-03ae87de6ba4b3a9> Christine Holmstedt
<here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Robert J Adams
The hemoglobinopathies, including sickle cell disease and its variants, are genetic abnormalities of hemoglobin. Hemoglobin SS (sickle cell disease) is the most common form of hemoglobin mutation in North America. Complications of hemoglobinopathies are numerous and involve many organ systems, including the nervous system. This article is intended to introduce the reader to the epidemiology, diagnosis, treatment, and prevention of neurologic complications of hemoglobinopathies, focusing specifically on sickle cell disease because of its prevalence.
Inherited and acquired risk factors for arterial ischemic stroke in childhood
<here is a image 5064b5a98f88f68b-8dd45ea6f3b32e00> Giuseppe Lippi
<here is a image bf230ebb3db7cdf4-e1b250c177ce232a> Massimo Franchini
<here is a image 870d4bca1f01d64a-fddc18ccc6850bd2> Martina Montagnana
<here is a image a7ae4c600511bc82-b829533060757b7b> Gian Cesare Guidi
Ischemic stroke in childhood is a rare but serious disorder, which is associated with significant morbidity and mortality.
The lack of causal homogeneity in the aetiology of this disorder presents problems for predicting and preventing it, making
the ischemic stroke in childhood a real dilemma for the clinician. Although a variety of potential inherited and acquired
causes have been now identified, including cardiac pathologies, infections, prothrombotic, metabolic and vascular disorders,
the aetiology of ischemic stroke in the young remains still unknown in more than one third of the patients. Presently, an
appropriate evaluation of some hypercoagulable conditions seems justified in adults with stroke. However, the etiologic contribution
of several thrombophilic conditions to initial and recurrent stroke in affected children has not been definitely clarified,
since more powerful and influential non-thrombophilic risk factors are usually present, making the thrombophilia screening
in such circumstance a matter of debate. In particular, the diagnostic yield of the screening is reportedly lower in children,
the role of several prothrombotic abnormalities is uncertain, especially in recurrent stroke, and there is no evidence-based
guidance to stroke prevention and therapy in children carrying a hypercoagulable state. Additional studies are needed to quantify
the risk for a cerebrovascular event in children with a prothrombotic disorder and to determine which combination of endogenous
and exogenous risk factors leads to greater rates of initial and recurrent stroke.
Sickle Cell Disease and Stroke
Jan 2010
<here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Maciej Swiat
Maciej Tomaszewski
<here is a image bbf7575d6db67863-e3d90c4fdac4e28a> Jaroslaw Krejza
Elias R Melhem
Implementation of the Stroke Prevention Trial in Sickle Cell Anemia (STOP) primary prevention strategy that uses transcranial Doppler screening resulted in lower rates in stroke admissions in California (limited evidence).
■ Presence of silent infarcts on MR scans in asymptomatic children with SCD is associated with higher risk for future stroke (limited evidence).
■ The risk of first stroke can be substantially reduced by chronic transfusions in asymptomatic children with SCD and hemoglobin (Hb) SS, in whom intracranial arterial mean velocities are over 200 cm/s on transcranial Doppler examination (strong evidence).
■ Management of children with SCD and acute stroke requires immediate non-contrast CT to exclude intracranial hemorrhage (moderate–strong evidence).
■ Children with symptoms of stroke and negative CT for hemorrhage require urgent MRI/DWI/MRA to assess the degree and extent of brain structural abnormalities and PET/SPECT or MRS to determine the degree of ischemia (moderate evidence).
■ Presence of intracranial arterial stenosis and new lesions on MR imaging in patients with stroke history is associated with high risk for recurrent stroke (limited evidence).
■ There are no specific neuroimaging findings which can suggest that blood transfusions be safely halted in children with SCD (strong evidence).
■ No data were found that evaluate the cost-effectiveness of the different neuroimaging modalities in the evaluation of symptomatic and asymptomatic patients with SCD and suspected stroke (limited evidence).
Coma in Childhood
<here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Shashikant S Seshia
<here is a image 1937ee36a50dd27a-fa33d150fae83bfe> William T Bingham
Robert W Griebel
Coma is an important and common clinical problem in pediatric practice. The comatose state in children results from trauma or a wide variety of nontraumatic causes. It is clinically useful to classify causes into (1) those generally associated with structural changes in the brain and (2) those with predominant metabolic dysfunction. The metabolic causes of coma can be associated with structural changes in the brain. The assessment and management of a child in coma requires a multidisciplinary coordinated team approach with each member of the team being assigned a specific responsibility especially when coma is complicated by poor cardiorespiratory function, shock, or status epilepticus, and all of them must be rapidly addressed. Investigations have to be tailored to the individual case and the clinician's diagnostic considerations. Tests for infection (sepsis, meningitis, and encephalitis) include toxicology screen, neuroimaging, conventional electroencephalogram (EEG), continuous EEG monitoring, and serum biomarkers. Those who have suffered a metabolic or toxic encephalopathy have a good outcome provided the secondary effects of the cause are minimized and systemic complications avoided. Several advances have improved our understanding and management of coma in children. These include recognition of a number of inborn errors of metabolism, progress in the prevention, diagnosis, and treatment of infective diseases, prevention of head trauma, magnetic resonance imaging (MRI), and an emerging consensus on the management of raised intracranial pressure (ICP).
Neuroimaging in assessment of risk of stroke in children with sickle cell disease
<here is a image 2d906317166726e4-595bdbdac932e0fa> Michal Arkuszewski
Elias R Melhem
<here is a image bbf7575d6db67863-e3d90c4fdac4e28a> Jaroslaw Krejza
Purpose:
Stroke and subclinical "silent infarcts" are major causes of morbidity in children with Sickle Cell Disease (SCD). Ischemic strokes are more common in younger children while hemorrhagic strokes are more frequent in adults. The goal of neuroimaging in acute stroke is to document whether the stroke is ischemic or hemorrhagic, to assess the extent of parenchymal abnormalities and to determine the presence of other cerebrovascular lesions. Computed Tomography (CT) is the primary modality for the assessment of acute stroke patients because of its 24/7 availability and ability to exclude hemorrhagic causes. Magnetic resonance imaging (MRI) and MR angiography (MRA) are recommended to determine precisely extent of infarction and detect cerebrovascular abnormalities. The goal of neuroimaging in patients with hemorrhagic stroke is to identify an arteriovenous malformation or aneurysm(s) amenable to surgery or catheter intervention.The risk of first stroke is very high in asymptomatic children with intracranial arterial mean velocities over 200 cm/s on transcranial Doppler (TCD) examination. The risk can be substantially reduced if chronic blood transfusions are timely implemented. Large cerebral vessel disease detected by TCD can be confirmed or excluded by MRI/MRA. Those with evidence of parenchymal and/or cerebrovascular lesions should be followed by preventive therapy. In patients with neurologic symptoms and negative MRI/MRA findings Positron Emission Tomography or single photon emission CT is recommended. There are no specific neuroimaging findings that suggest that blood transfusions can be safely halted in children with SCD.
Seizures in the Jamaica cohort study of sickle cell disease
BRIT J HAEMATOL
<here is a image f81db3414ae4b848-0410271e4726380c> Susanna Bortolusso Ali
<here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Marvin Reid
Raphael A Fraser
<here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Amza Ali
Although there is some evidence that epilepsy is more common in Sickle Cell Disease (SCD), we sought to establish the incidence rates, risk factors for and specific types of seizures in a SCD cohort followed from birth, and how seizure occurrence affects morbidity and mortality. We examined all records of persons in the Jamaica cohort Study of Sickle Cell Disease (JSSCD) clinically identified as having experienced a seizure during their lifetime. At first presentation, seizures were classified as Febrile Convulsion, Acute Symptomatic Seizure or Single Unprovoked Seizure. The seizure classification was revised to include Epilepsy if seizures recurred. Thirty-eight persons in the JSSCD (N = 543) were identified with seizures. The 5-year cumulative incidence of febrile convulsions was 2·2%. The incidence rate of epilepsy (all genotypes) was 100/100 000 person-years, 139/100 000 for the SS genotype. Despite limited availability of diagnostic investigations, clinical seizures were associated with increased all-cause mortality. Male gender (Odds Ratio [OR]: 4·0[95% confidence interval [CI]; 1·03-20·0]) and dactylitis in childhood (OR: 17·4 [95% CI; 4·82-62·85]) were associated with increased risk of developing epilepsy. Epilepsy in persons with SCD is 2-3 times more common than in non-sickle populations and is associated with increased all-cause mortality in all sickle cell genotypes.
Treatment of acute and remote symptomatic seizures
Barbara S. Koppel
In principle, the use of anticonvulsant drugs does not differ between acute and remote symptomatic seizures, but control of acute symptomatic seizures requires simultaneous treatment of the underlying etiology. Prevention of remote seizures when the risk is known to be high has been the subject of intense efforts at antiepileptogenesis, but the optimal duration of treatment after an injury is not yet known. Appropriate evaluation of a seizure depends on individual circumstances, but findings on examination, laboratory tests (serum electrolytes, magnesium, glucose, assessment of hepatic and renal function), and brain imaging (CT scan or MRI) are necessary to determine the most likely cause. Lumbar puncture is always required when there is suspicion of meningitis or encephalitis. Preferred medications for treatment of acute symptomatic seizures or status epilepticus are those available for intravenous use, such as benzodiazepines, fosphenytoin or phenytoin, valproate, levetiracetam, and phenobarbital. Diazepam is also available as a gel for rectal administration. Seizures that occur in patients with epilepsy because of missed antiepileptic drugs or inadequate serum levels should be treated with additional doses of their regular medications; loading doses can be administered with minimal toxicity in tolerant patients. Surgery is rarely necessary in the acute setting except for intracerebral lesions with rapidly rising intracranial pressure and impending herniation. After seizures are controlled, the provoking condition must also be determined and treated.
Sickle cell disease and electroencephalography hyperventilation
<here is a image 1d59b378b22c86ed-dc4f0b2dc02446f5> J. Gordon Millichap
Treatment of chronic visceral pain with brain stimulation
Dec 2005
<here is a image 51fa96d7406eebd8-f6477b394fb48d29> Felipe Fregni
Debora DaSilva
Kimberly M Potvin
Steven D. Freedman
Methylenetetrahydrofolate reductase in Parkinson's disease
Dec 2005
<here is a image ccfeb3b156e7933f-6e90a5697c4ea89f> Ullrich Wüllner
Heike Kölsch
<here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Michael Linnebank
| https://www.researchgate.net/publication/230222227_Sickle_cell_disease_Ischemia_and_seizures |
Major differences in dissolved organic matter characteristics and bacterial processing over an extensive brackish water gradient, the Baltic Sea | Request PDF
Request PDF | Major differences in dissolved organic matter characteristics and bacterial processing over an extensive brackish water gradient, the Baltic Sea | Dissolved organic matter (DOM) in marine waters is a complex mixture of compounds and elements that contribute substantially to the global carbon... | Find, read and cite all the research you need on ResearchGate
Major differences in dissolved organic matter characteristics and bacterial processing over an extensive brackish water gradient, the Baltic Sea
May 2018
Marine Chemistry 202
DOI: 10.1016/j.marchem.2018.01.010
Abstract
Dissolved organic matter (DOM) in marine waters is a complex mixture of compounds and elements that contribute substantially to the global carbon cycle. The large reservoir of dissolved organic carbon (DOC) represents a vital resource for heterotrophic bacteria. Bacteria can utilise, produce, recycle and transform components of the DOM pool, and the physicochemical characteristics of this pool can directly influence bacterial activity; with consequences for nutrient cycling and primary productivity. In the present study we explored bacterial transformation of naturally occurring DOM across an extensive brackish water gradient in the Baltic Sea. Highest DOC utilisation (indicated by decreased DOC concentration) was recorded in the more saline southerly region where waters are characterised by more autochthonous DOM. These sites expressed the lowest bacterial growth efficiency (BGE), whereas in northerly regions, characterised by higher terrestrial and allochthonous DOM, the DOC utilisation was low and BGE was highest. Bacterial processing of the DOM pool in the south resulted in larger molecular weight compounds and compounds associated with secondary terrestrial humic matter being degraded, and a processed DOM pool that was more aromatic in nature and contributed more strongly to water colour; while the opposite was true in the north. Nutrient concentration and stoichiometry and DOM characteristics affected bacterial activity, including metabolic status (BGE), which influenced DOM transformations. Our study highlights dramatic differences in DOM characteristics and microbial carbon cycling in sub-basins of the Baltic Sea. These findings are critical for our understanding of carbon and nutrient biogeochemistry, particularly in light of climate change scenarios.
... The Baltic Sea is the second largest estuarine system in the world and encompasses separate sub-basins with a unique geology and a strong north-south salinity gradient driven by river outlets (Rönnberg and Bonsdorff 2004). The north is characterized by high DOM concentrations and phosphorous (P)-limited plankton production whereas the south has lower DOM concentrations and N-limited plankton productivity (Bernes 2005;
Rowe et al. 2018)
. Further, catchment characteristics vary from primarily forest in the north to agricultural landscapes in the south. ...
... Climate change is predicted to increase precipitation and the allochthonous DOM input via rivers to the Baltic Sea (Andersson et al. 2015). The loading and characteristics of the DOM will likely affect the future microbial community composition, activity, DOM utilization and nutrient biogeochemistry in the Baltic Sea (Traving et al. 2017;
Rowe et al. 2018
). However, responses will conceivably vary between north and south due to differences in catchments, characteristics of the incoming DOM and composition of the recipient microbial communities. ...
... Reasons for this may include multiple site characteristics, seasonality (sampling in April vs. July) or the difference in N:P ratios between the two sites, with N limitation in the north (N:P = 7; Table 1). Moreover, it is noteworthy that DOC levels naturally, and in our experiment, are highest in the northern Baltic (Table 1) (Sandberg et al. 2004;
Rowe et al. 2018)
. Bacterioplankton in this environment may, therefore, be particularly adaptable and responsive to pulses of riverine DOM. ...
Effects of allochthonous DOM input on microbial composition and nitrogen cycling genes at two contrasting estuarine sites
Heterotrophic bacteria are important drivers of nitrogen (N) cycling and the processing of dissolved organic matter (DOM). Projected increases in precipitation will potentially cause increased loads of riverine DOM to the Baltic Sea and likely affect the composition and function of bacterioplankton communities. To investigate this, the effects of riverine DOM from two different catchment areas (agricultural and forest) on natural bacterioplankton assemblages from two contrasting sites in the Baltic Sea were examined. Two microcosm experiments were carried out, where the community composition (16S rRNA gene sequencing), the composition of a suite of N cycling genes (metagenomics), and the abundance and transcription of ammonia monooxygenase (amoA) genes involved in nitrification (quantitative PCR) were investigated. The river water treatments evoked a significant response in bacterial growth, but effects on overall community composition and the representation of N cycling genes were limited. Instead, treatment effects were reflected in the prevalence of specific taxonomic families, specific N related functions, and in the transcription of amoA genes. The study suggests that bacterioplankton responses to changes in the DOM pool are constrained to part of the bacterial community, whereas most taxa remain relatively unaffected.
... The effects of higher tDOM inputs can be observed in the different basins of the Baltic Sea, where an increasing gradient in tDOM concentration is found from South to North (Sandberg et al., 2004;
Rowe et al., 2018)
. The southern regions receive terrestrial loadings richer in nutrients (particularly phosphorus), while the northern regions are exposed to terrestrial loadings richer in humic substances . ...
... The southern regions receive terrestrial loadings richer in nutrients (particularly phosphorus), while the northern regions are exposed to terrestrial loadings richer in humic substances . In addition, the higher concentrations of humic substances and colored dissolved organic matter (CDOM) typically found in the northern areas of the Baltic Sea (Harvey et al., 2015;Paczkowska et al., 2016) have been observed to increase light attenuation, which can have negative consequences for phytoplankton production and biomass (Roulet and Moore, 2006;Frigstad et al., 2013) and alter the bacterial metabolic response, as well as the characteristics of the processed DOM (Berggren and del Giorgio, 2015;
Rowe et al., 2018)
. Allochthonous DOM (ADOM) has been implicated in the uncoupling of phytoplankton and bacterioplankton production due to the presence of an external carbon source available for bacteria Figueroa et al., 2016). ...
... Dissolved organic matter characteristics and inputs can influence bacterial activity (Berggren and del Giorgio, 2015;
Rowe et al., 2018)
, even if production is only temporarily elevated (Figueroa et al., 2016). Furthermore, allochthonous DOM can influence the bacterial community (Judd et al., 2006;Logue et al., 2016), and the processing of the DOM can have consequences for ecosystem function and global biogeochemical cycles (Jiao et al., 2010;Benner and Amon, 2015). ...
Effects of Organic Pollutants on Bacterial Communities Under Future Climate Change Scenarios
Sari Timonen
Owen Rowe
Coastal ecosystems are highly dynamic and can be strongly influenced by climate change, anthropogenic activities (e.g., pollution), and a combination of the two pressures. As a result of climate change, the northern hemisphere is predicted to undergo an increased precipitation regime, leading in turn to higher terrestrial runoff and increased river inflow. This increased runoff will transfer terrestrial dissolved organic matter (tDOM) and anthropogenic contaminants to coastal waters. Such changes can directly influence the resident biology, particularly at the base of the food web, and can influence the partitioning of contaminants and thus their potential impact on the food web. Bacteria have been shown to respond to high tDOM concentration and organic pollutants loads, and could represent the entry of some pollutants into coastal food webs. We carried out a mesocosm experiment to determine the effects of: (1) increased tDOM concentration, (2) organic pollutant exposure, and (3) the combined effect of these two factors, on pelagic bacterial communities. This study showed significant responses in bacterial community composition under the three environmental perturbations tested. The addition of tDOM increased bacterial activity and diversity, while the addition of organic pollutants led to an overall reduction of these parameters, particularly under concurrent elevated tDOM concentration. Furthermore, we identified 33 bacterial taxa contributing to the significant differences observed in community composition, as well as 35 bacterial taxa which responded differently to extended exposure to organic pollutants. These findings point to the potential impact of organic pollutants under future climate change conditions on the basal coastal ecosystem, as well as to the potential utility of natural bacterial communities as efficient indicators of environmental disturbance.
... Freshwater river discharge not only affects salinity, but simultaneously increases nutrient influx, including nitrate, phosphate and dissolved organic carbon (Frigstad et al., 2020;Korth et al., 2012). Southern, high-salinity areas in the Baltic are characterized by high levels of autochthonous DOM (dissolved organic matter derived from, for example, phytoplankton primary production), whereas northern, low-salinity areas are richer in allochthonous DOM of terrestrial origin discharged by rivers
(Rowe et al., 2018)
. ...
... This increased nutrient load is a major stimulator of bacterioplankton growth and pelagic productivity (Stepanauskas et al., 2002), and pelagic bacterial growth efficiency is highest in the low-salinity regions
(Rowe et al., 2018)
. The community composition of bacteria living in association with Ulva may be impacted by prevailing nutrient conditions as well, but not necessarily following the same patterns as bacterioplankton, as the Ulva host probably provides its microbial partners (and other associates) with carbon and nutrients (Hudson et al., 2019). ...
Salinity and host drive Ulva associated bacterial communities across the Atlantic‐Baltic Sea gradient
Luna van der Loos
Sofie D'Hondt
Aschwin Engelen
Sophie Steinhagen
The green seaweed Ulva is a model system to study seaweed‐bacteria interactions, but the impact of environmental drivers on the dynamics of these interactions is little understood. In this study, we investigated the stability and variability of the seaweed‐associated bacteria across the Atlantic‐Baltic Sea salinity gradient. We characterised the bacterial communities of 15 Ulva sensu lato species along 2000 km coastline in a total of 481 samples. Our results demonstrate that Ulva‐associated bacterial composition was strongly structured by both salinity and host species (together explaining between 34‐91% of the variation in the abundance of the different bacterial genera). The largest shift in the bacterial consortia coincided with the horohalinicum (5‐8 PSU, known as the transition zone from freshwater to marine conditions). Low salinity communities especially contained high relative abundances of Luteolibacter, Cyanobium, Pirellula, Lacihabitans and an uncultured Spirosomaceae, whereas high salinity communities were predominantly enriched in Litorimonas, Leucothrix, Sulfurovum, Algibacter, and Dokdonia. We identified a small taxonomic core community (consisting of Paracoccus, Sulfitobacter, and an uncultured Rhodobacteraceae), which together contributed to 14% of the reads per sample, on average. Additional core taxa followed a gradient model, as more core taxa were shared between neighbouring salinity ranges than between ranges at opposite ends of the Atlantic‐Baltic Sea gradient. Our results contradict earlier statements that Ulva‐associated bacterial communities are taxonomically highly variable across individuals and largely stochastically defined. Characteristic bacterial communities associated with distinct salinity regions may therefore facilitate the host’s adaptation across the environmental gradient.
... Freshwater environments come in many shapes and forms, from pristine mountain lakes to highly polluted wastewater treatment facilities, each hosting a complex and dynamic microbial community ("microbiome"; Bruno et al., 2018;Bautista-de los Santos et al., 2019;Zorz et al., 2019). Such aquatic microbiomes are strongly affected by environmental conditions within the water body (e.g., temperature and nutrients availability), and in turn shape its biogeochemistry, for example by processing and recycling organic and inorganic matter (Liu et al., 2017;
Rowe et al., 2018;
Hach et al., 2020). Aquatic microbial communities may also affect other organisms living within the water body, as well as human communities in contact with the water. ...
Seasonal Dynamics Are the Major Driver of Microbial Diversity and Composition in Intensive Freshwater Aquaculture
Article
Full-text available
Jun 2021
Sophi Marmen
Eddie Fadeev
Ashraf Al Ashhab
Daniel Sher
Aquaculture facilities such as fishponds are one of the most anthropogenically impacted freshwater ecosystems. The high fish biomass reared in aquaculture is associated with an intensive input into the water of fish-feed and fish excrements. This nutrients load may affect the microbial community in the water, which in turn can impact the fish health. To determine to what extent aquaculture practices and natural seasonal cycles affect the microbial populations, we characterized the microbiome of an inter-connected aquaculture system at monthly resolution, over 3 years. The system comprised two fishponds, where fish are grown, and an operational water reservoir in which fish are not actively stocked. Clear natural seasonal cycles of temperature and inorganic nutrients concentration, as well as recurring cyanobacterial blooms during summer, were observed in both the fishponds and the reservoir. The structure of the aquatic bacterial communities in the system, characterized using 16S rRNA sequencing, was explained primarily by the natural seasonality, whereas aquaculture-related parameters had only a minor explanatory power. However, the cyanobacterial blooms were characterized by different cyanobacterial clades dominating at each fishpond, possibly in response to distinct nitrogen and phosphate ratios. In turn, nutrient ratios may have been affected by the magnitude of fish feed input. Taken together, our results show that, even in strongly anthropogenically impacted aquatic ecosystems, the structure of bacterial communities is mainly driven by the natural seasonality, with more subtle effects of aquaculture-related factors.
... An experimental study showed that terrestrial DOM alters the bacterial enzyme activity, which in turn affect the recycling of nutrients in the system (Traving et al., 2017). Furthermore, bacteria can alter the DOM pool by a selective processing of substances (Boyd and Osburn, 2004;Berggren and Giorgio, 2015;
Rowe et al., 2018)
. Yet, the influence of terrestrial DOM on the ecological functioning of bacterial communities is poorly understood, particularly under natural conditions. ...
Terrestrial dissolved organic matter inflow drives temporal dynamics of the bacterial community of a subarctic estuary (northern Baltic Sea)
Article
Full-text available
May 2021
Daniela Figueroa
Eric Capo
M. Lindh
Agneta Andersson
Climate change is projected to cause increased inflow of terrestrial dissolved organic matter to coastal areas in northerly regions. Estuarine bacterial community will thereby receive larger loads of organic matter and inorganic nutrients available for microbial metabolism. The composition of the bacterial community and its ecological functions may thus be affected. We studied the responses of bacterial communities to inflow of terrestrial dissolved organic matter in a subarctic estuary in the northern Baltic Sea, using a 16S rRNA gene metabarcoding approach. Betaproteobacteria dominated during the spring river flush, constituting ~60% of the bacterial community. Bacterial diversity increased as the runoff decreased during summer, when Verrucomicrobia, Betaproteobacteria, Bacteroidetes, Gammaproteobacteria and Planctomycetes dominated the community. Network analysis revealed that a larger number of associations between bacterial populations occurred during the summer than in spring. Betaproteobacteria and Bacteroidetes populations appeared to display similar correlations to environmental factors. In spring, freshly discharged organic matter favoured specialists, while in summer a mix of autochthonous and terrestrial organic matter promoted the development of generalists. Our study indicates that increased inflows of terrestrial organic matter‐loaded freshwater to coastal areas would promote specialist bacteria, which in turn might enhance the transformation of terrestrial organic matter in estuarine environments. This article is protected by copyright. All rights reserved.
... The extension of hydraulic retention time makes the terrestrial OC easier to be intercepted and deposit in reservoirs. Meanwhile, the nutrient retention increases the primary productivity and generates more autochthonous OC in reservoirs (Wang et al. 2009;Deemer et al. 2016;
Rowe et al. 2018)
, which is considered as a new C sink (Raquel et al. 2017). The frequent and signi cant input of allochthonous OM in many lake sediments contributed the high OC burial e ciency (Sebastian et al. 2009;Gudasz et al. 2012;Huang et al. 2017). ...
Lignin phenols in sediment cores and its indications of degradation and organic carbon sources of the Yantan Reservoir, China
Preprint
Full-text available
Feb 2021
Xin Lin
Li Gao
Jiaqi Huang
Fushun Wang
Three sediment cores collected from the Yantan Reservoir, located in the Pearl River, southwest China, were analyzed for lignin phenols, elemental and stable carbon isotopic composition to investigate the variation patterns, vegetation sources, degradation stage, and relative proportions of terrestrial sedimentary organic carbon (OC). Significant temporal and spatial heterogeneity in terrestrial OC burial was indicated by the changes of lignin contents at different depths in different sampling sites: the inlet zone, the central reservoir zone in front of dam and the reservoir bay. The interception impact of upstream dam, the influence of artificial regulation, as well as the role of interzonal recharge made the terrestrial OC burial remains complex in the reservoir. The oxidized lignin signatures showed spatial heterogeneity suggesting active oxidative degradation and demethylation/demethoxy degradation of sedimentary lignin during deposition, especially in the inlet zone. An angiosperm herbaceous tissue and gymnosperm woody tissue contributed the sedimentary lignin. A soil-plankton-plant three-end-member mixing model revealed that soil-derived OC dominated before impoundment and at the early stage of reservoir operation, while the contribution of autochthonous OC began to dominate after gradually aging and eutrophicating of the reservoir. Our study of lignin evolution in reservoir highlights important temporal and spatial reservoir carbon components and their contribution to sedimentary carbon pools, providing new insights into the estimation of organic carbon burial in reservoirs.
... Lund-Hansen & Christiansen, 2008;Meier et al., 2012;Stramska & Świrgoń, 2014) • Increase in coloured DOM in general (Harvey, Kratzer, & Andersson, 2015;Kratzer et al., 2014Kratzer et al., , 2020Kratzer & Moore, 2018;Stedmon et al., 2010;Traving et al., 2017) • Importance of (increased) SPM especially in coastal zones • Land management (e.g.-Land use (e.g. forestry; Kritzberg, 2017;Kritzberg et al., 2020) • Nutrient runoff (stimulating eutrophication) (Carstensen et al., 2020;Hoikkala et al., 2015;Kritzberg et al., 2014) • Decline and alteration in macrophyte coverage (Krause-Jensen et al., 2009;Lappalainen et al., 2019;Luhtala et al., 2016;Sahla et al., 2020) • Alteration and stimulation of bacterial food webs (Lindh et al., 2016;Meunier et al., 2017;
Rowe et al., 2018;
Traving et al., 2017), verus phytoplankton based food webs (A. Andersson et al., 2018;Asmala et al., 2013;Dahlgren et al., 2010;Hoikkala et al., 2015;Lefébure et al., 2013;Sandberg et al., 2004;Wikner & Andersson, 2012)-Alteration in phytoplankton community composition • Alteration phytoplankton community composition (A. ...
Increased light attenuation in Norwegian coastal waters - A literature review
Technical Report
Full-text available
Nov 2020
Helene Frigstad
E. Therese Harvey
Anne Deininger
Amanda Poste
This report describes the results of a literature review on increased light attenuation and biological effects in Norwegian waters and comparable global coastal regions. An overview of research projects on increased light attenuationis given.
... erosion, bioturbation or altered redox conditions in bottom sediments (Swedish E. P. A., 2000;Dachs et al., 2002;Ripszam et al., 2015b). The high sorption affinity of POPs to organic carbon, the content and type of organic carbon present (varying greatly within the Baltic Sea), and the sediment properties have all been linked to the degree of bioavailability and biotoxicity of POPs (Ripszam et al., 2015a;
Rowe et al., 2018;
Massei et al., 2019). Furthermore, such properties can also determine the type of microbes able to utilize, degrade or incorporate these pollutants at the base of the trophic chain, factors that can control partitioning and stability of deposited pollutants and also in turn influence microbial community structure (Mrozik and Piotrowska-Seget, 2010;Ripszam et al., 2015b;Rodríguez et al., 2018). ...
Bacterial communities as indicators of environmental pollution by POPs in marine sediments
Article
Jan 2021
ENVIRON POLLUT
Juanjo Rodríguez
Christine Monique Jeanine Gallampois
Peter Haglund
Owen Rowe
Decades of intensive discharge from industrial activities into coastal systems has resulted in the accumulation of a variety of persistent organic pollutants (POPs) in marine waters and sediments, having detrimental impacts on aquatic ecosystems and the resident biota. POPs are among the most hazardous chemicals originating from industrial activities due to their biotoxicity and resistance to environmental degradation. Bacterial communities are known to break down many of these aromatic compounds, and different members of naturally occurring bacterial consortia have been described to work in syntrophic association to thrive in heavily contaminated waters and sediments, making them potential candidates as bioindicators of environmental pollution. In this study environmental, sampling was combined with chemical analysis of pollutants and high-resolution sequencing of bacterial communities using Next Generation Sequencing molecular biology tools. The aim of the present study was to describe the bacterial communities from marine sediments containing high loads of POPs and to identify relevant members of the resident microbial communities that may act as bioindicators of contamination. Marine sediments were collected from a coastal bay area of the Baltic Sea historically influenced by intense industrial activity, including metal smelting, oil processing, and pulp and paper production. Different types of POPs were detected at high concentrations. Fiberbank sediments, resulting from historic paper industry activity, were found to harbour a clearly distinct bacterial community including a number of bacterial taxa capable of cellulolytic and dechlorination activities. Our findings indicate that specific members of the bacterial communities thrive under increasing levels of POPs in marine sediments, and that the abundances of certain taxa correlate with specific POPs (or groups), which could potentially be employed in monitoring, status assessment and environmental management purposes.
... Optically active organic constituents are not only imported from the catchment, but also produced by microbial processing of autochthonous (i.e., algal derived) DOM (Romera-Castillo et al. 2011). Aquatic microbial production of CDOM is evident from laboratory (Tranvik 1993;Shimotori et al. 2009) and marine
(Rowe et al. 2018)
studies, but corresponding observations in natural freshwaters are scarce. In brown-water lakes, CDOM tends to be consumed by bacteria faster that it is produced . ...
Systematic microbial production of optically active dissolved organic matter in subarctic lake water
Article
May 2020
LIMNOL OCEANOGR
Martin Berggren
Cristian Gudasz
François Guillemette
Jan Karlsson
... However, given the right environmental conditions, most organic carbon substrates are labile; in rivers and estuaries, substrates that are reactive on timescales faster than fluvial transport will be removed, with the remaining material persistent until conditions are optimum for its degradation. In coastal marine environments, DOM removal could be caused by combinations of photochemistry (Osburn et al., 2009;Stubbins et al., 2010;Vodacek et al., 1997), microbial degradation
Rowe et al., 2018)
, or combinations thereof (Moran et al., 2000). Based on experiments conducted in coastal watersheds, wetland DOM biodegradation was greater than stream DOM (Fellman et al., 2009). ...
| https://www.researchgate.net/publication/322860383_Major_differences_in_dissolved_organic_matter_characteristics_and_bacterial_processing_over_an_extensive_brackish_water_gradient_the_Baltic_Sea |
OBM Genetics | Repli-FISH (Fluorescence in Situ Hybridization): Application of 3D-(Immuno)-FISH for the Study of DNA Replication Timing of Genetic Repeat Elements
Background: Genetic repeat elements (interspersed or tandem repeats) have diverse functions within cells and at different phases of the cell cycle. Yet, their investigation at a genome-wide scale has been difficult ever since due to their repetitive nature. Here, we describe a method to study the DNA replication kinetics of different repeat elements in single cells throughout the S-phase of the cell cycle. Methods: Mouse major satellite, minor satellite and telomere repeat elements as well as human LINE-1 and Alu repeats are detected in Fluorescence In Situ Hybridization (FISH) assays by specific hybridization probes containing biotinylated nucleotides. We combine their visualization via fluorophore-tagged streptavidin with the detection of cellular DNA replication signals at the single-cell level. Results: All probes hybridized specifically to their intended target sequence as verified by microscopical analysis and with regard to their location on individual chromosomes. We detected DNA replication by labeling replisome components or nascent DNA synthesis by detecting incorporated thymidine analogues. The different spatial distribution of replication signals allowed us to classify the cells in different S-phase substages. We additionally measured genomic DNA content to time the progression throughout S-phase. Then, we performed colocalization analysis of the degree of signal overlap between DNA replication and DNA probe signal to determine the kinetics of DNA replication of repeat DNA in individual cells and by high-throughput/high-content microscopical analysis. Conclusions: Application of the probes mentioned above in 3-dimensionally preserved interphase nuclei with the simultaneous detection of newly synthesized DNA or components of the replication machinery allows to determine the replication kinetics of all elements during the synthesis phase of the cell cycle in human as well as embryonic and somatic mouse cells.
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OBM Genetics
(ISSN 2577-5790)
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OBM Geneticsis an internationalOpen Accessjournal published quarterly online by LIDSEN Publishing Inc. It accepts papers addressing basic and medical aspects of genetics and epigenetics and also ethical, legal and social issues. Coverage includes clinical, developmental, diagnostic, evolutionary, genomic, mitochondrial, molecular, oncological, population and reproductive aspects. It publishes research articles, reviews, communications and technical notes, etc. There is no restriction on the length of the papers and we encourage scientists to publish their results in as much detail as possible.
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Technical Note
Repli-FISH (Fluorescence in SituHybridization): Application of 3D-(Immuno)-FISH for the Study of DNA Replication Timing of Genetic Repeat Elements
Patrick Weber †<here is a image e21cf84eeaa752f8-bc95d944d2dffc14>, Cathia Rausch †<here is a image e21cf84eeaa752f8-bc95d944d2dffc14>, Annina Scholl<here is a image e21cf84eeaa752f8-bc95d944d2dffc14>, M. Cristina Cardoso *<here is a image e21cf84eeaa752f8-bc95d944d2dffc14>
† These authors contributed equally to this work.
Cell Biology and Epigenetics, Department of Biology, Technische Universität Darmstadt, 64287 Darmstadt, Germany
*Correspondence:M. Cristina Cardoso<here is a image e21cf84eeaa752f8-bc95d944d2dffc14>
OBM Genetics2019, Volume 3, Issue 1 doi:10.21926/obm.genet.1901062
Academic Editor:Thomas Liehr
Special Issue:Applications of Fluorescence in Situ Hybridization
Received:July 22, 2018 |Accepted:January 8, 2019 |Published:January 25, 2019
Recommended citation: Weber P, Rausch C, Scholl A, Cardoso MC . Repli-FISH (Fluorescence in SituHybridization): Application of 3D-(Immuno)-FISH for the Study of DNA Replication Timing of Genetic Repeat Elements. OBM Genetics2019; 3(1): 062; doi:10.21926/obm.genet.1901062.
© 2019 by the authors. This is an open access article distributed under the conditions of theCreative Commons by Attribution License, which permits unrestricted use, distribution, and reproduction in any medium or format, provided the original work is correctly cited.
Abstract
Background: Genetic repeat elements (interspersed or tandem repeats) have diverse functions within cells and at different phases of the cell cycle. However, their investigation at a genome-wide scale is challenging due to their repetitive nature. Here, we describe a method to study the DNA replication kinetics of different repeat elements in single cells throughout the S-phase of the cell cycle. Methods: Mouse major satellite, minor satellite and telomere repeat elements as well as human LINE-1 and Alu repeats were detected in fluorescence in situhybridization (FISH) assays using specific hybridization probes containing biotinylated, digoxigenin-conjugated or fluorescently-labeled nucleotides. We combined their visualization with the detection of cellular DNA replication signals at the single cell level. Results: Specific hybridization of all probes to their intended target sequence and their location on individual chromosomes were verified by microscopic analysis. DNA replication was detected by labeling replisome components or nascent DNA synthesis by detecting incorporated thymidine analogs. The different spatial distribution of replication signals allowed us to classify the cells in different S-phase substages. We also measured changes in genomic DNA content during the progression through S-phase. Using high-throughput/high-content microscopic analysis, we then performed colocalization analysis of the degree of overlap between DNA replication and DNA probe signals to determine the kinetics of DNA replication of repeat elements in individual cells. Conclusions:Application of these probes in 3-dimensionally preserved interphase nuclei with the simultaneous detection of newly synthesized DNA or components of the replication machinery allows determination of the replication kinetics of all elements during the synthesis phase of the cell cycle in human cells as well as in embryonic and somatic mouse cells.
Graphical abstract
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Keywords
3D-FISH; Alu; DNA replication timing; EdU; LINE-1; PCNA; genetic repeat elements; satellite DNA; single cell analysis; telomeres
1. Introduction
DNA replication is a fundamental cellular process that, like DNA transcription and repair, requires tight control. Dysregulation of this process results in the introduction of mutations or chromosomal aberrations that lead to multiple disorders, including cancer. Thus, elucidation of the molecular mechanism responsible for the control of DNA replication dynamics is of great importance.
Many studies have shown that different chromatin types are replicated at distinct times during S-phase (reviewed in [ 1]). This is reflected by the changing spatial nuclear distribution of replication signals (visualized by thymidine analog incorporation or labeled replication machinery proteins) observed by light microscopy and termed replication patterns. Each pattern has been shown to correspond to the duplication of a different chromatin type, i.e., euchromatin, facultative and constitutive heterochromatin.
Recently established genome-wide replication timing protocols confirmed that the different chromatin types initiate DNA replication within specific zones (replication domains) along the genome [ 2]. It was further shown that a substantial proportion of the genome undergoes large-scale chromatin reorganization during embryonic development [ 2].
Repetitive DNA elements account for more than half of the human genome and up to 40% of the mouse genome (Figure 1C), whereas protein-coding sequences constitute only 1.2% and 1.4% of the human and mouse genomes, respectively [ 3, 4]. In the human genome, repetitive and transposable genetic elements include, among others, LINEs (long interspersed nuclear elements) and SINEs (short interspersed nuclear elements). Both elements rely on reverse transcription of an RNA intermediate for integration into new genomic locations [ 5].
<here is a image 1114bf536df85cf0-ae49f419ac6a1994>
Figure 1Overview of the localization and sequence of mouse and human repetitive elements. A: Schematic overview of an acrocentric mouse chromosome showing the localization of telomeric, minor and major satellite DNA. B: Schematic overview of a human chromosome showing the localization of Alu and LINE-1 elements. The sequence information for telomeres, minor and major satellite and Alu elements depict the consensus sequence of one repeat unit. Underlined sequence regions represent primer binding sites for PCR amplification of FISH probes. Full-length LINE-1 elements are 6 kb in length and consist of a 5’ and a 3’ untranslated region (UTR) and two open reading frames (ORF1 and ORF2). C: Pie charts showing the mouse (left) and human (right) genome composition (Repeat Masker). Approximately half of the genomes are composed of different classes of repetitive DNA elements.
LINE-1 elements represent a family of autonomous and active retroelements that account for approximately 17% of the human genome [ 3]. These elements are found in gene-poor and AT-rich regions, which correspond to dark G-bands on Giemsa-stained metaphase chromosomes [ 6]. The majority of LINE-1 elements are retrotransposition defective due to 5’ truncations, rearrangements or mutations, resulting in 80-100 retrotransposition active LINE-1 elements out of the half a million LINE-1 copies in the human genome [ 3, 7]. Full-length LINE-1 elements have a total length of 6 kb and contain a 5’ untranslated region (UTR), three open reading frames (ORF) and a 3’ UTR ending in a AATAAA polyadenylation signal. ORF1 and ORF2 encode the p40 protein and a protein with endonuclease and reverse transcriptase activity that are necessary for retrotransposition [ 8, 9].
Alu elements are part of the SINE family and represent the most abundant class of non-autonomous retrotransposons. Alu elements cover approximately 11% of the human genome and are predominantly found in gene-rich regions, which, in contrast to LINE-1 elements, correspond to dark R-bands on metaphase chromosomes stained by reverse-Giemsa banding [ 3, 6]. Alu elements are approximately 290 bp long and have a dimeric structure, consisting of two highly similar left and right monomers separated by a linker sequence. The Alu element sequence does not encode proteins, although the left monomer contains a promoter for RNA polymerase III dependent transcription [ 3, 10]. In trans retrotransposition is mediated by LINE-1-encoded proteins [ 11, 12].
In mouse and human cells, telomeres are composed of non-coding, double-stranded TTAGGG array repeats bound by the shelterin complex [ 13, 14]. The ends of linear chromosomes mirror DNA damage breaks; however, their repair would lead to chromosome fusions. Shelterin prevents telomere recognition, DNA damage responses and chromosome end processing via repair pathways. Similar to telomerase, shelterin also serves to regulate telomere length [ 14].
In the mouse genome, centromeric and pericentromeric DNA is composed of highly conserved, tandem repeats of DNA consisting of multiple copies of the repeat unit organized in a head-to-tail manner and referred to as minor satellites (MiSat) and major satellites (MaSat) according to their size. MiSats occupy approximately 600 kb of the terminal centromeric regions of all acrocentric mouse chromosomes and are composed of 120-bp AT-rich repeat units [ 15]. The pericentric MaSat DNA spans 6 Mb adjacent to the MiSat and consists of 234-bp repeats that form clusters in mouse cells, visible as bright structures following DAPI counterstaining and referred to as chromocenters [ 16].
Although historically referred to as “junk”, “parasitic” or “selfish” DNA due to the lack of a clear function within the genome, repetitive elements are now believed to play a role in genome organization during the cell cycle and throughout development as well as in disease conditions [ 17, 18, 19, 20, 21, 22]. Complete and error-free DNA duplication prior to mitosis is an absolute requirement for the preservation of genome integrity and ultimately, the development and maintenance of an organism. This applies not only to the protein-encoding part of the genome, but also holds true for the repetitive elements that are interspersed throughout the genome [ 23]. However, due to their repetitive nature, repetitive elements are difficult to investigate in genome-wide studies and, hence, the spatio-temporal organization of the replication of repetitive DNA elements remains to be fully elucidated.
Here, we present a protocol that combines fluorescence in situhybridization (FISH) using repeat-specific probes with the detection of DNA replication signals (Repli-FISH) and DNA content. This method can be applied to 3-dimensionally preserved cells and allows high-throughput microscopic analysis at the single cell level.
2. Materials and Methods
A timeline of a typical Repli-FISH experiment is outlined inFigure 2A.
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Figure 2Representative timeline and setup of FISH experiments. A: Outline of the timelines of a typical replication FISH (Repli-FISH) experiment, showing that the combination of replication visualization and FISH can be performed over the course of four days. B: Experimental setup of the FISH denaturation and hybridization. A silicon wax mark is applied on a microscope slide and the coverslip is placed cell-side down on the probe; a silicon ring is used for additional sealing. A second microscope slide is then placed on top as a cover. For denaturation and hybridization, the entire apparatus is placed in a tightly sealed metal chamber.
2.1 Cell Culture
Human HeLa cervical carcinoma cells ([ 24], ATCC CCL-2) and mouse C2C12 myoblast cells ([ 25], ATCC CRL-1772) as well as mouse embryonic fibroblast cells (MEF W8, [ 26]) were cultured at 37°C under 5% CO 2in high glucose Dulbecco’s modified Eagle’s medium (DMEM; Cat. No.: D6429, Sigma–Aldrich Chemie GmbH, Steinheim, Germany) supplemented with 1 μM gentamicin (Cat. No.: G1397, Sigma–Aldrich Chemie GmbH), 20 mM L-glutamine (Cat. No.: G7513, Sigma–Aldrich Chemie GmbH) and fetal calf serum [FCS; 10% (HeLa and MEF W8) or 20% (C2C12)]. Cells were passaged every two days.
Murine embryonic stem cells (mESCs, J1, [ 27], ATCC SCRC-1010) were cultured in high glucose DMEM (Cat. No.: D6429, Sigma–Aldrich Chemie GmbH) containing 16% FCS, 1x non-essential amino acids (Cat. No.: M7145, Sigma–Aldrich Chemie GmbH), 1x penicillin/streptomycin (Cat. No.: P4333, Sigma–Aldrich Chemie GmbH), 1x L-glutamine (Cat. No.: G7513, Sigma–Aldrich Chemie GmbH), 0.1 mM beta-mercaptoethanol (Cat. No.: 4227, Carl Roth, Karlsruhe, Germany), PD 0325901 (0.1 µM; Cat. No.: Axon 1408, Axon Medchem BV, Groningen, The Netherlands), CHiR 99021 (0.3 µM; Cat. No.: Axon 1386, Axon Medchem BV) and LIF (1,000 U/ml; Cat. No.: ALX-201-242, Enzo Life Sciences GmbH, Lörrach, Germany). Cell culture medium was changed every day and cells were split every two days at a ratio of 1:8 – 1:10.
For Repli-FISH experiments, cells were seeded on gelatin-coated glass coverslips (0.2% gelatin; Cat. No.: G2500, Sigma–Aldrich Chemie GmbH).
2.2 Isolation of Genomic DNA
For the preparation of genomic DNA (gDNA), HeLa or C2C12 cells were harvested by centrifugation (10 min, 400 xg, 4°C) and incubated overnight at 50°C in TNES buffer (10 mM Tris [pH 7.5], 400 mM NaCl, 10 mM EDTA, 0.6% SDS and 1 mg/ml proteinase K (Carl Roth)). Subsequently, 0.6 mg/ml RNAse A (Qiagen, Hilden, Germany) was added and DNA was incubated for 30 min at 37°C to remove RNA. NaCl (6 M) was added to the extracted gDNA at a final concentration of 1.25 M. After centrifugation (15 min, 16,000 xg, room temperature), gDNA was precipitated from the supernatant by the addition of ice-cold 100% ethanol and incubation at -20°C for 1 h. The gDNA was pelleted by centrifugation (10 min, 16,000 xg, 4°C), washed with 70% ethanol, dried at room temperature and dissolved in ddH 2O.
2.3 Bio-16-dUTP Nucleotide Generation
Bio-16-dUTP labeling reactions contained 4.5 mM aminoallyl-dUTPs (5-(-3-aminoallyl)-2’-deoxyuridine 5’-triphosphate, Cat. No: A 0410, Sigma–Aldrich Chemie GmbH), 44.5 mM carbonate-bicarbonate buffer (0.2 M NaHCO 3stock with 0.5 M NaCl titrated to pH 8.3 with 0.2 M Na 2CO 3) with 0.5 M NaCl and 8.9 mM biotin-XX (6-((6-((biotinoyl)amino)hexanoyl)amino)hexanoic acid, Cat. No: B-1606, Molecular Probes) in a total volume of 45 μl. Reactions were incubated for 3–4 hours at room temperature and stopped by the addition of 20 mM glycine (pH 8.0). Subsequently, 20 mM Tris-HCl (pH 7.75) was added to stabilize the nucleotides [ 28].
2.4 Probe Generation
Details of primers used for all PCR-based labeling reactions (except for the LINE-1 probe, which was generated by nick-translation) are shown inTable 1.
Table 1Primers used for FISH probe generation.
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Table 1Primers used for FISH probe generation.
<table><tbody><tr><td> Primer name</td><td> Sequence [5’–3’]</td><td> Reference</td></tr><tr><td>Alu-F</td><td>GGATTACAGGYRTGAGCCA*</td><td>[ 29]</td></tr><tr><td>Alu-R</td><td>RCCAYTGCACTCCAGCCTG*</td><td>[ 29]</td></tr><tr><td>MaSat-F</td><td>AAAATGAGAAACATCCACTTG</td><td>[ 30]</td></tr><tr><td>MaSat-R</td><td>CCATGATTTTCAGTTTTCTT</td><td>[ 30]</td></tr><tr><td>MiSat-F</td><td>CATGGAAAATGATAAAAACC</td><td>[ 31]</td></tr><tr><td>MiSat-R</td><td>CATCTAATATGTTCTACAGTGTG</td><td>[ 31]</td></tr><tr><td>Telo-F</td><td>TTAGGGTTAGGGTTAGGGTTAGGGTTAGGG</td><td>[ 32]</td></tr><tr><td>Telo-R</td><td>CCCTAACCCTAACCCTAACCCTAACCCTAA</td><td>[ 32]</td></tr><tr><td colspan=3>*With Y being either pyrimidine (C or T) and R being either purine (G or A)</td></tr></tbody></table>
2.4.1 Alu-Specific Probe
Alu-specific probes were generated via a two-step PCR. First, Alu elements were amplified from HeLa cell genomic DNA using partially degenerate Alu-specific primers (Table 1andFigure 1A), followed by a PCR-based labeling with bio-16-dUTPs (Tables 2andTables 3). The product of the labeling PCR was subsequently purified with the QIAQuick PCR purification kit (Qiagen) according to the manufacturer’s instructions.
Table 2Reaction setup for Alu-specific probe PCR.
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Table 2Reaction setup for Alu-specific probe PCR.
<table><tbody><tr><td> PCR component</td><td> Template PCR (final concentration)</td><td> Labeling (final concentration)</td></tr><tr><td>PCR buffer</td><td>1x Taq buffer*</td><td>1x Taq buffer*</td></tr><tr><td>dATP/dGTP/dCTP</td><td>0.2 mM each**</td><td>0.2 mM each</td></tr><tr><td>dTTP</td><td>0.2 mM**</td><td>0.15 mM</td></tr><tr><td>Bio-16-dUTPs</td><td>-</td><td>0.05 mM</td></tr><tr><td>Primer F/R</td><td>1 μM each</td><td>1 μM each</td></tr><tr><td>Polymerase</td><td>1–2 U Taq</td><td>1–2 U Taq</td></tr><tr><td>DNA template</td><td>Human gDNA (150 ng)</td><td>1 μl 1:50 PCR product</td></tr><tr><td>Final volume</td><td>To 50 μl with ddH 2O</td><td>To 50 μl with ddH 2O</td></tr><tr><td colspan=3>*10x Taq buffer: 100 mM Tris/HCl pH 8.3, 500 mM KCl, 15 mM MgCl 2.** A dNTP mix containing all four nucleotides was used.</td></tr></tbody></table>
Table 3PCR cycling conditions for Alu-specific probe amplification.
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Table 3PCR cycling conditions for Alu-specific probe amplification.
<table><tbody><tr><td> Cycle step</td><td> Temperature</td><td> Time</td><td> Cycles</td></tr><tr><td>Initial denaturation</td><td>94°C</td><td>4 min</td><td>1</td></tr><tr><td>1. Denaturation</td><td>94°C</td><td>1 min</td><td rowspan=3>35</td></tr><tr><td>2. Annealing</td><td>57°C/65°C*</td><td>1 min</td></tr><tr><td>3. Extension</td><td>72°C</td><td>3 min 30 s</td></tr><tr><td>Final extension</td><td>72°C</td><td>10 min</td><td>1</td></tr><tr><td colspan=4>*Annealing at 57°C for the first amplification of Alu elements from gDNA (template PCR)/annealing at 65°C for the subsequent labeling PCR.</td></tr></tbody></table>
2.4.2 LINE-1-Specific Probe
LINE-1 probes were generated and labeled with bio-16-dUTPs by nick-translation of the pLRE3-eGFP plasmid containing the LRE wild-type LINE-1 sequence ([ 33], a kind gift from John V. Moran, University of Michigan Medical School, USA). Reactions contained 50 mM Tris-HCl pH 8, 5 mM MgCl 2, 0.5 mg/ml BSA, 10 mM beta-mercaptoethanol, 0.04 mM biotin-16-dUTPs or digoxigenin-11-dUTPs, 0.05 mM dATP/dGTP/dCTP each, 0.32 U DNase I (D5025, Sigma–Aldrich Chemie GmbH), 10 U Klenow fragment (M0210, NEB, Ipswich, MA, USA), 1 μg pLRE3-eGFP plasmid DNA in a total volume of 100 μL. Reactions were incubated for 90 min at 15°C and stopped by adding 5 μl 0.5 M EDTA.
Alu- and LINE-1-specific probes were sheared with a Covaris S220 device (Covaris Inc., Woburn, MA, USA) to a final size of approximately 250 bp in microTUBES (520045, Covaris Inc.). Quality and size were evaluated by 1% agarose gel electrophoresis.
2.4.3 Major and Minor Satellite Repeat-Specific Probes
Both major and minor satellite repeat-specific probes were generated via PCR amplification using repeat-specific primers (Table 1andFigure 1) and mouse genomic DNA from C2C12 mouse myoblasts as the template (Tables 4andTables 5). Since this amplification results in probes of varying lengths (detectable as a smear following agarose gel electrophoresis, seeFigure 3), samples need to be digested using DNase I (1:250 dilution in ddH 2O (stock: 2U/µl), 2 µl/reaction) for a maximum of 30 min at room temperature. The reaction was stopped by the addition of 1 µl 0.5 M EDTA and probe quality and size were evaluated by 1% agarose gel electrophoresis (15 µl of reaction mixture).
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Figure 3Assessment of FISH probe quality. Agarose gel showing probes before and after shearing. Amplification of repetitive DNA elements via PCR or nick-translation leads to amplicons of different sizes (left); digestion with DNase I or mechanical shearing decreases the length of the probes (right). M = marker.
Table 4Reaction mixture for major and minor satellite-specific probe PCR amplification.
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Table 4Reaction mixture for major and minor satellite-specific probe PCR amplification.
<table><tbody><tr><td> PCR component</td><td> PCR (final concentration)</td></tr><tr><td>PCR buffer</td><td>1x Taq buffer*</td></tr><tr><td>dATP/dGTP/dCTP</td><td>0.2 mM each</td></tr><tr><td>Bio-16-dUTPs/dig-11-dUTPs**</td><td>0.08 mM</td></tr><tr><td>Primer F/R</td><td>0.2 µM</td></tr><tr><td>Polymerase</td><td>1–2 U Taq</td></tr><tr><td>DNA template</td><td>1 µl mouse gDNA</td></tr><tr><td>Final volume</td><td>To 100 μl with ddH 2O</td></tr><tr><td colspan=2>* 10x Taq buffer: 100 mM Tris/HCl pH 8.3, 500 mM KCl, 15 mM MgCl 2.** Digoxigenin-11-dUTPs alkali-labile (Cat. No: 11573152910, Sigma–Aldrich Chemie GmbH).</td></tr></tbody></table>
Table 5PCR cycling conditions for major and minor satellite-specific probe amplification.
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Table 5PCR cycling conditions for major and minor satellite-specific probe amplification.
<table><tbody><tr><td> Cycle step</td><td> Temperature</td><td> Time</td><td> Cycles</td></tr><tr><td>Initial denaturation</td><td>95°C</td><td>5 min</td><td>1</td></tr><tr><td>1. Denaturation</td><td>95°C</td><td>1 min</td><td rowspan=3>40</td></tr><tr><td>2. Annealing</td><td>56°C</td><td>1 min</td></tr><tr><td>3. Extension</td><td>72°C</td><td>2 min</td></tr><tr><td>Final extension</td><td>72°C</td><td>5 min</td><td>1</td></tr></tbody></table>
2.4.4 Telomere Repeat-Specific Probe
Probes specific for telomeric repeats were generated by a two-step PCR using previously described self-annealing primers [ 32]. The first PCR reaction served to create elongated probe fragments with regular dNTPs, while the second reaction included biotinylated or cyanine dye-conjugated nucleotide analogues for efficient probe labeling (Table 6). For the initial amplification, a high-fidelity polymerase was used (e.g. Q5 polymerase (NEB, Cat#: M0491)). For labeling with bio-16-, Cy3- or Cy5-conjugated dUTPs in the subsequent PCR, however, Taq polymerase was required since the Q5 polymerase does not incorporate dUTPs. Identical cycling conditions were used in both reactions (Table 7).
Table 6Reaction mixture for telomere repeat-specific probe PCR amplification.
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Table 6Reaction mixture for telomere repeat-specific probe PCR amplification.
<table><tbody><tr><td> PCR component</td><td> PCR (final concentration)</td><td> Labeling (final concentration)</td></tr><tr><td>PCR buffer</td><td>1x Q5 buffer</td><td>1x Taq buffer*</td></tr><tr><td>MgCl 2</td><td>0.5 mM</td><td>-</td></tr><tr><td>dATP/dGTP/dCTP</td><td>0.2 mM each**</td><td>0.05 mM each</td></tr><tr><td>dTTP</td><td>0.2 mM**</td><td>0.01 mM</td></tr><tr><td>Bio-16-dUTPs/Cy3 or Cy5-dUTPs***</td><td>-</td><td>0.1 mM/0.08 mM</td></tr><tr><td>Primer F/R</td><td>0.2 µM each</td><td>0.2 µM each</td></tr><tr><td>Polymerase</td><td>1–2 UQ5 DNA polymerase</td><td>1–2 U Taq</td></tr><tr><td>DNA template</td><td>-</td><td>1 µl of PCR product</td></tr><tr><td>Final volume</td><td>To 50 μl with ddH 2O</td><td>To 50 μl with ddH 2O</td></tr><tr><td colspan=3>* 10x Taq buffer: 100 mM Tris/HCl pH 8.3, 500 mM KCl, 15 mM MgCl 2.** A dNTP mix containing all four nucleotides was used.*** Cy3-dUTP and Cy5-dUTP: GE Healthcare (Chicago, IL, USA) PA53022 and PA55022 respectively.</td></tr></tbody></table>
Table 7PCR cycling conditions for telomere-specific probe amplification.
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Table 7PCR cycling conditions for telomere-specific probe amplification.
<table><tbody><tr><td> Cycle step</td><td> Temperature</td><td> Time</td><td> Cycles</td></tr><tr><td>Initial denaturation</td><td>95°C</td><td>5 min</td><td>1</td></tr><tr><td>1. Denaturation</td><td>98°C</td><td>10 s</td><td rowspan=3>40</td></tr><tr><td>2. Annealing</td><td>50°C</td><td>15 s</td></tr><tr><td>3. Extension</td><td>72°C</td><td>20 s</td></tr><tr><td>Final extension</td><td>72°C</td><td>2 min</td><td>1</td></tr></tbody></table>
2.5 Probe Precipitation and Fluorescence in Situ Hybridization (FISH)
NOTE: Co-detection of incorporated EdU must be performed prior to FISH (seeFigure 2Aand refer to Section 2.6.2).
2.5.1 Probe Precipitation
Probes were ethanol-precipitated with 0.15 M sodium-acetate and 50 μg/ml fish sperm DNA, washed with 70% ethanol, air-dried and resuspended in hybridization solution containing formamide (70% formamide, 2x SSC (30 mM Na-citrate, 300 mM NaCl), 10% dextran sulfate, pH 7) for MaSat-, MiSat- and telomere-specific probes, and without formamide (10 mM Tris-HCl, 3 mM MgCl 2, 50 mM KCl, 10 μg/ml gelatin, 2x SSC, [ 34, 35]) for Alu- and LINE-1-specific probes. Probes were denatured for 5 min at 80°C and immediately placed on ice.
2.5.2 Cell Preparation
For subsequent hybridization and detection of replication signals, cells were washed twice with 1x PBS and immediately fixed with 3.7% formaldehyde/PBS for 10–15 min. After washing (2–3x) in PBS-T (0.02% Tween), cells were permeabilized in 0.5% Triton-X100/PBS for 10–15 min and washed again with PBS-T. At this point, cells may be used directly for hybridization, or stored for a few days in 1x PBS at 4°C.
For MaSat-, MiSat- and telomere-specific probe hybridization, cells were incubated for 15 min in 0.1 M HCl, washed 3x with 1x PBS. Cells were then and equilibrated for 2 min in 2x SSC and finally for 20 min in 50% formamide/2x SSC. For Alu and LINE-1 FISH, cells were equilibrated in hybridization solution without formamide (see Section 2.5.1). All incubation steps were performed at room temperature.
For metaphase spreads, asynchronously growing cells were treated with colcemid (0.1 µg/ml final concentration) for 1 h, harvested by trypsinization and centrifuged at 500 x gfor 5 min. After carefully removing the supernatant, the cell pellet was resuspended in pre-warmed KCl solution (0.075 M at 37°C) and incubated at 37°C for 5 min. To prevent clumping of the cells, the first
1–2 ml were added drop-wise and mixed well by flicking the tube. The rest of the solution was added to give a total volume of approximately 8 ml. After a second centrifugation step, the pellet was fixed by the initial drop-wise addition of freshly prepared fixative solution (methanol:acetic acid, 3:1), which was then filled up to 10 ml. After incubation at 4°C for at least 20 min (overnight incubation is preferred) the samples were again centrifuged and most of the supernatant was removed by decanting. The cell pellet was then finally resuspended in the remaining fixative solution by flicking. The chromosome preparations were made from 15–20 µl drops on microscope slides that were dipped into ddH 2O.
For the subsequent hybridization, the slides were air-dried overnight, rehydrated for 10 min in ddH 2O and digested at 37°C for 10 min in 0.005% pepsin (P6887, Sigma–Aldrich Chemie GmbH) in 0.01 M HCl. The slides were then dehydrated in 70% and 100% ethanol (5 min each) and air-dried overnight. Before hybridization, slides were equilibrated for 30 min in 50% formamide/2x SSC.
2.5.3 Hybridization
For hybridization of interphase cells, a circle/square the size of the glass coverslip carrying the cells was drawn onto a regular microscope glass slide (Menzel–Gläser Superfrost, Thermo Scientific, Cat. No: ABAA000080##32E) using an ImmunoPen (Calbiochem, Cat. No.: 402176-1EA). The hybridization solution containing the respective probe(s) was then applied to the center of this mark and cells were applied face down onto the hybridization solution. The coverslip was additionally sealed with a silicon ring/square (self-made) and a second microscope slide was applied on top. The whole apparatus was then transferred to a hybridization chamber and tightly sealed (Figure 2B).
For hybridization of metaphase spreads, the area of the slide containing the spreads was encircled using an ImmunoPen. The respective probe(s) were then applied, covered with a coverslip to ensure even distribution of the probe and further sealed with a silicon square and a second microscope slide.
The chamber was subsequently incubated at 80°C for 5 min in a water bath to denature both the genomic DNA and probe. This was followed by incubation in a second water bath at 37°C for 24 h (MaSat, MiSat and telomeres) or overnight at 42°C (Alu and LINE-1).
2.5.4 Washing and Blocking
After hybridization, cells were carefully removed from the microscope slide and washed three times for 5 min with 50% formamide/2x SSC pH 7 at 45°C followed by two washes for 5 min in 2x SSC at 45°C. For the Alu- and LINE-1-specific probes, the washing steps were performed with 2x SSC and 0.1x SSC without formamide. To block non-specific antibody binding sites, cells were incubated for 30 min in 1% BSA/4x SSC at room temperature.
NOTE: For PCNA detection, immunodetection must be performed before continuing with the probe detection (Section 2.6.1 andFigure 2).
2.5.5 Probe Detection
Probes were detected by incubation with a rabbit anti-digoxigenin antibody (1:500, Cat. No.: 700772, Thermo Fisher Scientific), a fluorescently-labeled anti-rabbit IgG antibody or fluorescently-tagged streptavidin diluted in 1% BSA/4x SSC, for 20 min at room temperature and washed three times for 5 min with 0.05% Tween/4x SSC.
A post-fixation step with 1%–4% formaldehyde/PBS for 10 min further stabilized the resulting antibody complexes.
DNA counterstaining was performed by incubating cells for 10 min at room temperature with DAPI (10 μg/ml, 4′,6-diamidin-2-phenylindol) and slides were mounted using Mowiol (Merck KGaA, Cat. No.: 81381-250G).
2.6 Replication Staining
2.6.1 Staining of the Replisome Component PCNA.
Immunofluorescent detection of PCNA usually requires additional fixation with methanol. This step ensures accessibility of the anti-PCNA antibody to the epitope, which is located at the interface between the monomeric subunits of the homotrimeric PCNA ring-complex (Figure S1). However, we noticed that this step could be omitted when the hybridization procedure has been performed before.
To achieve good signals, antibody detection of PCNA must be performed after hybridization and washing but before detection of the probe (Figure 2A). After blocking as described in Section 2.5.4, cells were incubated for 1–2 h at room temperature with an antibody specific for PCNA (mouse anti-PCNA, mAb, DABCO, Cat#: M0879, 1/200) diluted in blocking buffer (1x PBS/0.02% Tween20/2% BSA). After washing (2–3x) in PBS-T (0.02% Tween20), detection with secondary antibodies conjugated with fluorophores suitable for subsequent microscopic detection was performed, before continuing with the probe detection (see Section 2.5.5).
2.6.2 EdU Labeling and Visualization of Replicated DNA
EdU labeling and detection must be carried out before cells are equilibrated in SSC and hybridization is performed.
For detection and staining of active DNA synthesis sites, cells were incubated for 15 min with 10 μM EdU (5-ethynyl-2’-deoxyuridine, Thermo Fisher Scientific, Waltham, MA, USA), washed with 1x PBS and fixed with 3.7% formaldehyde/PBS for 10 min. After washing (3x) with PBS-T (0.02% Tween20), cells were permeabilized with 0.5% Triton-X100/PBS for 15 min and pre-denatured with 0.1 M HCl for 15 min, followed by a second permeabilization step with 0.5% Triton-X100/PBS for 15 min.
EdU was detected using ClickIT chemistry (EdU Click-ROTI kit, Carl Roth, Karlsruhe, Germany) according to the manufacturer's instruction. The 6-FAM and the 3-azido-7-hydroxycoumarin azides were used in final dilutions of 1:1,000 and 1:200, respectively. Cells were post-fixed with 1% formaldehyde/PBS for 10 min before proceeding with equilibration in SSC and hybridization buffer, followed by FISH and probe detection (see sections 2.5.2–2.5.5).
2.7 Confocal Microscopy and Line-Profile Colocalization Analysis
Confocal z-stacks of Repli-FISH stained cells were acquired using the UltraVIEW VoX spinning disc microscopy system (PerkinElmer Life Sciences, Waltham, MA, USA) equipped with an oil immersion 60x Plan Apochromat NA 1.45 objective lens.
To measure and compare the overlap between the major satellite-specific FISH probe signals and the replication signals (EdU), line intensity profile analysis was performed in the mid-focal planes of individual nuclei from cells in different stages of the cell cycle (non-S versus early, mid and late S-phase) using ImageJ (https://imagej.nih.gov/ij/). The intensities of both signals were measured along a line drawn manually through the nuclei and covering both euchromatic and heterochromatic (chromocenters) portions within the cell nucleus. The intensity values of both channels were subsequently plotted against the distance along the line.
2.8 High-Content/High-Throughput Imaging and Analysis
High-content/high-throughput imaging and analysis were performed with the Operetta High-Content Imaging System (Perkin Elmer, Part Number: HH12000000). Multiple fields-of-view (169 in total) were acquired with an immersion free 60x high NA objective (NA 0.9) and automatic image analysis was performed with the associated Harmonysoftware (v3.5). The analysis pipeline involved the initial automatic detection and segmentation of individual cell nuclei based on DAPI counterstaining. Cells overlapping the edge of the image or otherwise deformed cell nuclei were excluded from the analysis. Subsequently, segmentation of major satellite repeats within the individual cell nuclei was performed based on the fluorescence signal of the hybridized MaSat-specific probe. Based on this object segmentation, the fluorescence intensity of the replication signal (PCNA in this case) was measured within all spots per individual cell nucleus. This allowed the comparison of overlapping signals at the different S-phase substages with each other and also with non-S-phase cells (G1- and G2-phase) from the whole population. For this, the cells were sorted according to the different cell cycle stages based on the PCNA patterns in ImageJ using a custom written macro (available upon request). In addition, the DAPI intensity of each nucleus was measured to compare DNA content within the different subpopulations. Boxplots were used to plot (1) the increase in DNA content over the cell cycle (non-S-phase, early and late S-phase) and (2) the accumulation of PCNA at chromocenters in cells at the different cell cycle stages using RStudio (Version 0.99.893).
Harmony analysis pipeline:
1) Input image:
- Stack processing: Max. projection
- Flatfield correction: Basic
2) Find Nuclei (2):
- Channel: DAPI
- Method A
=> Output population: Nuclei
3) Find spots:
- Channel: Alexa 488
- Population: Nuclei
- Region: Nucleus
- Method: A
=> Output population: Alexa488 spots
4) Calculate morphological properties:
- Population: Nuclei
- Region: Nucleus
- Method: Standard
5) Select population (2):
- Population: Nuclei
- Method: Common filters
- Remove border objects
=> Output population: Nuclei inside [field-of-view]
6) Select population:
- Population: Nuclei inside
- Method: Filter by property
- Properties roundness: 0.8
- Properties area [µm 2] <300
- Properties area [µm 2] >60
=> Output population: Round nuclei inside (exclude deformed nuclei)
7) Calculate intensity properties (in whole nucleus and in spots):
- DAPI, MaSat, PCNA
3. Results
Repetitive DNA elements are difficult to investigate using genomic approaches due to their repetitive nature, which hinders their mapping to reference genomes. Here, we describe the use of probes for five different genetic repeat elements in different species (mouse and human) and at different developmental stages for the study of their DNA replication kinetics. The probes presented here are commonly used in our laboratory and were generated via standard procedures (PCR and nick-labeling) as described in Section 2 ( Material and Methods). However, we also emphasize the use of other probes that are suitable for the detection of specific DNA sequences and that have been proven useful in cytogenetic studies, e.g. peptide nucleic acids (PNAs; [ 36]), probes generated via primed in situ synthesis(PRINS; [ 37, 38]) or from bacterial artificial chromosomes (BACs).
In order to confirm their specificity, we performed metaphase FISH with all DNA probes.Figure 4Ashows the results for human Alu- and LINE-1-specific probes and their distribution along DAPI-counterstained chromosomes as measured by line-profile colocalization analysis (Figure 4A). Alu elements are abundant in GC-rich regions, whereas LINE-1 elements are predominantly found in AT-rich (GC-poor) regions. We found the distribution of Alu elements correlated negatively with the DAPI staining, which preferantially binds AT-rich regions of the DNA, wheras LINE-1 and DAPI signals correlated positively. Furthermore, double hybridization of mitotic chromosomes with biotin-labeled Alu- and digoxigenin-labeled LINE-1-specific probes showed mutually exclusive binding of the two elements (Figure 4A&Figure 4B), emphasizing their existence in distinct regions of the genome (Figure 1B).
The localization and specificity of the mouse probes against MaSat, MiSat and telomeres were evaluated by triple-color DNA FISH on chromosome preparations. For this, the probes were labeled via PCR using dUTPs conjugated to either digoxigenin-11, biotin-16- or Cy5. The results are summarized inFigure 4C. The telomere probe was found to hybridize specifically to the ends of chromatids, resulting in four signals per chromosome. Major satelite probes displayed only one large signal on each chromosome overlapping with DAPI-intense pericentromeric segments. In contrast, the minor satellite probe hybridization resulted in two distinct spots per chromosome; one per chromatid. In accordance with their chromosomal distribution, the centromeric (MiSat) and pericentromeric (MaSat) DNA signals were found in close proximity. Due to the acrocentric organization of mouse chromosomes (Figure 1A), a similar distribution was observed for proximal telomeres and minor satellite DNA. The clustering of pericentromeric and centromeric heterochromatin as well as the organization of chromosomal ends was also visualized by the simultaneous hybridization of all probes to interphase cells as shown inFigure S2. In summary, these data clearly confirmed the specificity of each probe for its intended target structure.
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Figure 4Validation of FISH probe specificity by hybridization to metaphase chromosome preparations. A:Whole metaphase spreads from HeLa cells were hybridized with human Alu-specific (upper row) and human LINE-1-specific (lower row) FISH probes. Chromosomes were counterstained with DAPI. Color line profiles represent the expected overlap between Alu with GC-rich (gene-rich) and LINE-1 with AT-rich (gene-poor) regions, which are differentially stained by DAPI. Scale bar: 5 µm. B:A metaphase spread hybridized to both human Alu-specific (red) and human LINE-1-specific (cyan) probes simultaneously reflects their widespread distribution along eu- and heterochromatic DNA segments (left). The two probes hybridize to mutually exclusive segments along chromosomes as represented by line-profile analysis of a single representative chromosome (right). Scale bar: 5 µm. C:Triple-color FISH combining major satellite-, minor satellite- and telomere-specific probes, each labeled with a different nucleotide analog and hybridized to metaphase chromosome preparations from diploid mouse cells. All probes bind specifically to the chromosomal regions in which the target sequences are organized (see also enlarged insets in each image), i.e. chromosome ends (telomeres, magenta), DAPI-dense pericentromeric regions (MaSat, red) and centromeric regions (MiSat, green). Scale bar: 10 µm.
In both mouse ESC and myoblast interphase nuclei, major satellite DNA was detected as large spots co-localizing with DAPI-intense regions (Figure 5A, upper row). In contrast, minor satellite signals were found in close proximity to the major satellite clusters, forming several distinct spots at their periphery, as expected from their physical location on individual chromosomes (Figure 5A, middle row andFigure 1A). Telomere-specific FISH signals were detected throughout the nucleus, with some localizing adjacent to pericentric heterochromatin (Figure 5A, lower row) due to the acrocentric nature of mouse chromosomes (seeFigure 1A).
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Figure 5Overview of the localization of MaSat, MiSat and telomeres in murine interphase cells. A:MaSat-, MiSat- and telomere-specific FISH was performed on interphase cells of mouse embryonic stem cells (mESC, left) and mouse myoblasts (right). DNA was visualized by DAPI counterstaining. B:DNA replication was visualized by PCNA co-staining or EdU incorporation and detection. Scale bar: 5 μm.
As interphase chromosomes distribute throughout the nuclear volume, signals for both LINE-1 and Alu interspersed repeats were found throughout the nuclei of human cells, albeit excluded from the nucleoli (Figure 6A). This reflects the fact that both classes of elements cover a large proportion of the genome (e.g. approximately 11% for Alu repeats [ 39]) as represented by the distribution of LINE-1 and Alu elements on metaphase chromosomes (Figure 1B,Figure 1CandFigure 4B) .Notably, the correlation of LINE-1 signals with heterochromatin was stronger than the correlation of Alu signals as judged by the distribution of the DNA and replication signals (note that chromocenters do not form in human cells) (Figure 6AandFigure 6B). A detailed analysis of the distribution of Alu and LINE-1 signals throughout S-phase as well as their replication timing are reported in [ 40]. In brief, it was shown that Alu elements are replicated during early S-phase, whereas LINE-1 elements are replicated throughout S-phase.
Next, we evaluated the DNA replication kinetics of Alu and LINE-1 elements. We were able to show that both signals, either PCNA or EdU, facilitated discrimination between replicating and non-S-phase cells within an asynchronous cell population (Figure 5B,Figure 6A&Figure 6B). While replicating cells are characterized by the dynamic focal accumulation of the respective signal throughout S-phase, cells in either the G1- or G2-phase of the cell cycle can be identified by the lack of such a pattern. Due to the different types of replication markers used in our approach, non-S-phase cells co-stained for PCNA showed a diffuse nuclear signal representing the unbound nuclear pool of the protein (Figure 5B, left panel, [ 41, 42, 43, 44]). In contrast, cells in which nascent DNA is marked by the incorporation of the thymidine analog EdU, were only labeled during S-phase and no signals were detected in the G1 and G2 phases (Figure 5B, right panel). Notably, the nuclear localization of the different repetitive elements did not change within the nucleus of S-phase cells, to which the analysis was restricted as can be seen by comparison of the FISH signal distribution in cells at the different stages of S-phase (Figure 5B). Taken together, our results showed that all probes used in this study were highly specific for their intended target sequence (Figure 4), resulting in clear signals with high signal-to-noise ratio when hybridized to interphase nuclei. Furthermore, both nascent DNA as well as replication factors were co-visualized successfully (Figure 5&Figure 6).
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Figure 6Overview showing the localization of Alu and LINE-1 elements in human interphase cells. A:HeLa interphase cells showing the nuclear distribution of Alu- and LINE-1-specific FISH signals. DNA was visualized by DAPI counterstaining. Alu- and LINE-1-specific FISH signals visualized in combination with EdU in S-phase cells. B:The same probes were observed in cells that are not in S-phase for comparison of their respective distribution in the cell nucleus. Scale bar: 5 μm.
Colocalization analysis (e.g., color line-profile analysis) of the overlapping FISH and replication signals serve as a measure of ongoing DNA replication during the substages of S-phase and, thus, indicate replication timing.Figure 7shows the outcome of such representative measurements performed on mouse myoblast cells hybridized with the MaSat-specific probe. Again, non-S-phase and replicating cells can be discriminated by the absence or presence of the EdU signal, respectively. Furthermore, the replication of euchromatin (early S), as well as facultative (mid-S) and constitutive heterochromatin (late S), are represented by the changing EdU patterns. The overlap between FISH and replication signals along the analysis path (white arrow) were strongest at late S-phase, which is in complete accordance with previous reports [ 45, 46].Figure S3shows the results from a similar analysis performed with cells hybridized to either MiSat- or telomere-specific probes. Here, we found minor satellite DNA replicated asynchronously throughout S-phase, indicated by the overlap of the MiSat FISH signal and replication foci (EdU) shown by line-profile analysis and similar to the results published by [ 47]. Furthermore, telomeres were also found to replicate throughout the course of S-phase, which is in accordance with previous findings [ 48, 49, 50].
<here is a image cf0c3b9d31425da1-d1a4083e85f906a6>
Figure 7MaSat probe localization in mouse myoblast cells at different S-phase substages.Cells were classified as non-S-phase, early, mid and late replication substage according to their EdU pattern. Colocalization of MaSat FISH (magenta) and replication (green) was analyzed via a color line-profile (black arrows). Scale bar: 5 μm.
These results were also validated and extended by high-content/high-throughput imaging and analysis of asynchronous cell populations (Figure 8). Here, suitable cells were automatically identified based on DNA counterstaining with DAPI (Figure 8A, left). The progression through S-phase was reflected not only by the replication signal pattern, but also by the increase in genomic DNA content over time as measured by the increasing DAPI intensity from cells at the different S-phase substages (Figure 8A, right). The broader signal distribution of non-S-phase cells can be explained by the fact that cells from both G1- and G2-phases of the cell cycle were grouped in this fraction. Cells were classified as non-S-phase cells and cells at either early or late S-phase based on the replication signal distribution (Figure 8B, left). The latter showed a similar increase in the replication signal overlap (PCNA) with major satellite repeats at late S-phase (Figure 8B, right), thus, supporting the previous results of individual cell measurements (Figure 7).
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Figure 8High-content/high-throughput Repli-FISH analysis of asynchronous cell populations.MEF W8 cells hybridized with a major satellite-specific probe and co-stained for PCNA were imaged with a high-content imaging system (Operetta High-content Imaging System, Perkin Elmer, 60x 0.9 NA air objective). A: Image analysis was performed with the Harmonysoftware. Automatic segmentation of cell nuclei was performed based on DNA counterstaining with DAPI (left, green circles). Cells out of focus or on the edge of the image were excluded from the analysis (left, red circles). Increasing DNA content during S-phase is represented by the increase in total DAPI intensity measured in cells at early or late S-phase compared to non-S-phase cells (right). B:Cells were classified by the PCNA signal distribution and sorted into non-S-phase cells (left, gray circles) and cells at either early (left, purple circles) or late S-phase (left, green circles). Comparison of the mean PCNA intensity within all major satellite spots per cell nucleus showed a clear increase toward late S-phase (right, green boxplot), allowing discrimination from the other classes in the population and confirmed the results of individual cell measurements shown inFigure 7.
4. Discussion
Modern next-generation sequencing methods have become increasingly cost and time-efficient. However, available software is still challenged by the correct mapping of repetitive elements both in resequencing and de novoassembly projects. This can be partially explained by the read-length that is now achievable (50–150 bp by next-generation sequencing compared to 800–900 bp obtained by Sanger sequencing), which is substantially shorter than the length of most repeats covering the genome. This results in reads that map to multiple locations within the genome (multi-reads) in resequencing experiments or gaps in de novogenome assemblies [ 39].
At the same time, several methods have been developed that combine the isolation of nascent DNA from replicating cells with subsequent deep-sequencing (Repli-seq) of the underlying DNA sequence [ 51]. This method can be used to study the replication timing from cell populations on a genome-wide scale and further offers the ability to relate the sequence information to underlying DNA and chromatin modifications, providing correlative information on the mechanism by which DNA replication is regulated.
Due to the length of time required to sufficiently label and precipitate hundreds of kilobases of labeled DNA (>60 min), these methods have a rather poor temporal resolution. Because of cell population averaging, the analysis focuses mainly on early versus late replicating cells, thereby masking intermediate replication states. Thus, given the fast underlying kinetics and potential variability of the replication process in individual cells, not all questions can be addressed with such methods. In addition, this method is problematic in the alignment of repetitive elements to a reference sequence as described previously.
Although described specifically for different repetitive elements in mouse and human cell lines, the Repli-FISH method can be easily extended using other probes, such as satellite repeat elements [ 40], rDNA repeat loci [ 52] or individual genes, e.g. via labeled bacterial artificial chromosomes (BACs) with sequence complementarity to specific genes [ 53]. In addition, the hybridization procedure can be combined with the detection of other signals of interest, including specific proteins and histone or DNA modifications.
Finally, individual cells can be analyzed either in 3-dimensions at the single cell level or using high-throughput/high-content microscopy techniques and at all levels of microscopical resolution (wide-field, confocal and super-resolution). Of note, the procedure described in this report preserves nuclear integrity (Figure S4), similar to other FISH procedures that include, for example, repeated freezing and thawing in liquid nitrogen [ 28].
In summary, the Repli-FISH method described here is an efficient and complementary approach to the study of replication kinetics of a broad range of DNA sequences that are otherwise difficult to map and study with the currently available next-generation sequencing methods.
Acknowledgments
We are indebted to Anne Lehmkuhl and Stephanie Meyer for excellent technical assistance. We thank John V. Morgan (U. Michigan Medical School, USA) for providing the pLRE3-eGFP plasmid.
Additional Materials
The following additional materials are upload at the page of this paper.
Figure S1: The epitope for the monoclonal anti-PCNA antibody (PC10) maps to the interface of the PCNA monomers.
Figure S2: Triple-color FISH combined with replication staining.
Figure S3: Localization of MiSat- and telomere-specific probes in mouse myoblast cells at different S-phase substages.
Figure S4: Effect of the hybridization procedure on nuclear integrity.
Author Contributions
C.R., P.W. and M.C.C. wrote the manuscript. A.S. performed experiments in HeLa cells with Alu and LINE-1 specific probes. C.R. and P.W. performed experiments in mouse myoblast and ES cells, respectively using probes for major, minor and telomeric repeats and in metaphase cells. C.R. and P.W. analyzed the data.
Funding
This work was supported by grants of the Deutsche Forschungsgemeinschaft (GRK1657/TP1B and DFG CA198/9-1 and 2) to M.C.C..
Competing Interests
The authors have declared that no competing interests exist.
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08/03/93 Jeffrey a. Fisher | Appellate Court of Illinois | 08-03-1993 | www.anylaw.com
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08/03/93 Jeffrey a. Fisher
Medical Business Associates, and STEVEN P.
NUERNBERGER, individually and d/b/a Southern
Illinois Medical Business Associates, Defendants-Appellees.
Appeal from the Circuit Court of Madison County. No. 84-CH-68. Honorable Michael J. Meehan, Judge Presiding.
APPELLATE judges:
CHAPMAN, LEWIS, GOLDENHERSH
DECISION OF THE COURT DELIVERED BY THE HONORABLE JUDGE CHAPMAN
Jeffrey A. Fisher filed a complaint against Harry Parks and Steven Neurnberger, alleging that he had been a partner with the defendants in a medical pathology practice known as Southern Illinois Medical Business Associates and that the defendants wrongfully expelled him from the partnership and failed to account for his financial interest in the business. The trial court, sitting without a jury, entered judgment for the defendants. Plaintiff appeals. We affirm.
The first issue on appeal is whether the trial court erred in finding that defendants complied with the procedural requirements of the partnership agreement. Specifically, Fisher argues that the notices of expulsion were not in accordance with the agreement and that he was wrongfully denied a 60-day probationary period. To resolve this issue, we must turn to the testimony adduced at trial.
In July of 1977, pathologists Steven Nuernberger and Harry Parks entered into a partnership agreement to provide clinical pathology services under the name of Southern Illinois Medical Business Associates. In July of 1978, Jeffrey Fisher, also a pathologist, joined the partnership. Throughout the term of the partnership, two of the partners in SIMBA would service several rural hospitals in Southern Illinois, including those at Sparta, Pinckneyville, Murphysboro, and DuQuoin. SIMBA also serviced the hospital in Mt. Vernon and Alton Memorial Hospital in Alton. At each hospital SIMBA pathologists operated the hospital's laboratory, supervised and trained hospital lab personnel, participated in the training of medical staff, and undertook any clinical pathology while on duty. The remaining partner would service and supervise SIMBA's Collinsville-Belleville laboratory and was on call for the coroners or physicians in St. Clair and Madison Counties to perform autopsies. In addition, all of the partners were on call to do any autopsies which were required on Saturday and Sunday. The duties of the three partners were rotated.
Neither Parks nor Nuernberger had any criticism of Fisher's performance during his first year with the partnership. The first complaint regarding Fisher came in September of 1979, from Mr. Nehrt, the administrator of the Sparta Community Hospital. Nehrt withheld a day's pay from SIMBA amounting to $250, for Fisher's failure to attend certain meetings. Parks testified that he believed SIMBA could forfeit its contract with Sparta Community Hospital if these actions continued. Parks testified that during this same period he was given the impression from others that Fisher had begun a practice of jogging during office hours when he should have been attending to matters at the laboratory or servicing client hospitals. Parks testified that this practice continued from the fall of 1979 until Fisher's departure from SIMBA in 1981.
Mary Cruzvergara, Ruth Joachimsthaler, and Arna Trotter, employees of SIMBA, testified that because of Fisher's jogging there were times when he could not be reached either at a particular hospital or at the laboratory. They testified that although the laboratory hours were 8:00 a.m. to 5:00 p.m., Fisher usually spent six hours at the laboratory, which included the 45 minutes to an hour and a half he spent jogging. Cruzvergara and Trotter both testified that Fisher's jogging during working hours and keeping minimal hours never changed. Cruzvergara testified that once Fisher got lost while jogging in Collinsville and someone from the laboratory had to retrieve him. She recalled that in early 1989 Fisher told her that he did not feel pathology was for him and that he would be happier practicing holistic or nutritional medicine in New York.
There was also testimony that Fisher jogged while he was on duty at client hospitals. Nancy Powles, a medical technologist at St. Joseph's Hospital in Murphysboro, testified that Fisher went out jogging more than half the times that he visited the hospital and that he would do this shortly after he arrived. On a number of occasions Powles had to tell physicians that Fisher was unavailable because he was out jogging. Jo Ellen Heggemeier, a medical technologist at Sparta Community Hospital, testified that Fisher went jogging nearly every time that he visited the hospital. Due to his jogging, he was unavailable for meetings and was not as available to her or the laboratory staff as Parks and Nuernberger were. She also testified that while Nuernberger's, Parks', and Fisher's hospital visits averaged two hours, Fisher's two hours included the time he spent jogging.
David Hosler, chief executive officer of Marshall Browning Hospital in DuQuoin, testified that, during the time SIMBA has provided services to the hospital, he has been critical of only one pathologist, Jeffrey Fisher. Hosler testified that Fisher would spend minimal time at the hospital and was not fulfilling the obligations for which the hospital had contracted with SIMBA. This matter, along with other problems, caused Hosler to rewrite the contract with SIMBA to specify more clearly the length of time a physician was required to spend at the hospital.
Ruth Lafferty, a pathology secretary at Alton Memorial Hospital, testified that Fisher serviced Alton Memorial Hospital on numerous occasions and that he would go jogging nearly every day. Lafferty testified that on one occasion Fisher could not be reached to perform a frozen section because he was out jogging.
SIMBA was also responsible for performing autopsies in St. Clair and Madison Counties. Alva Busch, a crime-scene technician for the State of Illinois, testified that in November of 1979 Fisher performed an autopsy of a man who was shot through the head. Busch testified that he feels it is difficult for a pathologist "not knowing the circumstances of the other facts of the case to be able to sit and make a total evaluation of what occurred to a body at a given time without knowing the surrounding facts of the case." Busch cited an incident where Fisher did not wait for Busch to present evidence of the crime-scene investigation but rendered his report without that information. As a result, Fisher's autopsy report was in error because he showed the entry and exit wounds in reverse. Busch testified that he believed some of Fisher's "priorities were a bit out of line."
Madison County assistant coroner, Dick Mizell, testified that Fisher was always in a hurry to do things and that he always talked of jogging. Mizell recounted an occasion where he wanted to have a body re-x-rayed, but that Fisher did not want to wait the half hour it would have taken to re-x-ray the body. Mizell spoke with the coroner about problems he had with Fisher. Mizell testified that he perferred not having Fisher perform autopsies.
Dr. Nuernberger wrote Fisher and Parks a letter dated March 27, 1980, outlining particular complaints he had regarding the partnership and the activities of his partners. With regard to Parks, Nuernberger complained of Parks' failure to complete autopsy reports in a timely manner. Parks agreed that he had been late in completing the reports, but he testified that he corrected the problem after receiving Nuernberger's letter.
In the letter of March 27, particular references regarding Dr. Fisher were set forth:
"I have been approached by the nursing coordinator at St. Joseph's Hospital in Murphysboro with a complaint concerning Dr. Fisher and the clinical pathological conferences which he has or has not given depending on whom you talked to. The nurse has stated that he has been late to both of his conferences number 1, and number 2, instead of finishing the first conference . . . he did a frozen section and went jogging instead of returning to finish the conference. This I feel is quite deplorable and shows an extreme lack of consideration to the fellow physicians who are giving their time and effort to be at the conference. I see no reason for any of us to be late to a CPC since it is scheduled as much as three months in advance. . . .
Once again, it appears to myself and to the employees of SIMBA that Dr. Fisher is spending more time in personal life than he is concerned about the business. I do not like him leaving surgical specimens in baskets, buckets or whatever for me to do on the next day. It is easy enough to open a colon and to take biopsies and leave them in cassettes in formalin over night rather than leave the entire specimen for someone else to do. If he is in such a rush, that he cannot do the specimens, I think he had better look for a new job.
Despite these complaints and the seriousness I attribute to them, I have enjoyed for the most part our relationship over the past year. I just do not want the quality of service rendered by SIMBA to its customers and physicians to deteriorate from the standards set in 1977 when I arrived at SIMBA. . . .
. . . I write this letter with the hope that we can improve our service and resolve our differences in a manner which would preclude my leaving SIMBA. . . ."
In an undated letter addressed to Nuernberger, Fisher denied any alleged deficiencies in his own performance.
In April of 1980, SIMBA received a letter from Dr. Thomas, a pathologist and director of laboratories at Memorial Hospital in Carbondale. Thomas described an oversight on the part of Dr. Fisher, wherein Fisher failed to send tissue from a malignant adenocarcinoma to the clinical laboratories in St. Louis for estrogen and progesterone receptor assays. In addition to detailing this incident, Thomas noted that Fisher gave the personnel in the histology laboratory and the pathology office the impression that he was terribly rushed and really did not have time to deal with the load of work confronting him.
Admitted into evidence was a list of SIMBA's Sunday autopsy schedule from January 1980 through June of 1981, reconstructed from reports of the coroner's physician on file at SIMBA. According to the schedule there were six occasions where Fisher was on call to perform autopsies but could not be located. In each instance Parks or Nuernberger was called to perform the autopsy. It is not documented whether Nuernberger or Parks was ever unavailable when they were otherwise scheduled to perform autopsies. Documented in the schedule are three incidents Fisher was allegedly involved in in 1980:
May 1, 1980 - Patient autopsied and signed out as death due to natural causes, i.e., Lobar Pneumonia. Medical record indicated patient strangled in bedside rail and ceased breathing. CPR given but patient remained comatose until her death three (3) weeks later. Corrected report dictated by Dr. Fisher six (6) weeks after autopsy.
May 13, 1980 - Numerous inaccuracies in Dr. Fisher's report brought out in letter to Coroner Dallas Burke from parents of decedent and corrected addendum report requested. No corrected addendum report found in S.I.M.B.A. files.
September 26, 1980 - Dr. Fisher's autopsy report erroneously attributes multiple skull fractures and rib fractures to homicide when reliable witnesses at the scene indicated he had been run over by a semi-trailer truck after jumping/falling into the traffic lane on I-270, while intoxicated. Dr. Steven P. Nuernberger was asked to render a second opinion correcting the erroneous interpretation of Dr. Fisher.
Nuernberger testified that, as a result of Fisher's continued inability and disinterest in performing, he and Parks decided to expel Fisher from the partnership. Nuernberger and Parks testified that they held an informal meeting on November 5, 1980, to discuss Fisher's deficiencies. Fisher was not advised of the meeting. As a result of their meeting Nuernberger and Parks sent Fisher a letter by certified mail, dated November 5, 1980, which provided as follows:
"This is to give Dr. Fisher a 60 day written notice of expulsion according to the contract signed by Dr. Fisher, Dr. Nuernberger, and Dr. Parks (Section XIII, paragraph A, "ground" number 5).
It is felt by the remaining partners that Dr. Fisher has continuously failed to fulfill his obligations and duties as a partner as stated in Section IV, paragraph A. He has purposely and repeatedly failed to cover SIMBA Laboratory when assigned "CB' on the schedule, he has caused SIMBA to be fined by an Administrator, thus tarnishing the excellent reputation SIMBA enjoys, he has refused to perform autopsies in a prompt and timely manner, thus straining SIMBA's relationship to the various coroners served, and he has repeatedly set a bad example for SIMBA employees by his repeated tardiness to work and early exits from the laboratory. Thus, his overall attitude is incompatible with the values vital to the well-being of SIMBA Laboratory and this partnership.
We, the remaining partners, therefore, are giving Dr. Fisher the sixty day (60) written notice of expulsion required by our contract with him.'
On November 7, 1980, the three partners met to discuss the notice of expulsion. Notes of the meeting, admitted into evidence, demonstrate that Fisher denied most of the allegations against him and questioned the sources of information relied upon by Parks and Nuernberger.
Nuernberger and Parks testified that Fisher's conduct did not change during the ensuing months. Parks testified that on Sunday, November 16, 1980, Fisher was on call to perform two autopsies but could not be located. Parks was called to perform the autopsies on Monday, November 17. Parks also testified that on November 18, 1980, a tissue sample from a patient at Marshall Browning Hospital was lost. The hospital felt that Fisher was directly responsible as the tissue sample was under his care at the time it was lost. In a letter dated January 29, 1981, from David Hosler, the administrator of Marshall Browning Hospital, to Dr. Parks, Hosler stated:
"tissue was lost that required a second operation for the patient involved. This incident caused everyone involved a great deal of discomfort and could have involved all of us in litigation. We feel Dr. Fisher was directly responsible for this problem, as he was in charge at your lab when the incident occurred.'
On January 6, 1981, Parks and Nuernberger hand-delivered a letter to Fisher which provided:
"In accordance with our partnership agreement following a 60 day probation period after written notice of expulsion we are giving our notice in writing of our final decision in regard to previous notice of expulsion and will expect that your partnership will terminate Friday, March 6, 1981.', Plaintiff argues on appeal that the procedural requirements for partner expulsion were not complied with. The partnership agreement provides in pertinent part:
"This agreement is entered into on the 1st day of July 1978, by and between Harry W. Parks, M.D. Steven P. Nuernberger, M.D. and Jeffrey A. Fisher, M.D. . . . and [they] agree to operate this partnership pursuant to the Uniform Partnership Act of the State of Illinois on the following terms and conditions: III. Duration of Partnership
The partnership shall commence operation on July 15, 1978 and shall continue until dissolved pursuant to the provisions of Article XIV of this agreement. VI. Rights, Duties, and Liabilities of Partners
A. Each of the partners shall devote his full time and efforts to the business of the partnership and none of the partners shall practice medicine or pathology in any name other than that of the partnership. Each partner will work to maintain a harmonious relationship with all patients, clients, laboratory staff and all medical staffs in client institutions.
C. Vacations and leaves of absence. Each partner shall be entitled to be absent on vacation without loss of compensation . . . and such vacation shall be at such time, and for such length of time as may be mutually agreed upon and as may be convenient and feasible in carrying on said practice . . .. VII. Management of Business
A. Participation in management. All of the partners shall have equal rights in the management of the affairs and business of the partnership. The decision by a majority in number of the partners shall be required as to the partnership affairs and business (unless a greater number is required pursuant to specific paragraphs of this agreement) and once obtained shall be binding on all partners.
E. Meetings of Partners. Without call or notice, the partners shall hold quarterly meetings at times [and] places to be selected by the partners. In addition special meetings may be called by any partner after giving two (2) days notice to all partners. XIII. Expulsion of a Partner
A. Grounds for Expulsion. Any individual partner or partner in a partnership who is a party to this agreementmay be expelled from membership in this partnership or his partnership as herein provided. Each partner shall have one vote.
The grounds for expulsion shall be as follows:
(1) Failure of a partner to make when due any contribution required to be made under the terms of this agreement, when such failure is continued to sixty (60) days after written notice of the failure to make contribution.
(2) Adjudication of the partner to be insane or incompetent.
(3) Disability of an individual partner to the extent that he is unable to fulfill his obligation to the partnership as specified in this Agreement in Article XII.
(4) The making of an assignment for the benefit of creditors . . ..
(5) The failure of the partner to fulfill any other obligations, including the management obligations, as specified in this agreement when such failure is continued for a period of 60 days after written notice thereof.
(6) Conviction of a crime involving moral turpitude, homicide, [or] felonious theft . . ..
(7) Loss of a license necessary to perform the work contemplated under this agreement.
B. Notice. Upon the occurrence of any event listed in section A of [this] Article, the defaulting partner may be expelled from membership in the partnership by a majority vote, said votes to be apportioned as provided in this Article. The defaulting party shall receive sixty (60) days notice of expulsion, such notice setting forth the grounds for expulsion and being delivered, in writing, by registered or certified mail. Any tie vote shall be referred to arbitration. . . ."
We note that the partnership agreement expressly provides that it is governed by the Illinois Uniform Partnership Act (805 ILCS 205/1 et seq.). Section 31(1)(d) of the Act provides that dissolution of the partnership is caused "without violation of the agreement between the partners . . . by the expulsion of any partner from the business bona fide in accordance with such a power conferred by the agreement of the partners. " (Emphasis added.) (805 ILCS 205/31(1)(d).) Thus, a partnership is controlled by the terms of the agreement under which it is formed. (In re Estate of Johnson (1984), 129 Ill. App. 3d 22, 472 N.E.2d 72.) Because a partnership is a contractual relationship, the principles of contract law fully apply to it. (Allen v. Amber Manor Apartments Partnership (1981), 95 Ill. App. 3d 541, 549, 420 N.E.2d 440, 446.) A contract's meaning is determined from the words or language used, and a court cannot place a construction on a contract which is contrary to the plain and obvious meaning of the language. Johnstowne Centre Partnership v. Chin (1983), 99 Ill. 2d 284, 287, 458 N.E.2d 480, 481; Gordon v. Bauer (1988), 177 Ill. App. 3d 1073, 1088, 532 N.E.2d 855, 864.
According to the partnership agreement, in order to expel Fisher the other partners had to first provide Fisher with written notice of Fisher's failure to fulfill obligations. (See Article XIII, section (5), of the partnership agreement.) Because we agree that the November 5, 1980, letter fulfilled the notice provision, we decline to address plaintiff's contention that the March 27, 1980, letter was insufficient notice under the partnership agreement.
Sections and of Article XIII each contain a notice provision. The initial notice described in Article XIII, section (5), is a threshold requirement for commencing the expulsion procedures. This notice must be in writing and advise the subject partner of his failures. It commences a 60-day period wherein the partner may attempt to cure his deficiencies. The second notice, that described in Article XIII, section , which is also required to be in writing, advises the
subject partner what the grounds for expulsion are. This expulsion notice must be given 60 days prior to the date of expulsion. Expulsion can only be by majority vote after a finding that the occurrence of the event listed in the initial notice has occurred.
Plaintiff contends that the November 5, 1980, notice of expulsion was not issued in compliance with the partnership agreement because it was never discussed at a meeting of all the partners, it was never the subject of a partnership vote, and it did not provide for a 60-day probationary period. As to the charge that the expulsion notice was never discussed prior to issuance, plaintiff charges that Parks and Nuernberger met secretly on November 5, unlawfully depriving plaintiff of his right to respond to allegations of his deficient performance. In support of his argument, plaintiff cites Article VII, section , of the partnership agreement for the provision that the partners must be given two days' written notice of special meetings:
"Without call or notice, the partners shall hold quarterly meetings at times [and] places to be selected by the partners. In addition special meetings may be called by any partner after giving two (2) days notice to all partners." (Article VII, section , of the partnership agreement.) Defendants argue that there is no provision in the contract for a meeting to discuss the preparation of written notice of partnership failure or for the issuance of a notice of expulsion. We agree.
A court should construe a contract in accordance with its plain and ordinary meaning. (Johnstowne, 99 Ill. 2d at 287, 458 N.E.2d at 481.) The special-meetings provision of the contract is found in Article VII, which is entitled "Management of Business." Article VII, section , provides that quarterly meetings shall be held, and that special meetings may be called by any partner. There is no mandate that special meetings must be called. "May be called by any partner" indicates that a special meeting is subject to the partners' discretion. (See In re Muro (1980), 81 Ill. App. 3d 21, 23, 400 N.E.2d 1042, 1044.) More specifically, the partnership agreement does not specify in Article XIII, entitled "Expulsion of a Partner," that a special meeting must be
called to discuss the preparation of a notice of a partner's deficiencies or of an initial notice of expulsion.
Plaintiff also maintains that a vote of all partners was required before a notice under Article XIII, section (5), could be issued. The partnership agreement does not specify that the notice described in Article XIII, section (5), is subject to a vote or that it need be prepared or served with the same formality as an expulsion notice. Although a vote of all partners was not required, Nuernberger and Parks testified that they voted to send Fisher the notice.
As for plaintiff's contention that the notice did not advise him of a 60-day probationary period, once again we look to the plain and ordinary meaning of the contract. The partnership agreement specifies that a partner may be expelled when his failure to fulfill obligations "is continued for a period of 60 days after written notice thereof." Article XIII, section (5), does not mandate that the notice advise him of a
Plaintiff also alleges that the letter of January 6, 1981, was not in compliance with the partnership agreement. Plaintiff argues that he received no notice of a meeting to discuss issuance of the January 6 letter, that there was no notice of a vote, and that, in fact, no partnership vote was taken.
It is undisputed that the January 6, 1981, letter falls under Article XIII, section , of the contract, which requires the defaulting
partner to be expelled by a majority of the partners, with each partner having one vote. The notice of expulsion must be delivered, in writing, by registered or certified mail; set forth the grounds for expulsion; and give the subject partner 60 days' notice of the date of expulsion. It is clear that the contract's expulsion provision does not require that a meeting be held or even that a formal partnership vote be taken. A vote of the majority of the partnership members is required to expel. The evidence demonstrates that Parks and Nuernberger voted to expel Fisher, thus the voting requirement was satisfied.
Plaintiff's final attack on the January 6, 1981, notice is that it failed to set forth the grounds for expulsion. The January 6 letter provided in part: "we are giving our notice in writing of our final decision in regard to previous notice of expulsion. " (Emphasis added.) Although the notice does not expressly enumerate the grounds as set forth in the November 5 notice, the November 5 notice is specifically referred to and incorporated therein. We find that just as a contract may incorporate all or part of another document by reference (Arneson v. Board of Trustees (1991), 210 Ill. App. 3d 844, 849, 569 N.E.2d 252, 256), the January 6 letter incorporated the letter of November 5 by reference. We conclude that the trial court's determination that the letter of January 6, 1981, was sufficient notice under the partnership agreement was not against the manifest weight of the evidence.
The second issue on appeal is whether the trial court erred in finding that Fisher failed to meet his obligations under the partnership agreement. Plaintiff argues that he did not fail any management obligations during the probationary period from November 5, 1980, through January 6, 1981. Plaintiff contends there were only two purported failures which could remotely be identified as having occurred during the probationary period: the lost-specimen incident of November 17, 1980, and the failure to perform a Sunday autopsy on November 18, 1980. Plaintiff contends that these two incidents are inapplicable to establishing his failure to meet management obligations cited in the November 5, 1980, notice. On the contrary, it is evident that the two alleged incidents occurred during the probationary period and are directly related to Fisher's failure to fulfill his obligations and duties as a partner under the terms of the partnership agreement. In addition, the notice of November 5, 1980, specifically refered to Fisher's failure to perform autopsies in a prompt and timely manner and his failure to fulfill his obligations and duties as a partner in general. Once again we turn to the testimony rendered at trial.
Nuernberger and Parks testified that after November 5, 1980, Fisher did not give them any reason to believe he intended to change his unsatisfactory behavior. Fisher continued to jog while at the SIMBA laboratory after November 5, 1980, pursuant to testimony by Mary Cruzvergara and Arna Trotter. Ruth Lafferty, a pathology secretary for Alton Memorial Hospital, testified that Fisher jogged nearly every time he came to the hospital and that his disinterested attitude in his work never changed. Nancy Powles, a medical technologist at St. Joseph's Hospital, also testified that Fisher jogged more than half the time that he visited St. Joseph's Hospital and that his habit of jogging there never changed. Jo Ellen Heggemeier, a medical technologist at Sparta Community Hospital, also testified that Fisher jogged when he was supposed to be on duty at the hospital and that this habit did not change. All of these witnesses testified that Fisher's habit of jogging interfered with his work. In addition, Cruzvergara and Trotter testified that Fisher's habit of keeping minimal hours at the SIMBA laboratory never changed.
Jeffrey Fisher testified he never did anything contrary to the terms of the partnership agreement and that he had an explanation for each instance in which he was accused of not doing an autopsy promptly or otherwise fulfilling his duties. He testified that he never compromised his professional duties in order to jog and that he normally took 45 minutes during his lunch hour to jog. Fisher testified that if witnesses testified that he did not regularly spend seven to eight hours a day at SIMBA laboratory, they were mistaken.
Where a case is heard by a court sitting without a jury, unless the trial court's findings are against the manifest weight of the evidence or there is some other palpable error, the findings will not be disturbed on appeal. The trial court is in a better position than is a court of review to decide what weight should be given the testimony. (Brown v. Commercial National Bank (1969), 42 Ill. 2d 365, 371, 247 N.E.2d 894, 897; Pasulka v. Koob (1988), 170 Ill. App. 3d 191, 524 N.E.2d 1227.) Based on the record, we conclude that the trial court's determination that Fisher failed his management obligations during the period from November 5, 1980, through January 6, 1981, is not against the manifest weight of the evidence.
The final issue for our consideration is whether the court erred in awarding the plaintiff $276.15 as his interest in the partnership. Plaintiff contends that under the terms of the partnership agreement he is entitled to $343,357. The pertinent provisions of the partnership agreement are as follows:
"IV. CAPITAL CONTRIBUTIONS AND FIDUCIARY INTEREST OF EACH PARTNER
The capital of the partnership as of this date consists of a value of $80,329.83. In the prior partnership agreement, Nuernberger agreed to pay Parks the amount of $30,043.20 under a formula determined in paragraph IV of said prior partnership agreement and this amount was to be paid in
A. Books of Account. Books of account shall be kept by the partners, and proper entries made therein of all the sales, purchases, receipts, payments, engagements, transactions, and property of the partnership.
B. Method of Accounting. All accounts of the partnership shall be kept on the cash basis. All matters of accounting for which there is no provision in this agreement are to be governed by generally accepted methods of accounting.
E. Capital accounts. A capital account shall be maintained on the partnership books on behalf of each partner. Such account shall be credited with that partner's contributions to the capital of the partnership and shall be debited and credited in the manner prescribed in subsection (f) of this article. XI. DEATH, INCOMPETENCY, DISSOLUTION, ETC. OF A PARTNER
A. The death, adjudication in bankruptcy, retirement, insanity, incompetency, dissolution, withdrawal or expulsion of a partner shall not terminate the partnership.
B. In the event of any occurrence as stated in of an individual partner, the remaining partners shall immediately be vested with the deceased . . . or expelled partner's interest, subject however to the payment to the . . . partner, of his share or interest in the partnership as and in the manner hereinafter set forth. . . . current statement of the partnership's net asset value shall be made by the partnership's account and the retired, withdrawing or expelled partner . . . shall be paid as provided in this agreement
(1) For a deceased, retired, insane or incompetent or disabled partner, the greater of;
(a) The partner's capital account as of the end of the prior fiscal year preceding the event involved herein, plus the partner's share of receivables x 85% or the average of the net income (after salaries and expenses and before profit or additional income withdrawals) of the highest three year [sic] of the previous five years [or] if the partnership has not been in operation for five years the average of the years of operation, capitalized by a multiple of four (4) times said partner's percentage interest in the partnership.
(b) In addition to the amount determined in A 1 (a) the partner or the person so entitled shall also receive his shares in the profits of the partnership, if any, to the date of the event herein involved.
(c) The sum as determined in A 1 (a) and (b) shall be decreased by the partner's share of the partnership losses, if any, computed from the beginning of the partnership's taxable year in which the event herein involved took place to the last day of the month preceding such event and shall be decreased or adjusted for any and all contributions and withdrawals made by that partner and for any debts owed to the partnership.
(2) For a bankrupt or expelled partner, his interest shall be paid in like manner as provided in this Article except that he or the trustee in bankruptcy, as the case may be, shall receive an amount equal to the capital account of the bankrupt or expelled partner adjusted to the end of the nearest month prior to the event herein involved as adjusted as provided in A (1) (b) and (c). . . ."
What is significant about these provisions of Article XI is that section (2) refers to sections "A(1)(b) and (c)," which are nonexistent. This problem is further compounded if we assume that the reference in section (2) was intended as "B(1)(b) and (c),' because, any intent to limit section (2) to sections (1)(b) and (c) is thwarted where section (1)(b) refers specifically to "A(1)(a)," which is also nonexistent.
Defendants' accountant Earl Swink testified that in calculating the amount due Jeffrey Fisher, he based his findings on the assumption that the reference in section (2) to "A(1)(b) and (c)" refers to sections (1)(b) and (c). Swink further testified that in the case of an expelled partner, as we have here, adjustments as set forth in section (1)(a) are not to be considered in determining amounts due the expelled partner, as it is obvious from the agreement that expelled partners are to be treated differently from those who are deceased, retired, insane, incompetent, or disabled. Swink testified that, applying the formula set forth in section (1)(b) and (c), Fisher is entitled to $276.15.
Michael Hagenhoff, Fisher's accountant, testified that one cannot ignore the application of section (1)(a) if sections (1)(b) and (c) are utilized. He testified that if one calculates Fisher's interest in the partnership by assuming that section (1)(a) applies, Fisher's interest in the partnership is valued at $343,357. The parties dispute which of the two methods of calculation is appropriate under the partnership agreement.
It is well settled that a party asserting a fact or issue generally has the burden of proof as to such fact or issue. (In re Marriage of Douglas (1990), 195 Ill. App. 3d 1053, 1060, 552 N.E.2d 1346, 1351.) Plaintiff, as the party claiming an interest under the partnership agreement, had the burden of going forward with evidence to support his construction of the agreement. The term "burden of proof" includes both the burden of producing evidence and the burden of persuading the trier of fact. (People v. Ziltz (1983), 98 Ill. 2d 38, 43, 455 N.E.2d 70, 72.) There is no question that the partnership provisions concerning the capital contributions and fiduciary interests of the partners are unclear. Plaintiff produced no testimony as to what the parties intended when they entered into the partnership agreement. Michael Hagenhoff testified extensively as to calculations using sections (1)(a), (b), and (c); however, he did not offer proof as to why this formula was more appropriate than the formula adopted by defendants' accountant, Earl Swink.
Earl Swink testified that in previous years he has prepared, or assisted in preparing, many of the partnership's income tax returns and has assisted SIMBA in general tax matters. He testified that in January of 1981 he met with Parks, Nuernberger, and SIMBA's attorney to determine the financial obligations between the Partners. Swink testified that it was agreed that under the expulsion clause of the partnership agreement Fisher was entitled to his capital account, $6,908, plus or minus any amounts otherwise owing to him or to the partnership.
It is a fundamental principle of contract construction that where an agreement is indefinite, the courts will look to and adopt the interpretation which the parties themselves have placed on it. (Pocius v. Halvorsen (1963), 30 Ill. 2d 73, 81, 195 N.E.2d 137, 141; Burgener v. Gain (1981), 101 Ill. App. 3d 699, 704, 428 N.E.2d 722, 727.) In this case, the parties' interpretation of the contract provisions regarding capital contributions and fiduciary interests came from Hagenhoff and Swink. For the most part, the witnesses' opinions as to the interpretation of the contract were couched in terms of their own personal beliefs. Swink, however, testified that he had handled SIMBA's accounting matters for years and that it was the opinion of Parks and Nuernberger that the expulsion provision of the contract governed, excluding section (1)(a) from the calculation of Fisher's entitlement. Contrary to plaintiff's Conclusion, a review of the testimony at trial supports the trial court's finding that the intent of the parties was to apply the contract's sections (1)(b) and (c) and not section (1)(a) in determining the amount due Fisher.
Fisher also argues that Swink's calculations are erroneous because they assume the partnership tax return's description of the capital account supplant the actual value as determined in the partnership agreement. Fisher further argues that Swink erroneously deducted interpartner obligations in his calculations, thus reducing Fisher's capital account. Defendants maintain that to adopt Fisher's arguments one has to ignore the definitions of capital account and earnings of income as they appear in the partnership agreement. Defendants also maintain that Fisher refuses to consider the difference created by the partnership agreement for expelled partners and nonexpelled partners. Having reviewed the testimony of the witnesses, and the exhibits to which they refer, we cannot find that the trial court erred in finding that Swink's calculations were proper.
The judgment of the circuit court of Madison County is, therefore, affirmed.
LEWIS, J., and GOLDENHERSH, J., concur.
CASE RESOLUTION
Affirmed.
| https://www.anylaw.com/case/08-03-93-jeffrey-a-fisher/appellate-court-of-illinois/08-03-1993/Y69jS2YBTlTomsSB32mg |
Homematic IP HmIP-WKP Smart Home Keypad User Manual
Learn how to operate the Homematic IP HmIP-WKP Smart Home Keypad with this comprehensive user manual. This wireless device allows for up to eight users to access your smart home through PIN entry, and can be paired with other Homematic IP components for versatile scenarios. Keep your home safe and secure by referring to this manual for installation and operation instructions.
Homematic IP HmIP-WKP Smart Home Keypad User Manual
Contents hide
1 Homematic IP HmIP-WKP Smart Home Keypad
2 Information
3 Hazard information
4 Function and device overview
5 General system information
6 Operation Pairing
7 Installation
8 Operation
9 Changing the batteries
10 Troubleshooting
11 Error codes and flashing sequences
12 Restoring factory settings
13 Maintenance and cleaning
14 General information about radio operation
15 Technical specifications
16 Documents / Resources
16.1 References
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Homematic IP HmIP-WKP Smart Home Keypad
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Information
Please read this manual carefully before beginning operation with your Homematic IP device. Keep the manual so you can refer to it at a later date if you need to. If you hand over the device to other persons for use, please hand over this manual as well.
Symbols used
Attention
This indicates a hazard.
Note:
This section contains important additional information.
Hazard information
Do not open the device. It does not contain any parts that can be maintained by the user. If you have any doubts, have the device checked by an expert.
For safety and licensing reasons (CE), unauthorized changes and/or modifications of the device are not permitted.
Do not use the device if there are signs of damage to the housing, control elements, or connecting sockets, for example. If you have any doubts, have the device checked by an expert.
The device is not a toy: do not allow children to play with it. Do not leave packaging material lying around. Plastic films/bags, pieces of polystyrene, etc. can be dangerous in the hands of a child.
We accept no liability for damage to property or personal injury caused by improper use or the failure to observe the hazard warnings. In such cases, all warranty claims are void. We accept no liability for any consequential damage.
The device must only be operated in locations where it is protected from the effects of weather. The device must be protected from the effects of vibrations, solar or other methods of heat radiation, and mechanical loads.
The device may only be operated within residential buildings.
Using the device for any purpose other than that described in this operating manual does not fall within the scope of intended use and will invalidate any warranty or liability.
Function and device overview
With the Homematic IP Keypad, combined with your Homematic IP door lock actuator, you can give up to eight family members, friends, etc. access to your smart home. The door can be opened, locked, or unlocked by entering a PIN. In addition, other Homematic IP components can be used to create versatile coming/leaving home scenarios (e.g. switching on the hallway lighting). You can configure the door and display its current status via the free Homematic IP app. Wireless communication and battery operation mean the keypad can be installed anywhere. A main connection near the door is not necessary. You can use the enclosed screws and wall plugs for installation at your chosen location.
The integrated proximity sensor gives you additional convenience. Thanks to the integrated illumination, you can always make out the keys on your keypad even in dim outdoor lighting.
Device overview
(A) Wall bracket
(B) Keypad
(C) Keypad panel with keys 0-9
(D) “Lock” button
(E) “Unlock” button
(F) Proximity sensor
(G) Device LED
(H) System button (pairing button)
(I) Tamper contact
(J) Battery compartment (and cover)
(K) Drainage hole
(L) Screw holes
(M) Latch
General system information
This device is part of the Homematic IP smart home system and works with the Homematic IP protocol. All devices of the system can be con-figured comfortably and individually with the user interface of the Central Control Unit CCU3 or flexibly via the Homematic IP smartphone app in connection with the Homematic IP cloud. All available functions provided by the system in combination with other components are described in the Homematic IP Wired Installation Guide. All current technical documents and updates are provided at
www.homematic-ip.com
Operation Pairing
Please read this entire section before starting the pairing procedure
You can connect the device either to the Access Point or to the Homematic Central Control Unit CCU3. For detailed information about pairing or configuration via a control unit, please refer to the Homematic IP User Guide, available for download in the download area of
www.homematic-ip.com
First set up your Homematic IP Access Point via the Homematic IP app to enable the operation of other Homematic IP devices within your system. For further information, please refer to the operating manual of the Access Point. To integrate the Homematic IP Keypad into your system and enable it to communicate with other Homematic IP devices, you must first add the device to your Homematic IP Access Point.
To add the Keypad, please proceed as follows:
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Open the Homematic IP app on your smartphone.
Select the menu item “Add device”.
Remove the Keypad (B) from the wall bracket (A), by inserting a thin object into the hole on the bottom of the wall bracket (A) and releasing the latch (M)
Open the Keypad’s rear battery compartment (J) by loosening the screw on the battery compartment cover
Pull the insulating strip out of the battery compartment of the Keypad (first start-up).
As soon as the insulating strip has been pulled out, the device sends a tamper message, and the device LED (G) flashes red six times (see „7.5 Error codes and flashing sequences“ on page 33).
The pairing mode is active for 3 minutes.
You can start the pairing mode manually for another 3 minutes by briefly pressing the system button (H).
Close the battery compartment (J) and tighten the screw on the battery compartment cover again.
The device automatically appears in the Homematic IP app
To confirm, enter the last four digits of the device number (SG-TIN) in the app or scan the QR code. The device number can be found on the sticker supplied or attached to the device.
Please wait until the pairing is completed.
If the pairing was successful, the device LED (G) lights up green. The device is now ready for use
If the device LED lights up red, please try again
In the app, give the device a name and allocate it to a room.
Set up access using the free Homematic IP app.
Only insert the Keypad into the wall bracket after installation.
Installation
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The Keypad housing has a drainage hole (K). Open it with a sharp tool if necessary. Please read this entire section before starting the installation.
Installing the wall bracket
When selecting a mounting location and drilling in the vicinity of switches or socket outlets, check for electrical wires and power supply cables.
The mounting location should be protected from the weather and not exposed to direct sunlight or other sources of heat radiation.
To install the wall bracket (A), proceed as follows:
Choose a suitable site for installation.
Remove the keypad (B) from the wall bracket (A), by inserting a thin object into the hole on the bottom of the wall bracket and releasing the latch (M)
If you have already paired the unit, you will receive a tamper message within the app. You can only acknowledge this after the installation has been completed and the Keypad has been reinserted.
Position the wall bracket (A) with the beveled surface facing upwards at a suitable place on the wall and mark the drill holes
Drill the pre-marked holes with a diameter of 5 mm and a depth of 35 mm.
If you are working with a stone wall, use a 5 mm drill bit for the wall plugs supplied. If you are working with wooden walls, you can use a 1.5 mm drill bit to make it easier to screw in the screws. When selecting a mounting location and drilling in the vicinity of switches or socket outlets, check for electrical wires and power supply cables.
Mount the wall bracket using the wall plugs and screws provided
Insert the Keypad (B) back in the wall bracket (A). A latching sound indicates whether the keypad has been inserted correctly
If you have already paired the device, you can now acknowledge the tampered message in your app.
Operation
After you have paired the Homematic IP Keypad to the Access Point and set it up via the app (see „5.1 Pairing“ on page 27), you can conveniently control the access function in combination with the Homematic IP door lock drive. To do this, enter your PIN on the Keypad (C) and select the desired action by pressing the “Lock” (D) or “Unlock” (E). Depending on the selected function, the Homematic IP Door lock drive reacts and locks or unlocks the front door.
Keypad illumination
Directly above the Keypad panel (C) is the slightly beveled surface of the proximity sensor (F). When your hand approaches the Keypad, the integrated proximity sensor reacts, and the Keypad illumination is switched on. This means you can always make out the keypad panel of your Keypad even in dim outdoor lighting.
Changing the batteries
If the battery symbol is displayed via the app or an empty battery is indicated on the device (see „7.5 Error codes and flashing sequences“ on page 33), replace the two used batteries with two new LR03/Micro/AAA batteries. Take care to observe the correct battery polarity.
To replace the Keypad batteries, please proceed as follows:
Remove the Keypad (B) from the wall bracket (A), by inserting a thin object into the hole on the bottom of the wall bracket and releasing the latch (M)
You will now receive a tamper message in your app. This can only be acknowledged when the Keypad has been reinserted in the wall bracket after replacing the batteries.
Open the rear battery compartment (J) of the Keypad (B), by loosening the screw of the battery compartment cover
Remove the used batteries.
Insert two new 1.5 V LR03/micro/batteries into the battery compartment, making sure that you do so with the correct polarity
Close the battery compartment and tighten the screw on the battery compartment cover again.
Insert the Keypad back in the wall bracket (A).
You can now acknowledge the tampered message in your app. Used batteries should not be disposed of with regular domestic waste! Instead, take them to your local battery disposal point.
Caution
There is a risk of explosion if the batteries are not replaced correctly. Replace only with the same or equivalent type. Never re-charge non-rechargeable batteries. Do not throw the batteries into a fire. Do not expose batteries to excessive heat. Do not short-cir-cuit batteries. Doing so will present a risk of explosion.
Troubleshooting
Low battery
Provided that the voltage value permits it, the Keypad will remain ready for operation even if the battery voltage is low. Depending on the load, it may be possible to transmit several times again once the batteries have been allowed a brief recovery period. If the battery voltage is too low, this will be displayed in the Homematic IP app and directly on the device via the LED (G). In this case, replace the used batteries with new ones (see „6 Changing the batteries“ on page 31).
Incorrect pin entry
You define in the Homematic IP app how often a PIN code can be entered incorrectly before the Keypad is locked. Once the Keypad is locked, you can only reactivate it via the app. There is also a factory-set off time for re-entering the PIN code. After the second incorrect entry, this off time is automatically increased by 15 (30, 60, 120) seconds.
Command not confirmed
If at least one receiver does not confirm a command, the device LED (G) lights up red at the end of the failed transmission process (depending on the cause, the LED may light up with a delay of up to 10 sec). The failed transmission may be caused by radio interference (see „10 General information about radio operation“ on page 36). This may be caused by the following:
The receiver cannot be reached.
The receiver is unable to execute the command (load failure, mechanical blockade, etc.).
Receiver is faulty.
Duty cycle
The duty cycle is a legally regulated limit of the transmission time of de-vices in the 868 MHz range. The aim of this regulation is to safeguard the operation of all devices working in the 868 MHz range. In the 868 MHz frequency range we use, the maximum transmission time of any device is 1% of an hour (i.e. 36 seconds in an hour). Devices must cease transmission when they reach the 1% limit until this time restriction comes to an end. Homematic IP devices are designed and produced with 100% conformity to this regulation. During normal operation, the duty cycle is not usually reached. However, repeated and radio-intensive pairing processes mean that it may be reached in isolated instances during the start-up or initial installation of a system. If the duty cycle limit is exceeded, this is indicated by the LED (G) emitting a long red flash, and the device may temporarily not function. The device will start working correctly again after a short period (max. 1 hour).
Error codes and flashing sequences
<table><tbody><tr><td> Flashing code</td><td> Meaning</td><td> Solution</td></tr><tr><td> Rapidorange flashing</td><td> Radio transmission/ configuration data is transmitted</td><td> Wait until the transmission is completed.</td></tr><tr><td> 1x long green flash</td><td> Transmission confirmed</td><td> You can continue operation.</td></tr><tr><td> Slow orange flashing followed by a long red flash</td><td> Transmission failed</td><td> Try again</td></tr></tbody></table>
<table><tbody><tr><td> 1x long red flash</td><td> PIN incorrect or not authorized at the current time/Entry temporarily or permanently locked/Duty cycle</td><td> Re-enter the PIN to check its correctness or whether you are authorized at the current time/Temporary or permanent lock after incorrect entry; reset the permanent lock in the app/Try again</td></tr><tr><td> Short orange flashing (every 10 s)</td><td> Pairing mode active</td><td> Enter the last four numbers of the device serial number to confirm</td></tr><tr><td> Short orange lighting (after green or red confirmation)</td><td> Battery empty</td><td> Replace the batteries</td></tr><tr><td> 1x orange and 1x green flash (after inserting batteries)</td><td> Test display</td><td> You can continue once the test display has stopped.</td></tr><tr><td> Long and short orange flashing (alternating)</td><td> Software update (OTAU)</td><td> Wait until the update is completed.</td></tr><tr><td> 6x short red flashing of the device LED (G)</td><td> Tamper message</td><td> Insert the Keypad (B)into the mounting plate (A)and acknowledge the tampered message in your app.</td></tr></tbody></table>
Restoring factory settings
The device’s factory settings can be restored. If you do this, you will lose all your settings.
To restore the Keypad’s factory settings, proceed as follows:
Remove the Keypad (B) from the wall bracket (A), by inserting a thin object into the hole on the bottom of the wall bracket and releasing the latch (M)
Open the Keypad’s rear battery compartment (J) by loosening the screw on the battery compartment cover
Remove one battery.
Insert the battery with the correct polarity and press and simultaneously hold down the system button (H) for 4 seconds, until the LED (G) starts rapidly flashing orange
Release the system button.
Press and hold down the system button again for 4 seconds, until the LED lights up green
Release the system button again to conclude the procedure.
The device will perform a restart.
Maintenance and cleaning
The device does not require you to carry out any maintenance other than replacing the battery when necessary. Enlist the help of an expert to carry out any repairs. Clean the device using a soft, lint-free cloth that is clean and dry. Do not use any detergents containing solvents, as they could corrode the plastic housing and label.
General information about radio operation
Radio transmission is performed on a non-exclusive transmission path, which means that there is a possibility of interference occurring. Interference can also be caused by switching operations, electrical motors, or defective electrical devices. The transmission range within buildings can differ greatly from that available in the open air. Besides the transmitting power and the reception characteristics of the receiver, environmental factors such as humidity in the vicinity have an important role to play, as do on-site structural/screening conditions. Hereby, eQ-3 AG, Marburger Str. 29, 26789 Leer/Germany declares that the radio equipment type Homematic IP HmIP-WKP is in compliance with Directive 2014/53/EU. The full text of the EU declaration of conformity is available at the following internet address:
www.homematic-ip.com
Technical specifications
Device short description: HmIP-WKP
Supply voltage: 2x 1.5 V LR03/micro/AAA
Battery life: 2 years (typically)
Current consumption: 60 mA max.
Protection rating: IP44
Ambient temperature: -20 to 55 °C
Dimensions (W x H x D): 71 x 161 x 29 mm
Weight: 137 g (incl. batteries)
Radiofrequency band: 868.0–868.6 MHz 869.4–869.65 MHz
Max. radio transmission power: 10 dBm
Typical radio free-field range: 200 m
Receiver category: SRD category 2
Duty cycle: < 1 % per h/< 10 % per h
Subject to technical changes
Instructions for disposal
Do not dispose of the device with normal domestic waste! Electron-ic equipment must be disposed of at local collection points for waste electronic equipment in compliance with the Waste Electrical and Electronic Equipment Directive.
Information about conformity
The CE mark is a free trademark that is intended exclusively for the authorities and does not imply any assurance of properties. For technical support, please contact your retailer.
Documents / Resources
<table><tbody><tr><td>
<here is a image 1cea88c0e45d1866-4ab74aa049fbb19c>
</td><td>Homematic IP HmIP-WKP Smart Home Keypad[pdf] User Manual
HmIP-WKP, Smart Home Keypad, HmIP-WKP Smart Home Keypad</td></tr></tbody></table>
References
<here is a image 2d1bbbeec56336ce-33b3b5efc62ae943 Startseite - eQ-3>
<here is a image 22947a693dc3e3bf-d0dc84f8ab63ab73> Home page | Homematic IP
<here is a image 719ab84568cb3677-2b306eee62220c20>
homematic 156450 Hmip sk15 Starter Set Beschattung Wlan User Guide
homematic 156450 Hmip sk15 Starter Set Beschattung Wlan How To Download How to Off Instructions How To On …
| https://manuals.plus/homematic-ip/hmip-wkp-smart-home-keypad-manual |
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An isolate of ‘Candidatus Phytoplasma australiense’ group associated with Nivun Haamir dieback disease of papaya in Israel | Request PDF
Request PDF | On Jul 26, 2005, A. Gera and others published An isolate of ‘Candidatus Phytoplasma australiense’ group associated with Nivun Haamir dieback disease of papaya in Israel | Find, read and cite all the research you need on ResearchGate
An isolate of ‘Candidatus Phytoplasma australiense’ group associated with Nivun Haamir dieback disease of papaya in Israel
DOI: 10.1111/j.1365-3059.2005.01236.x
... The Australian studies (White et al., 1998) had examined three papaya plants, one suffering from papaya dieback, one from yellow crinkle and one from mosaic, and whilst the yellow crinkle and mosaic plants had 16SrII phytoplasmas, the papaya dieback plant contained a 16SrXII phytoplasma. In Israel, a 16SrXII phytoplasma was found associated with Nivum-Haamir-dieback of papaya
(Gera et al., 2005)
, whilst a 16SrII phytoplasma was associated with bunchy top symptoms of papaya in Cuba (Pérez et al., 2010). In Malaysia, no phytoplasma was found associated with papaya dieback, and the causal agent was identified as Erwinia papayae (Maktar et al., 2008). ...
... Because of the possibility that 16SrII phytoplasmas might have been present in the samples but as mixed infections with 16SrXII phytoplasmas, all the papaya plants were initially used with both the 16SrII and 16SrXII LAMP assays and no evidence was found of either mixed infection or 16SrII in any papaya samples. These results are in agreement with the findings on Nivum-Haamir-dieback of papaya in Israel, which is also in 16SrXII
(Gera et al., 2005)
. Interestingly, Gera et al. (2005) implied that their phytoplasma most closely resembled the Australian papaya dieback 16SrXII-B phytoplasma based on sequence analysis. ...
... These results are in agreement with the findings on Nivum-Haamir-dieback of papaya in Israel, which is also in 16SrXII (Gera et al., 2005). Interestingly,
Gera et al. (2005)
implied that their phytoplasma most closely resembled the Australian papaya dieback 16SrXII-B phytoplasma based on sequence analysis. However, analysis here of their sequence suggests that their phytoplasma is in fact more similar to the 16SrXII-A stolbur group, and that the 16SrXII-B and 16SrXII-C phytoplasmas are geographically isolated to Australasia. ...
Use of a real-time LAMP isothermal assay for detecting 16SrII and XII phytoplasmas in fruit and weeds of the Ethiopian Rift Valley
PLANT PATHOL
B. Bekele
Jennifer Hodgetts
Jenny Tomlinson
M. Dickinson
A study to investigate the association of phytoplasmas with papaya dieback and citrus decline syndromes in Ethiopia was carried out between July 2009 and February 2010, with sampling performed in major papaya- and citrus-growing areas of the Rift Valley. Samples of plants with symptoms were collected from papaya, citrus and suspected phytoplasma weed hosts and crops in and around the papaya and citrus fields studied. Nested polymerase chain reaction (nested-PCR) was used for initial characterization, using primers that amplify regions of the 16S rRNA and secA genes, and results were then confirmed with rapid real-time group-specific LAMP (loop-mediated isothermal amplification) assays. The results identified the occurrence of a phytoplasma belonging to the stolbur (16SrXII-A) group in papaya plants showing dieback symptoms, whilst no phytoplasmas were found associated with citrus decline. These results contradict previous reports that a 16SrII phytoplasma was associated with both papaya dieback and citrus decline in Ethiopia, but correspond with the association of a 16SrXII phytoplasmas with Nivum-Haamir-Dieback of papaya in Israel and papaya dieback in Australia. No 16SrXII phytoplasmas were found in any of the weeds and potential alternative hosts studied, although 16SrII phytoplasmas were consistently found in Parthenium hysterophorus weed plants. These results indicate that a 16SrXII phytoplasma is associated with papaya dieback in Ethiopia, whilst the causal agent of citrus decline is not a phytoplasma and remains unidentified.
Gera et al. 2005;
Perez et al. 2010;Acosta et al. 2011;Abeysinghe et al. 2016;Mitra et al. 2020;Rao 2021). ...
... Phytoplasma strains belonging to several groups and subgroups (16SrI-D, 16SrII-B, 16SrXII-B and 16SrXVII) have already been reported in papaya from Australia, Cuba, Israel, Oman, India, Taiwan, Ethiopia and Sri Lanka associated with symptoms of mosaic, leaf yellows, little leaf, dieback, bunchy top and axillary shoot proliferation (White et al. 1998;Arocha et al. 2005;
Gera et al. 2005;
Perez et al. 2010;Acosta et al. 2011;Bau et al. 2011;Rao et al. 2011;Verma et al. 2012;Abeysinghe et al. 2016;Mitra et al. 2020). But till date no symptoms of flower malformation was reported with any phytoplasma associated disease in papaya from any parts of the world. ...
Multilocus gene-based characterization of peanut witches’ broom related phytoplasma strain associated with flower malformation of papaya in India
Smriti Mall
G. P. Rao
Papaya (Carica papaya L.) is an important fruit crop which significantly contributed to fulfill the national fruit requirement of India. Papaya plant is affected by many diseases that greatly effect on the growth and fruit yield. Flower malformation symptoms (PFM) were reported in papaya plantations in university campus at Faizabad, Uttar Pradesh during 2019. Flower samples from symptomatic and asymptomatic papaya trees were collected and analysed with nested and semi-nested PCR assays for the 16S rRNA, secA, tuf, and imp genes, in order to identify the relevant phytoplasma strain associated with the disease. Amplicons of ~ 1.2 kb DNA products were consistently amplified in five symptomatic flower samples of papaya using universal phytoplasma specific nested primer pairs P1/P7 and R16F2n/R2, but not from flowers collected from any asymptomatic plants. Pair wise sequence comparison, phylogeny and virtual RFLP analysis of 16S rRNA gene sequences confirmed the identification and taxonomic assignment of papaya flower malformation strain into ‘Candidatus Phytoplasma australasia’ strain subgroup D (16SrII-D). Phytoplasma association was further established and validated by amplifying phytoplasma specific multilocus candidate genes in all the symptomatic flower malformed samples by utilizing multilocus gene specific primers of secA, secY and tuf genes. The BLAST sequence comparison of secA (600 bp), tuf (1067 bp), and imp (727 bp) genes revealed that the PFM phytoplasma strain associated with symptomatic papaya tress belonged to Ca. P. australasia related strain. In phylogeny analysis, the 16Sr RNA, secA, secY and tuf genes sequences showed clustering of PFM isolate with the strains of peanut witches’ broom group. Our results confirmed association of Ca. P. australasia strain (16SrII-D subgroup) with papapa showing flower malformation symptoms in Eastern Uttar Pradesh, India.
... However, distinct phytoplasmas are associated with these diseases despite the similarity in symptoms. A representative of the 16SrXII group was identified in Australia (Gibb et al. 1996), Israel
(Gera et al. 2005)
, and Taiwan (Bau et al. 2011); whereas a phytoplasma belonging to group 16SrII was found in Ethiopia (Arocha et al. 2007). In Cuba, phytoplasmas affiliated with the groups 16SrXVII (Arocha et al. detected. ...
... In Ethiopia, a phytoplasma of the 16SrII group was found in papaya with symptoms of dieback (Arocha et al. 2007), and phytoplasmas belonging to groups 16Sr I and 16SrII were present in plants that exhibited some typical symptoms of dieback in India (Rao et al. 2011;Verma et al. 2012). A representative of the 16SrXII group was first identified as causing dieback in Australia (Gibb et al. 1996); later a phytoplasma belonging to this same group was reported in plants with some symptoms related to dieback in Israel
(Gera et al. 2005)
and Taiwan (Bau et al. 2011). ...
Article
Nov 2013
Luciano de Aquino Melo
Eliane G. Silva
Daniela Flores
Ivan Paulo Bedendo
Papaya apical curl necrosis (PACN) has frequently been observed in several Brazilian states. Affected plants exhibit foliar chlorosis, curvature of the apex, shortening of the internodes leading to bunching of the crown leaves, necrosis of the young apical parts, leaf drop, and dieback. Naturally infected plants were sampled and subjected to PCR assays, which confirmed that a phytoplasma was associated with the disease. Sequencing of the 16S rRNA gene, conventional and computer-simulated RFLP analyses, and phylogenetic analysis allowed the determination of the PACN phytoplasma as a representative of a new subgroup, designated 16SrXIII-E. The phytoplasmas of various 16Sr groups, including 16SrI, 16SrII, 16SrX, 16SrXII, and 16SrXVII, are known to be involved in anomalies in papaya plants in several countries. However, the present study reports, for the first time, the occurrence of a 16SrXIII phytoplasma in association with a papaya disease.
... A destructive disease namely Nivun Haamir dieback (NHDB) has been reported in association with 16SrXII-A subgroup in papaya from Israel
(Gera et al., 2005)
. Papaya plants showing chlorosis, yellowing, and shriveling of leaves, dieback, and lateral growth of branches, bending of apical branches, latexosis of fruits, and brown necrosis in phloem tissues were observed in southern Taiwan, and the symptomatic plants were found infected with a subgroup 16SrXII-A strain (Bau et al., 2011). ...
Updates on phytoplasma diseases associated with fruit crops in Asia
Chapter
Jan 2023
Çiğdem Ulubaş Serçe
Mona Gazel
Surabhi Mitra
G. P. Rao
... However, phytosanitary limitations seriously affect production of the fruit, including diseases caused by plant pathogens and vector insects. Papaya is seriously affected by phytoplasma and rickettsia transmitted by arthropods of Hemiptera (Lee et al. 2000, Acosta et al. 2017) causing mosaic yellow crinkling and dieback symptoms (Gibb et al. 1996, White et al. 1998
, Gera et al. 2005
. Some reports point to Empoasca papayae Oman leafhopper (Hemiptera: Cicadellidae) as the vector of "Bunchy Top" disease, associated with Candidatus Phytoplasma aurantifolia (Arocha et al. 2006(Arocha et al. , 2007. ...
Effectiveness of Biorational Insecticides Against Empoasca papayae Oman Leafhopper1 in Carica papaya L.
Article
Full-text available
Dec 2021
SOUTHWEST ENTOMOL
Karla A. Pérez-Cacho
Gerardo Loera-Alvarado
Carlos Granados-Echegoyen
Esperanza Loera-Alvarado
Use of biorational insecticides reduces environmental and health damage caused by conventional insecticides. The leafhopper, Empoasca papayae Oman (Hemiptera: Cicadellidae), is one of the most important pests of papaya (Carica papaya L., Brassicales: Caricaceae), because the insect is a vector of phytoplasmas and rickettsia causing irreversible economic damage. The research aimed to determine the biological effectiveness of biorational products: calcium hydroxide, diatomaceous earth, potassium soap, prepared calcium sulfide broth (calcium hydroxide, wettable sulfur, and water at 1:2:10), Terramax, Terra-oil, Terrax CE, imidacloprid as a positive check, and an absolute check without insecticide, on adult leafhoppers in a laboratory. Each treatment had five replications, randomly placed in a humidity chamber. Terramax and Terrax CE killed more pests, 82.98 and 87.23% at 24 hours, followed by increase to 95.65 and 93.48% at 48 hours, respectively. Terraoil, Quimex 95, and Prevents killed 78.26, 76.09, and 74.64%, respectively, 48 hours after application. Diatomix and calcium sulfide killed only 56.52 and 54.34%, respectively. Terramax, Terrax CE, Terraoil, Quimex 95, and Prevents biorational products can be alternatives to control the leafhopper in papaya.
... In Australia, papaya dieback disease associated with a phytoplasma within 16SrXII group can cause 10-100% papaya plant losses in any given production season (Guthrie et al., 1998). Along with Australia, papaya phytoplasma diseases have also been reported in Cuba, China, India, Taiwan, Brazil, Ethiopia, Peru, Mexico, Israel, Sri Lanka, and Philippines (Arocha et al., 2006, 2007a, 2007bYang et al., 2016;Verma et al., 2012;Bau et al., 2011;Melo et al., 2013;Wei et al., 2017;Lebsky et al., 2010;
Gera et al., 2005;
Abeysinghe et al., 2014;Billones, 2005). ...
Molecular identification and characterization of ‘Candidatus Phytoplasma convolvuli’-related strains (representing a new 16SrXII-O subgroup) associated with papaya bunchy top disease in Nigeria
Article
Jun 2021
CROP PROT
Shakiru Adewale Kazeem
Junichi Inaba
Wei Wei
Yan Zhao
Beginning in 2018, a new papaya disease occurred in Ibadan, Oyo State, Nigeria. Affected papaya trees exhibited symptoms including excessive shoot proliferation at the top of the crown, leaf mosaic and crinkling, and dieback. The disease was designated as Nigerian papaya bunchy top (NGPBT) disease. Since excessive shoot proliferation was the most characteristic symptom of the disease and it was indicative of phytoplasma infection, a polymerase chain reaction (PCR)-based phytoplasma molecular diagnostic method was employed in this study. Phytoplasmas were detected in diseased papaya samples by semi-nested PCR using phytoplasma 16S rRNA gene-specific primers. Subsequent determination and analysis of the amplified 16S rRNA gene sequences and phylogenetic analysis revealed that NGPBT phytoplasmas were most closely related to ‘Candidatus Phytoplasma convolvuli’ in the Stolbur (16SrXII) group. Virtual restriction fragment length polymorphism (RFLP) analysis based on the 16S rRNA gene F2nR2 fragment showed that NGPBT strains represented a novel subgroup in the Stolbur phytoplasma group, designated as 16SrXII-O. This is the first report of a phytoplasma disease in papaya in Nigeria. Identification of the NGPBT strains not only broadened the genetic diversity of the Stolbur phytoplasma group but also signaled an expansion of the phytoplasma group’s geographic distribution. Notably, two previously reported phytoplasmas associated with papaya diseases in Australia and Taiwan also belong to the 16SrXII group and exhibit symptoms similar to NGPBT disease. It would be interesting to learn how these three diseases relate to each other. Further in-depth study on weed reservoirs and insect vectors of NGPBT phytoplasmas will contribute to a better understanding of pathosystem and epidemiology of the NGPBT disease.
... P. pruni' in central and northeast Iran and phytoplasma belonging to subgroups 16SrII-B and 16SrII-C were reported in Chicoo and Barberry in Iran, respectively [126,127]. A destructive disease, named Nivun Haamir dieback (NHDB), has been reported in association with 16SrXII-A subgroup on papaya (Carica papaya) in Israel
[128]
. ...
History and Current Status of Phytoplasma Diseases in the Middle East
Article
Full-text available
Mar 2021
Chamran Hemmati
Mehrnoosh Nikooei
Ali Al-Subhi
Abdullah Al-Sadi
Simple Summary: Phytoplasmas are microorganisms that have been reported to be associated with hundreds of plant diseases in most parts of the world. Several reviews were published regarding diseases associated with phytoplasmas in different countries. However, no comprehensive review is available on the phytoplasma diseases in the Middle East, which is an important region with arid to semi-arid conditions. This review describes the most common phytoplasmas that are associated with diseases in this part of the world. It also describes some of the insect vectors that help to transmit these phytoplasmas. Information is also presented regarding the distribution of the diseases and host ranges. Abstract: Phytoplasmas that are associated with fruit crops, vegetables, cereal and oilseed crops, trees, ornamental, and weeds are increasing at an alarming rate in the Middle East. Up to now, fourteen 16Sr groups of phytoplasma have been identified in association with more than 164 plant species in this region. Peanut witches' broom phytoplasma strains (16SrII) are the prevalent group, especially in the south of Iran and Gulf states, and have been found to be associated with 81 host plant species. In addition, phytoplasmas belonging to the 16SrVI, 16SrIX, and 16SrXII groups have been frequently reported from a wide range of crops. On the other hand, phytoplasmas belonging to 16SrIV, 16SrV, 16SrX, 16SrXI, 16SrXIV, and 16SrXXIX groups have limited geographical distribution and host range. Twenty-two insect vectors have been reported as putative phytoplasma vectors in the Middle East, of which Orosius albicinctus can transmit diverse phytoplasma strains. Almond witches' broom, tomato big bud, lime witches' broom, and alfalfa witches' broom are known as the most destructive diseases. The review summarizes phytoplasma diseases in the Middle East, with specific emphasis on the occurrence, host range, and transmission of the most common phyto-plasma groups.
... Phytoplasmas are associated with diseases in many fruit species like apple, plum, peach, berries, papaya, grapevines, mango, pineapple, cashew nut worldwide, which are responsible for severe losses and reduced market value Rao et al., 2020;Kirdat et al., 2019;Mitra et al., 2019aMitra et al., , 2019bDebnath et al., 2020). Different phytoplasmaassociated diseases are reported in papaya worldwide such as dieback (Guthrie et al., 1998;
Gera et al., 2005;
Arocha et al., 2006;Rao et al., 2011), bunchy top (Arocha et al., 2007), yellow crinkle and mosaic (Guthrie et al., 1998) and shoot proliferation (Verma et al., 2012). ...
Aster yellows phytoplasma association with a little leaf disease of papaya in Kerala, India
Article
Full-text available
Jan 2021
Surabhi Mitra
Prasenjit Debnath
Radhika Nurani
G. P. Rao
... En Israel se ha reportado la enfermedad de papaya Nivun Haamir (NH), muy parecida a la PDB, del mismo grupo de 'Ca. Phytoplasma australiense' (16SrXII)
(Gera et al., 2005)
. En Cuba el fitoplasma causante de una enfermedad de papaya similar al "cogollo arrepollado "(Bunchy top-like)" ha sido asociado con el grupo 16SrII, Candidatus Phytoplasma aurantifolia (Arocha et al., 2008). ...
"Fitoplasmas y su estudio en México" (In Libro "Biodiversidad de microorganismos de México: Importancia, aplicación y conservación"
Chapter
Full-text available
Jan 2019
Vladimir Lebsky
Iván Córdova-Lara
Arevik Poghosyan
Reyna Rojas-Martinez
Se presenta información integral sobre el conocimiento y estudio de fitoplasmas y enfermedades asociadas con estos patógenos en México. Se analizan la historia de los estudios, las enfermedades de cultivos de mayor importancia económica para el país, los métodos de diagnóstico aplicados, los logros y los retos, las demandas actuales y las perspectivas para los estudios futuros.
... En Israel se ha reportado la enfermedad de papaya Nivun Haamir (NH), muy parecida a la PDB, del mismo grupo de 'Ca. Phytoplasma australiense' (16SrXII)
(Gera et al., 2005)
. En Cuba el fitoplasma causante de una enfermedad de papaya similar al "cogollo arrepollado "(Bunchy top-like)" ha sido asociado con el grupo 16SrII, Candidatus Phytoplasma aurantifolia (Arocha et al., 2008). ...
Biodiversidad de microorganismos de México Importancia, aplicación y conservación Coordinadores
Chapter
Aug 2020
A.Poghosyan
Reyna Rojas-Martinez
Ivan Cordova
V.Lebsky
... Occurrence of aster yellows phytoplasmas is also reported in Sri Lanka in papaya dieback (Abeysinghe et al. 2016) and in a papaya yellows disease in Taiwan (Bau et al. 2011). Phytoplasmas belonging to different 16Sr groups have been identified in the Asian continent including groups 16SrI and 16SrII in India associated with similar dieback symptoms (Rao et al. 2011) and axillary shoot proliferation (Verma et al. 2012); and group 16SrXII in Israel
(Gera et al. 2005)
. ...
Fruit Crop Phytoplasmas: Characterisation and Epidemiology of Phytoplasma - Associated Diseases
Chapter
Sep 2018
Nicola Fiore
Assunta Bertaccini
Piero Attilio Bianco
Fabio Quaglino
The present chapter focuses on phytoplasmas and phytoplasma diseases affecting stone, pome, and small fruit worldwide. An outlook is also provided on other fruit tree species growing mainly in tropical and subtropical areas that are oftern infected by phytoplasma diseases usually associated with crop losses or loss of fruit quality and marketability.
... Several phytoplasma diseases have been reported worldwide affecting papaya crops, including dieback, yellow crinkle and mosaic in Australia (4) and Nivun Haamir dieback in Israel
(5)
. Others papaya diseases associated with phytoplasmas are dieback in Ethiopia (6), yellow crinkling in Mexico (7), and an axillary shoot proliferation in India (8). ...
A phytoplasma representative of a new subgroup 16SrI-Z associated with Bunchy Top Symptoms (BTS) on papaya in Cuba Fitoplasma representante de un nuevo subgrupo, 16SrI-Z, asociado con síntomas de Cogollo Arrepollado del Papayo (PBT) en Cuba
Article
Full-text available
Apr 2017
Karel Ismar Acosta Pérez
Berta E 1
Piñol-Pérez
Yaima Arocha-Rosete
Phytoplasmas are associated with two papaya diseases in Cuba, Papaya Bunchy Top (PBT) and Bunchy Top Symptoms (BTS), which decrease fruit production. Assessment of the 16S ribosomal DNA by nested PCR, conventional RFLP, sequencing, and in silico RFLP analyses allowed the identification of a new phytoplasma subgroup designated BTSp-16SrI-Z associated with BTS disease in the eastern region of the country. BTSp-16SrI-Z subgroup was detected in 60.42 % of the surveyed plants with crown leaf chlorosis and necrosis of the young leaves. Results confirmed that this phytoplasma strain was consistently associated with the observed BTS symptoms, implying new epidemiological constraints for the disease management. RESUMEN: Los fitoplasmas se asocian con dos enfermedades del papayo en Cuba, Cogollo Arrepollado del Papayo (PBT) y Síntomas de Cogollo Arrepollado (BTS), que disminuyen la producción de frutos de papaya. La detección del ADN ribosomal 16S por análisis de PCR anidada, RFLP convencional, secuenciación y RFLP in silico permitió la identificación de un nuevo subgrupo de fitoplasmas 16SrI-Z asociado a la enfermedad BTS en la región oriental del país. El fitoplasma BTSp-16SrI-Z se detectó en el 60,42 % de las plantas muestreadas con clorosis en las hojas de la región apical y necrosis en las hojas jóvenes. El resultado confirma que este aislado de fitoplasma está consistentemente asociado con síntomas de BTS, lo cual implica nuevas restricciones para el manejo de la enfermedad. Palabras clave: papayo, PCR anidada, fitoplasma, secuenciación, RFLP in silico. Autor para correspondencia: Karel I. Acosta-Pérez.
... Papaya disease, Nivun Haamir (NH), similar to PDB, was reported in Israel (Lju et al., 1996), and attributed to the same taxon as PDB, Ca. Phytoplasma australiense
(Gera et al., 2005)
. Phytoplasma associated with bunchy top-like disease (BTS), known in Cuba (Arocha et al, 2006), was recently reported in mixed infection with a potyvirus (Arocha et al., 2009). ...
Application of scanning electron microscopy for diagnosing phytoplasmas in single and mixed (virus-phytoplasma ) infection in Papaya
Article
Full-text available
Jan 2010
V.¹ Lebsky
Arevik Poghosyan
Laura Silva-Rosales
Phytoplasma and some viruses, papaya ring spot (PRSV) and papaya mosaic (PapMV) have been reported in papaya, from different Mexican states. Some symptoms of yellow type diseases, such as mosaics, stunting, bunchy top and leaf chlorosis, necrosis and malformations are somewhat similar in appearance, but caused by distinct pathogens. Using a scanning electron microscopy (SEM) technique phytoplasmas were detected in the phloem tissues of field and greenhouse-indexed papaya plants from Baja California Sur (BCS). Samples from 32 local varieties, as well as cv. Maradol, showing numerous symptoms of dieback, mosaics, bunchy top, and yellow crinkle were analyzed. The pathogen was detected in stems, leafstalks, roots, axillary leaflets, leaf veins and flowers. Phytoplasma was also detected in dry and in germinated seeds within the fruit, suggesting seed transmission of the pathogen. Some ultrastructural peculiarities of phytoplasma in infected tissues were also observed. No viral infection with PRSV and PapMV was revealed neither in test-plants nor by molecular techniques. Application of SEM technique for analysis of papaya samples from Veracruz and Irapuato, both from field-grown and mechanically inoculated plants with PRSV and PapMV in various combinations also revealed phytoplasmas in the phloem of most of tested samples. In some cases, along with phytoplasmas, rod-shaped bacteria were distinguished.
Keywords: Papaya, phytoplasma, papaya ringspot virus, papaya mosaic virus, scanning electron microscopy, Mexico.
... Phytoplasma solani' (group 16SrXII) (Bau et al., 2011), 'Ca. Phytoplasma australiense' (group 16SrXII) (Elder et al., 2002;
Gera et al., 2005)
, 'Ca. Phytoplasma hispanicum' (group 16SrXIII) (Melo et al., 2013) and 'Ca. ...
‘Candidatus Phytoplasma brasiliense’-related strains associated with papaya bunchy top disease in northern Peru represent a distinct geographic lineage
Full-text available
Feb 2017
CROP PROT
Wei Wei
Edel Pérez-López
Robert Edward Davis
Yan Zhao
During the 2015–2016 fruit production season, a papaya bunchy top (BPT) disease was observed in a papaya production
farm located at Region de Piura, northern Peru. Affected plants exhibited symptoms of excessive proliferation of
auxiliary shoots at the top or near top of the main stem, shortening of internodes, leaf yellowing, and necrosis of leaf
veins. The symptom syndrome suggested possible infection by a phytoplasma, and the recent discovery of a phytoplasmal
disease in a nearby vineyard also indicated that a phytoplasma reservoir and potential vector(s) were present in the
area. Molecular diagnostic assays for phytoplasma detection were therefore employed. Nested polymerase chain reactions
and subsequent nucleotide sequence analysis confirmed that phytoplasma infection did occur in the papaya production
farm. The phytoplasma strains found to be associated with the PBT disease are affiliated with ‘Candidatus Phytoplasma
brasiliense’, a species that had previously never been implicated in a papaya disease anywhere in the world. We provide
molecular evidence to suggest that the papaya-infecting phytoplasma strains identified in this study are closely related to
a phytoplasma associated with the first grapevine yellows (GY) disease that we recently identified in Peru. The results of
our study indicate that these PBT and GY phytoplasma strains in Peru represent an emerging geographic lineage that is
distinct from those of all other known ‘Ca. Phytoplasma brasiliense’ strains in the Americas.
... Acosta et al. (2011) previously reported a phytoplasma from group 16SrI associated bunchy top-like symptoms of papaya in Cuba. Moreover, phytoplasmas belonging to different 16Sr groups have been identified in papaya, particularly in the Asian continent including group 16SrII ('Candidatus Phytoplasma aurantifolia') in India associated with similar dieback symptoms (Rao et al., 2011) and axillary shoot proliferation (Verma et al., 2012); and group 16SrXII 'Stolbur' associated with a dieback-like disease of papaya in Israel
(Gera et al., 2005)
, and yellows disease in Taiwan (Bau et al., 2011). To our knowledge, this is the first record of the identification of a 16SrI 'Ca. ...
Occurrence of phytoplasma diseases of papaya in Sri Lanka
Article
Full-text available
Feb 2016
Saman Abeysinghe
Shirani Widanagamage
I.M.M. Arachchi
Matt Dickinson
... A betegség más nevei: Fekete vesszôjûség, Legno nero, Schwarzholzkrankheiz, Vergilbungskrankheit, Black wood, Mediterranean yellows, Grapevine bois noir phytoplasma, EPPO computer code: GVBNXX, EPPO A2 list: No. 94, EU Annex designation: II/A2. Kórokozója a Stolbur fitoplazma 16Srl törzse (aster yellows) Franciaországban (Quartau et al. 2001), a Stolbur 16Srl-B (aster yellows) Olaszországban (Borgo et al. 2005) és Tuniszban (M'hirsi et al. 2004), a Stolbur fitoplazma közelebbrôl nem identifikált törzse Ukrajnában (Milkus et al. 2005) és Szerbiában
(Gera et al. 2005)
, valamint a Stolbur fitoplazma 16SrXII-A törzse Chilében. Az utóbbi években a Bois noir járványszerû fellépését észlelték Ausztriában (Leitner 2004), Szlovéniában (Petrovic et al. 2004) és Dél-Tirolban (Roschatt és Has 2005), a kórokozó rassz közelebbi identifikálása nélkül. ...
Risk of a spreading a dangerous new grapevine disease, Flavescence dorée (FD) phytoplasma, and the distribution of its leafhopper vector (Scaphoideus titanus Ball) in Hungary
Jan 2014
Pál Benedek
... An association between NH and a 'Ca. Phytoplasma australiense' isolate was recently demonstrated
(Gera et al. 2005)
. ...
Papaya (Carica papaya L.) Biology and Biotechnology
Article
Full-text available
Jun 2007
Jaime A. Teixeira da Silva
Zinia Rashid
Nhut Duong Tan
Paula F. Tennant
Papaya (Carica papaya L.) is a popular and economically important fruit tree of tropical and subtropical countries. The fruit is consumed world-wide as fresh fruit and as a vegetable or used as processed products. This review focuses primarily on two aspects. Firstly, on advances in in vitro methods of propagation, including tissue culture and micropropagation, and secondly on how these advances have facilitated improvements in papaya genetic transformation. An account of the dietary and nutritional composition of papaya, how these vary with culture methods, and secondary metabolites, both beneficial and harmful, and those having medicinal applications, are discussed. An overview of papaya post-harvest is provided, while ‘synseed’ technology and cryopreservation are also covered. This is the first comprehensive review on papaya that attempts to integrate so many aspects of this economically and culturally important fruit tree that should prove valuable for professionals involved in both research and commerce.
... Papaya (Carica papaya) is a popular fruit crop widely cultivated in India and affected by a number of phytoplasma diseases worldwide such as dieback (Guthrie et al., 1998;
Gera et al., 2005;
Arocha et al., 2007a;Rao et al., 2011), bunchy top (Arocha et al., 2007b) and yellow crinkle and mosaic (Guthrie et al, 1998). During December 2011, phytoplasma-like symptoms were observed in a papaya field at the IARI Regional Station, Pune, Maharashtra, India. ...
First report of a phytoplasma associated with an axillary shoot proliferation disease in papaya in India
Article
Jun 2012
Raj Verma
Dhanashri Mungekar
Poornima Gaikwad
V V Datar
Papaya (Carica papaya) is a popular fruit crop widely cultivated in India and affected by a number of phytoplasma diseases worldwide such as dieback (Guthrie et al., 1998; Gera et al., 2005; Arocha et al., 2007a; Rao et al., 2011), bunchy top (Arocha et al., 2007b) and yellow crinkle and mosaic (Guthrie et al, 1998). During December 2011, phytoplasma-like symptoms were observed in a papaya field at the IARI Regional Station, Pune, Maharashtra, India. These included bright yellowing of the upper young leaves followed by drying of upper leaves, proliferation of axillary shoots, reduction in leaf size and interveinal chlorosis (Fig. 1). The symptoms observed in the papaya fields of Pune, Western India differed from those associated with the dieback disease of papaya reported from Gorakhpur, Western India (Rao et al., 2011) in the lack of tip necrosis of leaves and dieback symptoms. Leaf samples from four symptom-bearing plants and four symptomless plants were collected and total genomic DNA was extracted from leaf midribs and petioles (100 mg) using the DNeasy Plant Minikit (Qiagen, Germany). Two sets of universal primers were used to amplify the phytoplasma 16S rDNA by nested PCR; this included direct PCR with primers P1/P7 that prime a region of approximately 1.8 kb, followed by nested PCR with primers R16mF2/R16mR1 (Gundersen & Lee, 1996) that flank a 1.2 kb genomic fragment. A phytoplasma-infected Catharanthus roseus plantmaintained in the glasshouse at the IARI Regional Stationwas used as the positive reference control. Three representative nested PCR products were purified (Wizard SV Gel and PCR Clean Up System, Promega, USA) and directly sequenced (Genombio Technologies, Pune, India). A phylogenetic tree based on the consensus and reference phytoplasma 16S rDNA sequences was constructed by using the Neighbor-Joining method and 1000 replicates for the bootstrap values (MEGA5, USA). The evolutionary distances were computed using the Maximum Composite Likelihood method and are reported as number of base substitutions per site. A nested PCR product of approximately 1.2 kb corresponding to the phytoplasma 16S rDNA was amplified from the four infected papaya plants (Fig. 2). No PCR band was observed for the symptomless papaya plants. The partial 16S rDNA sequence of the three representative phytoplasma isolates shared 100% sequence identity with each other, while the BLAST analysis of the consensus sequence (GenBank Accession No. JQ346525) revealed 99% sequence identity with that of phytoplasmas of group 16SrII ('Candidatus Phytoplasma aurantifolia') including the Ethiopian papaya phytoplasma (DQ285659) (Fig. 3). In India, phytoplasmas of group 16SrI 'Ca. Phytoplasma asteris' and 16SrII (Rao et al., 2011) have been associated with dieback disease of papaya. However, the 16SrII phytoplasma associated with axillary shoot proliferation clearly differs from the 16SrII dieback phytoplasma in symptomatology and occurrence within Western India. This suggests that there may be two different 16SrII phytoplasma eco-strains able to infect the same host in the country. To our knowledge, this is the first record of 16SrII group 'Ca. Phytoplasma aurantifolia' associated with an axillary shoot proliferation disease of papaya in India.
... Acosta et al. (2011) previously reported a phytoplasma from group 16SrI associated bunchy top-like symptoms of papaya in Cuba. Moreover, phytoplasmas belonging to different 16Sr groups have been identified in papaya, particularly in the Asian continent including group 16SrII ('Candidatus Phytoplasma aurantifolia') in India associated with similar dieback symptoms (Rao et al., 2011) and axillary shoot proliferation (Verma et al., 2012); and group 16SrXII 'Stolbur' associated with a dieback-like disease of papaya in Israel
(Gera et al., 2005)
, and yellows disease in Taiwan (Bau et al., 2011). To our knowledge, this is the first record of the identification of a 16SrI 'Ca. ...
First report of the molecular identification of a phytoplasma associated with dieback disease of papaya in Sri Lanka
Article
Full-text available
Apr 2014
Saman Abeysinghe
Shirani Widanagamage
I.M.M. Arachchi
Matt Dickinson
Papaya ( Carica papaya) is a very popular fruit crop in Sri Lanka, grown as a home garden and commercial crop for local and export markets. Papaya is commercially cultivated in Sri Lanka in about 8,000 ha with production of about 32,000 …
... Phytoplasma australiense', respectively. A dieback disease of papaya, named Nivun Haamir dieback
(Gera et al., 2005)
, has been also reported in Israel, associated with a 16SrXII phytoplasma. In Mexico, a 16SrI phytoplasma has been associated with papaya mosaic and yellow crinkling (Rojas et al., 2011). ...
Identification and molecular characterization of phytoplasmas and rickettsia pathogens associated with 'Bunchy Top Symptom' (BTS) and 'Papaya Bunchy Top' (PBT) of papaya in Cuba
Article
Mar 2013
CROP PROT
Lucero Zamora
Karel Ismar Acosta Pérez
Berta Piñol
Y. Arocha
... An association between NH and a 'Ca. Phytoplasma australiense' isolate was recently demonstrated
(Gera et al. 2005)
. ...
Tree and Forestry Science and Biotechnology ©2007 Global Science Books Papaya (Carica papaya L.) Biology and Biotechnology Jaime A. Teixeira da Silva1* • Zinia Rashid1 • Duong Tan Nhut2 • Dharini Sivakumar3 • Abed Gera4 • Manoel Teixeira Souza Jr.5 • Paula F. Tennant6
Book
Full-text available
Jan 2007
Jaime A. Teixeira da Silva
Zinia Rashid
Nhut Duong Tan
Paula F. Tennant
http://www.globalsciencebooks.info/JournalsSup/images/Sample/TFSB_1(1)47-73.pdf
... Recently, strains of 'Ca. Phytoplasma australiense' were reported outside the Oceanic continent in association with peach yellow leaf roll-like disease in Bolivia and with Nivun Haamir dieback in Israel
(Gera et al., 2005)
. 'Ca. ...
'Candidatus Phytoplasma solani', a novel taxon associated with stolbur- and bois noir-related diseases of plants
Article
Jan 2013
INT J SYST EVOL MICR
Fabio Quaglino
Yan Zhao
Paola Casati
Robert Edward Davis
Phytoplasmas classified in group 16SrXII infect a wide range of plants and are transmitted by polyphagous planthoppers of the family Cixiidae. Based on 16S rRNA gene sequence identity and biological properties, group 16SrXII encompasses several species, including 'Candidatus Phytoplasma australiense', 'Ca. Phytoplasma japonicum', and 'Ca. Phytoplasma fragariae'. Other group 16SrXII phytoplasma strains are associated with stolbur disease in wild and cultivated herbaceous and woody plants and with bois noir disease in grapevines (Vitis vinifera L.). Such latter strains have been informally proposed to represent a separate species, 'Candidatus Phytoplasma solani', but a formal description of this taxon has not previously been published. In the present work, stolbur disease strain STOL11 was distinguished from reference strains of previously described 'Ca. Phytoplasma' species based on 16S rRNA gene sequence (16S rDNA) similarity and a unique signature sequence in 16S rDNA. Other stolbur and bois noir associated ('Ca. Phytoplasma solani') strains shared >99% 16S rDNA sequence similarity with strain STOL11 and contained the signature sequence. 'Ca. Phytoplasma solani' is the only phytoplasma known to be transmitted by Hyalesthes obsoletus. Insect vectorship and molecular characteristics are consistent with the concept that diverse 'Ca. Phytoplasma solani' strains share common properties and represent an ecologically distinct gene pool. Phylogenetic analyses of 16S rRNA, tuf, secY, and rplV-rpsC gene sequences supported this view and yielded congruent trees on which 'Ca. Phytoplasma solani' strains formed, within the group 16SrXII clade, a monophyletic subclade that was most closely related to, but distinct from, that of 'Ca. Phytoplasma australiense'-related strains. Based on distinct molecular and biological properties, stolbur and bois noir associated strains are proposed to represent a novel species level taxon, 'Ca. Phytoplasma solani'; STOL11 is designated the reference strain.
... Papaya disease, Nivun Haamir (NH), similar to PDB, was reported in Israel (Lju et al., 1996), and attributed to the same taxon as PDB, Ca. Phytoplasma australiense (
Gera et al., 2005
). Phytoplasma associated with bunchy top-like disease (BTS), known in Cuba (Arocha et al, 2006), was recently reported in mixed infection with a potyvirus (Arocha et al., 2009). ...
Application of scanning electron microscopy for diagnosing phytoplasmas in single and mixed (virus-phytoplasma ) infection in Papaya
Conference Paper
Full-text available
Jan 2010
V.Lebsky
Arevik Poghosyan
Laura Silva-Rosales
Phytoplasma and some viruses, papaya ring spot (PRSV) and papaya mosaic (PapMV) have been reported in papaya, from different Mexican states. Some symptoms of yellow type diseases, such as mosaics, stunting, bunchy top and leaf chlorosis, necrosis and malformations are somewhat similar in appearance, but caused by distinct pathogens. Using a scanning electron microscopy (SEM) technique phytoplasmas were detected in the phloem tissues of field and greenhouse-indexed papaya plants from Baja California Sur (BCS). Samples from 32 local varieties, as well as cv. Maradol, showing numerous symptoms of dieback, mosaics, bunchy top, and yellow crinkle were analyzed. The pathogen was detected in stems, leafstalks, roots, axillary leaflets, leaf veins and flowers. Phytoplasma was also detected in dry and in germinated seeds within the fruit, suggesting seed transmission of the pathogen. Some ultrastructural peculiarities of phytoplasma in infected tissues were also observed. No viral infection with PRSV and PapMV was revealed neither in test-plants nor by molecular techniques. Application of SEM technique for analysis of papaya samples from Veracruz and Irapuato, both from field-grown and mechanically inoculated plants with PRSV and PapMV in various combinations also revealed phytoplasmas in the phloem of most of tested samples. In some cases, along with phytoplasmas, rod-shaped bacteria were distinguished.
... Maradol Roja (MR) was introduced to the competitive market (Pages, 2005), is severely affected by phytoplasmas, cell wall-less Mollicutes transmitted by Hemiptera species (Lee et al., 2000). Phytoplasma papaya diseases include mosaic, yellow crinkle and dieback in Australia (Gibb et al., 1996;White et al., 1998), Nivun Haamir dieback in Israel
(Gera et al., 2005)
, and dieback in Ethiopia (Arocha et al., 2007a). ...
Transmission of the Phytoplasma Associated with Bunchy Top Symptom of Papaya by Empoasca papayae Oman
Article
Full-text available
May 2009
J PHYTOPATHOL
Karel Ismar Acosta Pérez
Bertha Piñol
Yaima Arocha Rosete
John A Lucas
Transmission tests were conducted with field-collected Bunchy Top Symptoms (BTS) phytoplasma-infected specimens of Empoasca papayae. BTS developed in all eight inoculated papayas 3 months later. The BTS phytoplasma was identified in six of eight inoculated papayas, whose partial 16S rRNA sequence (GenBank Accession no. FJ6492000) was 99.9% identical with those from the collected papayas (GenBank Accession no FJ649198) and E. papayae (GenBank Accession no. FJ649199), all of which are members of group 16SrII, ‘Candidatus Phytoplasma aurantifolia’. Results confirmed the ability of E. papayae to transmit the BTS phytoplasma.
... Phytoplasma aurantifolia'' and 16SrXII, Candidatus Phytoplasma australiense, respectively. A dieback disease of papaya, named Nivun Haamir dieback
(Gera et al., 2005)
, has been also reported from Israel, associated with a 16SrXII phytoplasma; recently, a papaya dieback in Ethiopia has been also recorded and associated with a phytoplasma of group 16SrII (Arocha et al., 2007b). ...
Detection of phytoplasma and potyvirus pathogens in papaya (Carica papaya L.) affected with ‘Bunchy Top Symptom’ (BTS) in eastern Cuba
Article
Full-text available
Aug 2009
CROP PROT
Y. Arocha
Berta Piñol
Karel Ismar Acosta Pérez
John A Lucas
Symptoms associated with the papaya ringspot virus (PRSV) were observed in papaya fields from eastern Cuba affected with the ‘Bunchy Top Symptom’ (BTS) phytoplasma. Total DNA and RNA extracted from symptomatic and asymptomatic papayas, were respectively subjected to nested PCR by using phytoplasma 16S rDNA primers, and to RT-PCR with generic coat-protein potyvirus primers. Nested PCR products were obtained for 45/47 of BTS-symptomatic papayas, as well as RT-PCR amplicons for 36/47. No PCR products were observed for asymptomatic plants. The BTS phytoplasma was identified as a member of group 16SrII, “Candidatus Phytoplasma aurantifolia”, while the potyvirus showed a 94% of CP identity with that of PRSV from Ivory Coast. Both typical phytoplasma pleomorphic bodies and potyvirus-like particles were observed in symptomatic papayas examined. Results suggest that the BTS phytoplasma and PRSV coexist in BTS-affected papayas, which must be considered for further management strategies, including investigations of further epidemiological implications.
Diversity, distribution, and status of phytoplasma diseases in Israel
Chapter
Jan 2023
Vered Naor
Tirtza Zahavi
Rakefet Sharon
Candidatus Phytoplasma australiense
Article
Jan 2022
Lia W. Liefting
This datasheet on Candidatus Phytoplasma australiense covers Identity, Overview, Distribution, Dispersal, Hosts/Species Affected, Diagnosis, Biology & Ecology, Impacts, Prevention/Control, Further Information.
Molecular identification of 16SrII-C and 16SrII-D phytoplasma strains associated with phyllody and axillary shoot proliferation in papaya
Article
Jun 2021
AUSTRALAS PLANT PATH
Abhishek Verma
S. Tripathi
Raj Verma
Papaya plants exhibiting phyllody and excessive axillary shoot proliferation were observed in 10 different fields during surveys conducted in 2019 in Pune district, Maharashtra, India. The average disease incidence for phyllody and excessive shoot proliferation was 12% and 4% respectively. The presence of phytoplasma in the infected plants was confirmed by nested PCR assay using R16F2n/R2 primer pair amplifying the 16S rRNA gene and sequence analysis. In BLASTn analysis, the sequences of nested PCR products shared 99–100% identity with phytoplasmas belonging to 16SrII group. These phytoplasmas clustered with phytoplasma sequences belonging to 16SrII group in the phylogenetic analysis. The virtual restriction fragment length polymorphism pattern derived from the sequences identified these two phytoplasmas as 16SrII-C and -D. To our knowledge, this is the first report of 16SrII-C phytoplasma in papaya worldwide and 16SrII-D phytoplasma in India.
Genomics of Papaya Disease Resistance
Chapter
Jul 2014
Brad W. Porter
David A. Christopher
Yun J. Zhu
From seedling emergence through postharvest fruit distribution, Carica papaya is challenged by a wide range of pests and pathogens that diminish fruit yield and marketability. Because chemical control may be costly, unavailable, or ineffective, comprehensive pathogen management strategies, including increased genetic resistance, are needed. Today, heterologous transformation and interspecific and intergeneric hybridization are used to improve disease resistance. Transgene approaches have been used to control several strains of papaya ringspot virus and, along with the introgression of resistance from wild relatives, may be used for controlling other pathogens as well. Expansions of these sources of resistance are needed to ensure that modern cultivars evolve with microbial populations. The papaya genome sequence is available and can be used to provide markers to identify and isolate R-genes from C. papaya and related species. These genes can be introduced into susceptible lines using transformation. The emergence of new diseases and movement of pathogens suggests that extending resistance durability will require a comprehensive strategy of integrating genetic resistance, cultural practices, and factors including innate protection provided by beneficial plant–microbe interactions. Transgene efficacy will need to be monitored during disease epidemics and, likewise, evaluated for changes that may occur over generations in the absence of pathogen selection pressure. Developing and coordinating the use of papaya’s disease resistance resources will ensure that this species continues to provide a valuable source of nutrition for the world’s tropical and subtropical regions and the markets that rely upon these regions for imported fruit.
Detection of phytoplasmas in dieback, yellow crinkle, and mosaic diseases of papaya using polymerase chain reaction techniques
Article
Full-text available
Jan 1996
AUST J AGR RES
Liu BD
D. T. White
Kerry Brian Walsh
Paul T. Scott
Oligonucleotide primers complementary to regions specific to plant-pathogenic mycoplasma-like organisms (phytoplasmas) were used in polymerase chain reactions on tissue samples from dieback, yellow crinkle, and mosaic affected papaya plants. The primer pair P068/P069, which hybridise to internal regions of the 16S rRNA gene, amplified an approximately 560 bp product in dieback, yellow crinkle and mosaic affected papaya. The primer pair P3/P7, which hybridise to the spacer region between the 16S and 23S rRNA genes, amplified an approximately 300 bp fragment in yellow crinkle and mosaic affected papaya, with no product from dieback affected plants. No PCR product was obtained with either set of primers from healthy plants: An identical AluI restriction enzyme profile was obtained with all three 560 bp products. This study provides the first evidence for the association of phytoplasmas with papaya mosaic and Australian papaya dieback.
Article
Full-text available
Aug 1998
Int J Syst Bacteriol
Daniel T. White
Linda Louise Blackall
Paul T. Scott
Kerry Brian Walsh
DNA extracted from three papaya (Carica papaya L.) plants, individually affected by dieback, yellow crinkle or mosaic diseases, was subjected to PCR using phytoplasma-specific primers to amplify the 16S rRNA gene plus 16S-23S rRNA intergenic spacer region. Near-complete DNA sequences obtained for the three PCR amplimers were subjected to phylogenetic analyses and direct sequence comparison with other phytoplasma 16S rDNA and 16S-23S spacer region DNA sequences. The papaya yellow crinkle (PpYC) and papaya mosaic (PpM) sequences were identical to each other, but distinctly different from the papaya dieback (PpDB) sequence, showing 90.3% identity in the he 16S rDNA and 87.8% identity in the 16S-23S spacer region DNA sequences. A phylogenetic tree based on 16S rDNA sequences was calculated, in which PpYC and PpM are most closely related to the tomato big bud phytoplasma (TBB; 99.7% 16S rDNA sequence identity) from Australia, within subclade iii. This subclade consists of strains only reported occurring in the Southern Asian region and Australia, which indicates an Asian/Australasian origin. PpDB is most closely related to the Phormium yellow leaf phytoplasma from new Zealand (PYL; 99.9% identity) and the Australian grapevine yellows phytoplasma (AGY; 99.7% identity). These three phytoplasma strains form a distinct clade within subclade xii, which also includes the European strains STOL and VK as another distinct clade. The origin of the closely related but geographically separated AGY-like strains and STOL-like strains of subclade xii is unclear. It is proposed that phytoplasma strains PpDB, PYL and AGY be included in the previously described taxon 'Candidatus Phytoplasma australiense', and that PbYC, PpM and TBB be assigned to a new taxon, "Candidatus Phytoplasma australasia'.
Use of netting and whitewash spray to protect papaya plants against Nivun Haamir (NH)-dieback disease
Article
Dec 1992
CROP PROT
A FRANCK
M BARJOSEPH
A disease causing the decline of papaya (Carica papaya) plants was noticed in the Jordan Valley in 1982. The disease caused severe yellowing of the upper leaves and dieback of the apex. The disease was not transmissible mechanically and continued efforts to associate viruses and viroids have so far been unsuccessful. Epidemiological observations suggested that the disease is airborne and probably caused by a mollicute. In order to test this hypothesis, plots were covered by an insect-proof net and with white nets providing 15, 30 and 50% shade. The 30%, 50% and insect-proof nettings provided complete protection, and the 15% netting reduced disease incidence to <2%, compared with >37% in the uncovered control plot. Spraying plants at weekly intervals with a commercial whitewash solution was also found to be effective in reducing disease incidence. The advantages of using a range of netting field treatments as a simple means for obtaining information on the epidemiological nature of a new disease are described.
at www.bspp.org.uk/ndr where figures relating to this paper can be viewed
Mar 2005
| https://www.researchgate.net/publication/230173278_An_isolate_of_%27Candidatus_Phytoplasma_australiense%27_group_associated_with_Nivun_Haamir_dieback_disease_of_papaya_in_Israel |
Polymers | Free Full-Text | Conductive Polymer Composites from Renewable Resources: An Overview of Preparation, Properties, and Applications
This article reviews recent advances in conductive polymer composites from renewable resources, and introduces a number of potential applications for this material class. In order to overcome disadvantages such as poor mechanical properties of polymers from renewable resources, and give renewable polymer composites better electrical and thermal conductive properties, various filling contents and matrix polymers have been developed over the last decade. These natural or reusable filling contents, polymers, and their composites are expected to greatly reduce the tremendous pressure of industrial development on the natural environment while offering acceptable conductive properties. The unique characteristics, such as electrical/thermal conductivity, mechanical strength, biodegradability and recyclability of renewable conductive polymer composites has enabled them to be implemented in many novel and exciting applications including chemical sensors, light-emitting diode, batteries, fuel cells, heat exchangers, biosensors etc. In this article, the progress of conductive composites from natural or reusable filling contents and polymer matrices, including (1) natural polymers, such as starch and cellulose, (2) conductive filler, and (3) preparation approaches, are described, with an emphasis on potential applications of these bio-based conductive polymer composites. Moreover, several commonly-used and innovative methods for the preparation of conductive polymer composites are also introduced and compared systematically.
Background:
Conductive Polymer Composites from Renewable Resources: An Overview of Preparation, Properties, and Applications
by
Yao Huang 1,† ,
Semen Kormakov 1,† ,
Xiaoxiang He 1 ,
Xiaolong Gao 1 ,
Xiuting Zheng 1 ,
Ying Liu 2 ,
Jingyao Sun 1,* and
Daming Wu 1,2,*
1
College of Mechanical and Electrical Engineering, Beijing University of Chemical Technology, Beijing 100029, China
2
State Key Laboratory of Organic-Inorganic Composites, Beijing 100029, China
*
Authors to whom correspondence should be addressed.
†
Equal contribution.
Received: 17 December 2018 / Revised: 12 January 2019 / Accepted: 19 January 2019 / Published: 22 January 2019
(This article belongs to the Special Issue Renewable Polymer Composites )
Abstract
:
This article reviews recent advances in conductive polymer composites from renewable resources, and introduces a number of potential applications for this material class. In order to overcome disadvantages such as poor mechanical properties of polymers from renewable resources, and give renewable polymer composites better electrical and thermal conductive properties, various filling contents and matrix polymers have been developed over the last decade. These natural or reusable filling contents, polymers, and their composites are expected to greatly reduce the tremendous pressure of industrial development on the natural environment while offering acceptable conductive properties. The unique characteristics, such as electrical/thermal conductivity, mechanical strength, biodegradability and recyclability of renewable conductive polymer composites has enabled them to be implemented in many novel and exciting applications including chemical sensors, light-emitting diode, batteries, fuel cells, heat exchangers, biosensors etc. In this article, the progress of conductive composites from natural or reusable filling contents and polymer matrices, including (1) natural polymers, such as starch and cellulose, (2) conductive filler, and (3) preparation approaches, are described, with an emphasis on potential applications of these bio-based conductive polymer composites. Moreover, several commonly-used and innovative methods for the preparation of conductive polymer composites are also introduced and compared systematically.
Keywords:
renewable resources
;
polymer composites
;
electrical/thermal conductivity
;
properties and applications
1. Introduction
Conductive polymer composites have a range of excellent properties, such as high conductivity, high specific strength, high specific modulus, high temperature, corrosion resistance, fatigue resistance and so on [ 1 , 2 , 3 , 4 , 5 , 6 , 7 ]. They can be used not only as a structural material to carry loads, but also as functional materials.
With the application of composite materials and the increase of annual production, a large amount of composite material waste has also been generated. In particular, the high modulus and corrosion resistance of carbon fiber composites has led to the difficulty of disposal and utilization of waste materials [ 8 , 9 ]. The environmental pollution caused by carbon fiber composite materials has attracted extensive attention [ 10 ]. Therefore, the technology of recovery and utilization of conductive polymer composites has become an international research hotspot [ 11 , 12 , 13 , 14 ].
The production of fillers like carbon fiber requires a lot of energy, so it is very expensive. To recycle and reuse the filler, on the one hand can reduce the production of new carbon fiber energy consumption, and on the other hand, the recycled carbon fiber still has good mechanical properties and utilization value, and can be used in components with relatively low requirements.
There are two main sources of polymer composite waste: one is the waste in the process of production and molding, such as prepreg materials, expired materials, scrap materials, unsuitable parts, flash edges, test waste, etc. [ 8 , 15 , 16 ]; the other is end-life products. Some developed countries, such as Germany, the United Kingdom, the United States, Japan, and so on, have attached great importance to the development of carbon fiber composite recycling techniques. They have set up special research institutions to solve this problem, and have made some industrial attempts [ 17 , 18 , 19 , 20 ]. Potential recycling technologies for polymer composite waste with carbon fillers can be mainly classified into mechanical and chemical recycling. Mechanical recycling comprises mixing some waste materials with original materials and then processing them to form a new material. For carbon fiber reinforced composite waste, carbon fibers are recycled as powders or short fibers, which can only be reused as fillers in the production of new composite materials [ 21 ]. In chemical recycling, carbon fillers can be recycled using the following technologies: solvolysis at low temperature, pyrolysis, fluidized bed processing, and solvolysis using near- or super- critical fluids. Carbon fillers can be recycled with good mechanical and surface properties, and then be reused as raw materials in this way. Other methods such as gasification and pyrolysis/gasification can also be used in carbon filler recycling [ 22 ]. In this article, the progress of conductive composites from natural or reusable filling contents and polymer matrices including (1) natural polymers, such as starch and cellulose, (2) conductive fillers, and (3) preparation approaches, are described with an emphasis on potential applications [ 23 , 24 , 25 ]. Moreover, several commonly used and innovative methods for the preparation of conductive polymer composites are also introduced and compared systematically.
2. Natural Polymers and Conductive Fillers
2.1. Polymers
Natural polymer materials occur widely in animals and plants, in the form of e.g., cellulose, starch, chitin, chitosan, collagen, gelatin and silk. With the increasing demand for materials, synthetic polymer materials began to replace natural polymer materials. However, in recent years, oil resources are decreasing, environmental pollution is becoming more and more serious, and natural polymer materials have received increasing attention by more and more countries.
Natural polymers come from animal, plant and microbial resources in nature, which are inexhaustible renewable resources. These materials are easily decomposed into water, carbon dioxide and inorganic molecules by natural microorganisms or enzymes. They are not only environmentally friendly, but are also biodegradable materials.
2.1.1. Cellulose
Cellulose is highly crystalline, including glucose units linked together in long chains; hemicellulose, as a polysaccharide, acts as a cementing matrix between micro-cellulose fibrils, forming the main structural component of the fiber cell [ 26 ].
2.1.2. Starch
Starch-based biodegradable materials with good biodegradability and processability have become a research hotspot in the field of materials.
Whole starch plastics comprise starch molecules which become disordered by adding a small amount of plasticizer and other auxiliaries to form a thermoplastic starch resin. This kind of plastic is the most promising in this category, because it can be completely biodegradable.
Whole starch plastics with starch contents of 90–100% have been developed by the Sumitomo Corporation from Japan, the Warner-lambert Company from USA and the Ferruzzi Company from Italy. The product can biodegrade in one year.
The sequence of addition of components (starch/plasticizer (glycerol)/clay) has a significant effect on the nature of composites formed, and accordingly, the properties are altered. Glycerol and starch both have the tendency to penetrate into the silicate layers, but the penetration of glycerol is favored, owing to its smaller molecule size. The filler dispersion becomes highly heterogeneous, and the product becomes more brittle when starch is plasticized before filling with clay due to the formation of a bulky structure resulting from electrostatic attractions between starch and the plasticizer. It was concluded that the best mechanical properties can be obtained if a plasticizer is added after the mixing of clay in the starch matrix, as shown in
Figure 1
[
27
].
Recently a new class of hybrid materials of polymers and layered silicates has emerged. Starch has been filled with layered silicates, and an improvement in mechanical and barrier properties was observed [ 28 , 29 ].
2.1.3. Chitin
Chitin is a rich natural polymer which is widely distributed in low plant fungi, algae cell walls, and arthropods. It has good biocompatibility and biodegradability, and has unique application advantages in the biomedical field. It is of great significance in the construction of a new chitin material for biomedical development. To create the chitin-silk biocomposite, solutions of squid pen β-chitin and B. Mori cocoon silk co-dissolved in hexafluoroisopropanol (HFIP) are dried on a polydimethylsiloxane mold to yield homogeneous films. So, a one-step solution-based chitin nanofiber silk biocomposite that closely replicates the nanostructure of the insect cuticle organic phase, which is made of chitin nanofibers embedded in a silk-like protein matrix, is introduced, as shown in Figure 2 [ 30 ].
2.1.4. Protein
Soy protein has been considered recently as an alternative to petroleum polymer in the manufacture of adhesives, plastics, and various binders. Soybean protein, the major component of the soybean, is readily available from renewable resources and agricultural processing by-products. Utilizing these proteins for biodegradable resins will help alleviate environmental problems and add value to agricultural by-products [ 31 , 32 ].
2.1.5. Natural Rubber
The main component of natural rubber is polyisoprene, which comes from latex in the rubber tree. It is a renewable natural resource with excellent comprehensive properties. In order to broaden the application field of natural rubber materials, natural rubber is modified by processes including epoxidation modification, powder modification, resin fiber modification, chlorination, hydrogen chlorination, cyclization and graft modification and blending with other substances.
Natural rubber degradable materials were prepared with different preoxidation systems by Albertsson, as shown in Figure 3 [ 33 ]. The effect of the modification of silicon on the resilience of natural vulcanized rubber reinforced by silicon and carbon black was studied. The results show that the vulcanized natural rubber containing silane additive recovers elasticity more easily, and the elastic recovery ability increases with the increase of the silane content [ 34 , 35 , 36 ]. The natural rubber composites of soybean flour were prepared by mixing calcium sulfate as compatibilizer by Wu [ 37 ], in which the content of soybean powder and natural rubber was as follows. Natural rubber is uniformly dispersed in a soybean flour matrix, and there are hydrogen bonds between them, which can improve the mechanical properties and water resistance of the material.
2.1.6. Polylactic Acid
In order to reduce pollution and the waste of petroleum resources, the development of environment-friendly, biodegradable materials is a hot research topic at present. Polylactic acid (PLA) is a chemically-synthesized, degradable polymer. Polylactic acid is a kind of polyester plastic. Because of its advantages of good biodegradability and good mechanical properties, it is becoming a hot topic in the research of polymer materials. However, polylactic acid also has its own shortcomings, such as its brittleness, low glass transition temperature, poor impact resistance and high cost, which hinders its commercial application. Therefore, it is necessary to modify polylactic acid physically or chemically.
The composite of conductive fillers such as graphene, carbon black, graphite and biodegradable polylactic acid can make full use of the special properties of conductive fillers such as graphene to improve the performance of polylactic acid.
Graphene nanoparticles/PLA composites were prepared by solution blending of two kinds of graphene nanoparticles (x Gn-25 and N02) with polylactic acid by Mohammad et al. The electrical conductivity of composites is increased by nearly 12 orders of magnitude compared with pure PLA [ 38 ].
2.2. Conductive Fillers
There are two main kinds of conductive fillers: carbons and metal. Fillers based on carbon include carbon nanotubes (CNT), carbon fibers (CF), and carbon black (CB). For metallic fillers, there are metallic powders, metal flakes, metal-coated fibers and metal nanowire. Table 1 shows the conductivity of metal and carbon fillers [ 39 , 40 , 41 ].
Different types of fiber waste exist according to the steps taken in the manufacturing process. Fiber waste is produced during the first steps of the production of composite parts. It can also arise from prepreg rolls that did not pass the quality control. After a part is manufactured, processed material waste will be produced that cannot be directly reused, and some parts can be scrapped after quality control. A significant amount of waste is produced during these steps. According to Alex Edge from ELGCF carbon fiber Ltd. in United Kingdom, the majority of the carbon fiber waste that is treated actually arises from these steps. This is due to the long service life of these materials, but also because the waste stream has to be implemented between the dismantling sites and the recyclers.
2.2.1. Carbon Fiber
Carbon fiber as a reinforced fiber of high strength and toughness composite material, with the rapid development of aviation and automobile industry, its demand is also increasing day by day.
In the early stage, the undegradable carbon fiber composite material waste was mainly used in incineration to utilize the thermal energy generated by its combustion. Although this method of recycling was simple and feasible, in the process of incineration, the composite releases a lot of toxic gas, and burying the ash after burning can cause secondary pollution to the soil. As a result, industrial developed countries have strictly prohibited the use of this method to deal with composite waste [ 8 , 42 ].
Carbon materials have long proven themselves as fillers in the manufacture of composite materials based on polymers [ 43 ]. The positive qualities of carbon fillers can be attributed to the relative ease of their production and low cost. Moreover, they possess low density, especially in comparison with metals, and have high values of mechanical, electrical and heat-conducting properties, and stability, as well as relative simplicity of storage and easy processing.
Silva’s group [
44
] prepared green hybrid films by regenerating cellulose/exfoliated graphite nanosheets in ionic liquid. The tensile strength and Young’s modulus of the prepared nanocomposites was improved by 97.5% and 172% respectively after the incorporation of 0.75 and 1 wt % graphite nanoplates. Ruedas and co-workers [
45
] reported the development of a proprietary formulation based on materials based partially on renewable resources and graphite. The obtained material could be used in the production of capacitive lamps. Wang et al. [
46
] proposed a novel method of carbon aerogel anode preparation for lithium batteries. Carbon aerogel with large open pores and high surface area can be prepared by the pyrolysis of a three dimensional bacterial nanocellulosic hydrogel construct. Carbon aerogel shows very good electrochemical performance in terms of both the capacity retention and rate performance required for lithium ion batteries.
Lightweight and flexible composite paper has been produced by incorporating nanofibrillated-with-graphite nanoplatelets by Li and co-workers [ 47 ]. The authors noted that cellulose, with a high tensile strength but a low thermal conductivity, forms interconnected networks existing in the interspace of graphite nanoplatelets (GNPs), which can significantly improve the tensile strength of the as fabricated composite paper. The hybrid film with 75 wt % GNPs shows an in-plane and through-plane thermal conductivity of 59.46 and 0.64 W/mK, respectively, with a satisfactory tensile strength of 46.39 MPa.
Figure 4 shows the electrical conductivity of the composite paper as a function of the GNPs amount, which varies by around 7 orders of magnitude, i.e., from 10 wt % GNPs to pristine GNPs papers.
Along with other advantages such as low through-plane thermal conductivity and density, this robust composite paper with superior thermal conductivity promises huge potential applications for heat dissipation. The authors noted that the incorporation of nanofibrillated cellulose (NFC) poses a controllable effect on the electrical and thermal conductivity of the composite paper, while its mechanical strength is dramatically enhanced, revealing the further direction of exploring more advanced thermally-conductive composite paper through tailoring the properties of GNPs, such as by increasing their aspect ratio.
High Temperature Pyrolytic Cracking
Pyrolysis is the only commercially-available retracement of carbon fiber reinforced composites, which degrades the composite materials at high temperatures to obtain clean carbon fibers. At the same time, part of the organic liquid fuel can be recovered.
A new technology in which carbon fiber will not be carbonized during heating has been developed by Karborek from Italy, which can obtain carbon fibers of shorter lengths than those of the original material [ 48 ].
American adherent technologies had invented a low-temperature and low-pressure thermal decomposition process for carbon fiber composite recycling. The test results show that the surface of the carbon fiber treated by this method is basically undamaged. The strength of the carbon fiber is about 9% lower than that of the original fiber [ 49 , 50 ].
Fluidized Bed Process
Fluidized bed thermal decomposition is a carbon fiber recovery method that uses high temperature air heat flux to decompose carbon fiber composites at high temperatures. Usually, this process also uses a cyclone separator to obtain filler particles and clean carbon fibers. The University of Nottingham has carried out a systematic study on the fluidized bed pyrolysis process. The results show that this method is particularly suitable for the recovery and utilization of end-of-life parts of carbon fiber composites containing other mixtures and pollutants [
51
]. Under the condition that the average particle size of sand in l m/s, fluidized bed is 0.85 mm, the thermal decomposition test of carbon fiber composite is carried out with the fluidized heat flux of 450 °C. The length of carbon fiber recovered was 5.9–9.5 mm. The test results show that the tensile strength of the recycled fiber is about 75% that of the original fiber, but the modulus of elasticity is basically unchanged, so the recovered carbon fiber can partially or completely replace the original short cut carbon fiber.
Subcritical and Supercritical Fluids
A team from the University of Validolid in Spain and the University of Nottingham in England studied the chemical recovery of carbon fiber composites using methanol, ethanol and acetone as supercritical fluids. The effects of temperature, pressure, flow rate and alkaline catalyst on the resin decomposition were studied. The results show that the fluid system and alkaline catalyst promote the degradation process and increase the overall reaction rate. By changing the flow rate and the ratio of alkaline catalyst, the resin can be degraded by more than 95% in 15 min, and the recovered fiber can reach a strength of 85–99% of the original [
52
].
The decomposition process of carbon fiber reinforced epoxy resin composites in supercritical water was studied by Pinero Hemanz R. et al. The results showed that the decomposition rate of epoxy resin was 79.3 by 30 min reaction at 673 K, 28 MPa, and the decomposition rate of epoxy resin reached 95.3 with the addition of a potassium hydroxide (KOH) catalyst. The tensile strength of the obtained carbon fiber can be maintained at 90% that of the original fiber.
2.2.2. Carbon Nanotube
Carbon nanotube (CNT) are linear carbon materials which are grown directly by the catalytic action of low molecular gaseous hydrocarbons, and have higher moduli and strength than ordinary carbon fibers. Conductive properties, such as small size, good flexibility, relatively weak damage in the processing process, and ability to maintain its high aspect ratio, have a wide range of applications in the reinforcement of polymers and the preparation of conductive functional materials.
In order to reduce the percolation threshold of low packing, the better scheme is for the filling to have good dispersion, and not even, but selective distribution, so as to form a two-dimensional conductance network with less content. For the arrangement of CNT in the matrix, Cebeci et al. [ 53 ] have studied two kinds of dispersive morphology pairs of CNT in cyclooxygenated lipoids: directed arrangement (A-CNTs) and random distribution (R-CNTs). Their results showed that the conductivity of A-CNTs can reach about 23 s/m, but that of R-CNTs can only reach 10 s/m.
2.2.3. Graphene
Graphene (graphene) is a two-dimensional honeycomb crystal formed by the arrangement of sp2 hybrid carbon atoms. Each carbon atom is connected to the adjacent three carbon atoms by σ bond, and provides an unbonded π electron. This electron can move freely in the plane of graphene, which makes graphene have excellent mechanical and electrical properties. It is widely used in high performance composites, electronic devices and other domains.
In order to reduce the percolation threshold of graphene in polymer, the double percolation structure is used in the compounding of graphene/polymer matrices. Mao et al. [ 54 ] found that graphene selectively distributed in the PS phase region when PS/PMMA formed a double continuous phase structure, and the percolation threshold of graphene decreased from 1.5% to 0.5%.
2.2.4. Aluminum Particle
Aluminum and plastic were separated from aluminum-plastic composite film by special processing, and were refined to make plastic particles and aluminum powder. In Brazil, aluminum plastic film is regenerated by plasma technology. This method produces temperatures of up to 15,000 °C by argon electrolysis to obtain liquid aluminum and paraffin. After condensation, aluminum ingots and high-purity stone wax can be formed [ 55 ].
2.2.5. Copper Particle
The precipitation potential of copper is much higher than that of other metals. According to the electrochemical theory, it is easier to reduce the electroplating sludge leachate by electrolysis with the potential of more positive metal, so copper ions preferentially reduce at the cathode compared with those of other metals. That is to say, the selective electrochemical separation and extraction of copper in leachate can be realized by electrochemical metallurgy in theory. Researchers taking copper, nickel and other heavy metals as research objects and their sulfate solutions as simulated wastewater, systematically studied the effects of various factors in electrolysis on the current efficiency and recovery rate of metal deposition [ 56 , 57 , 58 ].
2.2.6. Stainless-Steel Fiber
As a new type of metal fiber, stainless steel fiber (SSF) has been widely studied in the 1980s because of its excellent electrical conductivity and processability. The most outstanding performance of stainless steel fiber is that it is resistant to surface oxidation and rust during high temperature processing, which eliminates the process of complex deoxidization and surface protection. At the same time, it can also maintain conductivity and its electromagnetic shielding function.
The appearance (color), mechanical properties and processing properties of the matrix after adding SSF are the least variable, and a small amount of SSF can achieve reasonable conductivity and electromagnetic shielding efficiency. Polycarbonate (PC), polystyrene (PS) and ethylene-vinyl acetate copolymers (EVA) were filled with stainless steel fibers of about 7 μm in diameter to make conductive composites. When the mass fraction of SSF was 6%, the shielding efficiency could reach 40 dB.
Carbon nanotubes/stainless steel fiber/nylon 6 composites were prepared by a prefabricated master batch method. The material density was less than 1.16 g/mm 3 . The electromagnetic shielding efficiency of the composites increased with the increase of stainless steel fiber content. Percolation occurs in the fiber content from 4 to 6 wt %. When the fiber content reaches 12 wt %, the electromagnetic shielding efficiency is higher than 35db in the range of 30 MHz~1.5 GHz [ 59 ].
3. Preparation Approaches
Conductive polymer composites are mainly composed of conductive fillers with high conductivity and insulating polymer matrices, in which conductive fillers provide carriers. The carriers transfer into polymer composites by interaction between conductive fillers.
The key to the preparation of conductive polymer composites is how to distribute the filler evenly into the polymer matrix to obtain good processability. The filler can form a conductive network structure in the nanocomposites and provide good conductivity. There are three main methods for preparing conductive polymer composites: melt blending, solution blending and in situ polymerization.
3.1. Traditional Compounding Methods
Since the electrical conductivity of the composites was strongly influenced by the volume of conducting filler involved in making conducting paths, the carbon fillers/resin composites were prepared with various volume fractions of conducting fillers and resin. Different dispersion techniques are used to prepare conductive composites (as shown in Table 2 ). The conductivity of the conductive composite is different due to the filler, matrix and dispersion method.
3.2. Organic Molecule Cross-Linking Method
The preparation of crosslinked conductive polymer nanomaterials uses chemical or electrochemical polymerization
The methods of chemical polymerization are usually used as a hard template method (anodic alumina (AAO), polycarbonate (PC), zeolite, thin film as template) and a soft template method (surfactant such as naphthalene sulfonic acid and benzenesulfonic acid, etc.) [ 74 , 75 , 76 ].
Electrochemically synthesizing cross-linked conductive polymers with nanostructures are prepared by different polymerization methods, such as potentiostatic polymerization, constant-current polymerization, electrodeposition, etc. The reaction is confined to the surface of the electrode and precipitated on the electrode in the form of film. In many cases, nanostructures grow in the direction of an electric field to form a directional structure. The properties and morphology of nanomaterials can be adjusted by electro polymerization conditions, for example, controlling the rate of electrochemical reaction polymerization by controlling the applied voltage or current density, and the amount of the product can also be controlled by the total amount of charge applied in the electrosynthesis. The polymer prepared by the electrochemical method has good morphology, good properties, high conductivity and good stability [
77
,
78
].
3.3. Spatial Confining Forced Network Assembly (SCFNA)
Constructing a network of conductive fillers in polymeric matrix is essential for the preparation of conductive polymer composites. Although the conductivity of the composites could increase remarkably after the percolation threshold, it is still much lower than expected due to a limited self-assembly interaction between filler particles [ 79 , 80 , 81 ].
High-performance conductive polymer composites could be prepared by the method of spatial confining forced network assembly (SCFNA, Figure 5 ) [ 82 , 83 , 84 ]. A homogenous polymer and conductive fillers, prepared by conical twin-screw mixer, was placed in a compression mold with confining space to carry out two-stage compression, free compression and spatial confining compression [ 85 , 86 ]. The electrical conductivity of the SCFNA prepared polypropylene/short carbon fibers was increased to up to 4 orders of magnitude higher than that produced using ordinary compounding technology [ 87 , 88 ].
3.4. Intercalation Compounding Methods
Because of the high surface energy, small particle size and high viscosity of the polymer melt, it is not easy to mix evenly. In order to maintain the local order of layered nanometer thermal conductive fillers in the composites, intercalation and recombination technology can improve the thermal conductivity and distribute the polymers among the thermal conductive fillers.
a. Intercalation polymerization
The monomer is dispersed and intercalated into the lamellar layer of the thermal conductive filler, and then the polymerization is initiated and the polymer is formed between the layers, from which the nano-scale recombination is achieved.
b. Polymer intercalation
The polymer solution or melt is mixed with the layered filler, and then the lamellar layer is stripped and dispersed in the polymeric matrix by heating. Polyamide/graphite intercalation composites were prepared by in situ stripping and melting. It was found that the thermal diffusivity of the intercalated composites was much higher than those of polyamide/graphite composites. Higher thermal conductivity may be obtained by using intercalated graphite with a larger scale size and higher expansion ratio [ 89 ].
3.5. Coating Method
Conductive coating is a cheap, simple process; it can be automatically coated, and is especially suitable for coating the surface of complex shapes, suitable for the purpose of conducting, anti-static and shielding electromagnetic wave. The main research impetus for conductive coatings is to develop conductive coatings with high conductivity, low cost and environmental protection. The waterborne conductive coating has the advantages of low content and low pollution, which greatly save energy and resources; as such, the material has good development prospects.
A conductive nylon-6 nonwoven fabricated via melt-blowing nylon-6 into nonwoven films and dip-coating of the nonwoven matrices with GO dispersions in water is reported by Qin Pan, as shown in Figure 6 [ 90 ].
Graphene/cotton composite fabrics were successfully synthesized via a facile “dipping and drying” process followed by a NaBH 4 reduction method. The flexible 3D conductive network constructed by graphene sheets greatly enhances the conductivity of cotton fabrics [ 91 ].
4. Multi-Functional Properties of Bio-Based Composites and Their Applications
In recent decades, the demand for biodegradable polymers as environmental friendly packaging materials has increased due to their ability to biodegrade in nature. The term “biodegradable” refers to materials that, under a suitable situation of temperature, moisture, and oxygen availability, are degraded with no adverse environmental impact [ 92 , 93 ]. The importance of renewable products for industrial applications has become extremely clear in recent years, with increasing emphasis on environmental issues such as waste disposal and depleting non-renewable resources. Biopolymers derived from animal (polylactic acid, polyhydroxyalcanoates, polybutylene succinate) or vegetable sources (cellulose-based polymers, alginate, polyisoprene, starch), as well as from bacterial fermentation products (chitin, chitosan, collagen, sericin), have captured the attention of researchers. The materials obtained from the renewable bioresources could be alternatives to petroleum-based synthetic products, due to their advantages of relatively low cost, environmental friendly nature, easy availability, renewability, and nontoxicity. The development of novel materials based on biodegradable polymers is a complex task and is attracting increasing attention in the interests of energy and the environment [ 94 , 95 , 96 ].
Real applications of biodegradable materials have been limited due to their weak mechanical and thermal characteristics, and filler particles have been indicated to help overcome some of the shortcomings of these films. Biopolymers are generally insulating. To become electrically conductive, polymers should possess a cluster chains of conductive filler, which loosely holds electrons and allows relatively easier delocalization of electrons [ 77 , 97 ].
Currently, there are many composite materials based on the biopolymer matrix that meet the performance requirements. For the manufacture of these materials, a wide range of biopolymer matrices (cellulose, pectin, chitosan, starch, polylactide, etc.) is used. Fillers often use metal particles (copper, silver, aluminum etc.) and their oxides (titanium dioxide, zinc oxide, aluminum oxide etc.) and carbon fillers (carbon black, carbon fiber, carbon nanotubes etc.). Special attention should be paid to materials obtained using nanoparticles. Biopolymers require the incorporation of a nanofiller, and, due to their high production cost and inadequate characteristics, the integration of nanofiller is required to enhance the mechanical strength, electrical conductivity, anti-corrosion, thermal properties etc. [
98
,
99
].
These biocomposite materials can be produced in the form of thin films, hydrogels, aerogels, etc., depending on the requirements imposed on them [ 100 , 101 ]. For example, hydrogels prepared from natural polymers have received immense attention due to their safe nature, biocompatibility, hydrophilic properties, and biodegradable nature. Thus, they are considered as good candidates for some potential uses, including as bioconductors, biosensors, bioactuators, electro-stimulated drug delivery systems, as well as neuron-, muscle-, and skin-tissue engineering [ 102 , 103 , 104 , 105 , 106 ]. Aerogels based on piopolymers with the high surface areas and surface charges can be used for the layer-by-layer assembly of conductive polymer composites, carbon nanotubes, titanium dioxide, zinc oxide, and aluminum oxide to enhance the charge capacity, flexibility and mechanical properties for the application in energy storage and other electronic applications [ 107 , 108 ]. Nanocellulose based paper possesses superior optical clarity compared with the regular paper substrate. Transparent and conductive paper can be prepared by the deposition of titanium oxide, carbon nanotubes, silver nanorods, tindoped indium oxide, boron nitride, silica nanoparticles, quantum dot and molybdenum disulfide on nanocellulosic paper substrate [ 109 , 110 , 111 , 112 , 113 ]. Kaolin and a nanocellulose composite could be promising for the cost effective, flexible, low surface roughness and porosity substrate for printed electronic applications [ 114 , 115 ]. Biopolymer-based composites have been used in numerous applications with increasing interest not only due to their renewable, eco-friendly nature, but also because of the flexibility in their processing conditions and competitive cost of their end products [ 116 ].
In this section, we will give a more detailed overview of the research aiming at manufacturing and applying conductive biocomposites with different types of fillers.
4.1. Carbon Nanotube Based Conductive Biocomposites
One of the most popular nanofillers on the basis of carbon is carbon nanotubes (CNTs). СNTs represent allotropes of carbon with cylindrical structure with a diameter of 1–10 nm, length of several micrometers and high aspect ratio, sometimes reaching values of 10,000 [ 117 , 118 ]. CNTs can be divided into single-walled and multi-walled tubes, depending on the number of their constituent uniaxial carbon cylinders. CNTs were discovered in 1991 [ 119 ]. Recent studies have shown that most biopolymer matrices can be successfully used to produce biocomposite materials by incorporating CNTs. The biocompatibility of two main variants of SWCNT and MWCNT has been investigated. One early study revealed that the incorporation of SWCNT into a biodegradable polymeric scaffold did not induce any in vitro cytotoxicity [ 120 ]. This type of nanofiller has been successfully electrospun with biopolymers such as chitosan, cellulose triacetate and biodegradable polylactide [ 121 , 122 ]. CNT is used with many types of biopolymers to produce composites with high mechanical and conductive properties [ 123 , 124 ]. It was shown that CNT/biopolymer composites possess excellent mechanical performance. Good biocompatibility and high electrical and electrochemical sensitivity are advantages for implantable biosensor applications. The initial research found that noncovalently functionalzed CNTs could detect serum proteins, including disease markers, autoantibodies, and antibodies [ 125 ].
Recently, biocomposites based on CNT and bacterial cellulose have been widely used. Bacterial cellulose (BC), a natural polymer hydrogel, is produced by a primary metabolism process of several genera, such as Agrobacterium, Aerobacter, Salmonella, Escherichia etc. [ 126 ]. In recent works, nanofibrillated cellulose has emerged as an alternative for conventionally-used polymers in the fabrication of thermally-conductive papers [ 127 , 128 ]. Among several methods, the integration of a unique carbon nanofiller into the cellulose matrix is regarded as one of the ideal building blocks for the improvement of the mechanical and electrical properties. CNTs have been incorporated into the BC matrix, showing enhanced mechanical strength and electrical conductivity [ 129 , 130 ]. Yoon and co-workers [ 130 ] presented the preparation BC/CNT nanocomposite by dipping cellulose pellicles into a multi-walled carbon nanotube (MWCNT) solution. The morphology of the MWCNTs-adsorbed cellulose showed densely adsorbed nanotubes over the surface of the cellulose pellicle. The four-probe electrical measurements of the membrane gave a room-temperature, DC conductivity of approximately 2.0 × 10 −2 to 1.4 × 10 −1 S/cm, based on the total cross-sectional area; this result dependent on the amount of MWCNTs in the cellulose membranes.
CNTs, especially SWCNTs possess surface areas which are as large as 2600 m
2
/g, which makes them suitable as drug carriers for biomedical applications. Pantarotto’s group [
131
] introduced CNTs as a template for presenting bioactive peptides to the immune system. Bcell epitope of the foot-and mouth disease virus (FMDV) was covalently attached to amine group-functionalized CNTs. As a result, the peptides around the CNT adopt the appropriate secondary structure due to the recognition by specific monoclonal and polyclonal antibodies. The immunogenic features of peptide-CNT conjugates were subsequently assessed in vivo. Immunisation of mice with FMDV peptide-nanotube conjugates elicited high antibody responses compared with the free peptide. These antibodies were peptide-specific, since antibodies against CNT were not detected. In addition, the antibodies displayed virus-neutralizing ability. Kim’s group [
132
] presented a novel, all-solid-state flexible supercapacitor produced by bacterial nanocellulose, carbon nanotubes and ionic liquid based polymer gel electrolytes. The obtained material was characterized by high physical flexibility, desirable electrochemical properties, excellent cyclability and superior mechanical properties.
The incorporation of CNTs as filler materials could be another strategy to enhance the conductive properties of nerve tissue engineered composites. For example, Hasirci’s group [ 133 ] demonstrated that MWCNT-poly(2-hydroxyethyl methacrylate) (pHEMA) composite hydrogel conduits could maintain SHSY5Y neuroblastoma cell viability.
Electrical conductivity and electromagnetic interference shielding efficiency of carbon nanotube/cellulose composite paper were evaluated after putting CNT in a continuously interconnected network on cellulose fibers [ 134 ]. The produced material was characterized by a volume resistance of 5.3 × 10 −1 Ω cm.
Farjana’s group [
135
] reported a flexible conductive sensor based on a conductive biocomposite based on BC and CNT. The authors reported the strain sensitivity of flexible, electrically conductive, and nanostructured cellulose, which was prepared by the modification of bacterial cellulose with double-walled carbon nanotubes. The conductivity of the samples obtained from bacterial cellulose modified with CNT was in the range from 0.034 to 0.39 S/cm. Further, the use of Ionic liquids, 1-butyl-3-methylimidazolium chloride ([BMIM]Cl, 20%), in the production of electrospun hybrid carbon nanotube nanofibers with styrene-acrylonitrile resin showed a significant increase in the conductivity from 1.08 × 10
−6
to 5.9 × 10
−6
S/cm for samples containing 3 wt % carbon nanotubes [
136
,
137
]. In order to study the sensitivity of the obtained biomaterial, the strain-induced electromechanical response and resistance versus strain were monitored during the application of tensile force.
Research results showed that a mechanically-strong and highly-conductive composite of nanocellulose and carbon nanotube can be prepared from aqueous dispersion in the form of semi-transparent conductive films, aerogels and anisotropic microscale fibers [ 138 , 139 ]. Excellent colloidal stability of aqueous dispersion provided a simple and cost effective method for self-assembly of advanced hybrid nanocomposites for energy applications
The interaction between DNA and CNT surface has been intensively studied [ 140 , 141 ]. The DNA molecular chain composes of four bases: adenine, cytosine, guanine, and thymine. It has been experimentally and theoretically approved to be of high affinity contact with CNT sidewalls.
Hosseini et al. [ 142 ] applied in-situ biosynthesized bacterial cellulose (BC)/multiwall carbon nanotubes (MWCNTs) nanocomposite hydrogels converted to the conductive nanocomposite aerogels via the supercritical CO 2 method. The authors obtained a very low percolation threshold value of 0.0041 (volume concentration), predicted for BC/MWCNTs nanocomposite aerogels. The results of measuring the samples’ electro conductivity are presented in Figure 7 .
The results of this work indicated that introducing nanotubes BC decreased the average pore size and volume shrinkage of aerogels to 8.6 nm and 2%, respectively. Strain-sensing behavior of the fabricated composite material under tensile loading was also studied. By increasing the strain, the relative resistivity increased and then slightly decreased at critical strain. The strain-sensing behavior over 10 loading/unloading cycles revealed that the max value of ΔR/R
0
at strain amplitude of 2% was not substantial. On the contrary, a dramatic fall of the max ΔR/R
0
value observed for strain amplitude of 8% upon cyclic loading unloading. A gauge factor of 21 was obtained for BC/MWCNTs nanocomposite aerogel, indicating the capability of the nanocomposite aerogel as a strain sensor. It is also necessary to note that nanocomposite paper based on nanocellulose with surface carboxylic group sand carbon nanotube has good mechanical properties, flexibility, and excellent electrical conductivity, and is inexpensive and environmental friendly; it therefore has potential for a wide range of flexible electronics applications [
143
].
Some recent studies have reported on the potential applications of conductive poly(lactic acid) (PLA) compounds for 3D Printing. Lebedev et al. [
144
] explored the use of carbon nanotubes and natural graphite to increase thermal and electrical conductivity. They achieved increments in the volume resistivity of more than ten orders of magnitude compared with neat PLA. Researchers found that the addition of 0.8% of functionalized carbon nanotubes to the PLA matrix may cause a 78% enhancement in tensile strength and efficient load transfer [
145
]. The obtained strength is due to the interfacial interaction between the nanotube and polymer matrix which also affects the mobility of polymeric chain.
One of the most interesting directions in the field of Biomedicine is the study of the influence of CNTs functionalized with carboxylic acid, poly-maminobenzene sulfonic acid, and ethylenediamine on the formation of neurites and the growth of neurons [
146
]. It was noted that the manipulation in surface charge may regulate the neuronal activities. The neurite outgrowth was characterized by the presence of more numerous growth cones, longer neurite length, and enhanced neurite branching when neurons were grown on positively-charged CNTs, as opposed to a neutral or negatively charged filler. In order to facilitate the functionality of CNT- based biomaterials, the incorporation of biological moieties such as growth factor and natural ECM components has also been investigated [
147
].
Within all those biopolymer functionalized CNTs, Chitosan-wrapped CNT is one of most important for potential applications in variety of fields, such as drug delivery, tissue engineering, electrochemical sensing and actuation. Chitosan also functions as a structural component in the exoskeleton of crustaceans and insects, and is the second most abundant natural biopolymer on earth after cellulose. Owing to its pH-responsiveness and film-forming properties, chitosan can be electrodeposited as a hydrogel on electrodes [ 148 , 149 ]. Chitosan-wrapped CNTs could be directly dispersed at a concentration of 3mg/ml. However, chitosan-wrapped CNT only stabilize in acidic solutions. The solution behavior of chitosan-wrapped CNTs was also investigated [ 150 ]. To reveal the influence of electrostatic interaction on the stabilization of chitosan-wrapped CNTs, derivates of chitosan have been used. It was found that the composite material chitosan/CNT has good biocompatibility for the growth of neutral cells [ 151 ]. Their suspension coated on a glass carbon substrate could rapidly detect NaDH (t90% < 5s). The sensitivity of chitosan to chemical modifications was used for covalent immobilization of glucose dehydrogenase (GDH) in chitosan/CNT films using glutar dialdehyde (GDI). By dispersing a small fraction of CNTs into a polymer, significant improvements in the mechanical strength of the composite have been also observed. For example, MWCNTs blended with chitosan showed significant improvement in mechanical properties compared with those of chitosan [ 152 ]. The composite composed of 2 wt % MWCNT showed a more than doubled Young’s modulus and tensile strength compared to one of neat chitosan. The tuning of the mechanical properties of the polymer can be adjusted depending on CNT loading, and very small amounts may counterbalance the high stability of their structure. Jin et al. [ 153 ] noted that incorporating 3% ( w / w ) MWCNT into a pHEMA hydrogel did not significantly change cell viability of neuroblastoma, while 6% ( w / w ) MWCNT reduced its viability over 7 days of culturing on composite membrane. A relatively high concentration (6% ( w / w )) of MWCNT improved the mechanical property to 0.32 MPa of elastic modulus and conductivity to 8.0 × 10 −2 Ω/cm, as compared with pHEMA control. The bionanomultilayer biosensor of CNTs and horseradish peroxidase was prepared by a method of layer by layer assembly, and can be successfully applied for the detection of hydrogen peroxide, representing a linear response for hydrogen peroxide from 0.4 to 12 µm with a limit of detection of 0.08 µm [ 154 ]. The MWCNTs in the biosensor provided a suitable microenvironment to retain horseradish peroxidase (HRP) activity, and acted as a transducer for improving the electron transport and enhancing the electrochemical signal of the enzymatic reaction product, showing a fast, sensitive and stable response. Paper batteries based on electrodes made with cellulose nanofibrils (CNF)/MWCNTs demonstrated ultrathin electrodes far beyond those accessible with conventional battery technologies. Ultrathin electrodes in combination with readily deformable CNF separators allows for the fabrication of user-friendly paper batteries via origami folding techniques [ 155 ]. A composite of MWCNTs-chitosan was used as a material for the entrapment of lactate dehydrogenase onto a glassy carbon electrode in order to fabricate an amperometric biosensor [ 156 ]. A CNT-chitosan-lactate dehydrogenase nanobiocomposite film exhibits the abilities to raise current responses, to decrease the electrooxidation potential and to prevent electrode surface fouling. The optimized biosensor for the determination of lactate shows a sensitivity of 0.0083 A M −1 cm −2 and a response time of about 3 s. The proposed biosensor retained 65% of its original response after 7 days. For the high weight fraction of CNTs in uniform chitosan/CNT in a homogeneous composite electrode chitosan/CNT, the conductivity of the composite electrode could high 34.25 S/cm, which was used to enhance the electrochemical charge-discharge capacity of the bimorphic structure. The bending actuation performance of 15mm long composite strip show 2 mm/s high speed actuation performance under a 3 V low voltage stimulation. These rates are higher than those of most traditional IPMC actuator strips, while no heavy metal element is needed, which is important for biomedical and harptic interface applications.
Farahnaky and co-workers [ 157 ] presented a study on the mechanical properties of a biocomposite material based on pectin and CNT. Pectin, a structural heteropolysaccharide, mainly extracted from renewable resources such as citrus fruits and apple pomace, is used in food and non-food systems as a gelling and viscosifying agent. Pectin is a suitable biomaterial for its biodegradability, and has a wide range of applications depending on its degree of esterification and polymerization
Viscosity-shear rate curves of dispersions of two types of pectin and carbon nanotubes composites produced by either physical mixing (PM) or chemical interaction (CI) are presented in Figure 8 .
The viscosity difference between PM-pectin-CNTs and CI pectin-CNTs was found to be greater at lower shear rates. This is due to greater hydrodynamic volumes of composites of pectin nanocarbon tubes prepared by chemical interaction as compared to physical mixing when dispersed in water.
Biopolymer/CNT composite actuators were initially found to play an important role for smart drug delivery. A novel gelatin-CNTs hybrid hydrogel was synthesized. Cooperation with CNT could maintain the stability of the hybrid hydrogel without crosslinking at 37.8 °C. It has also been noted that the novel hybrid hydrogel, with or without crosslinking, can be used in protein separating. Silk fibroin in the sol state can interact with nanotubes through hydrophobic interactions [ 158 ].
To overcome the poor barrier properties and weak mechanical properties of biopolymers, the inclusion of functional fillers with strong physical properties is recommended for the reinforcement of their electrical, mechanical and thermal properties. Special physical and mechanical properties of CNTs make them a suitable candidate for the modification of biodegradable films. This type of nanofiller has been successfully used for different types of biopolymers. This review shows that the addition of CNTs, even in small quantities, leads to a significant increase in the physical and mechanical properties of obtained biocomposites. These materials can find potential applications in many industries and in medicine.
4.2. Graphene Based Conductive Biocomposites
Graphene is an example of allotropic 2-dimensional sheet of carbon. Sheets of graphene represent a hexagonal lattice of carbon atoms with thickness of 1 atom. Graphene, like carbon nanotubes, is formed by the organized compounds carbon-carbon, the result of which has a high Young’s modulus and tensile strength. Graphene sheets can be stacked to form three-dimensional graphite, rolled up for the formation of 1D nanotubes and 0D fullerenes [ 159 ]. Graphene has been incorporated into polymeric nanocomposites to create advanced materials for flexible electronics, sensors and tissue engineering. Typically, these graphene-based nanofibers are prepared by electrospinning synthetic polymers, whereas electrospun graphene biopolymer nanofibers have been rarely reported due to the poor compatibility of graphene with biopolymers. Graphene has gained particular interest owing to its multifunctional properties such as high specific surface area, electrical and thermal conductivity and superior mechanical strength [ 160 ]. Most pertinently, the excellent electrical properties of graphene renders it a promising nanomaterial for novel practical applications such as smart fabrics, nanosensors and flexible electrode materials [ 161 , 162 , 163 , 164 ]. The effect of gelatin in collagen reinforced with graphene oxide (GO) was analysed by Bigi’s group [ 165 ]. A more than 50% increment in young’s modulus and >60% in fracture stress were observed by adding only 1% of graphene oxide into polymer composite. Also, it should be noted that the addition of graphene oxide can significantly increase the ionic conductivity of the composite material. This filler can be successfully used as a porous separator, which can significantly increase the ion transport. For example, Pan et al. [ 166 ] developed an electrospun mat based on GO as a novel solid-state electrolyte matrix, which offers better performance retention upon drying after infiltration with an aqueous electrolyte. Special attention is paid by the authors to the question of how to reduce the ionic conductivity of PVA-based electrolytes upon drying. The developed technology makes it possible to significantly reduce the decay of the ionic conductivity of a material for a month under given conditions, which can be successfully used as a stable power source for flexible electronics.
Sen et al. [
167
] fabricated 0.1–0.5 wt % graphene nanoplates cellulose composite films using a solution casting method. The 0.25 wt % graphene nanoplates/cellulose composite film produced 0.8 GPa in tensile modulus and 22.6 MPa in strength, an increase of 45% and 31% respectively. The highest electrical conductivity of 5.1 × 10
−3
S/cm was obtained at 0.50 wt % graphene loading. Peng et al. [
168
] successfully fabricated graphene-cellulose nanocomposite films by casting, through the exploitation of imidazolium chloride-based Ionic liquids. These cast films showed conductivities of up to 3.2 × 10
−2
S/cm, thus demonstrating an approach for ionic liquid-biopolymer conductive nanocomposites with graphene.
Javed and co-workers [
169
] applied cellulose acetate (CA) as biopolymer, graphene oxide (GO) nanoparticles as the source of graphene and 1-butyl-3-methylimidazolium chloride ([BMIM]Cl) as the ionic liquid (IL) to create CA-[BMIM]Cl-GO nanofibers by electrospinning. In this work a new method of exploiting a [BMIM]Cl ionic liquid for the fabrication of graphene-based, bio-inspired (cellulose acetate) conductive CA-[BMIM]Cl-GO nanofibers through electrospinning has been introduced. Combining the advantages of both GO and [BMIM]Cl materials allowed the homogeneous dispersion of GO and better solubility of CA to be achieved. The low concentration of 0.43% graphene oxide into the obtained material enhanced the electrical conductivity of the nanofiber mats by more than four orders of magnitude to 5.30 × 10
−3
S/cm. The uniform nanostructure of graphite oxide and BMIM in CA nanofibers forms conductive paths, which have been enhanced by chemical reduction of hydrazine via an ultrasonic process.
Wang et al. [ 128 ] presented a water-based method to fabricate strong, electrically- and thermally-conductive hybrid thin films from the combination of graphene nanoplatelets and cellulose nanocrystals. Flexible hybrid papers with tunable conductivity as well as good mechanical properties were fabricated. It was noted that the hot-press process can improve the inplane thermal properties up to an optimum addition of cellulose nanocrystal (CNC) loading of 15 wt %, but that this has a negative effect on the through-plane thermal conductivity due to more CNC-GNP contacts being produced. These flexible, electrically- and thermally-conductive hybrid GNP/CNC papers with good mechanical properties may be useful in many applications in the packaging, electrical and heat-conducting fields. Graphene-enhanced laccase-ABTS oxidation showed the pivotal role of graphene for the enzymatic oxidation of the renewable starting material lignin [ 170 ]. Graphene served as an effective conductor for electron transfer during the oxidation cycle of laccase-ABTS catalyzed lignin. The outstanding catalytic reinforcement effect makes graphene a candidate for reactivity magnification in enzyme engineering, and can greatly expand the range of applications of carbon-based material. Liang et al. [ 171 ] showed a fabrication process of PVA-GO nanocomposite and reported 76% enhancement in tensile strength and 62% in Young’s modulus by the addition of 0.7 wt % of graphene oxide. Nguyen and co-workers [ 172 ] noted that composite paper prepared by using nanocellulose and reduced graphene possesses high electrical conductivity, excellent mechanical properties in wet and dry condition, and could have potential applications in humid environments as a conductor, antistatic coating, and electronic packaging. Si and co-workers [ 173 ] prepared graphene oxide-bacterial cellulose nanocomposites with a GO content of 0.19, 0.29, and 0.48 wt %. The 0.48 wt % case showed the best mechanical properties with an increase of 38% in tensile strength and 120% in tensile modulus. A relatively low electrical conductivity of 1.24 × 10 −9 S/cm was noted due to the partial reduction of GO to rGO during the sample preparation. Huang et al. [ 174 ] fabricated composite aerogels based on graphene/carboxymethylcellulose for compressive strain sensing evaluation, and a gauge factor (GF) value of 1.58 was obtained.
Feng et al. [
175
] presented a highly flexible nanocomposite film of bacterial cellulose and graphene oxide with a layered structure produced by the vacuum-assisted self-assembly technique. It was noted that mechanical properties of the BC/GO nanocomposite films depend not only on fibril modulus, but also on orientation and degree of interaction between BC and GO within the film obtained with the assistance of a vacuum. The modulus and tensile strength of the BC/GO film with 5 wt % GO are measured to be 1.7 ± 0.2 GPa and 242 ± 7 MPa, respectively. The values are 10% and 20% higher than those of BC film, indicating that the interaction between BC and GO makes a great contribution to the mechanical enhancement. As discussed above, the oxygen-containing groups on GO can interact with BC through hydrogen bonding. The high aspect ratio of the GO sheets is also favorable for stress transfer. Also, the electrical conductivity of samples was measured. When the RGO content increased from 0.1 to 1 wt %, the conductivity of the film increased by 6 orders of magnitude to 1.1 × 10
−4
S/m. The conductive properties of the BC-based nanocomposite films make them promising candidates for biosensor and tissue engineering applications.
Composite aerogels were prepared by using carboxymethyl cellulose (CMC) as raw materials, 2D graphene oxide (GO) nanosheets as reinforcement, boric acid (BA) as cross-linker [
176
]. Composite aerogels with isotropic and anisotropic structures were prepared by controlling the heat transfer rate of the system. The obtained material had a compression strength of 110 kPa at 60% compression, which was 5 times that of the axial and 14 times of the radial of anisotropy structure composite aerogels, and thermal conductivity was also lower than those of the two directions of an anisotropy composite aerogel. The results showed that the mechanical properties of composite aerogels increased with an increase of GO content. When the GO content increased from 0 to 5 wt%, the compressive strength of the composite aerogels increased by 62%, and the Young’s modulus was 3.5 times higher than that of the CMC aerogel. The thermal conductivity of isotropic aerogel (1% BA–5% GO) was as low as 0.0417 W/mK, which was comparable with that of polystyrene foam (0.03–0.04 W/m·K). So, it has the potential to replace traditional insulation materials in thermal insulation.
Nanocellulose and graphene foams having light weight and good combustion efficiency can be used to improve the energy efficiency of buildings [ 177 ]. These matrix and conductive electro-active composite materials retain both constituent’s unique responsive properties with nanocellulose as a matrix provide flexibility, while their electroactive properties open possibilities for other applications. The developed composite material has potential applications for the flexible electrodes, flexible display, biocompatible energy scavenging [ 178 ]. Zhuo and co-workers [ 179 ] presented a carbon aerogel via carbonization of cellulose nanocrystalline/graphene oxide in compression strain and pressure detection. It should be noted that the presence of cellulose plays a critical influence on the viscoelastic properties of the resultant strain sensor. Moreover, the homogeneous dispersion of carbon-based nanofiller within the polymer matrix is vital to improving the performance of sensory materials. Shan et al. [ 180 ] fabricated a chitosan-based graphene nanocomposite by a self-assembly approach in an aqueous media. The examined dispersion of GO into chitosan precursor demonstrated an increment of 122% in tensile strength and 64% of Young’s modulus upon the addition of 1 wt % of GO. The T g of nanocomposite increased gradually by the addition of GO component. A glucose biosensor-based chitosan GO nanocomposite was produced, showing good electrocatalytic activity; it also showed good amperometric response at a range of 2–10 mM, and high sensitivity, which makes it a desired candidate for electrochemical detection of glucose [ 180 ]. An easily modifiable blend membrane consisting of chitosan and sodium alginate biopolymers forming a poly ion complex with low methanol permeability, high mechanical strength, and high proton conductivity has been used for fuel cell applications due to its abundance in nature and low cost [ 181 , 182 ]. Such membranes are particularly useful in the low to intermediate temperature range. To overcome the low mechanical strength of alginate due to its hydrophilic nature, inorganic fillers or graphene oxide nanocomposites can be used. Hydrogen bonding and high interfacial adhesion between the GO filler and the alginate matrix enhance the thermal and mechanical stabilities. Chitosan-based graphene nanofibers were synthesized by an electrospinning method to improve the electrical conductivity of suspensions [ 182 ]. On increasing the loading of GO, a reduction in porosity and permeability of nanofibrous mats occurred, which can be utilized in healing process of wounds. In vivo evaluations showed efficiency in rats. A Brunauer Emmett Teller (BET) test revealed that the incorporation of a GO nanofiller increased the surface are and absorptive properties of the nanocomposite. This green approach showed high absorption efficacy, and can replace petroleum-based membranes. Yang et al. [ 183 ] investigated the effect of reduced GO on the electrical conductive properties of PVA nanocomposites, and mentioned the enhancement in conductivity from 6.04 × 10 −3 to 5.92 S/m on addition of 14 wt % of rGO.
The mechanical and electrical properties of exfoliated graphene and PLA nanocomposite fabricated by melt blending at 175–200 °C temperature were reported by Kim and Jeong [ 184 ]. Poly ( l -lactic acid) reinforced with GO was fabricated via in-situ polycondensation of lactic acid monomer through lypholization; it was shown that the functionalization of GO improved thermal stability and mechanical properties of the resultant nanocomposite by 105% in tensile strength upon the addition of 0.5 wt % of GO compared to neat PLA, and displayed little effect on crystallinity [ 185 ].
4.3. Metal Based Conductive Biocomposites
Metallic particles were among the alternative types of fillers for the design of conductivity enhancement of biopolymer-based composite materials. From the fundamental point of view, metallic particles provided strong interest due to their conductivity [ 186 , 187 , 188 , 189 , 190 ]. For example, metallic particles such as Ag, Au and Cu find a wide range of applications. An array of metallic particles can be employed as a pathway for an electrical current. The purpose of the development of technology to generate metal-based polymer biocomposites is to overcome the demerits of polymer matrices in terms of biomedical applications, environmental decontamination, edible packaging applications and many more which has been already reported. The approaches to synthesize metal nanoparticles are chemical vapor deposition (CVD), spray pyrolysis, electrodeposition and chemical methods, sol gel process, rapid solidification, etc. [ 58 , 191 ]. Metal nanoparticles have antibacterial properties, electrical conductivity, optical polarizability and good chemical properties. Metal-based nanocomposites undergo a reduction in size and functionalization of surface, which can also be exploited in plasmonic and sensing applications [ 192 , 193 ].
On the other hand, not only metallic particles but also metal oxide particles still attract attention for their conductivity or polar clustering along structures of composite. Significant efforts have been made with many types of metal oxide such as WO 3 , TiO 2 , ZnO as well as ZrO. From a fundamental point of view, metal oxide particles are categorized as a heterostructure class of material, which refers to the interface that occurs between two layers or region of dissimilar crystalline semiconductor [ 194 , 195 , 196 ].
Composite biopolymer materials based on titanium dioxide have been widely used in recent years [
197
,
198
]. Cellulose nanofibril-TiO
2
nanoparticle composite membrane electrodes have been reported as membrane electrodes. The novel bio-nanocomposite of chitosan/activated carbon/iron nanoparticles was synthesized via the sonochemical method by Rad’s group [
199
]. The characterization analysis indicated the successful interactions between oxygen functional groups of activated carbon, amine groups of chitosan and iron ions. The kinetic analysis indicated that the rate-controlling step is a chemical reaction. Adsorption experiments indicate that this bionanocomposite may be an excellent candidate for the removal of heavy metals from industrial wastewaters. Cellulose/polypyrrole and cellulose/polypyrrole-TiO
2
composites were prepared via in situ oxidative chemical polymerization of pyrrole using FeCl
3
as an oxidant [
200
]. Conductive cellulose composites were prepared by the in situ polymerization of pyrrole in the cellulose fiber in the presence of TiO
2
nanoparticles. TiO
2
helps to ease the energy crisis through the effective utilization of solar energy based on photovoltaic devices. The authors noted that increasing polypyrrole content in the composite enhanced the dielectric properties of cellulose, where the dielectric properties such as AC conductivity and dielectric permittivity were increased with increasing polypyrrole content in the nanocomposite. The dielectric permittivity (ε’) with frequency revealed that dielectric relaxation at low frequencies was due to the effects of electrode polarization at low frequencies.
Yao et al. [ 188 ] reported a flexible Ag/cellulose nanofiber aerogel, obtained from bamboo, with a maximum GF of 1 up to 20% strain. Cellulose films containing different amounts of polyaniline combined with silver nanoparticles were prepared in homogenous conditions by the dissolution of microcrystalline cellulose in 1-butyl-3-methylimidazolium chloride ionic liquid, followed by the mixing with dispersion of silver nanoparticles and polyaniline also prepared in an ionic liquid [ 201 ]. The authors obtained a flexible, self-supported film with high electrical conductivity (23–34 S/cm) and homogeneous distribution of constituents. This material can find potential applications as electronic devices, sensors and antimicrobial membranes. Patrycja and co-workers [ 202 ] prepared composite films of nanofibrillated cellulose/polypyrrole and nanofibrillated cellulose/polypyrrole-silver nanoparticles for the first time via in situ, one-step chemical polymerization. They found that composites containing silver nanoparticles exhibited electrical conductivity and strong antimicrobial activity. A novel electron conducting biocomposite was synthesized by Perveen et al. [ 203 ]. This material was obtained by layer-by-layer assembly of Ppy-Ag-GO/ferritin (Frt)/glucose oxidase (GOx). The presented biocomposite was used to construct a bioanode for glucose-based biofuel cells; it exhibited good electrochemical properties accompanied with considerable stability owing to the synergistic effects between the conductive polymer (i.e., polypyrrole) and silver nanoparticles and graphene oxide. The fabricated bioanode exhibited good electrochemical performance with a maximum current response of 5.7 mA/cm 2 . Zhang et al. [ 204 ] prepared solid-state flexible hybrid aerogels based on the combination of cellulose nanofibers (CNF), PANI and AgNP, to be used as an active material for supercapacitors. CNF aerogel was prepared by the freeze-drying of a cellulose nanofibers in aqueous suspension. Next, AgNP were in-situ synthesized in the CNF aerogel in order to make them conductive, and then PANI was electrodeposited onto the Ag/CNF aerogel. The combination of the porous structure of CNF aerogel to the high pseudocapacitive performance of PANI provided an excellent supercapacitor electrode, while the presence of AgNP enabled fast electron transportation channels to achieve high capacitance.
A chitosan-reinforced graphene oxide nanocomposite containing by ZnO may be useful in developing novel antibacterial agents against E. coli and S. aureus bacteria. It can also be utilized as a disinfection agent to inhibit bacterial growth [
205
]. A high performance nanometric metallic material for Li-ion batteries involving the use of cellulose was made by reducing SbCl
3
with NaBH4 in the presence of commercial cellulose fibers [
206
]. Wang and co-workers [
207
] described the production of a flexible electrode for high performance superconductors, composed of a hybrid film of PANI, AgNP and exfoliated graphite (ExG). The fabrication process involved firstly the electrochemical exfoliation of graphite rods in order to produce the ExG, followed by aniline chemical polymerization in a dispersion containing ExG, cellulose and silver nitrate. The as-prepared mixture was then vacuum-filtered and dried, yielding a self-supported thin film. The ExG/aniline ratio influenced the capacitance, conductivity, rate capability and cyclic stability. Despite this, studies describing the production of self-supported electrical conductive films composed of CEL/PANI/AgNP are still scarce.
5. Conclusions
In summary, the preparation, properties, and applications of conductive polymer composites from renewable resources have been reviewed in this paper. An enormous volume of synthetic polymers accumulating in the natural environment has become a major threat to the planet due to their poor degradability. Recent research has highlighted the potential applications of biocomposites using eco-friendly approaches. These types of materials have many interesting properties (such as nontoxicity, biodegradability, renewability, biocompatibility etc.) which make them ideal candidates for many potential applications, including chemical sensors, light-emitting diodes, batteries, fuel cells, heat exchangers, biosensors, and so on.
Biocomposites are gradually becoming a realistic substitute for conductive polymer composites. Because biocomposites are entirely or partially derived from renewable resources, producing them on a large-scale can significantly reduce the cost of materials. Recent advances in obtaining and recycling natural or reusable filling contents and polymers, and new preparation techniques for composites have provided significant opportunities for the use of renewable resources to improve valuable additional materials, and have enhanced support for global sustainability. Further, biocomposites derived from bacterial synthesis have been shown to be promising biomaterials for various biomedical applications such as tissue engineering, drug delivery, wound dressing, cardiovascular applications, etc.
Natural filling contents and polymers are biodegradable, but conductive polymer composites based on renewable resources can be designed to be biodegradable, or not, according to specific application requirements. Their unique properties and potential applications would undoubtedly bring new market opportunities in the 21st century.
Acknowledgments
The authors acknowledge the financial support from the National Natural Science Foundation of China (No. 51673020 and No. 51173015).
Conflicts of Interest
The authors declare no conflict of interest.
Abbreviations
SSF stainless steel fiber
HRP horseradish peroxidase
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Figure 1. Representation of interactions between plasticizer and starch during migration towards clay galleries (Reproduced with permission [ 27 ]).
Figure 2. One-step solution based chitin nanofiber silk biocomposite (Reproduced with permission [ 30 ]).
Figure 2. One-step solution based chitin nanofiber silk biocomposite (Reproduced with permission [ 30 ]).
Figure 3. Polydispersity of unaged samples and samples aged at 100 °C for 14 days (Reproduced with permission [ 33 ]).
Figure 3. Polydispersity of unaged samples and samples aged at 100 °C for 14 days (Reproduced with permission [ 33 ]).
Figure 4. The electrical conductivity of GNP/NFC composite paper measured with different amounts of GNPs (Reproduced with permission [ 47 ]).
Figure 4. The electrical conductivity of GNP/NFC composite paper measured with different amounts of GNPs (Reproduced with permission [ 47 ]).
Figure 5. Scheme of technological pathway of SCFNA and conventional compounding method (Reproduced with permission [ 82 ]).
Figure 5. Scheme of technological pathway of SCFNA and conventional compounding method (Reproduced with permission [ 82 ]).
Figure 6. Fabrication process of NGO for conductive and capacitive fabrics (Reproduced with permission [ 90 ]).
Figure 6. Fabrication process of NGO for conductive and capacitive fabrics (Reproduced with permission [ 90 ]).
Figure 7. The plot of predicted effective electrical conductivity compared with experimental data for BC/MWCNT nanocomposite aerogels (the inset illustrates the log conductivity against log (ϕ-ϕc)) (Reproduced with permission [ 142 ]).
Figure 7. The plot of predicted effective electrical conductivity compared with experimental data for BC/MWCNT nanocomposite aerogels (the inset illustrates the log conductivity against log (ϕ-ϕc)) (Reproduced with permission [ 142 ]).
Figure 8. Viscosity-shear rate curves of dispersions (1%) of PM-pectin-CNTs (▲) and CIpectin-CNTs (■) at 25 °C as measured by rotational viscometry (Reproduced with permission [ 157 ]).
Figure 8. Viscosity-shear rate curves of dispersions (1%) of PM-pectin-CNTs (▲) and CIpectin-CNTs (■) at 25 °C as measured by rotational viscometry (Reproduced with permission [ 157 ]).
Table 1. The conductivity of metal and carbon fillers.
Table 1. The conductivity of metal and carbon fillers.
Filler Type Electrical Conductivity (S/cm) Thermal Conductivity (W/mK) Density (g/cm 3 ) Aluminium 3.538 × 10 5 234 2.7 Copper 5.977 × 10 5 386–400 8.9 Silver 6.305 × 10 5 417–427 10.53 Nickel 1.43 × 10 5 88.5 8.9 CNTs 3.8 × 10 5 2000–6000 2.1 CF 10 2 ~10 5 10–1000 1.5~2.0 Graphene 6000 4000–7000 1.06 Graphite 10 4 100–500 2.25 Aluminium nitride ˂10 −13 100–319 3.235 Boron nitride 10 −14 185–400 2.27
Table 2. Different dispersion techniques for the preparation of conductive composites.
Table 2. Different dispersion techniques for the preparation of conductive composites.
Matrix Filler Dispersion Technique Max. Conductivity S/cm @ Filler Concentration Reference Epoxy Graphite High speed mixer 124 @ 75 vol % graphite [ 60 ] PPS Graphite Melt mix 73 @ 80 wt % graphite [ 61 ] Epoxy Graphite Melt mix 53 @ 80 wt % graphite [ 62 ] COC CF Melt mix twin screw 1.2 × 10 −2 @ 60 phr CF [ 63 ] Epoxy CF Melt compounding 6.34 @ 80 wt % CF [ 64 ] epoxy resin CF chemical vapor deposition 0.022 [ 65 ] LDPE Copper Internal mixer 0.11 @ 24 vol % Copper + 76 vol % LDPE [ 66 ] HDPE Silver Melt mix, twin screw 0.01 @ 24 vol % silver + 76 vol % HDPE [ 67 ] HDPE Aluminum Melt mix 10 −2 @ 55 vol % Aluminum + 45 vol % HDPE [ 68 ] HDPE Copper Melt mix 10 −5.7 @ 55 vol % Copper + 45 vol % HDPE [ 68 ] HDPE Iron Roll mill [ 69 ] PVDF Zinc Solution mix 5 × 10 −4 @ 50 vol % zinc + 50 vol % PVDF [ 70 ] SBS Copper nanowires Vacuum filtrated 1858 @ 20 wt % CUNWS + 80 wt % SBS [ 71 ] PVC Copper Dry mix, hot press 10 3.8 @ 38 vol % copper + 62 vol % PVC [ 72 ] PS Silver In-situ bulk polymerization 103 @ 20 wt % silver + 80 wt % PS [ 73 ]
MDPI and ACS Style
Huang, Y.; Kormakov, S.; He, X.; Gao, X.; Zheng, X.; Liu, Y.; Sun, J.; Wu, D. Conductive Polymer Composites from Renewable Resources: An Overview of Preparation, Properties, and Applications. Polymers 2019, 11, 187.
https://doi.org/10.3390/polym11020187
AMA Style
Huang Y, Kormakov S, He X, Gao X, Zheng X, Liu Y, Sun J, Wu D. Conductive Polymer Composites from Renewable Resources: An Overview of Preparation, Properties, and Applications. Polymers. 2019; 11(2):187.
https://doi.org/10.3390/polym11020187
Chicago/Turabian Style
Huang, Yao, Semen Kormakov, Xiaoxiang He, Xiaolong Gao, Xiuting Zheng, Ying Liu, Jingyao Sun, and Daming Wu. 2019. "Conductive Polymer Composites from Renewable Resources: An Overview of Preparation, Properties, and Applications" Polymers11, no. 2: 187.
https://doi.org/10.3390/polym11020187
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Huang Y, Kormakov S, He X, Gao X, Zheng X, Liu Y, Sun J, Wu D. Conductive Polymer Composites from Renewable Resources: An Overview of Preparation, Properties, and Applications. Polymers. 2019; 11(2):187.
https://doi.org/10.3390/polym11020187
Chicago/Turabian Style
Huang, Yao, Semen Kormakov, Xiaoxiang He, Xiaolong Gao, Xiuting Zheng, Ying Liu, Jingyao Sun, and Daming Wu. 2019. "Conductive Polymer Composites from Renewable Resources: An Overview of Preparation, Properties, and Applications" Polymers11, no. 2: 187.
https://doi.org/10.3390/polym11020187
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U.S. Census Bureau QuickFacts: Maine; Lake County, Tennessee; Crockett County, Tennessee; Minnesota; United States
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Mean travel time to work (minutes), workers age 16 years+, 2016-2020
Median household income (in 2020 dollars), 2016-2020
Per capita income in past 12 months (in 2020 dollars), 2016-2020
Facts updated for Municipios, Places, Zona Urbanas, Comunidades, and Minor Civil Divisions on 3/17/22
Persons without health insurance, under age 65 years, percent, 2016-2020
Persons in poverty, percent, 2016-2020
Facts updated for Places, Zona Urbanas, Comunidades, and Minor Civil Divisions on 3/17/22
Persons under 5 years, percent, 2016-2020
Persons under 18 years, percent, 2016-2020
Persons 65 years and over, percent, 2016-2020
Female persons, percent, 2016-2020
Facts updated for Puerto Rico, Municipios, Places, Zona Urbanas, Comunidades, and Minor Civil Divisions on 3/17/22
White alone, percent, 2016-2020
Black or African American alone, percent, 2016-2020
American Indian and Alaska Native alone, percent, 2016-2020
Asian alone, percent, 2016-2020
Native Hawaiian and Other Pacific Islander alone, percent, 2016-2020
Two or More Races, percent, 2016-2020
Hispanic or Latino, percent, 2016-2020
White alone, not Hispanic or Latino, percent, 2016-2020
Facts updated for U.S., States, and Puerto Rico on 12/21/21
Population estimates, July 1, 2021, (V2021)
Population estimates base, April 1, 2020, (V2021)
Population, percent change - April 1, 2020 (estimates base) to July 1, 2021, (V2021)
Fact updated for States and Counties on 12/16/21
Persons in poverty, percent, 2020
Facts updated for the U.S on 9/14/21
Persons without health insurance, under age 65 years, percent, 2020
Persons in poverty, percent, 2020
Facts updated for Counties, Municipios, Places, Zona Urbanas, Comunidades, and Minor Civil Divisions on 8/12/21
Population, Census, April 1, 2020
Fact updated for Counties on 6/24/21
Persons without health insurance, under age 65 years, percent, 2019
Facts updated for U.S., States, and Puerto Rico on 5/18/21
Population, Census, April 1, 2020
Fact updated for U.S., States, and Counties on 5/18/21
Building permits, 2020
Facts updated for U.S., States, Puerto Rico, Counties, and Municipios on 4/22/21
Total employer establishments, 2019
Total employment, 2019
Total annual payroll, 2019
Total employment, percent change, 2018-2019
Why can't I find my ZIP Code?
QuickFacts is an easy to use application that provides tables, maps, and charts of frequently requested statistics from many Census Bureau censuses, surveys, and programs. Profiles are available for the nation, all 50 states plus the District of Columbia and Puerto Rico, and all counties. Cities and towns with a population of 5,000 or more are also included.
What are the recommended browsers?
IE11+, Chrome, Firefox and Safari (Safari on MAC only)
How do I begin?
QuickFacts begins in TABLE view with data shown for the UNITED STATES. You can change to MAP view, CHART view, or the DASHBOARD view, that shows all three views at once.
How do I “Enter state, county, city, town, or ZIP code?”
Begin typing the name of the geography or ZIP code. After the second character, a list of choices will appear on the drop down. Locate and select your area by single-clicking the mouse or by using the up and down arrows and then pressing the Enter/Return key. The Enter/Return key may also be used if only one geography appears or your highlighted selection is at the top of the list. This becomes one of your selected geographies and is added to the TABLE in the first data column, moving UNITED STATES to the second data column.
How do I “SELECT A FACT?”
Simply click on SELECT A FACT to show the dropdown list, which is grouped by topic. Scroll down to highlight the FACT you want and click on the FACT to select it. In addition, you can double click on the row of the FACT in the TABLE.
How do I narrow the results?
In TABLE view, click ALL TOPICS and select the topic you want. The table view will show only facts within that topic. To view all facts again, select ALL TOPICS.
In MAP view, you can further narrow results down to counties, county subdivisions, or places by selecting a geography color-coded circle and a small pop-up window appears with further area selections to view. For example, if your selected geography is a city, and you chose a city in that state on the map, you will have the option to Add this geography to your table, view at the United States level or view the counties in that state.
In CHART view, you can toggle between all geographies at the same level as your selected area or those you have selected by using the ‘Show selected locations' checkbox.
In DASHBOARD view, you can narrow down only what facts are showing by using the ALL TOPICS dropdown, as indicated above.
In TABLE view, how many geographies can I see?
TABLE view allows six geographies in the table. To add additional geographies use the search box. As you add geographies, they are added to the TABLE in the first data column, moving other geographies to the next column to the right. If there are more than one geography present, you may delete any geography by clicking theicon. An orange circle on the TABLE icon indicates the total number of geographies currently selected. This is visible throughout the application above the data views.
In MAP view, how many geographies can I see? Can I zoom in and see data?
There are 3 additional controls in addition to the zoom in/out and full screen controls:
Left Border Slide-out - Allows the user to quickly move to and remove their selected geographies.
Switch Control in the upper right corner - Turns on the ability to select geographies across state boundaries.
Toggle Button in the upper right corner - Toggles view between Townships and Places.
Clicking on a geography opens an info window. Within the info window you can:
Add or remove a geography to your selection.
View the current selected fact's value and footnote notations.
The new switch and toggle button are present on the map only when needed. All new controls will be pointed out to the user with a "NEW!" tooltip when first presented to the user. Hovering over the new control will give the user a description of the control's function as well as its current status if applicable.
Changing geography level is accomplished by zooming in/out. The progression as you zoom in is: States, Counties, Places & Townships. When zoomed into Places & Townships level a toggle button will be available within the upper right map controls to swap between the two.
When you select the MAP view icon, you are given a choice from your selected geographies to view one on the map. Once you click on a geography, you will see your selected geography outlined in red and all geographies at the same level. For example, if you selected a county, you will see all the counties in that state.
Geographies with numeric fact values are placed in ascending order and distributed into five groups containing the same number of geographies. The geography groups are then shaded from cyan (lowest values) to dark cyan (highest values). The value range for these groups will depend on the fact and geographies that fall within the group. Geographies with non-numeric fact values and footnotes are shaded with colors other than cyan and assigned to a specific footnote.
When viewing the entire US there are icons for Alaska, Hawaii and Puerto Rico in the corners that allow you to focus the map directly on those locations. When the map focuses on one of these locations their associated icon changes to the 48 contiguous states an allows you to reset the map to view the entire US.
In CHART view, how many geographies can I see? Can I see data?
When you select he CHART view icon, you are given a choice to ‘View Selected Locations' or choose one of the selected geographies. If you chose ‘View Selected Locations', you will see a chart for all selected geographies. If you only have one geography selected, the chart will open with this geography along with all sibling geographies. For example, if you have selected a state, you will see all the states, plus the District of Columbia and Puerto Rico. Hover over or click on each bar in the CHART to see the actual data value.
In DASHBOARD view, how many geographies can I see?
DASHBOARD view is a combination of all three views.
When you select the DASHBOARD view icon, you are given a choice to create a dashboard for one of your selected geographies.
DASHBOARD's TABLE shows fact data only for one selected geography.
On DASHBOARD's TABLE you cannot add a geography.
DASHBOARD's CHART shows data for the selected geography and all its siblings, same as the expanded CHART view. You can add and remove a selected geography from the dashboard chart. Selected Locations checkbox is not available on the DASHBOARD's CHART.
The DASHBOARD's MAP shows data for the selected geography and places at the same level, just as in the expanded MAP view.
Where can I get data for other levels of geography, like metropolitan areas?
While not available in QuickFacts profiles, there are a number of sources oncensus.govfor data about metropolitan areas.
How can I browse more datasets for my selected location?
Whenever you see an orange magnifying glass, click it for all the detailed links to other datasets.
Can I share data from QuickFacts?
Yes. The MORE menu item opens a popup where you have options to PRINT, download a CSV, EMAIL, EMBED, and post on TWITTER and FACEBOOK.
What do these icons mean and what happens when I click them?
Click for additional information such as Sources, Definitions, and sometimes Margins of Error, or More Information.
Click for all the detailed links to other sets of data about the respective geography.
Click to set the application to its default state. This will remove all selected geographies and begin a new search. Your prior searches and results will not be saved.
What are the footnotes at the bottom of all QuickFacts pages?
Value Notes
1 Includes data not distributed by county.
Estimates are not comparable to other geographic levels due to methodology differences that may exist between different data sources.
Some estimates presented here come from sample data, and thus have sampling errors that may render some apparent differences between geographies statistically indistinguishable. ]
Click the Quick Info icon to the left of each row in TABLE view to learn about sampling error.
In Vintage 2022, as a result of the formal request from the state, Connecticut transitioned from eight counties to nine planning regions. For more details,
please see the Vintage 2022 release notes available here:Release Notes.
The vintage year (e.g., V2022) refers to the final year of the series (2020 thru 2022). Different vintage years of estimates are not comparable.
Users should exercise caution when comparing 2017-2021 ACS 5-year estimates to other ACS estimates.
For more information, please visit the2021 5-year ACS Comparison Guidancepage.
Fact Notes
(a) Includes persons reporting only one race
(c) Economic Census - Puerto Rico data are not comparable to U.S. Economic Census data
(b) Hispanics may be of any race, so also are included in applicable race categories
Value Flags
- Either no or too few sample observations were available to compute an estimate, or a ratio of medians cannot be calculated because one or both of the median estimates falls in the lowest or upper interval of an open ended distribution.
F Fewer than 25 firms
D Suppressed to avoid disclosure of confidential information
N Data for this geographic area cannot be displayed because the number of sample cases is too small.
FN Footnote on this item in place of data
X Not applicable
S Suppressed; does not meet publication standards
NA Not available
Z Value greater than zero but less than half unit of measure shown
| https://www.census.gov/quickfacts/fact/faq/ME,lakecountytennessee,crockettcountytennessee,MN,US/PST045222 |
Feasibility of Once/Daily Administered GLP/1 Receptoragonist (Lixisenatide) in Combination With Basal Insulin - Full Text View - ClinicalTrials.gov
Feasibility of Once/Daily Administered GLP/1 Receptoragonist (Lixisenatide) in Combination With Basal Insulin (LixiBIT)
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government.
Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02168491 Recruitment Status :
Completed First Posted : June 20, 2014 Results First Posted : April 4, 2017 Last Update Posted : May 9, 2017
Sponsor:
Medical University of Vienna
Information provided by (Responsible Party):
Prof. Dr. Michael Krebs, Medical University of Vienna
Tabular View
Study Description
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Brief Summary:
Premixed insulin-based therapy is a standard insulin treatment strategy in Austria. The widespread use of premixed insulin is explained by high acceptance by health care professionals and patients due to one single product and flexible number of injections (1-3 daily) which covers the demand in controlling fasting and postprandial glucose excursions of most patients with diabetes. However, the use of pre-mixed insulin frequently leads to a high insulin demand and consequently weight gain and an increased risk of hypoglycemia. Hence, achieve good metabolic control in these patients remains a major challenge.
For those patients, the approach to treatment intensification without facing the typical risks of insulin treatment (hypoglycemia and weight increase) is of major importance. One, so far not exploited option may be the BIT-strategy: Basal insulin in combination with incretin-based therapy.
Pathophysiologically basal insulin inhibits glucose production in the liver, decreases hepatic insulin resistance and improves the function of beta cells in the postprandial state by discharge of fasting insulin secretion. During further diabetes progression steadily increasing HbA1c levels - despite good fasting blood glucose control - indicate the need for additional intervention of meal-related glucose excursions. In this stage of type-2 diabetes basal insulin can be combined with prandial (short-acting) insulin or prandial GLP-1 receptor agonists. However, regarding important safety parameters: risks of hypoglycemia and weight gain in the long-term treatment GLP-1 receptor agonists are beneficial.
Lixisenatide is a novel GLP-1 receptor agonist with a pronounced postprandial (PPG) effect which fits with basal insulin mode of action primarily focused on fasting blood glucose reduction.
Therefore 10 patients (both gender) under treatment with premixed insulin (2-3 times daily) and HbA1c>7% will be switched to basal insulin glargine (Lantus, once daily) and GLP-1 receptor agonist Lixisenatide (Lyxumia, once daily). The investigators hypothesize that switching from a therapy based on premixed insulin to a simple, once daily administered combination of basal insulin plus a GLP-1 receptor agonist in patients with type-2 diabetes not achieving therapeutic target (HbA1c>7%) is clinically feasable in an out patient setting
Condition or disease Intervention/treatment Phase Type 2 Diabetes Mellitus Drug: Lixisenatide Drug: Insulin glargine Phase 3
Study Design
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Layout table for study information Study Type : Interventional
(Clinical Trial) Actual Enrollment : 10 participants Allocation: N/A Intervention Model: Single Group Assignment Masking: None (Open Label) Primary Purpose: Treatment Official Title: Feasibility of Once-daily Administered GLP-1 Receptoragonist (Lixisenatide) in Combination With Basal Insulin in Patients With Type-2 Diabetes Mellitus Not Achieving Therapeutic Targets With Premixed Insulin Study Start Date : November 2014 Actual Primary Completion Date : July 2015 Actual Study Completion Date : August 2015
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics: Type 2 diabetes
Drug Information available for: Insulin Insulin human Insulin glargine Lixisenatide
U.S. FDA Resources
Arms and Interventions
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Arm Intervention/treatment Experimental: Intervention group 10 type 2 diabetic patients will be included to perform in this study and will be switched from premixed insulin to insulin glargine and lixisenatide Drug: Lixisenatide Patients will be switched to basal insulin glargine (Lantus, once daily in the morning) and GLP-1 receptor agonist Lixisenatide (Lyxumia, once daily in the morning before breakfast; days 1-14 10 µg thereafter 20 µg). The (mean) daily dose of premixed insulin will be calculated based on the records of the run in period. The initial dose of insulin glargine will be adjusted at about 60% of the daily insulin dose of premixed insulin. This is based on the observed reduction of required insulin dose described in recent literature upon initiation with a GLP-1 agonist. Other Name: Lyxumia Drug: Insulin glargine Patients will be switched to basal insulin glargine (Lantus, once daily in the morning) and GLP-1 receptor agonist Lixisenatide (Lyxumia, once daily in the morning before breakfast; days 1-14 10 µg thereafter 20 µg). The (mean) daily dose of premixed insulin will be calculated based on the records of the run in period. The initial dose of insulin glargine will be adjusted at about 60% of the daily insulin dose of premixed insulin. This is based on the observed reduction of required insulin dose described in recent literature upon initiation with a GLP-1 agonist. Other Name: Lantus
Outcome Measures
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Primary Outcome Measures
:
Change in HbA1c From Baseline to End [ Time Frame: 12 weeks ]
A change between two time points is reported. Time Frame: baseline and 12 weeks.
Secondary Outcome Measures
:
Change in Fasting Plasma Glucose (FPG, Mean Over 2 Weeks) [ Time Frame: 12 weeks ]
Patients will be instructed to record all insulin injections and a complete 7-point-blood glucose profile (fasting, 2h after breakfast, before lunch, 2h after lunch, before dinner, 2h after dinner, late before going to bed) during a one-week prestudy run-in period to confirm compliance and document current metabolic control and doses of premixed insulin.
Patients will be asked to record not only glucose profiles (at least 4 measurements per day) but also the occurrence of hypoglycemic symptoms or other adverse effects daily throughout the study.
During the last week of the study patients will be asked to again record a complete 7-point-blood glucose profile (fasting, 2h after breakfast, before lunch, 2h after lunch, before dinner, 2h after dinner, late before going to bed) and drug injections to confirm compliance and document metabolic control.
Change in Body Weight From Baseline to End of Study [ Time Frame: 12 weeks ]
A change between two time points is reported. Time Frame: baseline and 12 weeks.
Eligibility Criteria
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
Layout table for eligibility information Ages Eligible for Study: 18 Years to 70 Years (Adult, Older Adult) Sexes Eligible for Study: All Accepts Healthy Volunteers: No
Criteria
Inclusion Criteria:
Age 18 - 70a
Subjects understand study related activities and give written informed concent
HbA1c between 7 - 10 % under treatment with premixed insulin (2-3 injections)
Exclusion Criteria:
Females of child-bearing age
History of hypoglycemia unawareness
Gastrointestinal disease associated with prolonged nausea and vomiting
Impaired liver function (transaminase >2x than normal)
Impaired kidney function (creatinin > 1,2 mg/dl)
Known intolerance against GLP-1 receptor agonists
History of pancreatitis or pancreas tumor
Malignancies, autoimmune diseases
Severe dyslipidemia (serum triglycerides > 400 mg/dl, cholesterol > 300 mg/dl)
Psychiatric disorder
Oral glucose lowering medication except for metformin
Contacts and Locations
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02168491
Locations
Layout table for location information Austria Medical University Of Vienna, Department of Internal Medicine III Vienna, Austria, 1090
Sponsors and Collaborators
Medical University of Vienna
Investigators
Layout table for investigator information Principal Investigator: Michael Krebs, MD, Prof. Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria
More Information
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Harreiter J, Kosi-Trebotic L, Lukas A, Wolf P, Winhofer Y, Luger A, Kautzky-Willer A, Krebs MR. Switch to Combined GLP1 Receptor Agonist Lixisenatide with Basal Insulin Glargine in Poorly Controlled T2DM Patients with Premixed Insulin Therapy: A Clinical Observation and Pilot Study in Nine Patients. Diabetes Ther. 2017 Jun;8(3):683-692. doi: 10.1007/s13300-017-0249-4. Epub 2017 Mar 29.
Layout table for additonal information Responsible Party: Prof. Dr. Michael Krebs, Prof. MD, Medical University of Vienna ClinicalTrials.gov Identifier: NCT02168491 History of Changes Other Study ID Numbers: LixiBIT_V3 2013-005334-37 ( EudraCT Number ) First Posted: June 20, 2014 Key Record Dates Results First Posted: April 4, 2017 Last Update Posted: May 9, 2017 Last Verified: March 2017
Additional relevant MeSH terms:
Layout table for MeSH terms Diabetes Mellitus Diabetes Mellitus, Type 2 Glucose Metabolism Disorders Metabolic Diseases Endocrine System Diseases Insulin Glargine Lixisenatide Hypoglycemic Agents Physiological Effects of Drugs
U.S. Department of Health and Human Services
| https://clinicaltrials.gov/ct2/show/NCT02168491 |
New Lab & IT Products for Integrated Biology: Apr 1, 2005 | GenomeWeb
BIOINFORMATICS Gene Logic Genesis Enterprise System 2.5 Version 2.5 of Gene Logic’s Genesis Enterprise System further expands and accelerates researchers'' ability to assess drug risks using genomics and toxicogenomics data and related clinical information. Users can now use the software to import and analyze their own Affymetrix GeneChip array data and annotate their samples. The latest software update reflects significant customer input regarding group-share abilities for a collaborative, secure
New Lab & IT Products for Integrated Biology: Apr 1, 2005
Apr 01, 2005
Premium Save for later BIOINFORMATICS
Gene Logic Genesis Enterprise System 2.5
Version 2.5 of Gene Logic’s Genesis Enterprise System further expands and accelerates researchers'' ability to assess drug risks using genomics and toxicogenomics data and related clinical information. Users can now use the software to import and analyze their own Affymetrix GeneChip array data and annotate their samples. The latest software update reflects significant customer input regarding group-share abilities for a collaborative, secure environment and visualization tools for rapid, simultaneous examination of expression data and clinical attributes.
Gene Logic
800.GENE.LOGIC
www.genelogic.com
Lion Bioscience SRS Version 8.1
Version 8.1 of SRS has been enhanced with a redesigned search interface and new Related Information Browser, which automatically links search results in SRS to related information. LION has also expanded its range of Linux-supported platforms for SRS. The SRS data integration platform provides integrated access to all life science data.
Lion Bioscience
+44 1223 224747
www.lionbioscience.com/srs
MultiQTL v. 2.5 Gene Mapping Software
MultiQTL software integrates a broad spectrum of data mining, statistical analysis, interactive visualization, and modeling tools that allow QTL analysis based on advanced and sophisticated methods for maximum extraction of the mapping information from data. This includes tools for multilocus, multiple-trait, and multiple-environment QTL analysis in controlled crosses of economically important plants and animals, as well as model organisms.
MultiQTL
+972-48240-449,
http://esti.haifa.ac.il/~poptheor/MultiQtl/MultiQtl.htm
Nonlinear Dynamics TotalLab Now Mac Compatible
TotalLab, Nonlinear’s general image analysis software, is now compatible with the Apple Mac by using Virtual PC for Mac v7.0. The core component of the software is the comprehensive 1D analysis module, which is simple to use and allows a fast and consistent analysis of 1D gel electrophoresis images in a few clicks. TotalLab also includes three additional modules, for the quantitative analysis of arrays, colonies, and a toolbox for general image analysis.
Nonlinear Dynamics
+44 (0)191 230 2121
www.nonlinear.com
Spotfire DecisionSite Version 8.1
Version 8.1 of Spotfire’s DecisionSite visual analysis software puts more of DecisionSite''s interactive capabilities on the Web, allowing for wider sharing of analysis results among researchers throughout the drug discovery chain. DecisionSite Posters allows researchers to share results — from gene expression dendograms to drug safety signal detection — in one online application that now supports heat maps, bar charts, pie charts, trellising, and text search.
Spotfire
800 245.4211
www.spotfire.com
BIOLOGICAL ASSAYS
BD Biosciences Clontech ZsGreen Fluorescent Protein Vectors
The pIRES2-ZsGreen1 vector contains an internal ribosome entry site, which permits both the cloned gene and the ZsGreen1-encoding region to be translated from a single mRNA. ZsGreen1 fluorescence intensity directly correlates with the expression level of your gene of interest. The pZsGreen1-1 is a promoterless vector for studying transcriptional regulation.
BD Biosciences Clontech
877.232.8995
www.bdbiosciences.com
BioSource Multiplex Mouse Cytokine and Chemokine Detection Kit
This antibody 20-plex kit from BioSource allows precise quantification of mouse IL-1a, IL-1b, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12p40/p70, IL-13, IL-17, IFN-g, IP-10, FGF-b, GM-CSF, MCP-1, MIP-1a, MIG, RANTES, TNF-a, and VEGF from just 50 mL of either serum or cell culture supernatant. Designed for use with the Luminex system.
BioSource
800.242.0607
www.biosource.com
Genpathway TranscriptionPath, FactorPath, and PromoterPath
Rather than measure RNA levels, Genpathway’s TranscriptionPath, FactorPath, and PromoterPath tools measure levels of transcription machinery; including differential gene transcription, components and processes for gene regulation, and corresponding genetic pathways. TranscriptionPath is designed for identifying and quantifying of gene transcription based on isolation and characterization of DNA/transcription machinery complexes; FactorPath for the discovery and quantification of binding by transcription factors and coactivators; and PromoterPath for the identification of promoters and enhancers, and quantification of their use.
Genpathway
858.457.6898
www.genpathway.com
Stratagene ElectroTen-Blue Electroporation-Competent Cells
The ElectroTen-Blue cells are designed to transform large DNA molecules with high efficiency. The cells exhibit the high electroporation efficiency (Hee) phenotype. The Hee phenotype improves survival of these cells during electroporation treatment, dramatically improving transformation efficiency. The high cloning efficiency makes this strain an ideal host for generating large, more representative libraries.
Stratagene
800.424.5444
www.stratagene.com
Stratagene PathDetect Cis-Reporting Systems
The PathDetect cis-reporting systems were designed for rapid and convenient assessment of the in vivo activation of enhancer element pathwas. Each cis-reporter plasmid contains the luciferase reporter gene driven by a basic promoter element (TATA box) joined to tandem repeats of AP-1, CRE, SRE, ISRE, GAS, NFAT, NF-kB, p53, SRF, or TARE binding elements. The cis-reporting plasmids can also be used to evaluate uncharacterized genes, growth factors, drug candidates, or the effects of extracellular stimuli.
Stratagene
800.424.5444
www.stratagene.com
Stratagene SignalScout Phosphatase Profiling System
The new SignalScout phosphatase profiling system allows researchers to study dephosphorylation by 39 protein tyrosine phosphatases. This system will include three types of products: a) tagged human phosphatase expression clones for mammalian expression, b) tagged substrate trapping mutant human phosphatase expression clones matched to each phosphatase, and c) purified GST-tagged phosphatases (enzymatically active either as a full-length construct, a truncated protein, or a catalytic domain).
Stratagene
800.424.5444
www.stratagene.com
IMAGING
Thermo Electron OMNIC Atlus 7.2 Imaging Software for Infrared and Raman Microspectroscopy
Version 7.2 of the Atlus imaging software from Thermo Electron now provides a complete imaging solution for infrared and Raman microscopes with the addition of content analysis of both video and chemical images for particle dimensions and advanced image statistics. Images can also be reproduced through the added ability to pull information from the software''s history, allowing users to easily recreate an image from raw data and processing steps. Spectral statistics allow users to group spectra and perform advanced statistics, as well as employ Principal Component Analysis to minimize the spectral contribution of undesired features while improving the signal to noise and the spatial resolution of the overall set of data.
Thermo Electron
800.532.4752
www.thermo.com/spectroscopy
LIQUID HANDLING
BD FACSArray Bioanalyzer
The BD FACSArray bioanalyzer is a new platform for fast and sensitive high-content analysis of proteins in cell biology, immunology, and proteomics. Capable of both multiplexed bead and cellular assays, the BD FACSArray bioanalyzer is a platform that is easy to use, yet flexible and sensitive.
BD Biosciences Pharmingen
877.232.8995
www.bdbiosciences.com
Beckman Coulter P50 Liquid Handling Tips
Designed for use with Beckman’s Biomek 3000, NX, and FX Multimek liquid handlers, these new narrow-length tips enable pipetting from the bottom of deep labware for maximum retrieval of valuable samples. The disposable, non-conducive P50 Tips are ideal for work in both 96- and 384-well formats in applications such as compound library profiling and assay development, MALDI-TOF plate spotting, sample pooling, plate replication, and hit picking. The new tips pipette a volume of 50 µl with barrier and are certified to be Rnase/Dnase-free.
Beckman Coulter
800.742.2345
www.beckmancoulter.com
MICROARRAY ANALYSIS
Agilent Technologies Whole Rat Genome Oligonucleotide Microarray
With probes for more than 41,000 unique genes and transcripts, the Agilent Whole Rat Genome Oligo Microarray features highly sensitive 60-mer oligonucleotide probes, which allow increased detection of low-expressing, or rare, genes. Agilent''s microarray probes are based on recently released sequence information from the public genome databases RefSeq, UCSC GoldenPath, Ensembl, Genbank LocusLink, Homolgene, and UniGene.
Agilent Technologies
800.227.9770
www.agilent.com
PCR
Bio-Rad Laboratories iScript Select cDNA Synthesis Kit
This new reverse transcription system is optimized for reliable cDNA synthesis using from 1 µg down to as little as 1 pg of input RNA. This sensitive and flexible reverse transcription kit includes an optimized section of primers, providing researchers with the ability to use any first-strand priming approach. The flexible format of this kit is appropriate for a variety of applications including RT-PCR and real-time RT-PCR. In addition, this kit is quality controlled for the synthesis of cDNA fragments greater than 6 kb in length, making it appropriate for applications such as cloning.
Bio-Rad
800.4.BIORAD
www.bio-rad.com/amplification/
PROTEOMICS
Agilent Technologies HPLC Chip/Mass Spectrometry System
Smaller than a credit card, Agilent''s Protein ID HPLC-Chip for protein identification integrates sample enrichment and separation capability of a nanoflow LC system with the intricate connections and spray tips used in electrospray mass spectrometry. To enable compliance and experiment management, the HPLC-Chip includes a radio frequency tag that contains information such as chip ID and type, documentation, diagnostic, and operational data. The HPLC-Chip/MS Cube interface, which is mounted on Agilent''s Nanoflow Proteomics Solution XCT+ Ion Trap mass spectrometer, positions the sprayer tip orthogonal to the MS inlet to achieve maximum sensitivity and robustness, as well as automatically loads and seals the chip.
Agilent Technologies
800.227.9770
www.agilent.com
GeneBio Updated Phenyx Mass Spectrometry Analysis Software
The latest release of Phenyx, GeneBio’s protein identification platform, now incorporates the mzData standard and improves the results comparison functionality for all versions of Phenyx. A host of other features have also been added, including enhanced installer functionality for the standalone platform. Additionally, researchers can import results from other major software packages, such as Mascot and SEQUEST, in order to cross-validate or consolidate their identification results through the complementary use of several software packages.
GeneBio
+41 22 702 99 00
www.phenyx-ms.com
GWC Technologies SPRimager II Detection System
Designed for label-free analysis of protein and other molecular arrays, the SPRimager II relies on Surface Plasmon Resonance (SPR) for detection. The SPRimager II may be used to monitor protein-protein interactions as well as interactions involving DNA, RNA, carbohydrates, and ligands.
GWC Technologies
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Thermo Electron Finnigan Surveyor Plus HPLC System
The Finnigan Surveyor Plus HPLC system features an integrated column oven and the ability to use vials or plates. Thermo’s patented LightPipe technology ensures superior sensitivity, up to five times higher than that of conventional photo diode array detectors. The high-throughput Finnigan Surveyor Plus integrates seamlessly with the Finnigan Surveyor MSQ Plus.
Thermo Electron
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Thermo Electron 1.9 µm Hypersil GOLD HPLC Column
Due to its smaller particle size, the new 1.9 µm particle size Hypersil GOLD HPLC column allows higher efficiency and improved peak capacity, enabling accurate detection and quantification of lower concentrations of analytes. Designed primarily for applications in pharmaceutical and proteomics research, the columns are available in 20, 30, and 50 mm lengths and 2.1 to 4.6mm ID, as well as 10 and 20 mm Javelin columns.
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To tell GT about new recently released products, e-mail John MacNeil, Senior Editor, at
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Military Family Housing: Opportunities Exist to Reduce Costs and Mitigate Inequities | U.S. GAO
Pursuant to a congressional request, GAO reviewed the Department of Defense's (DOD) military family housing program to determine whether the program:...
Military Family Housing: Opportunities Exist to Reduce Costs and Mitigate Inequities
Highlights
Pursuant to a congressional request, GAO reviewed the Department of Defense's (DOD) military family housing program to determine whether the program: (1) is cost-effective; and (2) provides equal housing benefits to all military families.
Recommendations
Recommendations for Executive Action
Agency Affected
Department of Defense
The Secretary of Defense should develop information to better quantify the relationship between quality of life and family housing. The information should reflect service members' desires and preferences for private versus government housing under various circumstances, such as if housing allowances were increased, if rent or utilities were charged for government housing, and if no changes were made to the current program.
Closed – Implemented Closed – ImplementedActions that satisfy the intent of the recommendation have been taken.
DOD contracted with the RAND Corporation to conduct a study of service member desires and preferences for family housing. The study results were used in the development of a new housing allowance program implemented in 1998.
Department of Defense
The Secretary of Defense should direct installation commanders to redesignate, to the maximum practical level, government housing reserved for senior personnel for use by junior personnel in areas where private housing is available and affordable for senior personnel but not for junior personnel. To reduce the potential impact on the families of senior personnel, this action could be accomplished over a phased period of time.
Closed – Implemented Closed – ImplementedActions that satisfy the intent of the recommendation have been taken.
DOD reemphasized the need for installation commanders to provide for the housing needs of junior enlisted members and their families. However, DOD does not plan to direct installation commanders to redesignate senior housing for use by junior members.
Department of Defense
The Secretary of Defense should ensure that the DOD working group on housing allowances considers housing allowance changes that could result in greater flexibility in addressing housing problems and cost savings through greater reliance on private housing. For example, the group should consider whether: (1) housing allowances should be based on average housing costs in an area, rather than actual member housing expenditures; and (2) housing allowances could be used in new, innovative ways to solve specific housing problems more economically than constructing or renovating government housing.
Closed – Implemented Closed – ImplementedActions that satisfy the intent of the recommendation have been taken.
The Congress approved DOD's request for major changes in the housing allowance program starting in 1998. Allowances in the future will be based on average housing costs in each geographic area. This should make more private housing affordable for military members and their families.
Department of Defense
The Secretary of Defense should establish a long-term goal to reduce the use of government family housing in the United States to the minimum possible level. The goal should limit government housing to families assigned to locations where no adequate private housing alternative exists and to the small number of families that reside on base for military necessity.
Closed – Implemented Closed – ImplementedActions that satisfy the intent of the recommendation have been taken.
DOD is committed to constructing or acquiring new government housing only at locations where adequate private housing is unavailable. Congress has required the services to develop housing master plans that will show how each service plans to integrate various housing tools to meet service requirements. Plans are due by July 1, 2000. In addition, the Center for Naval Analysis is studying improvements in the DOD housing requirements determination process. This study is due to be completed in September 2000.
Department of Defense
The Secretary of Defense should revise the housing requirements process by issuing guidance to ensure that the process: (1) matches military housing requirements with available private housing before matching the requirements with government housing; and (2) considers suitable, affordable rental vacancies in excess of normal market levels to be available to the military. The revised guidance should take into account the results of the DOD Inspector General's review of the housing requirements process.
Closed – Implemented Closed – ImplementedActions that satisfy the intent of the recommendation have been taken.
The Center for Naval Analysis is studying improvements in the DOD housing requirements determination process. This study is due to be completed in September 2000.
Department of Defense
The Secretary of Defense should develop plans to reduce the difference in the average amounts paid for housing by families of service members in the same pay grade by requiring families that live in government housing pay a portion of their housing costs. These plans should include milestones for implementation.
Closed – Not Implemented Closed – Not ImplementedWhile the intent of the recommendation has not been satisfied, time or circumstances have rendered the recommendation invalid.
DOD does not plan to require members living in government housing to pay a portion of their housing costs. DOD believes that to begin charging members for any costs when living in government housing would be viewed as a cut in military benefits.
Full Report
Full Report (50 pages)
Office of Public Affairs
Chuck Young
Managing Director
[email protected]
(202) 512-4800
Topics
Housing
Cost effectiveness analysis Housing allowances Housing programs Military cost control Military dependents Military facilities Military housing Privatization Rental housing Military forces
| https://www.gao.gov/products/nsiad-96-203?order=field_status_code&sort=asc |
JCI - Beta blocker specificity: a building block toward personalized medicine
Beta blocker specificity: a building block toward personalized medicine
Center for Translational Medicine and George Zallie and Family Laboratory for Cardiovascular Gene Therapy, Department of Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
Real-time optical recording of β 1 -adrenergic receptor activation reveals supersensitivity of the Arg389 variant to carvedilol
Abstract
Drugs known as beta blockers, which antagonize the β-adrenergic receptor (β-AR), are an important component of the treatment regimen for chronic heart failure (HF). However, a significant body of evidence indicates that genetic heterogeneity at the level of the β 1-AR may be a factor in explaining the variable responses of HF patients to beta blockade. In this issue of the JCI, Rochais et al. describe how a single amino acid change in β 1-AR alters its structural conformation and improves its functional response to carvedilol, a beta blocker currently used in the treatment of HF (see the related article beginning on page 229). This may explain why some HF patients have better responses not only to carvedilol but to certain other beta blockers as well. The data greatly enhance our mechanistic understanding of myocardial adrenergic signaling and support the development of “tailored” or “personalized” medicine, in which specific therapies could be prescribed based on a patient’s genotype.
Chronic heart failure (HF) poses a major public health problem in this country, primarily due to the increasing proportion of our society surviving to the seventh and eighth decades of life and to improved treatment of acute ischemic cardiac events, resulting in more survivors who develop cardiac dysfunction. The group of drugs known as beta blockers block the effects of catecholamines, such as epinephrine and norepinephrine, on the body’s β-adrenergic receptors (β-ARs), slowing nerve impulses traveling through the heart and reducing the heart’s workload. While β-AR antagonists have become a mainstay of HF therapy, the most recent guidelines from the American College of Cardiology and the American Heart Association acknowledge that there are unresolved issues concerning the use of these drugs for the treatment of HF ( 1).
β1-AR polymorphisms and cardiac phenotype
The β-ARs are members of the G protein–coupled receptor (GPCR) superfamily, which consists of over 700 genes that are the targets of more than 50% of the drugs in clinical practice ( 2). There are 3 known types of β-ARs, β 1, β 2, and β 3. The β 1-ARs are located mainly in the heart, kidney, and adipose tissue. The β 2-ARs are located mainly in the heart, lung, gastrointestinal tract, liver, pancreas, and skeletal muscle. The role and location of β 3-ARs are less well defined. When stimulated by agonists, β-ARs primarily activate heterotrimeric guanine nucleotide–binding (G) proteins of the Gs family, causing dissociation of Gα-GTP and Gβγ subunits. The G proteins transduce intracellular signaling pathways via adenylyl cyclase (AC) activation, and this results in increased intracellular cAMP levels ( 3). This signaling cascade ultimately leads to positive regulatory input to the myocardial contractile apparatus. Importantly, β-ARs present on cardiomyocytes represent the most powerful means of enhancing the contractile performance of the heart.
The predominant β-AR subtypes of functional consequence to cardiac physiology are β 1-AR and β 2-AR, both of which have well-documented polymorphisms that exist in human populations. The coding region of the gene encoding the β 1-AR, located on chromosome 10q24-26, contains 2 known SNPs resulting in amino acid substitutions. At position 49 in the extracellular amino terminus of the receptor, a serine is substituted by a glycine (Ser49Gly) with an allele frequency of 0.87 and 0.13, respectively ( 4). At position 389 in the intracellular carboxy terminus in the proximity of the seventh transmembrane spanning segment, a glycine or arginine can be found at an allele frequency of 0.25 and 0.75, respectively ( 4). These polymorphic variants of the β 1-AR appear to have significant cardiovascular phenotypic consequences. For example, Ranade et al. found a significant functional association between the Ser49Gly polymorphism and resting heart rate, in which Gly49 homozygotes had the lowest heart rate, and each Ser49 allele increased the basal heart rate in an additive model ( 5). The Arg389 variant appears to be linked with HF in both clinical outcomes and response to therapy ( 6).
More specifically, the Arg389Gly polymorphism lies within the putative Gs-binding domain of the β 1-AR (Figure1), and consistent with this localization, previous in vitro studies in fibroblast cell lines transiently transfected with the Arg389 β 1-AR have demonstrated enhanced receptor-Gs coupling as measured by 35S-GTP binding and slightly increased basal and markedly increased agonist-induced AC activity as compared with Gly389 β 1-AR–transfected fibroblasts ( 7). Furthermore, in a study of transgenic mice with cardiac-specific overexpression of Arg389Gly β 1-AR variants, Akhter and colleagues demonstrated that not only does Arg389 β 1-AR lead to increased myocardial signaling properties, but it also confers cardioprotection following myocardial ischemia and reperfusion injury ( 8). This may involve the upregulation of GPCR kinase 2 (GRK2) activity, which was presumably induced by the increased signaling of the Arg389 variant, since the less active Gly389 form did not alter myocardial GRK2 levels.
Figure 1
The effect of the β 1 -AR Gly389Arg polymorphism on signal transduction and beta blockade by carvedilol.The Gly389Arg polymorphism of the β 1-AR occurs in the region between the seventh transmembrane domain and the intracellular tail of the receptor (R and G correspond to arginine and glycine, respectively, at position 389 of the receptor). This highly conserved region is putatively associated with coupling to the Gs protein. The change of the amino acid residue at position 389 of the β 1-AR from the polar, basic arginine (upper 3 panels) to the small, nonpolar glycine (lower 3 panels) may result in a modified structure that could alter receptor-Gs interaction. This region of the cytoplasmic tail of the receptor may participate in regulating the affinity of the receptor-Gs interaction. This could potentially explain the differences in receptor-Gs coupling and cAMP production associated with the Arg389 β 1-AR variant as compared with the Gly389 β 1-AR variant reported previously (7, 8). Under basal conditions, the Arg389 variant has been associated with increased cAMP production, which is markedly augmented as compared with the Gly389 variant following agonist stimulation ( 7). This effect could also be attributed to a more favorable structural environment for interaction with Gs. Carvedilol treatment induces a conformational change resulting in the intracellular tail of the receptor being positioned more closely to the third intracellular loop; this inverse agonism of the receptor in theory would lead to decreased Gs coupling and reduced cAMP accumulation. Both variants demonstrated inverse agonist properties in response to carvedilol; however, the effect was increased 2.5-fold in the Arg389 variant, apparently due to conformation of the Arg389 structure in the presence of the ligand as observed by Rochais et al. in this issue of the JCI( 14).
In HF, the myocardium has a significant loss of contractile function. In order to compensate for the loss of systemic perfusion due to pump failure, the heart must increase heart rate and contractility. This is done by increased neurohumoral activation through increases in the activity of the sympathetic nervous system and renin-angiotensin system. Increases in the sympathetic catecholamines norepinephrine and epinephrine lead to chronic activation of myocardial β-ARs in order to drive the failing heart. However, chronic activation of these pathways, in particular activation of the β 1-AR, leads to increased cardiotoxicity and cardiac pathology ( 3). This partially explains the clinical benefit achieved by β-AR antagonists, which block the overt noxious effects of catecholamines and have been shown to improve survival and reverse pathologic cardiac remodeling ( 9). Interestingly, sensitivity to the beneficial effects of β-AR blockade differs by ethnicity, as evidenced by data from the Beta-Blocker Evaluation of Survival Trial (BEST) demonstrating a lack of benefit in black patients with New York Heart Association class III or IV HF treated with the beta blocker bucindolol, compared with other patients ( 10). It was reasoned that racial differences in the incidence of HF and therapeutic response to β-AR antagonists may be heritable and that genetic heterogeneity with respect to β 1-ARs may partially account for this phenomenon. However, conflicting data from clinical studies analyzing the association of β 1-AR polymorphisms and response to β-AR antagonists have made it difficult to reach conclusions regarding the true clinical importance of β-AR polymorphisms with respect to treatment outcome (for review see ref. 11).
β1-AR signaling in real time
Recent advances in the fields of biochemistry and applied science have generated new classes of fluorescent probes to permit the direct assessment of the dynamic behavior of biological molecules. Specifically, fluorescence resonance energy transfer–based (FRET–based) techniques have allowed investigators to evaluate dynamic protein-protein interactions and protein conformational changes in real time (for reviews see refs. 12, 13). FRET fundamentally characterizes the spatiotemporal relationship of fluorescently labeled molecules within a system by way of recording the energy transfer from a donor fluorophore in an excited electronic state to an acceptor fluorophore of adequate proximity. In this issue of the JCI, Rochais and colleagues report on their exploitation of FRET technology to generate a β 1-AR FRET sensor to directly assess the effects of the Arg389Gly polymorphism in the β 1-AR on receptor activation, downstream signal transduction, and response to beta blockade in cultured human cells in real time ( 14). The β 1-AR FRET sensor used in this study was generated based on evidence that the receptor undergoes conformational changes upon agonist binding, specifically in the region of the carboxy terminus and third intracellular loop, which move apart upon receptor activation. The authors then tagged these regions with cerulean and yellow fluorescent proteins, respectively, allowing them to detect the movement of these regions in real time using FRET, thereby tracking the dynamic changes in the receptor in response to agonist and antagonist binding. The authors demonstrated that this β 1-AR FRET sensor shares pharmacological and signaling characteristics consistent with that of the WT β 1-AR, including similar activation kinetics and downstream signaling via cAMP formation.
Utilizing β 1-AR FRET sensors for both Gly389 and Arg389 variants of the β 1-AR, the authors were able to directly assess the functional consequences of β-AR polymorphisms with respect to receptor conformation in response to pharmacologic agonists and antagonists. In contrast with results in previous in vitro studies ( 7, 8), the authors identified no significant differences between Gly389 and Arg389 variants in β 1-AR–mediated Gs coupling or cAMP accumulation in response to agonist ( 14).
Perhaps the most exciting clinically relevant data from this study is the comparison of the FRET responses of the 2 β 1-AR variants generated by the β-AR antagonists bisoprolol, metoprolol, and carvedilol. Each β-AR antagonist induced an increase in FRET ratio, signifying the occurrence of an active change in receptor conformation upon antagonist binding, suggesting an inverse agonist mechanism of action on the β-AR. Increases in FRET ratio were minor with respect to decreases in receptor activation for metoprolol and bisoprolol, and the effects of these 2 beta blockers did not differ between β 1-AR variants ( 14). In contrast, carvedilol induced strong inverse agonism with regard to both β 1-AR variants; furthermore, the Arg389 β 1-AR variant exhibited a 2.5-fold increase in FRET ratio as compared with the Gly389 β 1-AR variant. The unique properties of this beta blocker were confirmed downstream of receptor inactivation at the level of decreased cAMP accumulation: both β 1-AR variants demonstrated marked reduction in basal cAMP levels ( 14). Carvedilol led to a much stronger reduction in basal cAMP content in the Arg389 β 1-AR variant as compared with the Gly389 β 1-AR variant (see Figure1). The authors further established the phenotypic relevance of the molecular alterations induced by the Arg389Gly polymorphisms using primary neonatal rat cardiac myocytes infected with adenoviruses containing the β 1-AR variants as a model system to study cardiac rate control. Under basal conditions, both β 1-AR variants induced an increase in contractile activity as compared with WT cardiac myocytes; however, the contractile activity of the Arg389 variant was increased nearly 1.5-fold as compared with the Gly389 variant, and carvedilol significantly decreased this activity preferentially in the Arg389 β 1-AR.
Overall, the study by Rochais et al. ( 14) represents the first directassessment of GPCR function using the well-characterized β 1-AR system that also happens to be critical for normal and pathological cardiac physiology. Of importance, the authors were able to assess the conformational changes that occurred during agonism and antagonism of the receptor. Moreover, the data reveal that different β 1-AR antagonists, particularly carvedilol, are capable of inducing varying degrees of inverse agonism on the receptor and that this effect of carvedilol is dependent on the amino acid residue present at position 389 of the β 1-AR. Carvedilol, unlike metoprolol or bisoprolol, is a nonselective beta blocker and can also act on α 1-ARs ( 15). Therefore, it would be interesting to address the potential effects of β 2-AR and α 1-AR signaling on cardiac rate control to ascertain whether any receptor crosstalk or dimerization is responsible for the decreased basal cAMP production mediated by the Arg389 variant or whether antagonism of these other receptors is involved in the beneficial effects of carvedilol in HF. However, what is important to remember based on the current work is that for the β 1-AR, carvedilol displays the greatest degree of inverse agonism, especially for the Arg389 variant (Figure1), and studies such as this could lead to research broadening our knowledge of this pharmacological property of GPCR ligands and therefore potentially increase their clinical utility ( 16).
Taking it personally
The implications of these findings are of potentially profound clinical importance when considering the interindividual and ethnic variation that occurs in response to β-AR blocker therapy in the treatment of HF. It has been reported that the allele frequency of the Arg389 variant is 20% less common in black patients compared with non-black patients, and this may partially explain the poorer response to β 1-AR antagonists seen in blacks compared with that of the rest of the population ( 17). Future efforts to characterize the effect of genetic heterogeneity in cellular response to pharmacological agents, such as the β 1-AR antagonists examined in this study, lend credence to the viability of the concept of pharmacogenomics — pharmacologic intervention adapted according to an individual’s genetic makeup — and the realization of “personalized” medicine for the treatment of cardiovascular disorders such as HF ( 18).
Footnotes
Conflict of interest:The authors have declared that no conflict of interest exists.
Reference information: J. Clin. Invest. 117:86–89 (2007). doi:10.1172/JCI30476.
References
Lee, T.H. 2001. Management of heart failure: AHA/ACC guidelines summary. Heart disease: a textbook of cardiovascular medicine . 6th editio
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n . E. Braunwald, editor. 101 :652-685.
Becker, O.M., et al. 2004. G-protein coupled receptors: in silico drug discovery in 3D. Proc. Natl. Acad. Sci. U. S. A. 101 :11304-11309.
Rockman, H.A., Koch, W.J., Lefkowitz, R.J. 2002. Seven-transmembrane-spanning receptors and heart function. Nature. 415 :206-212.
Maqbool, A., Hall, S.A., Ball, S.G., Balmforth, A.J. 1999. Common polymorphisms of β 1 –adrenoreceptor: identification and rapid screening assay [research letter]. Lancet. 353 :897.
Ranade, K., et al. 2002. A polymorphism in the β 1 adrenergic receptor is associated with resting heart rate. Am. J. Hum. Genet. 70 :935-942.
Small, K.M., McGraw, D.W., Liggett, S.B. 2003. Pharmacology and physiology of human adrenergic receptor polymorphisms. Annu. Rev. Pharmacol. Toxicol. 43 :381-411.
Mason, D.A., Moore, J.D., Green, S.A., Liggett, S.B. 1999. A gain-of-function polymorphism in a G-protein coupling domain of the human β 1 -adrenergic receptor. J. Biol. Chem. 274 :12670-12674.
Akhter, S.A., D’Souza, K.M., Petrashevskaya, N.N., Mialet-Perez, J., Liggett, S.B. 2006. Myocardial β 1 -adrenergic receptor polymorphisms affect functional recovery after ischemic injury. Am. J. Physiol. Heart Circ. Physiol. 290 : H1427-H1432.
Brauwald, E., Bristow, M.R. 2002. Congestive heart failure: fifty years of progress. Circulation. 102(20 Suppl. 4) :IV14-IV23.
Beta-blocker Evaluation of Survival Trial Investigators. 2001. A trial of the beta-blocker bucindolol in patients with advanced chronic heart failure. N. Engl. J. Med. 344 :1659-1667.
Leinweber, K. 2004. Beta-adrenergic receptor polymorphism in human cardiovascular disease. Ann. Med. 36 :64-69.
Giempmans, B.N., Adams, S.R., Ellisman, M.H., Tsien, R.Y. 2006. The fluorescent toolbox for assessing protein localization and function. Science. 312 :217-224.
Miyawaki, A. 2003. Visualization of the spatial and temporal dynamics of intracellular signaling. Dev. Cell. 4 :295-305.
Rochais, F., et al. 2007. Real-time optical recording of β
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-adrenergic receptor activation reveals supersensitivity of the Arg389 variant to carvedilol.
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Yancy, C.W., et al. 2001. Race and the response to adrenergic blockade with carvedilol in patients with chronic heart failure. N. Engl. J. Med. 344 :1358-1364.
Bond, R.A., Ijzerman, A.P. 2006. Recent developments in constitutive receptor activity and inverse agonism, and their potential for GPCR drug discovery. Trends Pharmacol. Sci. 27 :92-96.
Small, K.M., Wagoner, L.E., Levin, A.M., Kardia, S.L., Liggett, S.B. 2002. Synergistic polymorphisms of β 1 - and α 2c -adrenergic receptors and the risk of congestive heart failure. N. Engl. J. Med. 347 :1135-1142.
Zineh, I., Johnson, J.A. 2006. Pharmacogenetics of chronic cardiovascular drugs: applications and implications. Expert Opin. Pharmacother. 11 :1417-1427.
Version history
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1
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| https://www.jci.org/articles/view/30476 |
Appetitive instrumental learning task. (A) During the instrumental... | Download Scientific Diagram
Download scientific diagram | Appetitive instrumental learning task. (A) During the instrumental appetitive learning phase participants learn stimulus-response-outcome associations, which is stimulated by a reward system. (B) In the behavioral test of action-outcome learning, one of the two displayed outcomes is devalued. The participants are instructed to respond with the correct response that is associated with the outcome. (C) During the baseline test, participants are exposed to all six stimuli, of which two are devalued. After the stimuli exposure, stimuli appear on the screen one by one and participants are asked to respond with the learned correct response unless the stimulus is devalued. (D) In the slips-of-action test, all outcomes are shown to the participants. Two of these outcomes are devalued. After outcome presentation, the associated stimuli appear on the screen one by one. Participants are asked to respond with the correct learned response unless the associated outcome of the stimulus is devalued. Participants who have a stronger habit tendency will automatically respond to the stimuli with the learned response regardless the value of the associated outcome. from publication: Goal-Directed and Habitual Control in Smokers | Introduction: Harmful behavior such as smoking may reflect a disturbance in the balance of goal-directed and habitual control. Animal models suggest that habitual control develops after prolonged substance use. In this study, we investigated whether smokers (N = 49) differ... | Operant Conditioning, Avoidance Learning and Suggestion | ResearchGate, the professional network for scientists.
<here is a image 69223e5274af9bd5-c036d08d6dd3d1ed>
Appetitive instrumental learning task. (A) During the instrumental appetitive learning phase participants learn stimulus-response-outcome associations, which is stimulated by a reward system. (B) In the behavioral test of action-outcome learning, one of the two displayed outcomes is devalued. The participants are instructed to respond with the correct response that is associated with the outcome. (C) During the baseline test, participants are exposed to all six stimuli, of which two are devalued. After the stimuli exposure, stimuli appear on the screen one by one and participants are asked to respond with the learned correct response unless the stimulus is devalued. (D) In the slips-of-action test, all outcomes are shown to the participants. Two of these outcomes are devalued. After outcome presentation, the associated stimuli appear on the screen one by one. Participants are asked to respond with the correct learned response unless the associated outcome of the stimulus is devalued. Participants who have a stronger habit tendency will automatically respond to the stimuli with the learned response regardless the value of the associated outcome.
Source publication
Introduction:
Harmful behavior such as smoking may reflect a disturbance in the balance of goal-directed and habitual control. Animal models suggest that habitual control develops after prolonged substance use. In this study, we investigated whether smokers (N = 49) differ from controls (N = 46) in the regulation of goal-directed and habitual beha...
Contexts in source publication
Context 1
... appetitive instrumental learning task was exactly the same as in a previous study in cocaine-dependent individuals 5 (
Figure 1
and Supplementary Materials). During the instrumental appetitive learning phase consisting of 96 trials, participants learned associations between stimuli, responses, and outcomes that were worth points. ...
Context 2
... = .002, BF 10 = 37.58 (Supplementary Figure 1). To unravel the specificity of, and mechanisms contributing to this association, exploratory correlations were calculated. ...
Context 3
... 10 = .19 (Supplementary Figure 1). The control variables age, alcohol use, and impulsivity in the hierarchical regression analyses were not associated with habitual responding, F(3,44) = 0.60, p = .477, ...
Introduction
Depression is a global burden that is exacerbated by smoking. The association between depression and chronic smoking is well-known; however, existing findings contain possible confounding between nicotine dependence (ND), a latent construct measuring addiction, and objective smoking behavior. The current study examines the possible uni...
Citations
... Similarly, Sebold et al. (2017) found no overall differences in model-free/-based behavior and their neural correlates in patients with alcohol use disorder compared to HC, while no significant associations were found between individual differences in alcohol consumption and (neural) model-free/-based control in young adults (Nebe et al., 2018). A study comparing non-smokers with nicotine smokers also did not find differences in goal-directed versus habitual behaviors
(Luijten et al., 2019)
. Integrating these findings, one may conclude that substance use disorder induced changes are not responsible for goaldirected control deficits, and substance-specific and individual differences affect these findings. ...
Background:
Although the vast majority of smokers are aware of the enormous preventable health hazards caused by smoking, only a small percentage of smokers manage to remain abstinent in the long term. One possible explanation for this discrepancy lies in the inflexibility of addictive behavior and associated disadvantageous decision‐making. According to a dual‐process theory of decision‐making, two distinct decision systems can be identified. One slow deliberate system based on desirable expectations of outcome value described as goal‐directed behavior and a fast reflexive system based on habitual instrumental behavior and driven by reinforcement experienced in the past. In the course of addiction development, an imbalance occurs between habitual behavior and goal-directed. The present study aims to investigate the modifiability of the balance between habitual and goal-directed behavior at the neurobiological and behavioral level in smokers using two different novel add-on therapies. We hypothesize that both interventions change the balance between goal-directed and habitual behavior, but by different mechanisms. Whereas a cognitive remediation treatment should directly improve cognitive control, in contrast an implicit priming task should affect the early processing and the emotional valence of smoking and smoking cues.
Methods:
We will conduct a randomized controlled study in treatment-seeking individuals with tobacco use disorder applying either chess-based cognitive remediation training (N = 30) or implicit computer-based habit-modifying training (N = 30) as add on therapy compared to the standard smoking cessation group therapy (N = 30) only. We will address neurobiological and neuropsychological correlates associated with craving, reward devaluation, cue reactivity and attentional bias. In addition, various effects of treatment and prediction of treatment outcome will be examined using behavioral and neural measures.
Discussion: The present study will apply different examination methods such as functional magnetic resonance imaging, neuropsychological tests, and self-report before and after the interventions. This allows the identification of intervention-specific mechanisms and therefore potential neurobiology-based specific treatment targets for individuals with Tobacco Use Disorder.
Trial registration: Registered at clinicaltrials.gov/ct2/show/NCT03764969 (05 December 2018).
... However, the authors considered that the overall findings did not provide strong support for deficits in either system and concluded that "drug addiction results in an imbalance between goal-directed and habitual control over behavior" [53]. Using variants of the task used by Ersche et al. [14], Luijten et al.
[54]
reported intact goal-directed control in cigarette smokers compared to controls, as reflected by decreased responding to devalued outcomes in both appetitive and avoidance tasks. However, dovetailing with the findings in CUD [14], participants with more severe nicotine dependence (assessed by the Fagerström Test for Nicotine Dependence [55]) committed more slips-of-action in the appetitive task, suggesting increased habitual control in appetitive contexts [54]. ...
... Using variants of the task used by Ersche et al. [14], Luijten et al. [54] reported intact goal-directed control in cigarette smokers compared to controls, as reflected by decreased responding to devalued outcomes in both appetitive and avoidance tasks. However, dovetailing with the findings in CUD [14], participants with more severe nicotine dependence (assessed by the Fagerström Test for Nicotine Dependence [55]) committed more slips-of-action in the appetitive task, suggesting increased habitual control in appetitive contexts
[54]
. ...
... In summary, the studies reviewed here showed that sensitivity to devaluation appeared preserved in cigarette smokers [38,41,
54]
, was modulated by factors such as the expectation of alcohol consumption [40] or negative mood [41], but correlated with smoking severity [39,54]. Indeed, the use of discriminative stimuli in outcome devaluation tasks provides evidence of impaired goal-directed control in drug users compared to healthy controls [14,48,53]. ...
Goal-Directed and Habitual Control in Human Substance Use: State of the Art and Future Directions
[136]
Luijten et al., 2020)
Luijten et al., 2020)
Luijten et al. 2020)
(Luijten et al., 2020)
| https://www.researchgate.net/figure/Appetitive-instrumental-learning-task-A-During-the-instrumental-appetitive-learning_fig1_339104726 |
Grayson County, Virginia Genealogy • FamilySearch
Guide to Grayson County, Virginia ancestry, family history, and genealogy. Birth records, marriage records, death records, census records, family history, immigration records, and military records.
Grayson County, Virginia Genealogy
Revision as of 20:08, 19 January 2020 by Dianehumann1 ( talk | contribs ) ( →Populated Places )
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Grayson County
Guide to Grayson County, Virginia ancestry, family history, and genealogy.Birth records, marriage records, death records, census records, family history, immigration records, and military records.
Grayson County , Virginia
Location in the state of Virginia, United States Genealogy
Location of Virginia in the U.S.
Facts
Founded
1792
County Seat
Independence
Courthouse
Contents
1 County Information
1.1 Description
1.2 Grayson County Virginia Courthouse
2 Grayson County Virginia History
2.1 Parent County
2.2 Boundary Changes
2.3 Record Loss
3 Grayson County Virginia Places/Localities
3.1 Populated Places
4 Grayson County Virginia Genealogy Resources
4.1 Research Guides
4.2 African American
4.3 Bible Records
4.4 Cemeteries
4.5 Census
4.6 Church Records
4.6.1 Baptist
4.6.2 Quaker
4.7 Court
4.8 Genealogy
4.9 Immigration
4.10 Land and Property
4.11 Local Histories
4.12 Maps
4.13 Military
4.13.1 Revolutionary War
4.13.2 War of 1812
4.13.3 Civil War
4.14 Miscellaneous Records
4.15 Naturalization
4.16 Newspapers
4.17 Probate Records
4.18 Taxation
4.19 Vital Records
4.19.1 Birth
4.19.2 Marriage
4.19.3 Divorce
4.19.4 Death
4.19.5 Vital Record Substitutes
5 Grayson County Virginia Genealogy Societies and Libraries
5.1 Family History Centers
6 Grayson County Virginia Genealogy Websites
7 Grayson County Virginia Genealogy References
County Information
Description
Grayson County is located in the Southwestern portion of the Commonwealth of Virginia sharing a border with North Carolina. Grayson was named for William Grayson one of Virginia’s first two senators [1].
Grayson County Virginia Courthouse
Grayson County CourthouseP.O. Box 130129 Davis StreetIndependence, Virginia 24348-0130Phone: 276-773-2231
Clerk Circuit Court has marriage, divorce, probate, courtand land records from 1793 [2]
Known Beginning Dates for Major County Records [3] Birth* Marriage Death* Court Land Probate Census 1853 1793 1853 1793 1793 1793 1810 Statewide registration for births and deaths began in 1912. General compliance year is unknown.
Grayson County Virginia History
Parent County
1792--Grayson County was created 7 November 1792 fromWytheandPatrickCounties. County seat:Independence [2]
Boundary Changes
For animated maps illustrating Virginia county boundary changes,"Rotating Formation Virginia County Boundary Maps"(1617-1995) may be viewed for free at the MapofUS.org website.
Record Loss
There is no known history of courthouse disasters in this county.
Lost censuses: 1800, 1810, 1890
Grayson County Virginia Places/Localities
Populated Places
For a complete list of populated places, including small neighborhoods and suburbs, visitHomeTown Locator. The following are the most historically and genealogically relevant populated places in this county: [4]
Towns
Fries
Independence
Troutdale
Unincorporated communities
Baywood
Elk Creek
Mouth of Wilson
Whitetop
Whitetop
Grayson County Virginia Genealogy Resources
Research Guides
"A Guide to the Counties of Virginia: Grayson County," The Virginia Genealogist , Vol. 11, No. 4 (Oct.-Dec. 1967):157-159. Available at FHL ; digital version at American Ancestors ($) .
African American
Freedmen's Bureau Letters or Correspondence, 1865-1872
Grayson County, Virginia Slaveholders 1800-1860 (New River Notes) - free.
Heinegg, Paul. "Grayson County Personal Property Tax List, 1805-1818," Free African Americans.com. [Heinegg abstracted free blacks listed in these records.]
Bible Records
Images of theVirginia Historical Society'sfamily Bible collection have been digitized:
Virginia Historical Society Papers, 1607-2007 .
Cemeteries
Tombstone Transcriptions Online
Tombstone Transcriptions in Print
List of Cemeteries in the county
Findagrave.com
Family History Library
Findagrave.com
VAGenWeb
WorldCat
Billion Graves
VAGenWeb Archives
Tombstone Project
Billion Graves
See Virginia Cemeteries for more information.
1800-1986 - Virginia, Jewish Cemetery Records Index, ca. 1800-1986 at FamilySearch — index
Census
For tips on accessing Grayson County, Virginia Genealogy census records online, see:Virginia Census.
Historical populations
Census
Pop.
%±
1800
3,912
—
1810
4,941
26.3 %
1820
5,598
13.3 %
1830
7,675
37.1 %
1840
9,087
18.4 %
1850
6,677
−26.5 %
1860
8,252
23.6 %
1870
9,587
16.2 %
1880
13,068
36.3 %
1890
14,394
10.1 %
1900
16,853
17.1 %
1910
19,856
17.8 %
1920
19,816
−0.2 %
1930
20,017
1.0 %
1940
21,916
9.5 %
1950
21,379
−2.5 %
1960
17,930
−16.1 %
1970
15,439
−13.9 %
1980
16,579
7.4 %
1990
16,278
−1.8 %
2000
17,917
10.1 %
2010
15,533
−13.3 %
1800- Lost, but a substitute is available, seeTaxation.
1810- Lost, but a substitute is available, seeTaxation.
1840
Douthat, James L. 1840 Mountain Empire of Virginia Census . Signal Mountain, Tenn.: Mountain Press, 2001. FHL Collection 975.5 X2d 1840. Free online surname index and purchase details at Mountain Press website. [Includes Grayson County.]
1890 Union Veterans
"Virginia's Union Veterans: Eleventh Census of the United States 1890." Prince William County Virginia , by Ronald Ray Turner. FHL Collection. Includes residents of this county.
Church Records
Baptist
Early Baptist churches (with years constituted):
Cedar Island or Fox Creek (1782) [5]
Meadow Creek (1797). [5] A list of new members (1840) was published in Glimpses of Grayson , Vol. 7, No. 3 (Dec. 1985).
N. Fork of New River (1796) [5]
Grayson County fell within the bounds of the Holston and Mountain Associations.
Quaker
Early monthly meetings (with years of existence):
Chestnut Creek Monthly Meeting (1785-1841) [6]
Fruit Hill Monthly Meeting (1790-1814) [6]
Mount Pleasant Monthly Meeting (1790-1825, 1980s) [6]
Court
Genealogy
More than 25 genealogies have been published about Grayson County families. To view a list, visitGrayson County, Virginia Compiled Genealogies.
Immigration
During the War of 1812, American officials reported finding a total of 1 British alien living in Grayson County. [7]
Land and Property
Local Histories
Maps
County and state maps, historical and more current, are valuable research tools. For map collections, online and in libraries, seeVirginia Maps.
Click a neighboring county for more resources
Military
Revolutionary War
Kegley, Mary B. Revolutionary War Pension Applications of Southwest Virginia Soldiers . n.p.: M.B. Kegley, 1997. Available at FHL . [Includes Grayson County pensioners.]
A Census of Pensioners for Revolutionary or Military Services: With their Names, Ages, and Places of Residence, as Returned by the Marshalls of the Several Judicial Districts, Under the Act for Taking the Sixth Census] . 1841. Digital versions at U.S. Census Bureau and Google Books et. al . 1967 reprint: FHL Collection 973 X2pc 1840. [See Virginia, Western District, Grayson County on page 134.]
Rejected or Suspended Applications for Revolutionary War Pensions . Washington, D.C., 1852. Reprinted by Genealogical Publishing Co., Inc., 1969, and 1991. Reprints include "an Added Index to States." FHL Book 973 M24ur ; digital version at Ancestry ($) . [Includes veterans from this county; Virginia section begins on page 238.]
War of 1812
Grayson County, Virginia in the War of 1812
Grayson County men served in the 78th Regiment. [8]
List of Pensioners on the Roll, January 1, 1883; Giving the Name of Each Pensioner, the Cause for Why Pensioned, the Post-Office Address, the Rate of Pension Per Month, and the Date of Original Allowance... Washington, D.C.: Government Printing Office, 1883. FHL Collection 973 M2Lp v. 5; digital versions at Google Books and Internet Archive . [See Vol. 5, Virginia, Grayson County, p. 82. Identifies War of 1812 veterans living in this county in 1883.]
Civil War
Regiments.Service men in Grayson County, Virginia Genealogy served in various regiments. Men often joined a company (within a regiment) that originated in their county. Listed below are companies that were specifically formed in Grayson County, Virginia Genealogy:
- 4th Regiment, Virginia Infantry (Confederate) . Company F (Grayson Dare Devils). [9]
- 4th Regiment, Virginia State Line (Cavalry and Infantry) (Confederate) . Companies B and D. [10]
- 8th Regiment, Virginia Cavalry (Confederate) . Company C (Grayson Cavalry) [11]
- 22nd Regiment, Virginia Cavalry (Bowen's Virginia Mounted Riflemen) (Confederate) . Company G.
- 37th Battalion, Virginia Cavalry (Dunn's Battalion, Partisan Rangers) (Confederate) . Company D and Company I. [12]
- 45th Regiment, Virginia Infantry (Confederate) . Company C (Grayson Rifles). [13]
- 50th Regiment, Virginia Infantry (Confederate) . Company D (Wilson Rifles) (Grayson Hornets). [14]
- 51st Regiment, Virginia Infantry (Confederate) . Companies A and D. [15]
- 63rd Regiment, Virginia Infantry (McMahon's) (Confederate) . Companies C and G. [16]
Records and histories are available, including:
1861-1865 - Virginia, Civil War, Service Records of Confederate Soldiers, 1861-1865
1861-1865 - Virginia, Civil War, Service Records of Union Soldiers, 1861-1865
1861-1865 - U.S., Confederate Soldiers Compiled Service Records, 1861-1865 at Ancestry — index (free)
1861-1865 - U.S., Union Soldiers Compiled Service Records, 1861-1865 at Ancestry — index (free)
Miscellaneous Records
1607-2007 - Virginia, Historical Society Papers, 1607-2007 at FamilySearch — index and images
Naturalization
Virginia Naturalization Petitions, 1906-1929
Newspapers
TheVirginia Newspapers Projectidentifies local Grayson County, Virginia Genealogy newspapers.Professor Tom Costa and The Rector and Visitors of the University of Virginia have created a database of all runaway advertisements for slaves, indentured servants, transported convicts, and ship deserters listed in the Virginia Gazette and other Virginia newspapers (1736-1803), see:The Geography of Slavery in Virginia.
Probate Records
A free index to Grayson County, Virginia Genealogy wills and administrations (1796-1800) is available at theLibrary of Virginia.
1793-1849 - Grayson County, Virginia Wills 1793-1849 (New River Notes) - free.
Online Probate Records
Images of Wills and Estates 1796-1839;1839-1849. Virginia Pioneers ($)
Taxation
Online Grayson County, Virginia Tax Lists
Type
Index
Images
Free
FHC
Fee
Free
FHC
Fee
Personal Property
1794 , 1794
-
-
-
1794
1794
Personal Property
-
-
-
-
1795
1795
Personal Property
1796
-
-
-
1796
1796
Land
1796
-
-
-
-
-
Personal Property
-
-
-
-
1797
1797
Personal Property
-
-
-
-
1798
1798
Personal Property
1799
-
-
-
1799
1799
Land
1799
-
-
-
-
-
Personal Property
1800 , 1800
-
1800
1800
1800
1800
Personal Property
-
-
-
-
1801
1801
Personal Property
-
-
-
-
1802
1802
Personal Property
-
-
-
-
1803
1803
Personal Property
-
-
-
-
1804
1804
Personal Property
1805
-
-
-
1805
1805
Land
1805
-
-
-
-
-
Personal Property
-
-
-
-
1806
1806
Personal Property
-
-
-
-
1807
1807
Personal Property
-
-
-
-
1809
1809
Personal Property
1810
-
-
-
1810
1810
Personal Property
-
-
-
-
1811
1811
Personal Property
-
-
-
-
1812
1812
Personal Property
1813
-
-
-
1813
1813
Personal Property
-
-
-
-
1814
1814
Personal Property
-
-
-
-
1815-1816
-
Personal Property
1817
-
-
-
1817
-
Personal Property
-
-
-
-
1818-1823
-
Personal Property
1824
-
-
-
1824
-
Personal Property
1825
-
-
-
1825
-
Personal Property
-
-
-
-
1826-1827
-
Personal Property
1828
-
-
-
1828
-
Personal Property
-
-
-
-
1829-1834
-
Personal Property
1835
-
-
-
1835
-
Personal Property
-
-
-
-
1836-1850
-
Personal Property
1863
-
-
-
-
-
Personal Property
1890
-
-
-
-
-
How can Virginia tax lists help me?
Bibliography
Tax Laws, Local, Glimpses of Grayson , Vol. 9, Nos. 1-2 (Jun. 1988).
[1794-1814] Grayson County Personal Property Tax Lists 1794-1814 (images); digital version in Tax List Club at Binns Genealogy ($) .
[1794] Grayson County, Virginia Tax List - 1794 (New River Notes) - free.
[1794] 1794 Grayson County, Virginia Personal Property Tax List (New River Notes) - free.
[1796] The 1796 Grayson County, Virginia Land Tax List (New River Notes) - free.
[1799] The 1799 Grayson County, Virginia Land Tax List (New River Notes) - free.
[1800] The 1800 Grayson County, Virginia Tax List (New River Notes) - free.
[1800] "Grayson County, Virginia, 1800 Tax List," The Virginia Genealogist , Vol. 25, No. 3 (Jul.-Sep. 1981):204-210. Available at FHL ; digital version at American Ancestors ($) .
[1805] The 1805 Grayson County, Virginia Land Tax List (New River Notes) - free.
[1805] The 1805 Grayson County, Virginia Personal Property Tax List (New River Notes) - free.
[1805-1818] Heinegg, Paul. "Grayson County Personal Property Tax List, 1805-1818," Free African Americans.com. [Heinegg abstracted free blacks listed in these records.]
[1810] The 1810 Grayson County, Virginia Tax List (New River Notes) - free.
[1810] Schreiner-Yates, Netti. A Supplement to the 1810 Census of Virginia: Tax Lists of the Counties for which the Census is Missing . Springfield, Va.: Genealogical Books in Print, 1971. Available at FHL . [The source for this publication is the 1810 personal property tax list. Grayson County is included because the 1810 Census for that county has been destroyed.]
[1810] Tax List, 1810, Southwest Virginian , Vol. 5, No. 27 (Dec. 1982).
[1810] Tax List, 1810, Southwest Virginia Ancestors , Vol. 9, No. 1 (Spring 1995); Vol. 9, No. 2 (Summer 1995).
[1813] The 1813 Grayson County, Virginia Personal Property Tax Lists (New River Notes) - free.
[1815] Ward, Roger D. 1815 Directory of Virginia Landowners (and Gazetteer) . 6 vols. Athens, Georgia: Iberian Pub. Co., 1997-2000. Available at FHL . [The source for this publication is the 1815 land tax. Grayson County is included in Vol. 5.]
[1815] Kegley, Mary B. Southwest Virginia Tax Assessments, 1815: Grayson, Lee, Scott, Russell, Washington, and Wythe Counties . Wytheville, Va.: Kegley Books, 1991. Original edition and 1992 supplement available at FHL . [The source for this publication is a private collection of 1815 tax assessment tickets for the First District of Virginia. The tickets includes landowners' names, number of acres or lots, number of buildings along with descriptions, and number of slaves. N.B. These are not the 1815 land tax books.]
[1817] The 1817 Grayson County, Virginia Personal Property Tax List (New River Notes) - free.
[1824] The 1824 Grayson County, Virginia Personal Property Tax List (New River Notes) - free.
[1825] The 1825 Grayson County, Virginia Personal Property Tax List (New River Notes) - free.
[1828] The 1828 Grayson County, Virginia Personal Property Tax List (New River Notes) - free.
[1835] The 1835 Grayson County Virginia Personal Property Tax List (New River Notes) - free.
[1863] The 1863 Grayson County, Virginia Land Tax List (New River Notes) - free.
[1890] The 1890 Grayson County, Virginia Land Tax List (New River Notes) - free.
Vital Records
Indexes to Grayson County, Virginia Genealogybirths,marriages, anddeathsare available online. These collections are incomplete, but are easy to search. Most records can also beordered electronically onlineas well. Courtesy:FamilySearch. See alsoHow to order Virginia Vital Records
Birth
1853-1879, 1884-1888 - Grayson County, Virginia Birth Records 1853-1879, 1884-1888 , under Vital Statistics. (New River Notes).
1853-1870 - Grayson County Birth Index 1853-1870. Batch C868753 at FamilySearch - free. [17]
1853-1866 - Virginia, Slave Birth Index, 1853-1866 at FamilySearch — index and images
1912-1913 - Virginia, Birth Certificates, 1912-1913 at FamilySearch — index and images
Marriage
1660-1800 - Virginia Marriages 1660-1800 (Ancestry) ($) .
1660-1959 - Virginia, United States Marriages at FindMyPast — index $
1740-1850 - Virginia Marriages 1740-1850 (Ancestry) ($) .
1793-1836 - Grayson County, Virginia Marriages 1796-1836 (New River Notes) - free.
1793-1906 - Grayson County Marriage Index 1793-1906. Batch M868753 at FamilySearch - free.
1853-1931 - Grayson County, VA Marriages 1853-1931 (New River Notes) - free.
1936-1988 - Virginia, Marriage Certificates, 1936-1988 at FamilySearch — index and images
Divorce
1918-1988 - Virginia, Divorce Records, 1918-1988 at FamilySearch — index and images
Death
1853-1896 - Grayson County, Virginia Death Register 1853-1870 and Records 1870-1896 (New River Notes) - free.
1853-1870 - Grayson County Death Index 1853-1870. Batch B868753 at FamilySearch - free.
1912-1987 - Virginia, Death Certificates, 1912-1987 at FamilySearch — index and images
Vital Record Substitutes
For birth, marriage, and death record substitutes, see Bible Records , Cemeteries , Church Records , Newspapers , and Probate Records .
Grayson County Virginia Genealogy Societies and Libraries
FamilySearch Centers provide one-on-one assistance, free access to center-only databases, and to premium genealogical websites.
FamilySearch Affiliate Libraries have access to most center-only databases, but may not always have full services normally provided by a FamilySearch center.
Grayson Co., VAGenWeb . Part of the USGenWeb Project . Maps, name indexes, history.
FamilySearch Catalog
Grayson County, VA History, Records, Facts and Genealogy (Familytree101)
RootsWeb Mailing List: SW_VA-L (Topic: Southwest Virginia)
Cyndi's List
↑ J.L. Scott, 36th and 37th Battalions Virginia Cavalry (Lynchburg, Va.: H.E. Howard, 1986). FHL Book 975.5 M2vr v. 24 .
↑ J.L. Scott, 45th Virginia Infantry (Lynchburg, Va.: H.E. Howard, 1989). FHL Book 975.5 M2vr v. 58 .
↑ John C. Chapla, 50th Virginia Infantry (Lynchburg, Va.: H.E. Howard, 1997). FHL Book 975.5 M2vr v. 129 .
↑ James A. Davis, 51st Virginia Infantry (Lynchburg, Va.: H.E. Howard, 1984). FHL Book 975.5 M2vr v. 9 .
↑ Jeffrey C. Weaver, 63rd Virginia Infantry (Lynchburg, Va.: H.E. Howard, 1991). FHL Book 975.5 M2vr v. 76 .
↑ Genealogical Society of Utah, Parish and Vital Records List (July 1998). Microfiche. Digital version at https://www.familysearch.org/wiki/en/images/3/37/Igivirginia.pdf .
Abingdon • Accomac • Accomack • Albemarle • Amherst • Antrim • Appomattox • Argall's Gift • Augusta • Bath • Beckford • Berkeley • Blisland • Blount Point • Botetourt • Boutracy • Bristol • Bromfield • Brunswick • Bruton • Camden • Cameron • Charles City • Charles • Charles River • Chickacoan • Chickahominy • Chippokes • Chiskiack • Chotank • Christ Church (Lancaster Co.) • Christ Church (Middlesex Co.) • Chuckatuck • Cople • Cornwall • Cumberland • Dale • Denbigh • Dettingen • Drysdale • East • Elizabeth City • Elizabeth River • Fairfax • Fairfield • Farnham • Flowerdew Hundred • Fluvanna • Frederick • Fredericksville • Hamilton • Hampton • Hanover • Harrop • Henrico • Hog Island • Hungars • James City • Jordan's Journey • Kecoughtan • Kingston • King William • Lancaster • Lawnes Creek • Lee • Leeds • Lexington • Littleton • Lower (Elizabeth City Co.) • Lower (Isle of Wight Co.) • Lower (Lancaster Co.) • Lower (Nansemond Co.) • Lower (Northampton Co.) • Lower (Stafford Co.) • Lower (Upper Norfolk Co.) • Lower Suffolk • Lunenburg • Lynnhaven • Machodick • Manchester • Marston • Martin's Brandon • Martin's Hundred • Meherrin • Middle Plantation • Middletowne • Montgomery • Mulberry Island • New Poquoson • Newport • Nomini • Norborne • Northampton • North Farnham • Nottoway (Prince Edward Co.) • Nottoway (Southampton Co.) • Nutmeg Quarter • Occohannock • Overwharton • Patrick • Petsworth • Piankatank • Piscataway • Poropotank • Portsmouth • Potomac • Raleigh • Richmond • Rockbridge • Rockingham • Russell • St. Andrew's • St. Anne's (Albemarle Co.) • St. Anne's (Essex and Caroline Cos.) • St. Asaph's • St. Brides • St. David's • St. George's (Accomack Co.) • St. George's (Spotsylvania Co.) • St. James Northam • St. James Southam • St. James's (Goochland Co.) • St. James's (Mecklenburg Co.) • St. John's • St. Luke's • St. Margaret's • St. Mark's • St. Martin's • St. Mary's • St. Mary's Whitechapel • St. Patrick's • St. Paul's (Hanover Co.) • St. Paul's (King George Co.) • St. Peter's • St. Stephen's (King and Queen Co.) • St. Stephen's (Northumberland Co.) • St. Thomas • Shelburne • Sittenburne • Smith's Hundred • South • Southampton • South Farnham • Southwark • Stafford • Stanley Hundred • Stratton Major • Suffolk • Tillotson • Trinity (Lancaster Co.) • Trinity (Louisa Co.) • Truro • Upper (Elizabeth City Co.) • Upper (Isle of Wight Co.) • Upper (Lancaster Co.) • Upper (Nansemond Co.) • Upper (Northampton Co.) • Upper (Stafford Co.) • Upper Suffolk • Varina • Wallingford • Ware • Warrosquyoake • Warwick • Washington (Westmoreland Co.) • Washington (Washington Co.) • Waters Creek • West • West and Shirley • Westbury • Westover • Weyanoke • Wicomico • Wilmington • York • Yorkhampton
Major Repositories
Bristol Public Library · Germanna Foundation Library · Handley Regional Library · Historical Society of Pennsylvania (Philadelphia, PA) · Historical Society of Washington, D.C. · John D. Rockefeller Jr. Library at Colonial Williamsburg · Jones Memorial Library · Library of Congress (Washington, DC) · Library of Virginia · Mary Ball Washington Museum and Library · Maryland State Archives (Annapolis, MD) · National Archives I (Washington, DC) · National Archives II (College Park, MD) · National Archives at Philadelphia (PA) · National Genealogical Society · New York Public Library (New York City, NY) · Pennsylvania State Archives (Harrisburg, PA) · Portsmouth Public Library · Roanoke County Public Library · Salisbury University Edward H. Nabb Research Center for Delmarva History and Culture (Salisbury, MD) · Santa Cruz Public Library Downtown (Santa Cruz, CA) · University of Virginia Library · Virginia Department of Health · Virginia Historical Society · Virginia Theological Seminary · Washington National Records Center (Suitland, MD) · William and Mary College Swem Library
Migration Routes
Routes: Chesapeake Bay • James River • Potomac River • Rappahannock River • York River • Chesapeake and Ohio Canal • Chesapeake and Ohio Railroad • Fall Line Road (or Fall Line Road ) • Great Indian Warpath • Great Trading Path • Great Valley Road • Kanawha Trail • King's Highway • National Road ( Cumberland Road ) • New River and Southern Trail • Occaneechi Path • Old Cherokee Path • Old Northwestern Turnpike • Pamunkey-New River Trail • Pioneer Road • Richmond Road • Richmond-Williamsburg Road • Saura-Saponi Trail • Secondary Coast Road • Upper Road • Wilderness Road • Wilmington, Highpoint, and Northern Trail • Ports: Atlantic Coast Ports • Accomack • Alexandria • Belvoir Plantation • Bermuda Hundred • Dumfries • Falmouth • Fredericksburg • Hampton • Jamestown • Leedstown • Norfolk • Port Royal • Portsmouth • South Quay • Suffolk • Tappahannock (aka Hobb's Hole) • Urbanna • Williamsburg • Yorktown
| https://www.familysearch.org/en/wiki/index.php?oldid=3783523&title=Grayson_County%2C_Virginia_Genealogy |
Clinical efficacy of therapeutic intervention for subclinical hypothyroidism during pregnancy | GMR | Genetics and Molecular Research | The Original by FUNPEC-RP
This study explored the effects of levothyroxine (L-T4) replacement therapy on pregnancy outcomes in patients with subclinical hypothyroidism (SCH). We analyzed the effects on pregnancy outcomes with respect to gestational week when the desired thyroid-stimulating hormone (TSH) level was reached as well as the length of time required to reach the target level during L-T4 treatment. This study enrolled 457 patients diagnosed with SCH upon initial thyroid function screening. Subjects were assigned to the treatment group (N = 184), and the control group (N = 273). Two variables were analyzed in the treatment group: the gestational week when the target TSH level was achieved and the length of time required to reach the target level during treatment. Based on these criteria, the treatment group was further divided into subgroups, including three subgroups based on the time required to reach target levels (& lt;4 weeks, 4-8 weeks, and & gt;8 weeks) and gestational week when the target TSH level was achieved (before the 12th, between the 12th-28th, and after the 28th gestational week). The overall risk of complications in the control group was significantly higher than in the treatment group (P & lt; 0.05). After L-T4 treatment, the incidences of premature rupture of fetal membranes (PROM), gestational diabetes mellitus, fetal macrosomia, and postpartum hemorrhage in the group with treatment duration & lt;4 weeks were significantly lower than those in the groups with 4-8 and & gt;8 weeks treatment duration (P & lt; 0.05). L-T4 treatment can significantly reduce the risks of adverse pregnancy outcomes in pregnant women with SCH. The shorter the treatment duration required to reach the target TSH level and the earlier the gestational week when the target TSH level is achieved through treatment, the lower the incidence of complications.
Research Article
Clinical efficacy of therapeutic intervention for subclinical hypothyroidism during pregnancy
R. Ju L. Lin Y. Long J. Zhang J. Huang
Published: November 21, 2016
Genet. Mol. Res. 15(4): gmr15049019
DOI: https://doi.org/10.4238/gmr15049019
Cite this Article:
R. Ju, L. Lin, Y. Long, J. Zhang, J. Huang, R. Ju, L. Lin, Y. Long, J. Zhang, J. Huang (2016). Clinical efficacy of therapeutic intervention for subclinical hypothyroidism during pregnancy. Genet. Mol. Res. 15(4): gmr15049019. https://doi.org/10.4238/gmr15049019
Article
Authors
Abstract
This study explored the effects of levothyroxine (L-T4) replacement therapy on pregnancy outcomes in patients with subclinical hypothyroidism (SCH). We analyzed the effects on pregnancy outcomes with respect to gestational week when the desired thyroid-stimulating hormone (TSH) level was reached as well as the length of time required to reach the target level during L-T4 treatment. This study enrolled 457 patients diagnosed with SCH upon initial thyroid function screening. Subjects were assigned to the treatment group (N = 184), and the control group (N = 273). Two variables were analyzed in the treatment group: the gestational week when the target TSH level was achieved and the length of time required to reach the target level during treatment. Based on these criteria, the treatment group was further divided into subgroups, including three subgroups based on the time required to reach target levels (<4 weeks, 4-8 weeks, and >8 weeks) and gestational week when the target TSH level was achieved (before the 12th, between the 12th-28th, and after the 28th gestational week). The overall risk of complications in the control group was significantly higher than in the treatment group (P < 0.05). After L-T4 treatment, the incidences of premature rupture of fetal membranes (PROM), gestational diabetes mellitus, fetal macrosomia, and postpartum hemorrhage in the group with treatment duration <4 weeks were significantly lower than those in the groups with 4-8 and >8 weeks treatment duration (P < 0.05). L-T4 treatment can significantly reduce the risks of adverse pregnancy outcomes in pregnant women with SCH. The shorter the treatment duration required to reach the target TSH level and the earlier the gestational week when the target TSH level is achieved through treatment, the lower the incidence of complications.
INTRODUCTION
The effects of subclinical hypothyroidism (SCH) on pregnancy outcomes and whether SCH in pregnant women should be treated remain controversial. The “Guidelines for Diagnosis and Treatment of Thyroid Disease during Pregnancy and Postpartum”, jointly developed by the Chinese Society of Endocrinology and the Chinese Society of Perinatal Medicine, state that “SCH during pregnancy increases the risks of adverse pregnancy outcomes as well as brain damage and neurodevelopmental sequelae in the offspring, but due to the lack of scientific evidence, this guideline neither opposes nor recommends L-T4 treatment for SCH in pregnant women with negative test to thyroid peroxidase antibodies (TPOAb)” (Chinese Society of Endocrinology and Chinese Society of Perinatal Medicine, 2012). The “Guidelines of the American Thyroid Association for the Diagnosis and Management of Thyroid Disease during Pregnancy and Postpartum” (2011) state that “SCH is related to adverse maternal and fetal outcomes. However, due to the lack of randomized controlled trials, there is insufficient evidence to clarify whether L-T4 treatment should be recommended for SCH women with negative thyroglobulin antibodies (TgAb) during pregnancy” (Stagnaro-Green et al., 2011). Given that both guidelines acknowledge that SCH during pregnancy can increase the incidence of adverse pregnancy outcomes, and studies have reported that early levothyroxine (L-T4) replacement therapy can prevent progression of SCH to CH (Helfand and Redfern, 1998) and significantly improve symptoms and signs. Given that SCH may cause adverse pregnancy outcomes for mothers and infants, based on examination of the pros and cons, most experts and guidelines recommend treatment.
In the present study, L-T4 was used as a therapeutic intervention and the enrolled SCH pregnant patients were fully informed. This study aimed to provide evidence for the clinical treatment of SCH in pregnant women by analyzing the effects of therapeutic interventions on pregnancy outcomes as well as differences in unexpected pregnancy outcomes according to durations required for serum TSH levels to achieve therapeutic standards with L-T4 treatment and the gestational weeks at which serum TSH levels reached the therapeutic standard during treatment.
MATERIAL AND METHODS
General information
The subjects enrolled in this study included patients with SCH who gave birth and were registered in the maternity clinic at Beijing Friendship Hospital of Capital Medical University between October 2010 and September 2013. The inclusion criteria included: 1) patients without internal medicine and surgical chronic diseases such as chronic hypertension, diabetes mellitus, endocrine disorders, history of thromboembolism, severe gastrointestinal/cardiopulmonary/liver diseases, or cancer before pregnancy; 2) patients without thyroid disease and autoimmune diseases before pregnancy (i.e., type 1 diabetes mellitus and systemic lupus erythematosus); 3) patients with live singleton confirmed by early B-ultrasound; 4) patients without a history of infertility or assisted reproduction; 5) patients not receiving treatment with thyroid hormones or antithyroid drugs; 6) patients with a median urine iodine concentration of 156.43 ± 9.21 μg/L during early pregnancy; and 7) patients negative for TPOAb. A total of 457 qualified subjects who were screened, diagnosed, and confirmed to meet the inclusion criteria were divided into treatment (N = 184) and control (N = 273) groups.
The study protocol was approved by the Ethics Committees of Beijing Friendship Hospital of Capital Medical University, Beijing, and all participants provided written informed consent.
Diagnostic criteria
Using the 2.5th and 97.5th percentiles as the lower and upper limits of the normal values for thyroid stimulating hormone (TSH) and free thyroxin (FT4), a normal reference range of specific thyroid function during gestational weeks was established. Patients with TSH levels greater than the 97.5th percentile and FT4 levels at or above the 2.5th percentile and less than or equal to the 97.5th percentile were diagnosed with SCH.
Treatment
The treatment protocol adopted in this study was based on the recommendation in China “Guidelines for Diagnosis and Treatment of Thyroid Disease during Pregnancy and Postpartum” (2012): “III. SCH treatment and monitoring frequency in pregnancy are the same as in any other clinical hypothyroidism, for which the initial dose of L-T4 is determined based on the elevation of TSH level and the dose of L-T4 can be adjusted according to the TSH treatment goals”. The treatment target concentration was set as a serum TSH level lower than the upper limit of the specific reference value during pregnancy (97.5th percentile). Subjects included in the study received treatment with oral L-T4 (Euthyrox, Merck Pharmaceuticals, 100 µg/tablet) (Chinese Society of Endocrinology and Chinese Society of Perinatal Medicine, 2012).
Study parameters
Adverse pregnancy outcomes in the two groups of patients included premature rupture of fetal membranes (PROM), fetal macrosomia, gestational diabetes mellitus, hypertensive disorders in pregnancy, postpartum hemorrhage, preterm labor, oligohydramnios, fetal distress, and low birth weight (LBW).
Statistical methods
IBM SPSS Statistics for Windows, version 19.0 was used for statistical analysis. The enumeration data are reported as percentages (%) and intragroup comparisons were tested using χ 2tests. Measurement data are reported as means ± standard deviations and intragroup comparisons were tested using t-tests. P < 0.05 indicated statistically significant differences.
RESULTS
General study and control subjects characteristics
General characteristics, including age, body mass index (BMI) at the first gynecological examination, body weight, exponential growth during pregnancy, baseline TSH level, and gestational week at the time of diagnosis, were compared. The differences in the general characteristics were not statistically significant (P > 0.05), indicating that the two groups were similar ( Table 1).
Table 1
Intragroup comparison of general characteristics (means ± SD).
Group Number of cases Age (years) Gestational week at diagnosis Baseline TSH (μIU/mL) BMI at the first gynecological examination (kg/m 2 ) Body weight exponential growth (kg/m 2 ) Treatment 184 29.31 ± 3.36 10.96 ± 8.02 5.09 ±1.58 24.67 ± 3.96 3.77 ± 2.65 Control 273 28.88 ± 3.53 10.21 ± 9.27 4.92 ± 1.64 24.23 ± 3.61 3.87 ± 2.35 P value 0.171 0.067 0.246 0.110 0.701
Baseline TSH is the level at the time of the first gynecological examination (the time of enrollment) TSH, thyroid-stimulating hormone; BMI, body mass index.
Comparison of pregnancy outcomes between the two groups
The overall risk of pregnancy complications in the control group was significantly higher than that in the treatment group [odds ratio (OR) = 1.219, 95% confidence interval (CI) = 1.139-1.304], a significant difference (P < 0.05). Intergroup comparison demonstrated that the risks for gestational diabetes mellitus (OR = 1.938, 95%CI = 1.267-2.964) and fetal macrosomia (OR = 3.081, 95%CI = 1.783-5.326) in the control group were significantly higher than those in the treatment group, and the differences were significant (both P < 0.05). The differences in the risks for PROM, pregnancy hypertension, preterm labor, oligohydramnios, postpartum hemorrhage, fetal distress, and LBW between the two groups were not statistically significant (all P > 0.05) ( Table 2).
Table 2
Comparison of pregnancy outcomes between groups (n/%).
Pregnancy outcomes Treatment group (N = 184) Control group (N = 273) P values OR 95%CI PROM 28 (15.2) 57 (20.9) 0.127 1.372 0.909-2.071 Gestational diabetes mellitus 24 (13.0) 69 (25.3) 0.001 △ 1.938 1.267-2.964 Fetal macrosomia 14 (7.6) 64 (23.4) 0.000 △ 3.081 1.783-5.326 Pregnancy hypertension 11 (6.0) 21 (7.7) 0.481 1.287 0.636-2.604 Preterm labor 6 (3.3) 11 (4.0) 0.670 1.236 0.465-3.282 Oligohydramnios 9 (4.9) 9 (3.3) 0.390 0.674 0.273-1.666 Postpartum hemorrhage 7 (3.8) 9 (3.3) 0.772 0.867 0.329-2.286 Fetal distress 51 (27.7) 97 (35.5) 0.080 1.282 0.966-1.701 LBW 6 (3.3) 7 (2.6) 0.660 0.786 0.269-2.302 Total 105 (57.1) 252 (92.3) 0.000 △ 1.219 1.139-1.304
OR, odds ratio; CI, confidence interval; PROM, premature rupture of fetal membranes; LBW, low birth weight. △P < 0.05.
Pregnancy outcomes in the study group and impact of the treatment duration required to achieve the target serum TSH levels
Depending on the duration of treatment required to reach the target TSH level, the treatment group was divided into three subgroups (<4, between 4 and 8, and >8 weeks). The intragroup differences in pregnancy outcomes between the three subgroups were analyzed using χ
2
tests (
Table 3
).
Table 3
Treatment group: pregnancy outcomes according to the duration of treatment required to reach the target serum TSH level (N/%).
Pregnancy outcomes <4 weeks (N = 71) 4-8 weeks (N = 69) >8 weeks (N = 44) P1 value P2 value P3 value PROM 4 (5.6) 12 (17.4) 12 (27.3) 0.029 △ 0.001 △ 0.210 Gestational diabetes mellitus 3 (4.2) 10 (14.5) 11 (25.0) 0.036 △ 0.001 △ 0.161 Fetal macrosomia 1 (1.4) 5 (7.2) 8 (18.2) 0.033 △ 0.001 △ 0.076 Pregnancy hypertension 3 (4.2) 3 (4.3) 5 (11.4) 0.971 0.144 0.156 Preterm labor 0 (0) 3 (4.3) 3 (6.8) 0.076 0.026 △ 0.568 Oligohydramnios 3 (4.2) 3 (4.3) 3 (6.8) 0.971 0.543 0.568 Postpartum hemorrhage 0 (0) 4 (6.3) 3 (6.8) 0.040 △ 0.026 △ 0.826 Fetal distress 20 (28.2) 24 (34.8) 19 (43.2) 0.399 0.098 0.370 LBW 0 (0) 3 (4.3) 3 (6.8) 0.076 0.026 △ 0.568
P1: comparison between treatment times <4 and 4-8 weeks; P2: comparison between treatment times <4 and >8 weeks; P3: comparison between treatment times of 4-8 and >8 weeks. TSH, thyroid-stimulating hormone; PROM, premature rupture of fetal membranes; LBW, low birth weight. △P < 0.05.
The group with a treatment duration <4 weeks had a significantly lower incidence of PROM, gestational diabetes mellitus, fetal macrosomia, and postpartum hemorrhage compared to the group with treatment duration 4-8 weeks (P < 0.05). The group with a treatment duration <4 weeks had a significantly lower incidence of PROM, gestational diabetes, fetal macrosomia, premature delivery, postpartum hemorrhage, and LBW infants compared to the group with treatment duration >8 weeks, a statistically significant difference (P < 0.05).
Pregnancy outcomes in the study group and the impact of the target TSH value according to gestational age
The treatment group was also divided into three subgroups according to the gestational week when the target TSH level was reached after treatment: gestational age <12 weeks, 12-28 weeks, and >28 weeks. The difference in the incidence of complications between the three groups was measured using χ
2
tests (
Table 4
).
Table 4
Treatment group: pregnancy outcomes and the impact of target TSH values according to gestational age (N/%).
Pregnancy outcomes <12 weeks of gestation (N = 73) 12-28 weeks of gestation (N = 96) >28 weeks of gestation (N = 15) P1 value P2 value P3 value PROM 5 (6.8) 18 (18.8) 5 (33.3) 0.025 △ 0.003 △ 0.195 Gestational diabetes mellitus 4 (5.5) 20 (20.8) 0 (0) 0.005 △ 0.353 0.051 Fetal macrosomia 1 (1.4) 11 (11.5) 2 (13.3) 0.011 △ 0.021 △ 0.843 Pregnancy hypertension 3 (4.1) 5 (5.2) 3 (20) 0.739 0.026 △ 0.039 Preterm labor 2 (2.7) 4 (4.0) 1 (6.7) 0.655 0.445 0.664 Oligohydramnios 5 (6.8) 6 (6.3) 3 (20) 0.876 0.107 0.070 Postpartum hemorrhage 1 (1.4) 5 (5.2) 3 (20) 0.182 0.002 △ 0.039 △ Fetal distress 25 (34.2) 31 (32.3) 7 (46.7) 0.789 0.362 0.275 LBW 2 (2.8) 3 (3.1) 1 (6.7) 0.884 0.453 0.494
P1: comparison between the group with gestational age <12 weeks and the group with gestational age 12-28 weeks; P2: comparison between the group with gestational age <12 weeks and the group with gestational age >28 weeks; P3: comparison between the group with gestational age 12-28 weeks and the group with gestational age >28 weeks. TSH, thyroid-stimulating hormone; PROM, premature rupture of fetal membranes; LBW, low birth weight. △P < 0.05.
The group with gestational age <12 weeks had a significantly lower incidence of PROM, gestational diabetes mellitus, and fetal macrosomia than did the 12-28-week gestation group, a statistically significant difference (P < 0.05). The group with a gestational age of 12 weeks had a significantly lower incidence of PROM, fetal macrosomia, hypertensive disorders in pregnancy, and postpartum hemorrhage than did the >28-week gestation group, a statistically significant difference (P < 0.05). The 12-28-week gestation group showed a significantly lower incidence of postpartum hemorrhage than did the >28-week gestation group (P < 0.05).
DISCUSSION
TPOAb is a serological marker of autoimmune thyroid disease that more commonly affects pregnant women. Hence, TPOAb is associated with adverse pregnancy outcomes (Lin et al., 2014). The impact of TPOAb-negative SCH on pregnancy outcomes and the necessity of medical treatment remain controversial, both at home and abroad. We addressed these controversies through a prospective cohort study. Our study group included TPOAb-negative pregnant women with SCH identified in the early pregnancy period during thyroid function screening. This study analyzed the necessity of medical treatment based on adverse pregnancy outcomes in the absence of L-T4 treatment, the gestational week when the desired TSH level was reached, and the duration of treatment required to reach the desired TSH level.
The effects of SCH on pregnancy and its outcomes at home and abroad are controversial. A previous study found that the pregnancy complications associated with SCH include gestational hypertension, preeclampsia, preterm labor, LBW, placental abruption, and postpartum hemorrhage (Helfand and Redfern, 1998). Another study reported that the incidence of gestational diabetes mellitus in pregnant women with SCH could reach 47% (Gallas et al., 2002).Casey et al. (2005)showed that the risk of adverse pregnancy outcomes in pregnant women treated for SCH was 2-3 times higher than that in pregnant women without treatment.Haddow et al. (1999)reported that pregnant women with SCH had decreased maternal-fetal thyroid hormone transportation, causing harm to fetal brain development (Hollowell et al., 1999). In a prospective multicenter fat-adapted-substrate oxidation in-trained-elite-runners study byCleary-Goldman et al. (2008), thyroid function screening during early and mid-pregnancy stages of 10,990 pregnant women did not show a significant correlation between SCH and adverse pregnancy outcomes (Cleary-Goldman et al., 2008). Domestic studies have reported similar findings;Liu et al. (2009)found that the maternal and fetal outcomes of women with SCH during pregnancy showed no differences compared with the control group. The indicators for adverse pregnancy outcomes in this study were selected mainly based on previous research findings. For example, Helfand and Redfern (1998) reported that SCH-associated pregnancy complications include gestational hypertension, preeclampsia, preterm labor, LBW, placental abruption, and postpartum hemorrhage. Based on domestic and international guidelines, this study selected L-T4 as the first choice for thyroid hormone replacement therapy in pregnant women because the main role of the thyroid hormone is to increase metabolic activity and thus facilitate growth and development. Fetal development, especially brain development, depends on adequate maternal T4 levels, rather than T3 levels (Wartofsky, 2013). This study revealed that the overall risk of pregnancy complications in untreated SCH pregnant women was significantly higher than that in the L-T4 treatment group. Specifically, the risk of gestational diabetes mellitus was 1.938 times higher and the risk of fetal macrosomia was 3.081 times higher at the same time. Furthermore, the differences in the risks of PROM, hypertensive disorders in pregnancy, preterm labor, oligohydramnios, postpartum hemorrhage, fetal distress, and LBW between the treated and untreated groups were insignificant. These findings are consistent with those published byNegro et al. (2010)that administration of L-T4 to pregnant women with SCH can reduce the occurrence of pregnancy complications.
Fetal thyroid gland begins to secrete thyroid hormone from 12 weeks of gestation and the hypothalamic-pituitary-thyroid axis is functionally established at 18-20 weeks of gestation, indicating the maturity of thyroid function. Therefore, the thyroid hormone required by the fetal brain development before the 20th gestational week mainly comes from the mother’s thyroid gland. Important brain developmental events that are closely related to thyroid hormones, such as neuron proliferation and migration in the brain, begin at the 12th gestational week (Rovet, 1999).Abalovich et al. (2007)retrospectively analyzed pregnancy outcomes in 114 pregnant women with hypothyroidism, including 52 cases of clinical hypothyroidism and 62 cases of SCH. They found that among the pregnant women with hypothyroidism who did not receive sufficient L-T4 therapy, 60% of patients with clinical hypothyroidism had miscarriage and 20% had preterm labor, while 71.4 and 7.2% of patients with SCH had miscarriage and premature labor, respectively. However, they discovered that among the pregnant women with hypothyroidism successfully treated with L-T4, 100% of patients with clinical hypothyroidism and 90.5% of SCH patients had full-term labor, with a zero incidence rate of miscarriage. They concluded that the key factor deciding the impact of hypothyroidism on pregnancy is unrelated to the clinical or subclinical type, but rather whether timely and adequate treatment if offered; hence, hypothyroidism during pregnancy requires regular monitoring. Replacement therapy should be adjusted in a timely manner based on monitoring results. They also concluded that adverse pregnancy outcomes can be prevented through timely and effective treatment (Abalovich et al., 2007).Yu et al. (2010)believed that SCH diagnosed before the 8th gestational week could result in neuropsychological and motor function deficits in offspring and timely L-T4 treatment might restore the offspring's intelligence level to a level comparable to the offspring of a normal pregnancy. Thus,Yu et al. (2010)proposed that treatment for hypothyroidism should be initiated before the 12th week of gestation. Moreover, they stated that fetal brain development might still be impaired even if the hypothyroidism during pregnancy is mild and asymptomatic. Clinical studies have shown that an increasing need for thyroid hormone (or exogenous L-T4) begins within the first 4 to 6 weeks of pregnancy and is gradually enhanced from 16 to 20 weeks of pregnancy, ultimately reaching a steady state until delivery (Yu et al., 2010).
By studying the impact of the duration of treatment required to reach target TSH levels on pregnancy outcomes in the treatment group, the present study found that the incidences of PROM, gestational diabetes mellitus, fetal macrosomia, and postpartum hemorrhage in the group with a treatment duration <4 weeks were significantly lower than in the groups with treatment durations of 4-8 weeks and >8 weeks. In addition, the incidences of preterm labor and LBW were significantly decreased in the group with treatment duration <4 weeks compared to those in with treatment duration >8 weeks but did not show any significant differences compared with those in the group with a treatment duration of 4-8 weeks. The differences in the incidences of all complications were not significant between the group with treatment duration of 4-8 weeks and the group with treatment duration >8 weeks. These results suggest that the shorter the time required to reach the target serum TSH level after treatment, the fewer complications. In particular, in patients who achieved the target level within four weeks, treatment effectively reduced the incidence of pregnancy complications. In addition, this study investigated the impact of the gestational week when the target TSH level was reached on pregnancy outcomes. Our results demonstrated that the incidences of PROM, gestational diabetes mellitus, and fetal macrosomia in the group with gestational age <12 weeks significantly decreased compared to the groups with gestational ages of 12-28 weeks and >28 weeks. The incidences of gestational hypertension and postpartum hemorrhage in the group with gestational age <12 weeks were significantly lower than those in the group with gestational age >28 weeks, while the group with a gestational age of 12-28 weeks had a significantly reduced incidence of postpartum hemorrhage compared to the >28-week group. These results suggest that the earlier the gestational week when the target serum TSH level was reached in pregnant women with SCH, the lower the incidence of complications. The incidence of pregnancy complications can be most effectively reduced when the desired level is reached before the 12th week of gestation. These findings are consistent with those published byAbalovich et al. (2007)and confirmed that timely and effective treatment of SCH can reduce the occurrence of adverse pregnancy outcomes.
The results of this study support the conclusions that L-T4 replacement therapy is necessary for treatment of SCH during pregnancy and that treatment should be timely and should reach treatment goals as quickly as possible in order to effectively reduce the incidence of adverse pregnancy outcomes. However, this study was limited by its small sample size; the conclusions require confirmation in large-scale prospective randomized controlled studies. Furthermore, the subjects included in this study did not undergo thyroid function evaluations before pregnancy, making it impossible to assess the impact of SCH illness duration on pregnancy outcomes and medication efficacy.
Key words:
L-T4
Levothyroxine
Pregnancy outcomes
Subclinical hypothyroidism
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Serum Ferritin and C - Reactive Protein As Prognostic Factors in Patients with Novel Coronavirus 2019 - DocsLib
Section: Biochemistry Original Article ISSN (O): 2347-3398; ISSN (P): 2277-7253 Serum Ferritin and C - Reactive Protein as Prognostic Factors in
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Section: Biochemistry
Original Article ISSN (O): 2347-3398; ISSN (P): 2277-7253
Serum Ferritin and C - Reactive Protein
as Prognostic Factors in Patients with Novel Coronavirus 2019
1 2 3
Maharudra Shekhanawar , H.T Sarala , Riyaz Ahamed Shaik 1Associate Professor, Department of Biochemistry, Belagavi Institute of Medical Sciences (BIMS), Belagavi, Karnataka, India, 2Associate Professor, Department of General Medicine, Belagavi Institute of Medical Sciences (BIMS), Belagavi, Karnataka, India, 3Assistant Professor, College of Medicine, Al Majmaah University, Al Majmaah, Saudi Arabia.
Abstract
Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has resulted in Coronavirus disease 2019 (COVID-19) which has been widely spread in India and worldwide. We have aimed to investigate serum
ferritin and CRP along with routine investigations and to correlate them amongst non- ARDS cases and ARDS cases which may help to predict severity and outcome of COVID-19. Subjects and Methods: Total number of 100 cases taken for study, admitted on priority basis. Consecutive blood
tests that included ferritin and CRP in the study period were reviewed. Patients diagnosed with SARS-CoV-2 infection in whom, CBC, platelet count, RFT, LFT, RBS, serum ferritin and CRP had been analysed at the time of admission were selected. For assessment of severity and behaviour of the factors to be analysed the COVID-19 patients were grouped into Non-ARDS (mild) and ARDS (severely ill) cases, factors analysed in both groups and correlated. Results: For Non-ARDS patients, the median age was 48 years 72% were men. For ARDS patients, 60 years, and 74% were men. Out of 42 ARDS cases 28 are diabetic (66.7%) as compared to 11 cases being diabetic in total 58 Non-ARDS cases (19%) p<0.001. Out of 39 ARDS cases 35 had mild to severe dyspnea which accounts for 83.3% with p value <0.001. Lymhocyte count is drastically decreased in ARDS cases (Mean=10; 6-14 p<0.001). ESR is raised in most of the Covid cases, a significant increase in ARDS patients (Mean=36; 31.8-42.3 p<0.05). In LFT, T.Bilirubin and D.Bilirubin raised significantly (Mean=1.8 and 0.8 p<0.001 respectively) along with SGPT significantly increased (Mean=40.3 p< 0.001). Also, there is drastic decrease in platelet counts in these ARDS cases (Mean=1.6X103cells/cu.mm p<0.001) suggesting thrombotic storm and inflammatory signs in ARDS cases. In all ARDS cases there is significant increase in serum ferritin and CRP values (100%) whereas in Non-ARDS cases these values were raised in 84.5% of cases. we found that in COVID-19 patients the association between ferritin levels and CRP levels was stronger. Conclusion: Detailed investigation of 100 hospitalized COVID-19 cases suggests that the serum ferritin test and CRP test should be used for screening in patients with COVID-19 to evaluate the severity and to predict the prognosis and mortality in hospitalized COVID-19 patients. Lymphopenia, Thrombocytopenia, with more prominent laboratory abnormalities may be a potential indicator for diagnosis. Older age, high number of comorbidities were associated with severe patients.
Keywords: Covid-19, Non-ARDS cases, ARDS cases
Corresponding Author: H.T Sarala, Associate Professor, Department of General Medicine, Belagavi Institute of Medical Sciences (BIMS), Belagavi, Karnataka, India. E-mail:
[email protected]
Received: 08 April 2021 Revised: 22 June 2021 Accepted: 01 June 2021 Published: 21 June 2021
Introduction start of the outbreak. Countries of the South-East Asia reported the largest week-on-week increase. India has reported nearly The outbreak of 2019 Novel coronavirus disease (COVID-19) 5,00,000 new cases in seven days in the middle of august, has affected India and has become pandemic worldwide.Due largely due to increased case detections in India, a 9% increase to its rapid spread worldwide, COVID-19 was declared as a compared to the previous seven days and the highest numbers [1] public health emergency by the World Health Organization. of new cases globally. [1] In India 724 Local transmission of the disease was found by 25 March 2020 with first case of COVID-19 infection reported in Most Covid-19 cases in Karnataka were spread by a small [2] Thrissur, Kerala, on January 27, 2020. fraction of infected patients, called “superspreaders”, showed By August 2020, A cumulative total of nearly 25 million cases by an analysis of contact tracing data between March 9 and and 8,00,000 deaths have been reported by WHO since the July 21, 2020, of 17,008 Covid-19 patients who had tested 99 99 Asian Journal of Medical Research 99 Volume 10 Issue 2 April-June 2021 9 Shekhanawar et al; Prognostic Factors in Patients with Novel Coronavirus 2019 positive and were contact-traced by July 7. We faced total Institute of Medical Sciences, (BIMS), Belagavi. It has total lockdown situation in Karnataka from March 24, 2020. [3] bed strength of 740 which serves the diverse population of The causative agent responsible for the pneumonia cases in Belagavi district and some places of neighbouring districts. Wuhan, in China, has been identified as a novel coronavirus, A separate block in the hospital was dedicated with 300 (of the same family of SARS-CoV and MERS-CoV) by beds including ICU for the treatment of COVID 19 patients. next generation sequencing (NGS) from cultured virus or The laboratory-confirmed COVID-19 patient’s laboratory data directly from samples received from patients suffering from which was documented in medical records department of the pneumonia. [4] Even though majority of patients who were hospital was collected. We performed ongoing retrospective suffering from fever and cough, had good prognosis who manual data abstraction from the records of 100 patients with recovered well, severe COVID-19 cases presented with COVID-19 who received inpatient care at BIMS hospital from acute respiratory distress syndrome (ARDS) and systemic July 10, 2020 to December 20, 2020. Consent was taken by all inflammation. Despite the fact that COVID-19 rapidly spread COVID-19 hospitalized patients, included in the study, for use in India the study data on various biomarkers to evaluate the of data for research and education. [5] prognosis remains limited. Patient characteristics, disease Inclusion Criteria course and patterns, resource utilization, mortality associated with COVID-19 have been characterized in only limited Patients with laboratory-confirmed SARS-CoV-2 infection samples in India. Thus, it is urgent to evaluate and investigate according to World Health Organization guidance: a positive possible biomarkers to assess disease severity so as to make result of real-time reverse-transcriptase polymerase chain fast and correct clinical decisions. reaction (RT-PCR) assay of a nasopharyngeal swab. [9] In our study 3 patients were diagnosed as COVID negative as their Several laboratory investigations have been associated with RT-PCR came negative but still they were included in the worse outcomes in patients with COVID-19, of them acute study because they were symptomatic and had a typical clinical phase reactants or inflammatory biomarkers have important presentation of COVID-19. role such as Ferritin and C-Reactive Protein (CRP) which are known inflammatory biomarkers. Exclusion Criteria Ferritin is a blood protein that contains iron and releases in Patients who received monoclonal antibody
, at any time during a controlled fashion. Its ability to sequester the iron gives their hospital stay were excluded for the study because studies ferritin the dual functions of iron detoxification and iron show that this agent has been associated with a decrease reserve keeping iron in soluble and non-toxic form. It is in CRP and ferritin levels. [10] Patients on repeated blood composed of a spherical protein shell called an apoferritin and transfusion were also excluded because of iron overload. a mineral core. [6] The evaluation of ferritin levels is important in diseases characterized by inflammatory and infectious Consecutive blood tests that included ferritin and CRP in processes and tissue damage and repair. [7] the study period were reviewed. Patients diagnosed with COVID-19 in whom serum ferritin, CRP, CBC, platelet CRP is an inflammatory marker and also an important factor count, RFT, LFT, and RBS had been analysed at admission that affects the development of inflammation. High serum were selected. Serum ferritin was measured on an Diasorin levels of CRP are a result of an acute inflammatory condition; chemiluminescence System (Diasorin Laboratories, IL) using CRP measurement between 0.5 and 10.00 mg/L facilitates the a 2-step chemiluminescent microparticle immunoassay. CRP detection of low-intensity chronic inflammatory processes. [8] was determined in serum using Erba XL-640 Chemistry The literatures show that acute-phase proteins
are of interest analyzer system (Transasia, MH), using a particle-enhanced in the medical field in the context of the etiopathogenesis, immunoturbidimetric assay. severity and prognosis in diseases with chronic inflammatory processes. Hence in our setting, we aimed to identify serum Total number of 100 cases taken for study, admitted in ferritin and CRP along with routine investigations and to BIMS hospital on priority basis. The criteria for admission correlate them amongst non- ARDS (Mild cases; Non-Acute include positive RT-PCR test for COVID-19 with high grade Respiratory Distress Syndrome) cases and ARDS (Cases with fever with myalgia, SPo2 on pulse oximeter showing < severe illness due to COVID infection) cases which may help 90%, Dyspnea on mild exertion and cases referred by Govt. to predict severity and outcome of COVID-19. officials from peripheries for isolation. All the cases who were subjected for CT- chest were showing CORAD 1-5, and CT severity scoring was done accordingly. All these RT-PCR Subjects and Methods positive cases were grouped into 3 groups. This retrospective observational study was performed at Group 1 consists of mild fever, myalgia, no dyspnea, spo2> teaching Hospital (District Hospital) attached to Belagavi 90%. 99 99 Asian Journal of Medical Research 99 Volume 10 Issue 2 April-June 2021 10 Shekhanawar et al; Prognostic Factors in Patients with Novel Coronavirus 2019
2nd group consists of high-grade fever, myalgia, mild dyspnea, There is significant probability between normal and high spo2< 85-90% requiring oxygen inhalation and CORAD<3. values of ferritin and CRP in ARDS and Non-ARDS cases with There hospital stay ranged from 7-10 days. p value 0.009. In all ARDS cases there is significant increase in serum ferritin and CRP values (100%) whereas in Non-ARDS Group 3 consists of severe complications of COVID present- cases these values were raised in 84.5% of cases. ing with grade 4 dyspnea, SpO2<80% and CORAD>3, who were admitted in ICU. Lymhocyte count is drastically decreased in ARDS cases (Mean=10; 6-14 p<0.001) compared to Non-ARDS cases. Group 1 is named as Non-ARDS cases and Group 2 and 3 are ESR is raised in most of the covid cases, a significant named as ARDS cases. increase in ARDS patients (Mean=36; 31.8-42.3 p<0.05). Clinical and laboratory data extracted from medical records Both these show inflammatory condition in COVID patients. was evaluated till the discharge of the patient or death. In LFT, T.Bilirubin and D.Bilirubin raised significantly (Mean=1.8 and 0.8 p<0.001 respectively) along with SGPT significantly increased (Mean=40.3 p< 0.001). Also, there Results is drastic decrease in platelet counts in these ARDS cases (Mean=1.6X103cells/cu.mm p<0.001) suggesting thrombotic The study population included 100 hospitalized patients with storm in ARDS cases. RBS is significantly raised in ARDS COVID-19, in which 58 cases were Non-ARDS and 42 cases cases proving that uncontrolled/poorly controlled diabetics are were ARDS. For Non-ARDS patients, the median age was more prone to go for ARDS compared to non-diabetic patients. 48 years (IQR 33-58), and 42 (72%) were men. For ARDS patients, the median age was 60 years (IQR 52-69), and 74% were men [Table 1]. Both of the COVID-19 Non-ARDS and ARDS patients had 1 or more coexisting medical conditions, and compared with Non-ARDS patients, ARDS patients were more likely to have existing co-morbidies, including Diabetes, CAD and Pulmonary diseases. On admission most patients had fever, cough, mild to moder- ate dyspnea, myalgia, chest discomfort, and fatigue besides, numerous differences in laboratory findings [Table 2]. Com- pared with Non-ARDS patients, ARDS patients had higher neutrophil counts (N), Lymphocytopenia, as well as higher erythrocyte sedimentation rate (ESR), Thrombocytopenia and there were significant differences in other biomarkers levels as well between two groups, notifiable are increase in the Biliru- bin and SGPT levels. There is also significant increase in RBS levels suggesting diabetics are more prone to get severe illness of COVID i.e., ARDS. As shown in [Table 1] there is statistical significance between age, diabetes, dyspnea, ferritin and CRP with P value <0.05. There is positive association between age and ARDS cases and also there is significant increase in the number of ARDS cases with advanced age. ARDS cases are more between the age groups 40-59 and >60 years as compared to the age group of 20-39. There is total 39 cases of ARDS in >40 years age group to the total 42 ARDS cases. In the later age severity of COVID increased as compared to the earlier age group with probability p<0.001. There is positive association between diabetics and ARDS cases showing diabetics are more prone to get severe COVID infection. Out of 42 ARDS cases 28 are diabetic (66.7%) as compared to 11 cases being diabetic in total 58 Non-ARDS cases (19%) p<0.001. Out of 39 ARDS In univariate and multivariate analysis of these parameters, cases 35 had mild to severe dyspnea which accounts for 83.3% all the parameters show significance in univariate analysis with p value <0.001. p<0.001, while ferritin shows significance in both univariate 99 99 Asian Journal of Medical Research 99 Volume 10 Issue 2 April-June 2021 11 Shekhanawar et al; Prognostic Factors in Patients with Novel Coronavirus 2019
Table 1: General characteristics of COVID19 patients with and without ARDS Factors Categories ARDS (n=42) Non ARDS Total (n=100) P-value (n=58) Sex Male 31 (73.8%) 42 (72.4%) 73 (73.0%) 0.877 Female 11 (26.2%) 16 (27.6%) 27 (27.0%) Age 20-39 3 (7.1%) 20 (34.5%) 23 (23.0%) <0.001 40-59 16 (38.1%) 26 (44.8%) 42 (42.0%) >=60 23 (54.8%) 12 (20.7%) 35 (35.0%) Diabetic No 14 (33.3%) 47 (81.0%) 61 (61.0%) <0.001 Yes 28 (66.7%) 11 (19.0%) 39 (39.0%) Dyspnea No 7 (16.7%) 54 (93.1%) 61 (61.0%) <0.001 Yes 35 (83.3%) 4 (6.9%) 39 (39.0%) Ferritin Normal 0 (0.0%) 9 (15.5%) 9 (9.0%) 0.009 High 42 (100.0%) 49 (84.5%) 91 (91.0%) CRP <10mg/L 0 (0.0%) 9 (15.5%) 9 (9.0%) 0.009 >=10mg/L 42 (100.0%) 49 (84.5%) 91 (91.0%) * P-values based on Chi-square test, Statistically significant P<0.05
Table 2: Comparison of Laboratory Investigations of COVID19 patients with and without ARDS Parameters ARDS (n=42) Non ARDS (58) Total (n=100) P-value Age 60.0 (51.5-67.8) 48.0 (32.5-57.5) 54.0 (40.0-62.8) <0.001 TC 7800 (5800-12075) 9150 (6800-12850) 8550 (6325-12775) 0.296 Neutrophils 78.0 (68.0-85.0) 71.0 (66.8-82.0) 75.0 (67.0-82.8) 0.164 Lymphocytes 10.0 (6.0-14.0) 23.0 (17.8-29.3) 16.0 (10.0-25.0) <0.001 HB 12.8 (11.1-13.7) 12.8 (11.6-14.0) 12.8 (11.5-13.9) 0.647 ESR 36.0 (31.8-42.3) 32.0 (26.0-35.3) 32.0 (27.3-40.0) 0.010 Platelet Count 1.6 (1.1-2.1) 2.7 (2.2-3.1) 2.3 (1.6-2.9) <0.001 Blood Urea 36.0 (25.8-42.0) 30.0 (24.8-36.0) 32.0 (25.0-39.0) 0.072 Creatinine 1.2 (0.9-1.3) 1.1 (0.9-1.2) 1.1 (0.9-1.3) 0.670 T. Protein 6.8 (6.4-6.9) 6.8 (6.6-7.0) 6.8 (6.5-7.0) 0.436 Albumin
3.6 (3.3-3.9) 3.8 (3.5-4.1) 3.8 (3.5-4.0) 0.128 T. Bilirubin 1.8 (0.9-2.2) 0.9 (0.6-1.1) 1.0 (0.8-1.8) <0.001 D. Bilirubin 0.8 (0.2-1.1) 0.2 (0.2-0.4) 0.3 (0.2-0.8) <0.001 SGOT 42.5 (31.8-48.8) 30.0 (24.0-38.0) 35.0 (27.0-45.8) 0.052 SGPT 40.3 (40.3-66.0) 34.5 (28.0-42.0) 38.5 (30.0-57.0) <0.001 ALP 95.0 (75.0-110.0) 90.5 (76.8-110.0) 92.0 (76.3-110.0) 0.886 RBS 158.0 (129.0-281.0) 115.0 (85.5-135.3) 128.0 (104.0-180.5) <0.001 Ferritin ng/ml 1104.0 (773.2- 313.0 (271.1-378.7) 419.0 (303.3-897.8) <0.001 1203.6) CRP mg/l 86.0 (53.7-110.5) 21.0 (16.9-28.0) 33.5 (20.0-79.8) <0.001 * Data is presented with Median (Interquartile range), P-values based on Mann-Whitney U test, Statistically significant P<0.05 99 99 Asian Journal of Medical Research 99 Volume 10 Issue 2 April-June 2021 12 Shekhanawar et al; Prognostic Factors in Patients with Novel Coronavirus 2019
Table 3: Association of laboratory parameters in COVID patients with and without ARDS Parameters Univariate Analysis Multivariate Analysis P-value OR (95% CI) P-value OR (95% CI) Age <0.001 1.06 (1.03-1.09) - - Lymphocytes <0.001 0.80 (0.74-0.87) - - ESR 0.031 1.05 (1.00-1.10) - - PlateletCount <0.001 0.30 (0.15-0.50) - - T.Bilirubin <0.001 4.02 (1.96-8.22) - - D.Bilirubin <0.001 14.2 (3.84-52.73) - - SGPT <0.001 1.08 (1.04-1.11) - - RBS <0.001 1.02 (1.01-1.03) - - Ferritin ngml <0.001 1.02 (1.01-1.03) <0.001 1.02 (1.01- 1.03) CRP mgl <0.001 1.11 (1.06-1.17) - -
Table 4: Sensitivity analysis to predict ADRS using Serum Ferritin levels Sensitivity Specificity AUC Cut off score 0.98 0.97 0.98 531 as well as multivariate analysis showing high sensitivity and At the same time, we also analysed the association between specificity, proving itself an ideal biomarker for assessment of these indicators after treatments in COVID-19 patients, and severity and course of COVID-19 [Table 3&4]. found that there were still great correlations between ferritin and CRP in ARDS patients. However, due to the absence of follow-up data, we couldn’t study the relationships between biomarkers levels in the course of hospital stay of ARDS patients. More importantly, we could make out the association between ferritin and CRP levels before treatments was related to the levels of 0.05 significantly in COVID patients, especially when the levels of CRP was more than 10 mg/L, the correlation between ferritin and CRP was stronger.
We aimed to investigate whether ferritin and CRP levels is associated with infection related biomarkers levels in Non-ARDS and ARDS patients. As shown in Table 5, for In this regression analysis, in the ROC curve for ferritin values, the TPR/FPR>1 making it an ideal marker. AUC is more Non-ARDS patients, ferritin and CRP levels were positively significant. There is 97% sensitivity and 100% specificity in correlated with infection related biomarkers levels including the ferritin values making it an ideal biomarker for assessment Lymphocyte count, ESR, Total and Direct Bilirubin, SGOT, of severity and outcome of the disease prognosis. SGPT and RBS at the time of admission with significant In addition, for ARDS patients, there were also positive correlation at 0.05 and 0.01 level. Thus, there is great correlations of ferritin and CRP levels at the time of admission correlations with inflammatory cells levels and thrombosis- (Mean=1104; p<0.001 and Mean=86; p<0.001 respectively). related factors at the time of admission. 99 99 Asian Journal of Medical Research 99 Volume 10 Issue 2 April-June 2021 13 Shekhanawar et al; Prognostic Factors in Patients with Novel Coronavirus 2019
Table 5: Correlation analysis ParametersAge LymphocytesESR T. D. SGOT SGPT RBS Ferritin CRP Biliru- Biliru- ng/ml mg/l bin bin Age 0.07 0.07 -0.21 -0.307∗ 0.15 -0.313∗ 0.27 -0.16 0.02 Lymphocytes0.07 0.11 -0.09 -0.03 0.00 -0.04 -0.21 -0.16 -0.05 ESR 0.07 0.11 0.11 0.07 0.26 -0.02 0.09 -0.12 -0.25 T. -0.21 -0.09 0.11 0.847∗∗ 0.624∗∗ 0.796∗∗ 0.07 0.03 0.07 Biliru- bin D. -0.307∗ -0.03 0.07 0.847** 0.490∗∗ 0.745∗∗ -0.05 -0.05 0.04 Biliru- bin SGOT 0.15 0.00 0.26 0.624** 0.490** 0.593∗∗ 0.08 -0.08 -0.03 SGPT -0.313∗ -0.04 -0.02 0.796** 0.745** 0.593** -0.08 -0.03 0.22 RBS 0.27 -0.21 0.09 0.07 -0.05 0.08 -0.08 0.09 0.14 Ferritin -0.16 -0.16 -0.12 0.03 -0.05 -0.08 -0.03 0.09 0.05* ng/ml CRP 0.02 -0.05 -0.25 0.07 0.04 -0.03 0.22 0.14 0.05* mg/l *. Correlation is significant at the 0.05 level; **. Correlation is significant at the 0.01 level.
coronavirus disease, thereby guiding clinicians in the clinical management of the patients and the disease outcome. Our analysis showed that Serum ferritin and CRP are significantly elevated in severe cases of COVID-19 (ARDS cases) as compared to the mild course of the disease (Non- ARDS cases) and act as important predictors in the severity of the disease at the time of admission. Our results are consistent with the findings of review articles that concluded that ferritin and CRP, in patients infected with corona virus disease, are a crucial markers for predicting COVID-19 prognosis and mortality in these patients. [11–14] The following variables showed significant positive associa- tion to the disease severity (p < 0.01): Advanced age, Lym- phocyte count, ESR, Platelet count, Bilirubin (Total & Direct), SGOT, SGPT and RBS in known Diabetics, which is in accor- dance with the earlier studies. [11,14–16] Of these, CRP, and Discussion serum ferritin levels had particularly strong association in ARDS cases and to the above variables. Corona virus disease caused a rapid epidemic worldwide in In severe COVID-19 infection, a deviation of the protective less than three months. Although most patients with COVID- immune response into a dysfunctional program occurs, which 19 have suffered from mild symptoms without pneumonia, results into cytokine storm with severe inflammation and, a large proportion of patients develop a severe conditions of eventually, multisystemic failure. A better understanding of respiratory distress or even caused death. This has led the the mechanisms lying at the root of immune response failure researchers to explore effective predictors of disease severity which points towards the clinical spectrum of the COVID that can help in assessing the severity of virus. The main disease corresponding to variable spectrum of the immunity is purpose of this research was to establish the effectiveness of needed; Due to cytokine storm serum levels of inflammatory the biomarkers which can accurately predict the severity of markers are increased in COVID-19. [17] It shows an evidence 99 99 Asian Journal of Medical Research 99 Volume 10 Issue 2 April-June 2021 14 Shekhanawar et al; Prognostic Factors in Patients with Novel Coronavirus 2019 for the increase of serum levels of ferritin and CRP. articles that conclude CRP a crucial marker for predicting COVID-19 prognosis and mortality. [31] Qin et al. and Gao et Ferritin is an iron-storing protein; serum ferritin level increases al also found a significant association between increased CRP, during viral infections and can act as marker for replication disease severity and prognosis. [32,33] of the virus. [18,19] Increased levels of ferritin can contribute cytokine storm and same has been reported in severe This study has several limitations, in particular, the number COVID-19 patients. During the cytokine storm in COVID-19, of patients enrolled were less mainly due to less testing many inflammatory cytokines are rapidly produced, including and unavailability of the protocol in the initial period as IL-6, TNF-α, IL-1β, IL-12, and IFN-γ, which stimulate well as retrospective nature of the study. Therefore, a wider hepatocytes, Kupffer cells, and macrophages to secrete analysis including a greater number of patients covering a large ferritin. [20–22] The uncontrolled and dysfunctional immune demographic area would be necessary in order to prove our response, hyper ferritinemic syndrome, and thrombotic storm outcomes. finally leads to multiple organ damage. In the present study decreased platelet count and increased bilirubin levels can be Conclusion explained by thrombotic storm. Although ferritin is reported as an acute-phase protein, there This study revealed the association between the serum is misunderstanding in reporting of ferritin levels due to lack ferritin levels, CRP and other inflammatory and thrombotic of studies in the modifications of ferritin levels. [23] Zhou et parameters of COVID-19 patients including disease severity, al revealed that the increase in ferritin level is associated mortality, comorbidities, and after treatment assessments. We with the worsening of the COVID-19. [13] The cytokine storm strongly recommend that the serum ferritin test and CRP test and the exaggerated host immune response which results should be used for screening in patients with COVID-19 to in development of ARDS, which is the leading cause of evaluate the severity and to predict the prognosis and mortality mortality if progresses to respiratory failure can result increase in hospitalized COVID-19 patients. Future clinical studies in acute phase reactants like ferritin. In our study, higher should be performed to further clarify its prognostic role in ferritin levels were found in groups of patients with severe COVID-19, disease outcome and the potential therapeutic respiratory distress conditions compared with the levels in less value in the inflammation control before end-organ damage. severe patients. [24] Moreover, our study also demonstrated that COVID-19 patients having one or more comorbidities, like References Diabetes had a significantly higher level of ferritin compared to the patients without comorbidity, which suggests a poor 1. Sohrabi C, Alsafi Z, O’Neill N, et al. World Health Organi- prognosis. 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This result is consistent with the findings of review org/10.1016/0005-2728(96)00022-9. 99 99 Asian Journal of Medical Research 99 Volume 10 Issue 2 April-June 2021 15 Shekhanawar et al; Prognostic Factors in Patients with Novel Coronavirus 2019
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is Available from: https://dx.doi.org/10.1016/j.jcv.2020.104357. associated with systemic inflammation, hypercoagulability, and 12. Li H, Xiang X, Ren H. Serum amyloid A is a biomarker prognosis of COVID-19 patients. Diabetes Res Clin Pract. of severe coronavirus disease and poor prognosis. J Infect. 2020;164:108214. Available from: https://doi.org/10.1016/j. 2020;80:646–655. Available from: https://doi.org/10.1016/j. diabres.2020.108214. jinf.2020.03.035. 26. Wang F, Yang Y, Dong K. Analysis of clinical characteristics 13. Zhou P, Yang XL, Wang XG. A pneumonia outbreak associated of patients with diabetes mellitus complicated with novel with a new coronavirus of probable bat origin. Nature. coronavirus pneumonia. J Clin Intern Med. 2020;37:230–232. 2020;579:270–273. 27. Tillet WS, Francis T. Serological reactions in pneumonia with 14. Zhang JJ, Dong X, Cao YY, Yuan YD, Yang YB, Yan YQ, a non-protein somatic fraction of Pneumococcus. J Exp Med. et al. Clinical characteristics of 140 patients infected with 1930;52(4):561–571. Available from: https://doi.org/10.1084/ SARS-CoV-2 in Wuhan, China. Allergy. 2020;75(7):1730– jem.52.4.561. 1741. Available from: https://doi.org/10.1111/all.14238. 28. Gabay C, Kushner I. Acute-Phase Proteins and Other 15. Huang C, Wang Y, Lix. Clinical features of patients infected Systemic Responses to Inflammation. N Engl J Med. with 2019 novel coronavirus in Wuhan. China Lancet. 1999;340(6):448–454. Available from: https://dx.doi.org/10. 2020;395:497–506. Available from: https://doi.org/10.1016/ 1056/nejm199902113400607. S0140-6736(20)30183-5. 29. Clos TWD, Mold C. C-Reactive Protein: An Activator of Innate 16. Chen L, Liu HG, Liu W, Liu J, Liu K, Shang J, et al. Immunity and a Modulator of Adaptive Immunity. Immunol Analysis of Clinical features of 29 patients with 2019 novel Res. 2004;30(3):261–278. Available from: https://dx.doi.org/ corona virus pneumonia. Zhonghua Jie He He Hu Xi Za Zhi. 10.1385/ir:30:3:261. 2020;43(0):203–211. Available from: https://doi.org/10.3760/ 30. Pradhan AD, Manson JE, Rifai N, Buring JE, Ridker PM. C- cma.j.issn.1001-0939.2020.0005. reactive protein, interleukin 6, and risk of developing type 2 17. García LF. Immune response, inflammation, and the clinical diabetes mellitus. J Am Med Assoc. 2001;286(3). Available spectrum of COVID-19. Front Immunol. 2020;11:1441. from: https://doi.org/10.1001/jama.286.3.327. Available from: https://doi.org/10.3389/fimmu.2020.01441. 31. Siordia JA. Epidemiology and clinical features of COVID-19: 18. Li Y, Hu Y, Yu J, Ma T. Retrospective analysis of laboratory A review of current literature. J Clin Virol . 2020;127:104357. testing in 54 patients with severe- or critical-type 2019 novel Available from: https://dx.doi.org/10.1016/j.jcv.2020.104357. coronavirus pneumonia. Lab Invest. 2020;100:794–800. 32. Qin C, Zhou L, Hu Z. Dysregulation of immune response 19. Baraboutis IG, Gargalianos P, Aggelonidou E, Adraktas A. in patients with COVID-19 in Wuhan, China. Clin Infect Initial real-life experience from a designated COVID-19 Centre Dis. 2020;71(15):762–768. Available from: https://doi.org/10. in Athens, Greece: a proposed therapeutic algorithm. SN 1093/cid/ciaa248. Compr Clin Med. 2020;p. 1–5. Available from: https://doi.org/ 33. Gao Y, Li T, Han M. Diagnostic utility of clinical laboratory 10.1007/s42399-020-00324-x. data determinations for patients with the severe COVID-19. J Med Virol. 2020;92:791–796. Available from: https://doi.org/ 10.1002/jmv.25770. 99 99 Asian Journal of Medical Research 99 Volume 10 Issue 2 April-June 2021 16 Shekhanawar et al; Prognostic Factors in Patients with Novel Coronavirus 2019
Copyright: © the author(s), 2021. It is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits authors to retain ownership of the copyright for their content, and allow anyone to download, reuse, reprint, modify, distribute and/or copy the content as long as the original authors and source are cited.
How to cite this article: Shekhanawar M, Sarala HT, Shaik RA. Serum Ferritin and C - Reactive Protein as Prognostic Factors in Patients with Novel Coronavirus 2019. Asian J. Med. Res. 2021; 10(2):9-17.
DOI: dx.doi.org/10.47009/ajmr.2021.10.2.BC2
Source of Support: Nil, Conflict of Interest: None declared. 99 99 Asian Journal of Medical Research 99 Volume 10 Issue 2 April-June 2021 17 | https://docslib.org/doc/7069992/serum-ferritin-and-c-reactive-protein-as-prognostic-factors-in-patients-with-novel-coronavirus-2019 |
X-Band Photo injector Beam Dynamics - UNT Digital Library
SLAC is studying the feasibility of using an X-band RF photocathode gun to produce low emittance bunches for applications such as a mono-energetic MeV {gamma} ray source (in collaboration with LLNL) and a photoinjector for a compact FEL. Beam dynamics studies are being done for a configuration consisting of a 5.5-cell X-band gun followed by several 53-cell high-gradient X-band accelerator structures. A fully 3D program, ImpactT, is used to track particles taking into account space charge forces, short-range longitudinal and transverse wakefields, and the 3D rf fields in the structures, including the quadrupole component of the couplers. The effect of misalignments of the various elements, including the drive-laser, gun, solenoid and accelerator structures, are evaluated. This paper presents these results and estimates of the expected bunch emittance vs cathode gradient, and the effects of mixing between the fundamental and off-frequency longitudinal modes. An X-band gun at SLAC has been shown to operate reliably with a 200 MV/m acceleration gradient at the cathode, which is nearly twice the 115 MV/m acceleration gradient in the LCLS gun. The higher gradient should roughly balance the space charge related transverse emittance growth for the same bunch charge but provide a 3-4 times shorter bunch length. The shorter length would make the subsequent bunch compression easier and allow for a more effective use of emittance exchange. Such a gun can also be used with an X-band linac to produce a compact FEL or g ray source that would require rf sources of only one frequency for beam generation and acceleration. The feasibility of using an X-band rf photocathode gun and accelerator structures to generate high quality electron beams for compact FELs and g ray sources is being studied at SLAC. Results from the X-band photoinjector beam dynamics studies are reported in this paper.
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SLAC is studying the feasibility of using an X-band RF photocathode gun to produce low emittance bunches for applications such as a mono-energetic MeV {gamma} ray source (in collaboration with LLNL) and a photoinjector for a compact FEL. Beam dynamics studies are being done for a configuration consisting of a 5.5-cell X-band gun followed by several 53-cell high-gradient X-band accelerator structures. A fully 3D program, ImpactT, is used to track particles taking into account space charge forces, short-range longitudinal and transverse wakefields, and the 3D rf fields in the structures, including the quadrupole component of the couplers. The effect of …
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Zhou, Feng; Adolphsen, Chris; Ding, Yuantao; Li, Zenghai & Vlieks, Arnold
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Authors Bookmark this section Zhou, Feng Stanford Linear Accelerator Center, Menlo park, CA 94025, USA
Adolphsen, Chris Stanford Linear Accelerator Center, Menlo park, CA 94025, USA
Ding, Yuantao Stanford Linear Accelerator Center, Menlo park, CA 94025, USA
Li, Zenghai Stanford Linear Accelerator Center, Menlo park, CA 94025, USA
Vlieks, Arnold Stanford Linear Accelerator Center, Menlo park, CA 94025, USA
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SLAC is studying the feasibility of using an X-band RF photocathode gun to produce low emittance bunches for applications such as a mono-energetic MeV {gamma} ray source (in collaboration with LLNL) and a photoinjector for a compact FEL. Beam dynamics studies are being done for a configuration consisting of a 5.5-cell X-band gun followed by several 53-cell high-gradient X-band accelerator structures. A fully 3D program, ImpactT, is used to track particles taking into account space charge forces, short-range longitudinal and transverse wakefields, and the 3D rf fields in the structures, including the quadrupole component of the couplers. The effect of misalignments of the various elements, including the drive-laser, gun, solenoid and accelerator structures, are evaluated. This paper presents these results and estimates of the expected bunch emittance vs cathode gradient, and the effects of mixing between the fundamental and off-frequency longitudinal modes. An X-band gun at SLAC has been shown to operate reliably with a 200 MV/m acceleration gradient at the cathode, which is nearly twice the 115 MV/m acceleration gradient in the LCLS gun. The higher gradient should roughly balance the space charge related transverse emittance growth for the same bunch charge but provide a 3-4 times shorter bunch length. The shorter length would make the subsequent bunch compression easier and allow for a more effective use of emittance exchange. Such a gun can also be used with an X-band linac to produce a compact FEL or g ray source that would require rf sources of only one frequency for beam generation and acceleration. The feasibility of using an X-band rf photocathode gun and accelerator structures to generate high quality electron beams for compact FELs and g ray sources is being studied at SLAC. Results from the X-band photoinjector beam dynamics studies are reported in this paper.
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Subjects Bookmark this section Keywords Bookmark this section Acceleration
Accelerators
Accelerators,Accphy
Beam Dynamics
Cathodes
Compression
Configuration
Electron Beams
Linear Accelerators
Photocathodes
Quadrupoles
Rf Systems
Solenoids
Space Charge
Stanford Linear Accelerator Center Accelerators,Accphy
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Zhou, Feng; Adolphsen, Chris; Ding, Yuantao; Li, Zenghai & Vlieks, Arnold. X-Band Photo injector Beam Dynamics
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The HIV-1 Integrase: Modeling and Beyond | IntechOpen
Open access peer-reviewed chapter
Open access
The HIV-1 Integrase: Modeling and Beyond
Submitted: December 17th, 2011 Published: July 1st, 2013
DOI: 10.5772/52344
An Integrated View of the Molecular Recognition and Toxinology
Edited by Gandhi Rádis Baptista
Chapter sections
1. Introduction
Molecular recognition is a fundamental phenomenon observed in all biological systems organisation ‒ proteins, nucleic acids and their complexes, cells and tissues. Molecular recognition is governed by specific attractive interactions between two or more partner molecules through non-covalent bonding such as hydrogen bonds, metal coordination, electrostatic effects, hydrophobic and van der Waals interactions. The partners – receptor(s) and substrate(s) or ligands ‒ involved in molecular recognition, exhibit molecular complementarity that can be adjusted over the recognition process. Competition and cooperation, the two opposite natural effects contributing to selective and specific recognition between participating partners, are the basic principles of substrate/ligand/inhibitor or protein binding to its targets.
The tertiary structures of biological objects (proteins and nucleic acids) are formed mainly by hydrogen bonds (enthalpic contributions) and by hydrophobic contacts (mostly entropic contributions). With a few exceptions, (e.g. ligand binding to the Ah receptor), the organisation of ligand-protein complexes depends primarily on hydrogen bonding.
In the process of a ligand binding to its target the hydrogen bonds contribute to (i) the orientation of the substrates/ligands/inhibitors by a receptor, frequently associated with a conformational/structural adjustment of the interacting agents; (ii) the specific recognition of substrates/ligands/inhibitors and selectivity between sterically or structurally similar but biochemically different species; (iii) the affinity of ligands/inhibitors ‒ the most decisive factor in drug design.
To describe the pharmacological properties of a given ligand or inhibitor, the knowledge of the site where the inhibitor is to bind with the target and of which interaction(s) control the specific recognition of the inhibitor by its target(s), represents a corner stone factor. Only a limited number of target-ligand molecular complexes have been characterized experimentally at the atomic level (X-ray or NMR analysis) [1]. Part of them describes the binding mode of therapeutically relevant ligands to biologically non-relevant and non-pertinent targets (e.g., the HIV-1 integrase specific inhibitor RAL was published as a ligand fixed to the PFV intasome [2,3]). Consequently, a large quantity of reliable information on target-ligand binding is based on molecular docking methods which generate insights into the interactions of ligands with the amino acid residues in the binding pockets of the targets, and also predict the corresponding binding affinities of ligands [4]. The first step of a docking calculation consists of the choice or generation/construction of the therapeutically appropriate target. Frequently the target modeling is a hard computational task which requires the application of sophisticated theoretical methods and constitutes a fascinating creative process.
Therefore, theoretical studies contribute first, to establish biologically valid models of the targets; second, through the use of these models, to the understanding of the protein functional properties; and finally to apply this data to rational drug design.
Here we compile and review the data on the molecular structure, properties and interactions of the HIV-1 integrase representing from one side, a characteristic example of a poly-functional and complex biological object interacting with different viral and cellular partners and from another side, an attractive therapeutical target. We attempt to extract key messages of practical value and complement references with our own research of this viral enzyme. We characterized the structural and conformational features of Raltegravir (RAL), the first integrase specific inhibitor approved for the treatment of HIV/AIDS, and we analyzed the factors contributing to RAL recognition by the viral targets.
2. The HIV-1 integrase and integrase-viral DNA pre-integration complex
2.1. Activities
The HIV-1 integrase (IN) is a key enzyme in the replication mechanism of retroviruses, catalyzing the covalent insertion of the reverse-transcribed DNA into the chromosomes of the infected cells [5]. Once integrated, the provirus persists in the host cell and serves as a template for the transcription of viral genes and replication of the viral genome, leading to production of new viruses (Figure 1a). A two-step reaction is required for covalent integration of viral DNA (vDNA) into host DNA (hDNA). First, IN binds to a short sequence located at either end of the long terminal repeat (LTR) of the viral DNA and catalyzes an endo-nucleotide cleavage. This process is known as 3’-processing reaction (3’-P), resulting in the removal of two nucleotides from each of the 3’-ends of the LTR and the delivery of hydroxyl groups for nucleophilic attacks (Figure 1 b).
Figure 1.
The HIV-1 replication cycle (a) and catalytic steps involved in the insertion of viral DNA into the human genome (b) [
6
].
2.2. Structural data
The HIV-1 IN is a 288 amino acids enzyme (32 kDa) that consists in three structurally distinct domains: (i) the N-terminal domain (NTD, IN 1–49) with a non-conventional HHCC zinc-finger motif, promoting protein multimerization; (ii) the central core domain (CCD, IN 50–212) containing a canonical D,D,E motif performing catalysis and involved in DNA substrate recognition [35]; (iii) the C-terminal domain (CTD, IN 213–288), which non-specifically binds DNA and helps to stabilize the IN•vDNA complex [13]. Both integration steps, 3’-P and ST, involve the active site and the active site flexible loop formed by ten residues, IN 140-149.
Neither the structure of isolated full-length IN from HIV-1 nor that of IN complex with its DNA substrate has been determined. Nevertheless, the structures of the isolated HIV-1 domains or two domains were characterized by X-ray crystallography (34 structures) and NMR analysis (9 structures) [1]. NTD presented by 6 NMR structure solutions (1WJA, 1WJB, 1WJC, 1WJE, and 1WGF) [14-16] was classified by SCOP as the ‘all alpha helix’ structure and consists of four helices stabilized by a Zn 2+cation coordinated with the HHCC motif (His12, His16, Cys40 and Cys43); the sequence from 43 to 49 residue are disordered (Figure 2). Structure of CTD was also characterised by NMR (3 deposited solutions (1IHV, 1IHW and 1QMC) [17,18]. According to the SCOP classification it presents the ‘all beta strand’ structure and consists of five anti-parallel β-strands forming a β-barrel and adopting an SH3-like fold (Figure 2).
The human IN CCD characterized by X-ray analysis has been reported as 14 different crystal structures (1HYV, 1HYZ, 1EXQ, 1QS4, 1B92, 1B9D, 1BHL, 1BI4, 1BIS, 1BIU, 1BIZ, 1BL3, 1ITG and 2ITG). The wild-type IN was resolved with a poor precision (1ITG) [19], the other structures represent engineered mutants, either single (F185K/H) [20-23], double (W131E and F185K; G149A and F185K or C56S and F185K) [24-26] or multiple (C56S, W131D, F139D and F185K) [27] mutants which were designed to overcome the poor solubility of the protein. The core domain has a mixed α/β structure, with five β-sheets and six α–helices (Figure 2).
Figure 2.
Structural domains of the HIV-1 integrase. (Top) N-terminal (IN
1–49
, left), catalytic core (IN
50–212
, middle) and C-terminal (IN
219–270
, right) domains; (bottom) N-terminal with catalytic core domain (IN
1–212
, left) and catalytic core with C-terminal fragment (IN
52-288
, right). The structures are shown as cartoon with the side chains of the HHCC and DDE motifs in the N-terminal and catalytic core domains rendered in stick and the Zn
2+
and Mg
2+
cations as balls; dashed lines indicate ion coordination [
28
,
29
].
The active site residues D64, D116 and E152 are located in different structural elements: β-sheet (β1), coil and helix (α4), respectively. The catalytic core domain also encompasses a flexible loop comprising residues 140–149, in which conformational changes are required for 3’-P and ST reactions. These activities require the presence of a metallic cofactor(s), the Mg 2+ion(s), which binds to the catalytic residues D64, D116 and E152. The number of Mg 2+cations is different for the distinct enzymatic reactions and consequently, for the different IN states: a single Mg 2+cation in non-processed IN, and two in processed IN. The structures of avian sarcoma virus (ASV) IN [21] and the Tn5 transposase[30] have provided evidence of a two-metal active site structure, which has been used to build metal-containing IN models [31-33].
Crystallographic structures of IN 1–212and IN 50–288two-domain constructs have also been obtained for W131D/F139D/F185K and C56S/W131D/F139D/F185K/C180S mutants, respectively (Figure 2)[34,35]. In the first of these structures, there is an asymmetric unit containing four molecules forming pairs of dimers connected by a non-crystallographic two fold axis, in which the catalytic core and N-terminal domains are well resolved, their structures closely matching those found with isolated IN 1–45and IN 50–212domains, and connected by a highly disordered linking region (47–55 amino acids). The X-ray structure of the other two-domain construct, IN 50–288, showed there was a two-fold symmetric dimer in the crystal. The catalytic core and C-terminal domains were connected by a perfect helix formed by residues 195–221. The local structure of each domain was similar to the structure of the isolated domains. The dimer core domain interface was found to be similar to the isolated core domain, whereas the dimer C-terminal interface differed from that obtained by NMR.
2.3. Theoretical models
All these structural data characterising the HIV-1 IN single or two-domains allow the generation of biologically relevant models, representing either the unbound dimeric enzyme or IN complexed with the viral or/and host DNA [29].
IN acts as a multimer [36]. Dimerization is required for the 3’-processing step, with tetrameric IN catalyzing the ST reaction [37,38]. Dimeric models were built to reproduce the specific contacts between IN and the LTR terminal CA/TG nucleotides identified in vitro[39,40]. However, most models include a tetrameric IN alone or IN complex with either vDNA alone or vDNA/hDNA, recapitulating the simultaneous binding of IN to both DNAs required for strand transfer (Figure 3b–d).
Figure 3.
Integrase architecture and organization. Theoretical models: (a) dimeric model of the full-length IN•vDNAcomplex [
39
]; (b) tetramer models of the IN•vDNA [
27
]; (c and d) synaptic complexes IN4•vDNA•hDNA [
41
,
42
]; (e) X-ray structure of the PFV IN•vDNAintasome [
2
]; and (f) EM maps reconstitution of IN•vDNA•hDNA complex with LEGDF [
43
]. Protein and DNA structures are presented as cartoon with colour coded nucleotides and Zn
2+
and Mg
2+
cations shown as balls. The active site contains two Mg
2+
cations in (a) and one in (b–d).
These models were either based on the partial crystal structure of IN [32,44] or constructed by analogy with a synaptic Tn5 transposase complex described in previous studies [42,45,46].
Most models include an Mg 2+cationic cofactor and take into account both structural data and biologically significant constraints (Figure 2b–d). In particular, HIV-1 IN synaptic complexes (IN•vDNA•hDNA) have been constructed taken into account the different enzymatic states occurring during the integration process (Figure 3 d)[41,42]. Such complexes have also been characterized by electron microscopy (EM) and single-particle imaging at a resolution of 27 Å [47]. Recently the X-ray complete structure of the Primate Foamy Virus (PFV) integrase in complex with the substrate DNA and Raltegravir or Elvitegravir has also recently been reported (Figure 3 e)[2].
In this complex, the retroviral intasome consists of an IN tetramer tightly associated with a pair of viral DNA ends. The overall shape of the complex is consistent with a low-resolution structure obtained by electron microscopy and single-particle reconstruction for HIV-1 IN complex with its cellular cofactor, the lens epithelium-derived growth factor (LEDGF) (Figure 3 d)[43].
2.5. Targets models representing the HIV-1 integrase before and after 3’-processing
Recently new HIV-1 IN models were generated by homology modeling. They represent with a certain level of reliability two different enzymatic states of the HIV-1 IN that can be explored as the biological relevant targets for design of the HIV-1 integrase inhibitors (Figure 4). The generated models are based on the experimental data characterising either the partial structures of IN from HIV-1 or full-length IN from PFV. The models of the separated full-length HIV-1 integrase represent the unbound homodimers of IN (IN1-270) containing either one or two Mg 2+cations in the active site – a plausible enzymatic state before the 3’ processing. The catalytic site loop encompassing ten residues forms the boundary of the active site. This loop shows either a coiled structure [20,22,24] or contains an Ω-shaped hairpin [28,48].
Figure 4.
Structural models of the HIV-1 integrase. (a) Model of unbound IN representing the homodimeric enzyme before the 3’-processing; (b) Model of the simplified (dimeric form) IN•DNA pre-integration complex; (c) Superimposition of monomeric subunits from two models in which catalytic site loop residues 140-149 are shown by colours (red and green).The proteins are shown as cartoons, Mg 2+ions as spheres (in magenta). (d) Schematic representation of the HIV and PVF active site loop secondary structure prediction, according to consensus 1 and consensus 2.
It will be useful to note that we evidenced a high flexibility of the functional domains in unbound IN by using the Normal Modes Analysis (NMA) [49,50]. Particularly, CTD is characterized by a large scissors-like movement (Figure 5 a). We established that the catalytic site loop in unbound IN with two Mg 2+cations in the active site is more rigid due to the stabilising role of the coordination of the Mg 2+cations by three active site residues, D64, D116 and E152, whereas the catalytic site loop flexibility increases significantly (Figure 5 b, c).
Figure 5.
Normal modes illustrating fragments movement in unbound IN. A scissors-like movement in CTD (a); the catalytic site loop displacement in unbound IN with one and two Mg 2+cation(s) in the active site (b) and (c) respectively (S. Abdel-Azeim, personal communication).
The simplified model of the HIV-1 IN•vDNA pre-integration complex represents the homodimer of integrase non-covalently attached to the two double strains of the viral DNA with two removed nucleotides GT at each 3’-end (Figure 4 b), and likely depicts the biologically active unit of the IN•vDNA strand transfer intasome. The IN•vDNA model was generated from the X-ray structure of the PFV intasome [2]. Despite the very low sequence identity (22%) between the HIV-1 and PFV INs, the structure-based alignment of the two proteins demonstrates high conservation of key secondary structural elements and the three PFV IN domains shared with HIV-1 IN have essentially the same structure as the isolated IN domains from HIV-1 [51]. Moreover, the structure of the PFV intasome displays a distance between the reactive 3’ ends of vDNA that corresponds to the expected distance between the integration sites of HIV-1 IN target DNA (4 base pairs). Consequently, we suggested that the PFV IN X-ray structure represents an acceptable template for the HIV-1 IN model generation [52].
Two models of different states of the HIV-1 IN show a strong dissimilarity of their structure evidenced by divergent relative spatial positions of their structural domains, NTD, CCD and CTD (Figure 4 c). These tertiary structural modifications altered the contacts between IN domains and the structure and conformation of the linker regions. Particularly, the NTD-CCD interface exhibits substantial changes: in the unbound form the NTD-CCD interface belongs to the same monomer subunit whereas in the vDNA-bound form the interface is composed of residues from the two different subunits. Moreover, IN undergoes important structural transformation leading to structural re-organisation of the catalytic site loop; the coiled portion of the loop reduces from ten residues in the unbound form to five residues in the vDNA-bound form. Such effect may be induced either by the vDNA binding or it can derive as an artefact produced from the use of structural data of the PFV IN as a template for the model generation. Prediction of IN 133-155sequence secondary structure elements indicates a more significant predisposition of IN from HIV-1 to be folded as two helices linked by a coiled loop than the IN from PFV (Figure 4 d). Prediction results obtained with high reliability (>75%) correlate perfectly with the X-ray data characterising the WT HIV-1 integrase (1B3L) [22] and its double mutant G140A/G149A (1B9F) [26]. The helix elongation accompanied by loop shortening may be easily induced by the enzyme conformational/structural transition between the two integration steps prompted by substrate binding.
This structure can be used to generate reliable HIV-1 IN models for Integrase Strand Transfer Inhibitors (INSTIs) design. However, the active site loop adopts a five-residue coil structure, rather than the ten-residue extended loop observed in HIV-1IN. This difference may be due to a difference in the sequence of the two enzymes or an effect induced by DNA binding, and caution is therefore required in the use of this structure as a template for modelling biologically relevant conformations of HIV-1 IN [2,45].
2.6. Transition pathway between two IN states and the allosteric binding sites
Two different states of the HIV-1 IN represent the enzyme structures before and after 3’-processing. Under integration process, IN as many other proteins undergo large conformational transitions that are essential for its functions (Figure 6)[53-55]. Tertiary structural changes precede and accompany these quaternary transitions in the HIV-1 IN as was evidenced by Targeted Molecular Dynamics (TMD) [56] and Meta Dynamics (MD) [57] (Figure 6 c, d).
Figure 6.
Transition states ensemble between A and B structures (a) (A. Blondel, personal communication). A series of conformations visited by the HIV-1 IN over transition from unbound IN to IN•vDNA complex before (red) and after (blue) 3’-processing (b) obtained by Targeted Molecular Dynamics (TMD) (c) and Meta Dynamics (MD) simulations (d) (S. Abdel-Azeim, personal communication).
Our results, first, provide a description of structure-dynamics-function relationships which in turn supplies a plausible understanding of the IN 3’-processing at the atomic level. Second, the calculated intermediate conformations along the trajectories were scanned for molecular pockets - a means of exploring putative allosteric binding sites, particularly positioned on the IN C-terminal domain (CTD), which is responsible for the vDNA recognition (Figure 7).
Figure 7.
Pockets detected on the surface of the HIV-1 Integrase intermediate conformations obtained by Targeted Molecular Dynamics (TMD) simulations. (S. Abdel-Azeim, personal communication).
3. Raltegravir
The integrase inhibitors were developed to block either the 3’-processing or the strand transfer reaction [58-60]. Raltegravir (RAL), the first IN inhibitor approved for AIDS treatment [61] specifically inhibits the ST activity and was confirmed as an integrase ST inhibitor (INSTI), whereas the 3’-P activity was inhibited only up to a certain concentration [28,62]. The potency of RAL has been described at the level of half-maximal inhibitory concentration (IC50 values) in cellular antiviral and recombinant enzyme assays, kinetic analysis and slow-binding inhibition of IN-catalyzed ST reaction [62-68]. Particularly, it has an IC 50of 2 to 7nM for the inhibition of recombinant IN-mediated ST in vitroand an IC 95of 19 and 31 nM in 10% FBS (fetal bovine serum) and 50 % NHS (normal human serum), respectively. This drug has been reported to be approximately 100-fold less specific for the inhibition of 3'-processing activity compared to strand transfer. The dissociation rate of RAL with IN•vDNA complex was slow, with k offvalues of (22 ± 2) × 10 −6s −1. The dissociative half-life value measured for RAL with the wild type IN•vDNA complex was 7.3 h and 11.0 h obtained at 37°C and at 25°C respectively.
Like other antiretroviral inhibitors, RAL develops/induces a resistance effect. Resistance to RAL was associated with amino acids substitutions following three distinct genetic pathways that involve either N155H, either Q148R/K/H or Y143R primary mutation [69,70]. The last mutation was reported as rare [71]. It was supposed that the integrase active site mutation N155H causes resistance to raltegravir primarily by perturbing the arrangement of the active site Mg 2+ions and not by affecting the affinity of the metals or the direct contacts of the inhibitor with the enzyme [72].
G140S has been shown to enhance the RAL resistance associated with Q148R/K/H [73]. The kinetic gating and/or induced fit effect have been reported as possible mechanisms for RAL resistance of the G140S/Q148H mutant [74]. A third pathway involving the Y143R/C/H mutation and conferring a large decrease in susceptibility to RAL has been described [75].
3.1. Structure and conformational flexibility
No experimental data characterizing RAL unbound structure or RAL binding mode to the HIV-1 IN has been reported. In this regard, the characterization of RAL conformational preferences and the study of its binding to the HIV-1 IN represent an important task for determining the molecular factors that contribute to the pharmacological action of this drug. Crystallographic data describing the separate domains of the HIV-1 IN and the full-length PFV IN with its cognate DNA deposited in the PDB, provide useful experimental starting guide for the theoretical modeling of the structurally unstudied objects, IN and IN•vDNA complex of HIV-1 as the RAL targets.
RAL, incorporating two pharmacophores, is a multipotent agent capable to hit more than one target in HIV-1, the unbound IN, the viral DNA or IN•vDNA complex. RAL shows the configurational E/Z isomerism and a high conformational flexibility due to eight aliphatic single bonds. Two pharmacophores, (1) 1,3,4-oxadiazole-2-carboxamide and (2) carbonylamino-1-N-alkyl-5-hydroxypyrimidinone, possessing structural versatility through the orientation of carboxamide fragments respective to the aromatic rings, show E-, Z-configuration states characterizing the relative position of the vicinal 1‒4 and 1‒5 oxygen atoms [48] (Chart 1). The molecule has a set of multiple H-bond donor and acceptor centres. These molecular features together with high structural flexibility provide an abundance of alternative mono- and bi-dentate binding sites in a given RAL conformation.
Chart 1.
RAL structure. The E- and Z-isomers of 1,3,4-oxadiazole-2-carboxamide (1) and carbonylamino-1-N-alkyl-5-hydroxypyrimidinone (2) pharmacophores are stabilized by intramolecular H-bonds.
The chelating properties of protonated or deprotonated RAL are also determined by the E- or Z- configuration (Chart 2). Consequently, RAL can contribute in the recognition and binding of different partners – H-donor, H-acceptors, charged non-metal atoms and metal cations – in topologically distinct regions of IN by applying the richness of its molecular and structural properties. For instance, RAL as a bioisoster of adenine can block IN interaction with DNA [48] or sequester metal cofactor ions [76].
Chart 2.
Metal chelating properties of 1, 3, 4-oxadiazole-2-carboxamide (1) and carbonylamino-1-N-alkyl-5-hydroxypyrimidinone (2) moieties.
The conformational preferences of RAL were examined in the gas phase (conformational analysis), in water solution (molecular dynamics, MD, in explicit solvent) and in the solid state (the fragment-based analysis using the crystallographic data from Cambridge Structural Database, CSD [77]. Conformational analysis of the different isomeric states of RAL in the gas phase indicates a small difference between the energy profiles of the Z-1/Z-2 and E-1/Z-2 isomers suggesting a relatively low energetical barrier between these two inhibitor states (Figure 8).
Figure 8.
RAL conformations in the gas phase. Free energy profiles obtained by relaxed scans around the single bonds of RAL from 0 to 360⁰ with an increment step of 30⁰, considering the four RAL isomers: (a) Z-1/Z-2, (b) Z-1/E-2, (c) E-1/Z-2 and (d) E-1/E-2. The curves representing the rotations around torsion angles τ1, τ2, τ3 and τ4 are shown in blue, red, green and violet colours. The values of τ1, τ2, τ3 and τ4 observed in RAL crystal structure 3OYA are indicated by asterisks.
A slight preference for the Z-configuration of carbonylamino-hydroxypyrimidinonepharmacophore in the gas phase was observed, in coherence with the established predisposition of β-ketoenols – a principle corner stone of this pharmacophore – to adopt the Z-isomer in the solid state (Figure 9 b)[78-80]. The preference of aliphatic β-ketoenols to form energetically favorable Z-configurartion has been predicted early by ab initiostudies at the B3LYP/3-G** level of theory [81].
The Cambridge Structural Databank search (CSD) [77] based on molecular fragments mimicking the RAL pharmacophores statistically demonstrates the preferential E-configuration of oxadiazolecarboxamide–like molecules and the Z-configuration of carbonylamino-hydroxypyrimidinone-like molecules in the solid state (Figure 9 a and brespectively). The halogenated aromatic rings, widely used pharmacophores, show a great level of conformational flexibility (Figure 9, c), allowing to contribute to a better inhibitor affinity in the binding site.
Figure 9.
RAL conformations in the solid state. CSD fragment-based analysis of the RAL subunits indicates the E- (blue triangles) and Z- (red squares) conformations of oxadiazolecarboxamide–like molecules (a) and the Z-configuration of carbonylamino-hydroxypyrimidinone-like molecules (b). The halogenated phenyl ring conformation RAL geometry in PFV complex is shown in (c and d respectively). The RAL crystal structure parameters are indicated by asterisks. The alternative configurations of the carbonylamino-hydroxypyrimidinone derivatives are demonstrated by structure of RAL precursor molecules, GACMUT, MEADAP and POPYOJ, and RAL inhibitor (d-g).
3.2. Raltegravir-metal recognition
Synthesized as a metal cations chelating ligand, RAL can bind the metal by both pharmacophores in different isomerisation states. Probing the RAL chelating features with relevant cations, K, Mg and Mn, we evidenced that in the majority of metal complexes, the carbonylaminohydroxypyrimidinone-like fragments are observed in the Z configuration in the solid state (Figure 10).
The oxadiazolecarboxamide-like pharmacophore is observed in the metal complexes as two isomers and demonstrates a strong selectivity to the metal type: the Z isomer binds K and Mg while the E isomer binds mainly Mn. The higher probability of Mg 2+cation coordination by the Z-isomer of both pharmacophores indicates that the presence of two Mg 2+cations at the integrase binding site may be a decisive factor for stabilisation of the Z/Z configuration of RAL which is observed in the PFV intasome complex [2,3].
Therapeutically used RAL is in deprotonated state neutralised by K cation. Such drug formula corresponds to the optimal condition allowing efficient cations replacement in cells. The significantly higher affinity of both parmacophores to Mg relatively to K permits a positive competition between these cations, resulting in the change of RAL composition from a pharmaceutically acceptable potassium (K) salt to a biologically relevant Mg complex.
Figure 10.
Probing of ligand interactions with Mg, Mn and K by CSD fragment-based search for the metal-ligand complexes (Chart 2, and scatterplots (a-d). Metal complexes are indicated by bull symbols: red squares (Mg), blue circles (Mn) and orange triangles (K). The RAL crystal structure is shown (f) and the RAL parameters are indicated by asterisks in (a and c).
3.3. Raltegravir recognition by the HIV-1 targets
The published docking studies report located within the active site of either unbound IN or IN•vDNA complex. Distinct poses of RAL representing different RAL configuration and modes of Mg 2+cations chelation were observed [74,82-84].
Our docking calculations of RAL onto each model evidenced that (i) the large binding pocket delimited by the active site and the extended catalytic site loop in the unbound IN can accommodate RAL in distinct configurational/conformational states showing a lack of interaction specificity between inhibitor and target; (ii) the well defined cavity formed by the active site, vDNA and shortened catalytic site loop provides a more optimised RAL binding site where the inhibitor is stabilised by coordination bonds with Mg 2+cations in the Z/Z-configuration (Figure 11).
Additional stabilisation of RAL is provided by non-covalent interactions with the environing residues of IN and the viral DNA bases. Based on our computing data we suggested earlier the stabilizing role of the vDNA in the inhibitors recognition by IN•vDNA pre-integration complex [51]. It was experimentally evidenced that RAL potently binds only when IN is in a binary complex with vDNA [85], possibly binding to a transient intermediate along the integration pathway [86]. Terminal bases of the viral DNA play a role in both catalytic efficiency [87,88] and inhibitor binding [89-91].
It was reported recently that unprocessed viral DNA could be the primary target of RAL [92]. This study is based on the PFV DNA and several oligonucleotides mimicking the HIV-1 DNA probed by experimental and computing techniques.
To explore the role of the HIV-1 viral DNA in RAL recognition we docked RAL onto the non-cleaved and cleaved DNA (the terminal GT nucleotides were removed) [79]. We found that RAL docked onto the non-cleaved vDNA is positioned in the minor groove of the substrate. No stabilising interactions between the partners, RAL and vDNA, were observed. In contrast, in the processed (cleaved) vDNA the Z/Z isomer of RAL takes the place of the remote GT based and is stabilised by strong and specific H-bonds with the unpaired cytosine. These H-bonds characterize the high affinity and specific recognition between RAL and the unpaired cytosine similarly to those observed in the DNA bases pair G-C.
Figure 11.
RAL docking onto the active site of unbound IN, IN•vDNA complex and viral DNA. Proteins and DNA are shown as cartoons; inhibitors as sticks and Mg2+ cations as balls.
Based on the docking results we suggested that the inhibition process may include as a first step the RAL recognition by the processed viral DNA bound to a transient intermediate IN state. RAL coupled to vDNA shows an outside orientation of all oxygen atoms, excellent putative chelating agents of Mg 2+cations, which could facilitate the insertion of RAL into the active site. The conformational flexibility of RAL further allows the accommodation/adaptation of the inhibitor in a relatively large binding pocket of IN•vDNA pre-integration complex thus producing various RAL docked conformation. We believe that such variety of RAL conformations contributing to the alternative enzyme residue recognition may impact the selection of the clinically observed alternative resistance pathways to the drug [29] and references herein.
4. Conclusions and perspectives
The HIV-1 Integrase is an essential retroviral enzyme that covalently binds both ends of linear viral DNA and inserts them into a cellular chromosome. The functions of this enzyme are based on the existence of specific attractive interactions between partner molecules or cofactors ‒ IN, viral DNA and Mg 2+cations. Structure-based drug development seeks to identify and use such interactions to design and optimize the competitive and specific modulator of such functional interactions. Drug design and optimisation process require knowledge about interaction geometries and binding affinity contributing to molecular recognition that can be gleaned from crystallographic and modeling data.
We have resumed the available structural information related to the retroviral integrase. We used this data to generate biologically relevant HIV-1 targets ‒ the unbound IN, the viral DNA (vDNA) and the IN•vDNA complex ‒ which represent with a certain level of reliability, two different enzymatic states of the HIV-1 over the retroviral integration process.
We have characterised the RAL binding, a very flexible molecule displaying the E/Z isomerism, to the active site of its HIV-1 targets which mimic the integrase states before and after the 3’-processing. The docked conformations represent a spectrum of possible conformational/configurational states. The best docking scores and poses confirm that the generated model representing the IN•vDNA complex is the biologically relevant target of RAL, the strand transfer inhibitor. This finding is consistent with well-documented and commonly accepted inhibition mechanism of RAL, based on integral biological, biochemical and structural data.
RAL docking onto the IN•vDNA complex systematically generated the RAL chelated to Mg 2+cations at the active site by the pharmacophore oxygen atoms. The identification of IN residues specifically interacting with RAL is likely a very difficult task and the exact modes of binding of this inhibitor remain a matter of debate. Most probably the flexible nature of RAL results in different conformations and the mode of binding may differ in terms of the interacting residues of the target, which trigger the alternative resistance phenomenon.
The identified RAL binding to the processed viral DNA shed light on a putative, even plausible, step of the RAL inhibition mechanism.
We have implemented dynamic properties to the HIV-1 targets characterisation, particularly, the internal protein collective motions and the global conformational transition. Such transitions play an essential role in the function of many proteins, but experiments do not provide the atomic details on the path followed in going from one end structure to the other. For the dimeric IN, the transition pathway between the unbound and bound to vDNA is not known, which limits information of the cooperative mechanism in this typical allosteric system, where both tertiary and quaternary changes are involved. Description of the IN intermediate conformations open a way to localise the allosteric pockets, which in turn can be selected as the putative binding sites for small molecules in a virtual screening protocol.
Novel drugs, targeted the HIV-1 Integrase, outcome mainly due to the rapid emergence of RAL analogues (for example, GS-9137 or elvitegravir, MK-2048 and S/GSK 1349572, currently under clinical trials [93]). The clinical trials of several RAL analogues (BMS-707035, GSK-364735) were suspended. All these molecules specifically suppress the IN ST reaction. We conceive that the future HIV-1 integrase drug development will be mainly oriented to design of inhibitors with a mechanism of action that differs from that of RAL and its analogues. Distinct conceptions are potentially conceivable: (i) Design of the allosteric inhibitors, able to recognize specifically the binding sites that differ from the IN active site. Inhibitor V-165, belonging to such type inhibitors, prevents IN binding with the viral DNA such blocking 3’-processing reaction [94]. (ii) Design of the protein-protein inhibitors (PPIs) acting on interaction interface between either viral components (the IN monomers upon multimerization process or sub-units of the IN•vDNA complex) [95,96], or between viral and cellular proteins (IN/LEDGF) [97,98]. These alternative strategies represent rational and prospective directions in the HIV-1 integrase drug developement.
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| https://www.intechopen.com/chapters/44028 |
SCET 46 G-2274 G-2200 G-2201 G-2202 G-2203 G-2204 G-2275 G-2205 G-2206 G-2207 G-2276 G-2208 G-2209 G-2210 G-2211 G-2277 G-2212 G-2213 G-2214 G-2215 G-2278 G-2216 G-2217 G-2218 G-2219 G-2279 G-2220 G-2221 G-2222 G-2223 G-2282 G-2231 G-2232 G-2233 G-2234 G-2235 G-2236 G-2280 G-2224 G-2225 G-2226 G-2227 G-2228 G-2229 G-2281 G-2230
DN DN DN DN DN DN DN DN DN DN DN DN DN DN DN DN DN DN DN DN DN DN DN DN DN DN DN DN DN DN DN DN DN DN DN DN DN DN DN DN DN DN DN DN DN DN
%12s %12s %12s %12s %12s %12s %12s %12s %12s %12s %12s %12s %12s %12s %12s %12s %12s %12s %12s %12s %12s %12s %12s %12s %12s %12s %12s %12s %12s %12s %12s %12s %12s %12s %12s %12s %12s %12s %12s %12s %12s %12s %12s %12s %12s %12s
USM4usD0_POS POS_SWEAinSH POS_STATinSH POS_PrTnkSH2 POS_AppDmpSH POS_USM4_L04 USM4usD1_POS POS_SEP1inSH POS_RWA3_SH POS_Batt1iH2 USM4usD2_POS POS_USM4_L08 POS_SEP2inSH POS_NGM_Sw1S POS_NGM_Sw2S USM4usD3_POS POS_TcmTvSH POS_LPW1BmSH POS_LPW2BmSH POS_TWTAbpSH USM4usD4_POS POS_SWIAinSH POS_Cb2367SH POS_PAPU_SH POS_PIA_SH USM4usD5_POS POS_IMU_2 POS_SAibDmSH POS_Tv3456SH POS_IUVSisH2 USM4usLT_POS POS_PF2Act POS_USM4_LT1 POS_USM4_LT2 POS_USM4_LT3 POS_USM4_LT4 POS_USM4_LT5 USM4usLC_POS POS_WTS4pos1 POS_WTS4pos2 POS_RWA4rON POS_RWA4rOFF POS_PrXdcrS POS_USM4_LC5 USM4usHC_POS POS_TWTA_2
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An accurate symplectic calculation of the inboard magnetic footprint from statistical topological noise and field errors in the DIII-D | Request PDF
Request PDF | An accurate symplectic calculation of the inboard magnetic footprint from statistical topological noise and field errors in the DIII-D | Any canonical transformation of Hamiltonian equations is symplectic, and any area-preserving transformation in 2D is a symplectomorphism. Based on... | Find, read and cite all the research you need on ResearchGate
February 2011 Physics of Plasmas 18(2):022509-022509-17
DOI: 10.1063/1.3557893
Authors:
Alkesh Punjabi
Alkesh Punjabi
This person is not on ResearchGate, or hasn't claimed this research yet.
Halima Ali
Hampton University
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Citations (10)
References (32)
Abstract
Any canonical transformation of Hamiltonian equations is symplectic, and any area-preserving transformation in 2D is a symplectomorphism. Based on these, a discrete symplectic map and its continuous symplectic analog are derived for forward magnetic field line trajectories in natural canonical coordinates. The unperturbed axisymmetric Hamiltonian for magnetic field lines is constructed from the experimental data in the DIII-D [
J. L. Luxon and L. E. Davis, Fusion Technol. 8, 441 (1985)
]. The equilibrium Hamiltonian is a highly accurate, analytic, and realistic representation of the magnetic geometry of the DIII-D. These symplectic mathematical maps are used to calculate the magnetic footprint on the inboard collector plate in the DIII-D. Internal statistical topological noise and field errors are irreducible and ubiquitous in magnetic confinement schemes for fusion. It is important to know the stochasticity and magnetic footprint from noise and error fields. The estimates of the spectrum and mode amplitudes of the spatial topological noise and magnetic errors in the DIII-D are used as magnetic perturbation. The discrete and continuous symplectic maps are used to calculate the magnetic footprint on the inboard collector plate of the DIII-D by inverting the natural coordinates to physical coordinates. The combination of highly accurate equilibrium generating function, natural canonical coordinates, symplecticity, and small step-size together gives a very accurate calculation of magnetic footprint. Radial variation of magnetic perturbation and the response of plasma to perturbation are not included. The inboard footprint from noise and errors are dominated by m = 3, n = 1 mode. The footprint is in the form of a toroidally winding helical strip. The width of stochastic layer scales as ½ power of amplitude. The area of footprint scales as first power of amplitude. The physical parameters such as toroidal angle, length, and poloidal angle covered before striking, and the safety factor all have fractal structure. The average field diffusion near the X-point for lines that strike and that do not strike differs by about three to four orders of magnitude. The magnetic footprint gives the maximal bounds on size and heat flux density on collector plate.
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Citations (10) References (32)
... We presume potential applications to several fields of physics such as celestial mechanics [14,23] and plasma physics [24,25], among others. In particular, both the exit basins and the noise play an important role in the magnetic behavior in tokamaks [26][27] [28]
. Other possible applications include chaotic scattering problems in different fields of science, such as medicine [29], biology [30] or chemistry [31,32]. ...
Final state sensitivity in noisy chaotic scattering
Preprint Full-text available
May 2021
Alexandre R. Nieto Jesús M. Seoane
Miguel A F Sanjuán
The unpredictability in chaotic scattering problems is a fundamental topic in physics that has been studied either in purely conservative systems or in the presence of weak perturbations. In many systems noise plays an important role in the dynamical behavior and it models their internal irregularities or their coupling with the environment. In these situations the unpredictability is affected by both the chaotic dynamics and the stochastic fluctuations. In the presence of noise two trajectories with the same initial condition can evolve in different ways and converge to a different asymptotic behavior. For this reason, even the exact knowledge of the initial conditions does not necessarily lead to the predictability of the final state of the system. Hence, the noise can be considered as an important source of unpredictability that cannot be fully understood using the conventional methods of nonlinear dynamics, such as the exit basins and the uncertainty exponent. By adopting a probabilistic point of view, we develop the concepts of probability basin, uncertainty basin and noise-sensitivity exponent, that allow us to carry out both a quantitative and qualitative analysis of the unpredictability on noisy chaotic scattering problems.
View Show abstract
... This field line complex structure is essentially determined by the fractal structure of the homoclinic tangle in chaotic region (Viana et al. 2010). A study of escape patterns using a symplectic approach that represents the magnetic geometry of DIII- D revealed that the fractal dimension of footprints increases with the amplitude of topological noise (Evans 1991) and error fields ( Punjabi and Ali 2011
). Moreover, the radial profiles of connection lengths, poloidal turns before striking the plate, diffusion coefficient of magnetic field lines, and average of safety factor also present self- similarity. ...
Journal of Plasma Physics - Set of wires to simulate tokamaks with poloidal divertor Data Full-text available
Oct 2013
Tiago Kroetz Caroline G. L. Martins
Marisa Roberto Ibere Luiz Caldas
View
Final state sensitivity in noisy chaotic scattering
Article
Sep 2021 CHAOS SOLITON FRACT
Alexandre R. Nieto Jesús M. Seoane
Miguel A F Sanjuán
The unpredictability in chaotic scattering problems is a fundamental topic in physics that has been studied either in purely conservative systems or in the presence of weak perturbations. In many systems noise plays an important role in the dynamical behavior and it models their internal irregularities or their coupling with the environment. In these situations the unpredictability is affected by both the chaotic dynamics and the stochastic fluctuations. In the presence of noise two trajectories with the same initial condition can evolve in different ways and converge to a different asymptotic behavior. For this reason, even the exact knowledge of the initial conditions does not necessarily lead to the predictability of the final state of the system. Hence, the noise can be considered as an important source of unpredictability that cannot be fully understood using the conventional methods of nonlinear dynamics, such as the exit basins and the uncertainty exponent. By adopting a probabilistic point of view, we develop the concepts of probability basin, uncertainty basin and noise-sensitivity exponent, that allow us to carry out both a quantitative and qualitative analysis of the unpredictability on noisy chaotic scattering problems.
View Show abstract
Shaping Diverted Plasmas With Symplectic Maps
Article
Feb 2017 IEEE T PLASMA SCI
Geraldo Roberson Marisa Roberto Ibere Luiz Caldas Ricardo Viana
We construct an area preserving and integrable map to represent magnetic surfaces with triangularity in single-null divertor tokamaks. The magnetic surfaces obtained by the map can assume different asymmetric geometries and the position of X-point, through the choices of values for some free parameters. The safety factor profile is independent of the geometric parameters and can also be chosen arbitrarily. We combine the divertor integrable map with a nonintegrable map that simulates the effect of external magnetostatic perturbations. The application of this methodology permits to obtain the escape patterns of magnetic field lines on the divertor plates.
View Show abstract
Symplectic calculation of magnetic footprints in the DIII-D with low mn and magnetic noise and error fields perturbations Article
Oct 2013 RADIAT EFF DEFECT S
Alkesh Punjabi Halima Ali
The symplectic mathematical maps in natural canonical coordinates for forward and backward integration of magnetic field lines in the DIII-D tokamak [Luxon, J.L.; Davis, L.E. Fusion Technol. 1985, 8, 441] are used to calculate the magnetic footprints and their associated parameters on the inboard and outboard collector plates from the low mn magnetic perturbation with and without internal topological noise and magnetic field errors. The Grad–Shafranov solver equilibrium fit (EFIT) results from the experimental data for the DIII-D shot 115467 at 3000 ms [Lao, L.; St John, H.; Peng, Q.; Ferron, J.; Strait, E.; Taylor, T.; Meyer, W.; Zhang, C.; You, K. Fusion Sci. Technol. 2005, 48, 968] is used to construct an analytic expression for the equilibrium Hamiltonian function for the field line trajectories. The equilibrium Hamiltonian accurately represents the magnetic geometry of the DIII-D. The inboard and outboard footprints consist of a single toroidally winding stripe. Noise and error fields do not change the topology of the footprints, and have a marginal effect on the size of the footprint. Noise and error fields reduce the fraction of poloidal flux connecting the plates, and at the same time enhance the connection length. Noise and error fields reduce the safety factor. Backward trajectories starting close to the X-point have high safety factor. The new approach of symplectic mathematical maps in natural canonical coordinates can give an accurate and realistic picture of footprint reflecting the unique magnetic geometry of device in physical space.
View Show abstract
On collisional diffusion in a stochastic magnetic field
Article Full-text available
Aug 2013
S. S. Abdullaev
The effect of particle collisions on the transport in a stochastic magnetic field in tokamaks is
investigated. The model of resonant magnetic perturbations generated by external coils at the
plasma edge is used for the stochastic magnetic field. The particle collisions are simulated by a
random walk process along the magnetic field lines and the jumps across the field lines at the
collision instants. The dependencies of the local diffusion coefficients on the mean free path \lambda_{mfp},
the diffusion coefficients of field lines D_FL, and the collisional diffusion coefficients, \chi_parallel are
studied. Based on these numerical data and the heuristic arguments, the empirical formula,
Dr= \chi_pert+vjD_FL/(1+Lc/lambda_mfp) for the local diffusion coefficient is proposed, where Lc is the
characteristic length of order of the connection length l_c=pi*qR0, q is the safety factor, R_0 is
the major radius. The formula quite well describes the results of numerical simulations. In
the limiting cases, the formula describes the Rechester-Rosenbluth and Laval scalings.
View Show abstract
Set of wires to simulate tokamaks with poloidal divertor
Article Full-text available
Oct 2013
Tiago Kroetz Caroline G. L. Martins
Marisa Roberto Ibere Luiz Caldas
Simple wire models have been proposed to simulate magnetic configurations in tokamaks. Here we consider electric currents in five parallel infinite wires to obtain double-null magnetic surfaces with specific choices of magnetic axis positions, triangularity, and elongation. As an example, we choose the position and the electric current of each wire to obtain magnetic surfaces similar to those expected in the tokamak international thermonuclear experimental reactor. Moreover, we also integrate the perturbed field line differential equation to simulate chaotic layers near the hyperbolic points and deposition patterns at the divertor plate observed in tokamaks. To simulate that, we add to the model a perturbing error field, due to asymmetries in the tokamak coils, and introduce a random collisional term to the field line mapping to reproduce escape pattern alterations due to particle collisions.
View Show abstract
Divertor map with freedom of geometry and safety factor profile
Article Full-text available
Apr 2012 PLASMA PHYS CONTR F
Tiago Kroetz Marisa Roberto Ibere Luiz Caldas Philip J. Morrison
An explicit, area-preserving and integrable magnetic field line map for a single-null divertor tokamak is obtained using a trajectory integration method to represent equilibrium magnetic surfaces. The magnetic surfaces obtained from the map are capable of fitting different geometries with freely specified position of the X-point, by varying free model parameters. The safety factor profile of the map is independent of the geometric parameters and can also be chosen arbitrarily. The divertor integrable map is composed of a nonintegrable map that simulates the effect of external symmetry-breaking resonances, so as to generate a chaotic region near the separatrix passing through the X-point. The composed field line map is used to analyze escape patterns (the connection length distribution and magnetic footprints on the divertor plate) for two equilibrium configurations with different magnetic shear profiles at the plasma edge. (Some figures may appear in colour only in the online journal)
View Show abstract
Comparison of inboard and outboard magnetic footprints from topological noise and field errors in the DIII-D Article
Oct 2011 RADIAT EFF DEFECT S
Alkesh Punjabi Halima Ali
Any canonical transformation of Hamiltonian equations is symplectic, and any area-preserving transformation in 2D is a symplectomorphism. Based on these, a discrete symplectic map and its continuous symplectic analog are derived for forward magnetic field line trajectories in natural canonical coordinates. The unperturbed axisymmetric Hamiltonian for magnetic field lines is constructed from the experimental data in the DIII-D. The equilibrium Hamiltonian is a highly accurate, analytic, and realistic representation of the magnetic geometry of the DIII-D. These symplectic mathematical maps are used to calculate the trajectories of magnetic field lines in the DIII-D. Internal statistical topological noise and field errors are irreducible and ubiquitous in magnetic confinement schemes for fusion. It is important to know the stochasticity and magnetic footprint from noise and error fields. The estimates of the spectrum and mode amplitudes of the spatial topological noise and magnetic errors in the DIII-D are used as magnetic perturbation. The discrete and continuous symplectic maps are used to calculate the magnetic footprint on the inboard and outboard collector plates of the DIII-D by inverting the natural coordinates to physical coordinates. Radial variation of magnetic perturbation and the response of plasma to perturbation are not included. The footprints are in the form of toroidally winding helical strips. The area of footprint scales linearly with amplitude. The outboard footprint has higher transverse extent, higher area, and higher fractal dimension. The field diffusion near the X-point for backward lines is higher than that for forward lines. Diffusion for lines that strike the plate is about three to four orders of magnitude higher than for lines that do not strike. Line loss and flux loss show a drop when the amplitude of perturbation is about 18–19 × 10−6, indicating the possible presence of a barrier. The physical parameters such as toroidal angle, length, and poloidal angle covered before striking and the safety factor all have a fractal structure.
View Show abstract
Symplectic calculation of the outboard magnetic footprint from noise and error fields in the DIII-D Article
Dec 2011 J PLASMA PHYS
Halima Ali Alkesh Punjabi Ernest M Nyaku
The backward symplectic DIII-D map and continuous symplectic analog of the map for magnetic field line trajectories in the DIII-D [10] (Luxon, J. L. and Davis, L. E. 1985 Fusion Technol. 8, 441) in natural canonical coordinates are used to calculate the magnetic footprint on the outboard collector plate of the DIII-D tokamak from the field errors and internal topological noise. The equilibrium generating function for the DIII-D used in the map very accurately represents the magnetic geometry of the DIII-D. The step-size of the map is kept considerably small so that the magnetic perturbation added from symplectic discretization of the Hamiltonian equations of the magnetic field line trajectories is very small. The natural canonical coordinates allow inverting to the real physical space. The combination of highly accurate equilibrium generating function, natural canonical coordinates, symplecticity, and small step-size then together gives a very accurate calculation of magnetic footprint. Radial variation of magnetic perturbation and the response of plasma to perturbation are not included. The footprint is in the form of toroidally winding helical strips. The area of footprint scales as 1st power of amplitude. The physical parameters as toroidal angle, length, and poloidal angle covered before striking, and the safety factor all have fractal structure. The average field diffusion near X-point for lines that strike and that do not strike differs by about four orders of magnitude. The flux loss decreases for high values of amplitude of perturbation.
View Show abstract
Symplectic integrators for Hamiltonian problems: An overview Article Full-text available Jan 1992 J. M. Sanz-Serna In the sciences, situations where dissipation is not significant may invariably be modelled by Hamiltonian systems of ordinary, or partial, differential equations. Symplectic integrators are numerical methods specifically aimed at advancing in time the solution of Hamiltonian systems. Roughly speaking, ‘symplecticness’ is a characteristic property possessed by the solutions of Hamiltonian problems. A numerical method is called symplectic if, when applied to Hamiltonian problems, it generates numerical solutions which inherit the property of symplecticness. View Show abstract Experimental signatures of homoclinic tangles in poloidally diverted tokamaks Article Full-text available Apr 2005 J Phys Conf T. E. Evans Roland Roeder J. A. Carter C. J. Lasnier Small non-axisymmetric perturbations of poloidally diverted tokamaks create edge stochastic magnetic field lines that connect to material surfaces such as those in the divertors. Separatrix structure calculations show that the distribution of stochastic field lines on the vessel walls is closely related to the topology of homoclinic tangles formed in the perturbed system. Since these tangles prescribe how the stochastic fields are organized, they are of significant practical interest in tokamak experiments. Experimental measurements of heat and particle distributions on plasma facing surfaces sometimes show split peak patterns that are consistent with the presence of stochasticity and homoclinic tangles. These split peaks are often observed during locked modes and other types of edge instabilities. They are also observed when perturbation fields from magnetohydrodynamic control coils are pulsed during a plasma discharge. Numerical modeling of the perturbation field from these control coils shows that the homoclinic tangle produced by a coil pulse is not always large enough to produce the splitting patterns observed. Nevertheless, there is a clear correlation between the coil pulses and the appearance of the split profiles. These results suggest the presence of the plasma amplification mechanism that enhances the size of the non-resonant homoclinic tangles. View Show abstract Edge stability and transport control with resonant magnetic perturbations in collisionless tokamak plasmas Article Full-text available Jun 2006 T. E. Evans R. A. Moyer K. H. Burrell William P. West A critical issue for fusion plasma research is the erosion of the first wall of the experimental device due to impulsive heating from repetitive edge magneto-hydrodynamic (MHD) instabilities known as 'edge-localized modes' (ELMs). Here, we show that the addition of small resonant magnetic field perturbations completely eliminates ELMs while maintaining a steady-state high-confinement (H-mode) plasma. These perturbations induce a chaotic behavior in the magnetic field lines, which reduces the edge pressure gradient below the ELM instability threshold. The pressure gradient reduction results from a reduction in particle content of the plasma, rather than an increase in the electron thermal transport. This is inconsistent with the predictions of stochastic electron heat transport theory. These results provide a first experimental test of stochastic transport theory in a highly rotating, hot, collisionless plasma and demonstrate a promising solution to the critical issue of controlling edge instabilities in fusion plasma devices. View Show abstract Suppression of Large Edge-Localized Modes in High-Confinement DIII-D Plasmas with a Stochastic Magnetic Boundary Article Full-text available Jul 2004 T. E. Evans R. A. Moyer P.R. Thomas Lunwu Zeng A stochastic magnetic boundary, produced by an applied edge resonant magnetic perturbation, is used to suppress most large edge-localized modes (ELMs) in high confinement (H-mode) plasmas. The resulting H mode displays rapid, small oscillations with a bursty character modulated by a coherent 130 Hz envelope. The H mode transport barrier and core confinement are unaffected by the stochastic boundary, despite a threefold drop in the toroidal rotation. These results demonstrate that stochastic boundaries are compatible with H modes and may be attractive for ELM control in next-step fusion tokamaks. View Show abstract Big Dee - A Flexible Facility Operating Near Breakeven Conditions Article Jul 1985 J.L. Luxon L. G. Davis The Doublet III tokamak facility is presently undergoing an upgrade to Big Dee, a device projected to be capable of producing plasmas with parameters approaching breakeven conditions, albeit in hydrogen plasmas. The goal of the upgrade has been to develop a facility capable of studying confinement and beta in non-circular discharges at parameters near breakeven conditions while maintaining the flexibility and accessibility necessary to allow a wide range of problems to be addressed. The upgrade replaces the vacuum vessel and outermost plasma shaping coils allowing higher plasma currents and improved access. View Show abstract MHD Equilibrium Reconstruction in the DIII-D Tokamak Article Oct 2005 FUSION SCI TECHNOL Lalida Lao H. E. St. John Qihao Peng J. R. Ferron Physics elements and advances crucial for the development of axisymmetric magnetohydrodynamic equilibrium reconstruction to support plasma operation and data analysis in the DIII-D tokamak are reviewed. A response function formalism and a Picard linearization scheme are used to efficiently combine the equilibrium and the fitting iterations and search for the optimum solution vector. Algorithms to incorporate internal current and pressure profile measurements, topological constraints, and toroidal plasma rotation into the equilibrium reconstruction are described. Choice of basis functions and boundary conditions essential for accurate reconstruction of L- and H-mode equilibrium plasma boundary and current and pressure profiles is discussed. The computational structure used to efficiently integrate these elements into the equilibrium reconstruction code EFIT is summarized. View Show abstract The local structure of Poisson manifolds Article Sep 1983 J DIFFER GEOM Alan Weinstein Varietes de Poisson et applications. Decomposition. Structures de Poisson lineaires. Approximation lineaire. Systemes hamiltoniens. Le probleme de linearisation. Groupes de fonction, realisations et applications impulsion. Paires duales et groupes de jauge. Existence des realisations. Unicite des realisations. Les problemes des 3 corps restreints et autres exemples View Show abstract Evaluation of the structure of ergodic fields Article May 1983 Allen H Boozer A method of analyzing ergodic magnetic fields is given, including a generalization of magnetic coordinates to such fields. The results of this analysis can be used in existing Monte Carlo codes to assess the enhanced transport associated with imperfect surfaces. The Hamiltonian for a general magnetic field is given as part of this analysis. View Show abstract Derivation of the dipole map Article Sep 2004 Halima Ali Alkesh Punjabi Allen H Boozer In our method of maps [Punjabi et al., Phy. Rev. Lett. 69, 3322 (1992), and Punjabi et al., J. Plasma Phys. 52, 91 (1994)], symplectic maps are used to calculate the trajectories of magnetic field lines in divertor tokamaks. Effects of the magnetic perturbations are calculated using the low MN map [Ali et al., Phys. Plasmas 11, 1908 (2004)] and the dipole map [Punjabi et al., Phys. Plasmas 10, 3992 (2003)]. The dipole map is used to calculate the effects of externally located current carrying coils on the trajectories of the field lines, the stochastic layer, the magnetic footprint, and the heat load distribution on the collector plates in divertor tokamaks [Punjabi et al., Phys. Plasmas 10, 3992 (2003)]. Symplectic maps are general, efficient, and preserve and respect the Hamiltonian nature of the dynamics. In this brief communication, a rigorous mathematical derivation of the dipole map is given. View Show abstract Symplectic maps, variational principles, and transport Article Jul 1992 James Meiss Symplectic maps are the discrete-time analog of Hamiltonian motion. They arise in many applications including accelerator, chemical, condensed-matter, plasma, and fluid physics. Twist maps correspond to Hamiltonians for which the velocity is a monotonic function of the canonical momentum. Twist maps have a Lagrangian variational formulation. One-parameter families of twist maps typically exhibit the full range of possible dynamics-from simple or integrable motion to complex or chaotic motion. One class of orbits, the minimizing orbits, can be found throughout this transition; the properties of the minimizing orbits are discussed in detail. Among these orbits are the periodic and quasiperiodic orbits, which form a scaffold in the phase space and constrain the motion of the remaining orbits. The theory of transport deals with the motion of ensembles of trajectories. The variational principle provides an efficient technique for computing the flux escaping from regions bounded by partial barriers formed from minimizing orbits. Unsolved problems in the theory of transport include the explanation for algebraic tails in correlation functions, and its extension to maps of more than two dimensions. View Show abstract Stochastic layer scaling in the two-wire model for divertor tokamaks Article Jun 2008 Halima Ali Alkesh Punjabi Allen H Boozer The question of magnetic field structure in the vicinity of the separatrix in divertor tokamaks is studied. The authors have investigated this problem earlier in a series of papers, using various mathematical techniques. In the present paper, the two-wire model (TWM) [Reiman, A. 1996 Phys. Plasmas 3, 906] is considered. It is noted that, in the TWM, it is useful to consider an extra equation expressing magnetic flux conservation. This equation does not add any more information to the TWM, since the equation is derived from the TWM. This equation is useful for controlling the step size in the numerical integration of the TWM equations. The TWM with the extra equation is called the flux-preserving TWM. Nevertheless, the technique is apparently still plagued by numerical inaccuracies when the perturbation level is low, resulting in an incorrect scaling of the stochastic layer width. The stochastic broadening of the separatrix in the flux-preserving TWM is compared with that in the low mn (poloidal mode number m and toroidal mode number n) map (LMN) [Ali, H., Punjabi, A., Boozer, A. and Evans, T. 2004 Phys. Plasmas 11, 1908]. The flux-preserving TWM and LMN both give Boozer–Rechester 0.5 power scaling of the stochastic layer width with the amplitude of magnetic perturbation when the perturbation is sufficiently large [Boozer, A. and Rechester, A. 1978, Phys. Fluids 21, 682]. The flux-preserving TWM gives a larger stochastic layer width when the perturbation is low, while the LMN gives correct scaling in the low perturbation region. Area-preserving maps such as the LMN respect the Hamiltonian structure of field line trajectories, and have the added advantage of computational efficiency. Also, for a degree of freedom Hamiltonian system such as field lines, maps do not give Arnold diffusion. View Show abstract Effect of magnetic perturbations on divertor scrape-off width Article Apr 1978 Allen H Boozer A. B. Rechester A general method is developed for calculating the width, due to magnetic perturbations, of the scrape‐off layer of a tokamak with a divertor. The method, which assumes the plasma particles are tied to the field lines, should provide a good estimate provided the predicted width is large compared to that given by particle diffusion or finite particle drift orbit effects. The general theory is applied to a simple analytic model of a divertor to indicate the expected magnitude of the scrape‐off layer thickness. View Show abstract Symmetric simple map for a single-null divertor tokamak Article Feb 1997 Alkesh Punjabi Halima Ali Allen H Boozer A new map called the symmetric simple map is introduced to represent the chaotic trajectories of magnetic field lines in the scrape-off layer of a single-null divertor tokamak. Good surfaces of this map are very nearly axisymmetric. Therefore it gives a far better representation of the magnetic topology of a single-null divertor tokamak. The map is investigated in detail and used to analyze the generic features of the field line trajectories and their footprint on the divertor plate. The map is employed to calculate the variations in the fraction of magnetic flux from the stochastic layer diverted onto plate, in the footprint and in related parameters as the map parameter is varied. The Lyapunov exponents and the field diffusion coefficients are calculated. The low mode number map and the dipole map are introduced to include the effects of low and high mode number perturbations in the new map. View Show abstract The symmetric quartic map for trajectories of magnetic field lines in elongated divertor tokamak plasmas Article Apr 2009 Morgin Jones Hasina Wadi Halima Ali Alkesh Punjabi The coordinates of the area-preserving map equations for integration of magnetic field line trajectories in divertor tokamaks can be any coordinates for which a transformation to (ψt,θ,φ) coordinates exists [
A. Punjabi, H. Ali, T. Evans, and A. Boozer, Phys. Lett. A 364, 140 (2007)
]. ψt is toroidal magnetic flux, θ is poloidal angle, and φ is toroidal angle. This freedom is exploited to construct the symmetric quartic map such that the only parameter that determines magnetic geometry is the elongation of the separatrix surface. The poloidal flux inside the separatrix, the safety factor as a function of normalized minor radius, and the magnetic perturbation from the symplectic discretization are all held constant, and only the elongation is κ varied. The width of stochastic layer, the area, and the fractal dimension of the magnetic footprint and the average radial diffusion coefficient of magnetic field lines from the stochastic layer; and how these quantities scale with κ is calculated. The symmetric quartic map gives the correct scalings which are consistent with the scalings of coordinates with κ. The effects of m = 1, n = ±1 internal perturbation with the amplitude that is expected to occur in tokamaks are calculated by adding a term [
H. Ali, A. Punjabi, A. H. Boozer, and T. Evans, Phys. Plasmas 11, 1908 (2004)
] to the symmetric quartic map. In this case, the width of stochastic layer scales as 0.35 power of κ. The area of the footprint is roughly constant. The average radial diffusion coefficient of field lines near the X-point scales linearly with κ. The low mn perturbation changes the quasisymmetric structure of the footprint, and reorganizes it into a single, large scale, asymmetric structure. The symmetric quartic map is combined with the dipole map [
A. Punjabi, H. Ali, and A. H. Boozer, Phys. Plasmas 10, 3992 (2003)
] to calculate the effects of magnetic perturbation from a current carrying coil. The coil position and coil current coil are constant. The dipole perturbation enhances the magnetic shear. The width of the stochastic layer scales exponentially with κ. The area of the footprint decreases as the κ increases. The radial diffusion coefficient of field lines scales exponentially with κ. The dipole perturbation changes the topology of the footprint. It breaks up the toroidally spiraling footprint into a number of separate asymmetric toroidal strips. Practical applications of the symmetric quartic map to elongated divertor tokamak plasmas are suggested. View Show abstract Effects of dipole perturbation on the stochastic layer and magnetic footprint in single-null divertor tokamaks Article Oct 2003 Alkesh Punjabi Halima Ali Allen H Boozer In this paper, the method of maps is used to calculate the effects of high toroidal and poloidal mode number perturbation on the trajectories of magnetic field lines in a single-null divertor tokamak. First, a simplified derivation of the dipole map from the Hamiltonian mechanics of magnetic field is given. This map represents the effects of an externally located current carrying coil on the motion of field lines. The unperturbed magnetic field topology of a single-null divertor tokamak is represented by the symmetric simple map. The coil is placed across from the X-point on the line joining the X-point and the O-point at a fixed distance from the last good confining surface. The effects of coil on the stochastic layer and magnetic footprint are calculated using the symmetric simple map and the dipole map. Self-similarities, singularities, and topological equivalences in the pattern of physical parameters are found that characterize the stochastic layer and the magnetic footprint. The dipole perturbation increases the area of footprint, drastically reduces the fraction of heat flux escaping the stochastic layer, disperses the heat flux more evenly over a wider area, and reduces number of hotspots on the collector plate. © 2003 American Institute of Physics. View Show abstract Simple map in action-angle coordinates Article Jul 2008 Olivia Kerwin Alkesh Punjabi Halima Ali A simple map [
A. Punjabi, A. Verma, and A. Boozer, Phys. Rev. Lett. 69, 3322 (1992)
] is the simplest map that has the topology of divertor tokamaks [
A. Punjabi, H. Ali, T. Evans, and A. Boozer, Phys. Lett. A 364, 140 (2007)
]. Here, action-angle coordinates, the safety factor, and the equilibrium generating function for the simple map are calculated analytically. The simple map in action-angle coordinates is derived from canonical transformations. This map cannot be integrated across the separatrix surface because of the singularity in the safety factor there. The stochastic broadening of the ideal separatrix surface in action-angle representation is calculated by adding a perturbation to the simple map equilibrium generating function. This perturbation represents the spatial noise and field errors typical of the DIII-D [
J. L. Luxon and L. E. Davis, Fusion Technol. 8, 441 (1985)
] tokamak. The stationary Fourier modes of the perturbation have poloidal and toroidal mode numbers (m,n,) = {(3,1),(4,1),(6,2),(7,2),(8,2),(9,3),(10,3),(11,3)} with amplitude δ = 0.8×10−5. Near the X-point, about 0.12% of toroidal magnetic flux inside the separatrix, and about 0.06% of the poloidal flux inside the separatrix is lost. When the distance from the O-point to the X-point is 1 m, the width of stochastic layer near the X-point is about 1.4 cm. The average value of the action on the last good surface is 0.19072 compared to the action value of 3/5π on the separatrix. The average width of stochastic layer in action coordinate is 2.7×10−4, while the average area of the stochastic layer in action-angle phase space is 1.69017×10−3. On average, about 0.14% of action or toroidal flux inside the ideal separatrix is lost due to broadening. Roughly five times more toroidal flux is lost in the simple map than in DIII-D for the same perturbation [
A. Punjabi, H. Ali, A. Boozer, and T. Evans, Bull. Amer. Phys. Soc. 52, 124 (2007)
]. View Show abstract Symplectic approach to calculation of magnetic field line trajectories in physical space with realistic magnetic geometry in divertor tokamaks Article Dec 2008 Alkesh Punjabi Halima Ali A new approach to integration of magnetic field lines in divertor tokamaks is proposed. In this approach, an analytic equilibrium generating function (EGF) is constructed in natural canonical coordinates (ψ,θ) from experimental data from a Grad–Shafranov equilibrium solver for a tokamak. ψ is the toroidal magnetic flux and θ is the poloidal angle. Natural canonical coordinates (ψ,θ,φ) can be transformed to physical position (R,Z,φ) using a canonical transformation. (R,Z,φ) are cylindrical coordinates. Another canonical transformation is used to construct a symplectic map for integration of magnetic field lines. Trajectories of field lines calculated from this symplectic map in natural canonical coordinates can be transformed to trajectories in real physical space. Unlike in magnetic coordinates [
O. Kerwin, A. Punjabi, and H. Ali, Phys. Plasmas 15, 072504 (2008)
], the symplectic map in natural canonical coordinates can integrate trajectories across the separatrix surface, and at the same time, give trajectories in physical space. Unlike symplectic maps in physical coordinates (x,y) or (R,Z), the continuous analog of a symplectic map in natural canonical coordinates does not distort trajectories in toroidal planes intervening the discrete map. This approach is applied to the DIII-D tokamak [
J. L. Luxon and L. E. Davis, Fusion Technol. 8, 441 (1985)
]. The EGF for the DIII-D gives quite an accurate representation of equilibrium magnetic surfaces close to the separatrix surface. This new approach is applied to demonstrate the sensitivity of stochastic broadening using a set of perturbations that generically approximate the size of the field errors and statistical topological noise expected in a poloidally diverted tokamak. Plans for future application of this approach are discussed. View Show abstract The low MN map for single-null divertor tokamaks Article Apr 2004 Halima Ali Alkesh Punjabi Allen H Boozer T. E. Evans The low MN map is derived from the general theory of maps and the generating function for the low mn perturbation. The unperturbed magnetic topology of a single-null divertor tokamak is represented by the symmetric simple map. The perturbed topology is represented by the low MN map. The method of maps is applied to calculate the effects of low mn perturbation on the stochastic layer and the magnetic footprint. The low mn perturbation organizes the stochastic layer into large scale spatial structures. This is reflected in the phase portraits, safety factor, Liapunov exponents, magnetic footprints, and the semiconnection length. For the expected range of the amplitude of the low mn perturbation, the fraction of magnetic flux escaping the stochastic layer, the width of stochastic layer, the area of the magnetic footprints increase, while the number of hot spots and the fraction of flux going into the hot spots both decrease. The key features of the complex patterns in the heat deposition on the collector plates in divertor tokamaks are quite well recovered from the results of the low MN map. © 2004 American Institute of Physics. View Show abstract Physics of magnetically confined plasmas Article Jan 2005 Allen H Boozer The physics of magnetically confined plasmas has had much of its development as part of the program to develop fusion energy and is an important element in the study of space and astrophysical plasmas. Closely related areas of physics include Hamiltonian dynamics, kinetic theory, and fluid turbulence. A number of topics in physics have been developed primarily through research on magnetically confined plasmas. The physics that underlies the magnetic confinement of plasmas is reviewed here to make it more accessible to those beginning research on plasma confinement and for interested physicists. View Show abstract Noble magnetic barriers in the ASDEX UG tokamak Article Feb 2010 RADIAT EFF DEFECT S Halima Ali Alkesh Punjabi Justin Vazquez The second-order perturbation method of creating invariant tori inside chaos in Hamiltonian systems (Ali, H.; Punjabi, A. Plasma Phys. Contr. F. 2007, 49, 1565–1582) is applied to the axially symmetric divertor experiment upgrade (ASDEX UG) tokamak to build noble irrational magnetic barriers inside chaos created by resonant magnetic perturbations (m, n)=(3, 2)+(4, 3), with m and n the poloidal and toroidal mode numbers of the Fourier expansion of the magnetic perturbation. The radial dependence of the Fourier modes is ignored. The modes are considered to be locked and have the same amplitude δ. A symplectic mathematical mapping in magnetic coordinates is used to integrate magnetic field line trajectories in the ASDEX UG. Tori with noble irrational rotational transform are the last ones to be destroyed by perturbation in Hamiltonian systems. For this reason, noble irrational magnetic barriers are built inside chaos, and the strongest noble irrational barrier is identified. Three candidate locations for the strongest noble barrier in ASDEX UG are selected. All three candidate locations are chosen to be roughly midway between the resonant rational surfaces ψ32 and ψ43. ψ is the magnetic coordinate of the flux surface. The three candidate surfaces are the noble irrational surfaces close to the surface with q value that is a mediant of q=3/2 and 4/3, q value of the physical midpoint of the two resonant surfaces, and the q value of the surface where the islands of the two perturbing modes just overlap. These q values of the candidate surfaces are denoted by q MED, q MID, and q OVERLAP. The strongest noble barrier close to q MED has the continued fraction representation (CFR) [1;2,2,1∞] and exists for δ≤2.6599×10−4; the strongest noble barrier close to q MID has CFR [1;2,2,2,1∞] and exists for δ≤4.6311×10−4; and the strongest noble barrier close to q OVERLAP has CFR [1;2,2,6,2,1∞] and exists for δ≤1.367770×10−4. From these results, the strongest noble barrier is found to be close to the surface that is located physically exactly in the middle of the two resonant surfaces. View Show abstract The simple map for a single-null divertor tokamak Article Dec 1996 J PLASMA PHYS Alkes Punjabi Arun Verma Allen H Boozer We present the simple map for a single-null divertor tokamak. The simple map is an area-preserving map based on the idea that magnetic field lines are a single-degree- of-freedom time-dependent Hamiltonian system, and that the basic features of such systems near the X-point are generic. We obtain the properties of this map and the resulting footprints of field lines on the divertor plate. These include the width of the stochastic layer, the edge safety factor, the area of the footprint and the amount of magnetic flux diverted. We give the safety factor profile, the average and median values of strike angles, lengths and the Liapunov exponents. We describe how the effects of magnetic perturbations can be included in the simple map. We show how the map can be applied to the problem of the determination of heat flux on the divertor plate in tokamaks. View Show abstract Tokamak Divertor Maps Article Aug 1994 J PLASMA PHYS Alkesh Punjabi Arun Verma Allen H Boozer A mapping method is developed to investigate the problem of determination and control of heat-deposition patterns on the plates of a tokamak divertor. The deposition pattern is largely determined by the magnetic field lines, which are mathematically equivalent to the trajectories of a single-degree-of-freedom time-dependent Hamiltonian system. Maps are natural tools to study the generic features of such systems. The general theory of maps is presented, and methods for incorporating various features of the magnetic field and particle motion in divertor tokamaks are given. Features of the magnetic field include the profile of the rotational transform, single- versus double-null divertor, reverse map, the effects of naturally occurring low M and N, and externally imposed high-M, high-N perturbations. Particle motion includes radial diffusion, pitch angle and energy scattering, and the electric sheath at the plate. The method is illustrated by calculating the stochastic broadening in a single- null divertor tokamak. Maps provide an efficient, economic and elegant method to study the problem of motion of plasma particles in the stochastic scrape-off layer. View Show abstract Scaling results for the magnetic field line trajectories in the stochastic layer near the separatrix in divertor tokamaks with high magnetic shear using the higher shear map Article May 2009 Alkesh Punjabi Halima Ali Hamidullah Farhat Extra terms are added to the generating function of the simple map (Punjabi et al 1992 Phys. Rev. Lett. 69 3322) to adjust shear of magnetic field lines in divertor tokamaks. From this new generating function, a higher shear map is derived from a canonical transformation. A continuous analog of the higher shear map is also derived. The method of maps (Punjabi et al 1994 J. Plasma Phys. 52 91) is used to calculate the average shear, stochastic broadening of the ideal separatrix near the X-point in the principal plane of the tokamak, loss of poloidal magnetic flux from inside the ideal separatrix, magnetic footprint on the collector plate, and its area, and the radial diffusion coefficient of magnetic field lines near the X-point. It is found that the width of the stochastic layer near the X-point and the loss of poloidal flux from inside the ideal separatrix scale linearly with average shear. The area of magnetic footprints scales roughly linearly with average shear. Linear scaling of the area is quite good when the average shear is greater than or equal to 1.25. When the average shear is in the range 1.1–1.25, the area of the footprint fluctuates (as a function of average shear) and scales faster than linear scaling. Radial diffusion of field lines near the X-point increases very rapidly by about four orders of magnitude as average shear increases from about 1.15 to 1.5. For higher values of average shear, diffusion increases linearly, and comparatively very slowly. The very slow scaling of the radial diffusion of the field can flatten the plasma pressure gradient near the separatrix, and lead to the elimination of type-I edge localized modes. View Show abstract An area-preserving mapping in natural canonical coordinates for magnetic field line trajectories in the DIII-D tokamak Article Sep 2009 Alkesh Punjabi The new approach of integrating magnetic field line trajectories in natural canonical coordinates (Punjabi and Ali 2008 Phys. Plasmas 15 122502) in divertor tokamaks is used for the DIII-D tokamak (Luxon and Davis1985 Fusion Technol. 8 441). The equilibrium EFIT data (Evans et al 2004 Phys. Rev. Lett. 92 235003, Lao et al 2005 Fusion Sci. Technol. 48 968) for the DIII-D tokamak shot 115467 at 3000 ms is used to construct the equilibrium generating function (EGF) for the DIII-D in natural canonical coordinates. The EGF gives quite an accurate representation of the closed and open equilibrium magnetic surfaces near the separatrix, the separatrix, the position of the X-point and the poloidal magnetic flux inside the ideal separatrix in the DIII-D. The equilibrium safety factor q from the EGF is somewhat smaller than the DIII-D EFIT q profile. The equilibrium safety factor is calculated from EGF as described in the previous paper (Punjabi and Ali 2008 Phys. Plasmas 15 122502). Here the safety factor for the open surfaces in the DIII-D is calculated. A canonical transformation is used to construct a symplectic mapping for magnetic field line trajectories in the DIII-D in natural canonical coordinates. The map is explored in more detail in this work, and is used to calculate field line trajectories in the DIII-D tokamak. The continuous analogue of the map does not distort the DIII-D magnetic surfaces in different toroidal planes between successive iterations of the map. The map parameter k can represent effects of magnetic asymmetries in the DIII-D. These effects in the DIII-D are illustrated. The DIII-D map is then used to calculate stochastic broadening of the ideal separatrix from the topological noise and field errors, the low mn, the high mn and peeling–ballooning magnetic perturbations in the DIII-D. The width of the stochastic layer scales as 1/2 power of amplitude with a maximum deviation of 6% from the Boozer–Rechester scaling (Boozer and Rechester 1978 Phys. Fluids 21 682). The loss of poloidal flux scales linearly with the amplitude of perturbation with a maximum deviation of 10% from linearity. Perturbations with higher mode numbers result in higher stochasticity. The higher the complexity and coupling in the equilibrium magnetic geometry, the closer is the scaling to the Boozer–Rechester scaling of width. The comparison of the EGF for the simple map (Punjabi et al 1992 Phys. Rev. Lett. 69 3322) with that of the DIII-D shows that the more complex the magnetic geometry and the more coupling of modes in equilibrium, the more robust or resilient is the system against the chaos-inducing, symmetry-breaking perturbations. View Show abstract Anomalies in the applied magnetic fields in DIII-D and their implications for the understanding of stability experiments Article Dec 2003 J.L. Luxon Michael Schaffer G. L. Jackson E. J. Strait Small non-axisymmetric magnetic fields are known to cause serious loss of stability in tokamaks, leading to loss of confinement and abrupt termination of plasma current (disruptions). The best known examples are the locked mode and the resistive wall mode. Understanding of the underlying field anomalies (departures in the hardware-related fields from ideal toroidal and poloidal fields on a single axis) and the interaction of the plasma with them is crucial to tokamak development. Results of both locked mode experiments (Scoville J.T. and La Haye R.J. 2003 Nucl. Fusion 43 250) and resistive wall mode experiments (Garofalo A.M., La Haye R.J. and Scoville J.T. 2002 Nucl. Fusion 42 1335) done in DIII-D tokamak plasmas have been interpreted to indicate the presence of a significant anomalous field. New measurements of the magnetic field anomalies of the hardware systems have been made in DIII-D. The measured field anomalies due to the plasma shaping coils in DIII-D are smaller than previously reported (La Haye R.J. and Scoville J.T. 1991 Rev. Sci. Instrum. 61 2146). Additional evaluations of systematic errors have been made. New measurements of the anomalous fields of the Ohmic heating and toroidal coils have been added. Such detailed in situ measurements of the fields of a tokamak are unique. The anomalous fields from all the coils are one-third the values indicated from the stability experiments (Garofalo et al 2002, Scoville and La Haye 2003). These results indicate limitations in the understanding of the interaction of the plasma with the external field. They indicate that it may not be possible to deduce the anomalous fields in a tokamak from plasma experiments and that we may not have the basis needed to project the error field requirements of future tokamaks. View Show abstract Mathematics and Maxwell's equations Article Nov 2010 Allen H Boozer The universality of mathematics and Maxwell's equations is not shared by specific plasma models. Computations become more reliable, efficient and transparent if specific plasma models are used to obtain only the information that would otherwise be missing. Constraints of high universality, such as those from mathematics and Maxwell's equations, can be obscured or lost by integrated computations. Recognition of subtle constraints of high universality is important for (1) focusing the design of control systems for magnetic field errors in tokamaks from perturbations that have little effect on the plasma to those that do, (2) clarifying the limits of applicability to astrophysics of computations of magnetic reconnection in fields that have a double periodicity or have
on a surface, as in a Harris sheet. Both require a degree of symmetry not expected in natural systems. Mathematics and Maxwell's equations imply that neighboring magnetic field lines characteristically separate exponentially with distance along a line. This remarkably universal phenomenon has been largely ignored, though it defines a trigger for reconnection through a critical magnitude of exponentiation. These and other examples of the importance of making distinctions and understanding constraints of high universality are explained. View Show abstract Effect of magnetic perturbations on tokamak divertors Article Apr 2007 PHYS LETT A Alkesh Punjabi Halima Ali T. E. Evans Allen H Boozer The magnetic footprint on collector plates in a tokamak divertor is heavily constrained by the field lines obeying the equations of degree of freedom Hamiltonian mechanics. In a tokamak with broken axisymmetry, the last toroidal surface on which all field lines are confined encloses less toroidal flux than the ideal axisymmetric separatrix. The location of this surface is determined by the amplitude of the perturbations that resonate with the safety factor, q. Near a separatrix, such as that of a tokamak divertor, q has a logarithmic singularity as a function of the enclosed toroidal flux. The resonant perturbations produce islands in the field line trajectories that must overlap to fundamentally change the properties of the field line trajectories by making the field lines ergodically cover a volume. The qualitative features of the strike points of the file lines are determined by the mode numbers of the resonant perturbations. With low mode numbers a few large islands control the break up of the magnetic surfaces and the strike points lie within far sharper lines than when high mode numbers cause the break up. These features are studied using area preserving maps and the results are applied to the DIII-D divertor as an example. View Show abstract Noncanonical Hamiltonian mechanics and its application to magnetic field line flow Article Nov 1983 John R. Cary Robert G. Littlejohn A noncanonical Hamiltonian theory of dynamical systems is presented and applied to magnetic field line flow. The theory allows all of the theorems of Hamiltonian mechanics (most importantly, Noether's theorem, relating symmetries and invariants) to be applied to the magnetic field line system. The theory is not restricted to any particular geometry. An elementary derivation of noncanonical Hamiltonian perturbation theory, based on Lie transforms, is also presented. As an example, the perturbation theory is applied to magnetic field line flow in nearly azimuthally symmetric geometry. Other applications are to the adiabatic motion of charged particles. View Show abstract Symplectic Integration of Hamiltonian Systems Article May 1990 Paul J. Channell Clint Scovel The authors survey past work and present new algorithms to numerically integrate the trajectories of Hamiltonian dynamical systems. These algorithms exactly preserve the symplectic 2-form, i.e. they preserve all the Poincare invariants. The algorithms have been tested on a variety of examples and results are presented for the Fermi-Pasta-Ulam nonlinear string, the Henon-Heiles system, a four-vortex problem, and the geodesic flow on a manifold of constant negative curvature. In all cases the algorithms possess long-time stability and preserve global geometrical structures in phase space. View Show abstract Foundations of Mechanics, Second Edition Article Jan 1978 Ralph Abraham Jerrold E. Marsden Preface to the Second Edition
Since the first edition of this book appeared in 1967, there has been a great deal of activity in the field of symplectic geometry and Hamiltonian systems. In addition to the recent textbooks of Arnold, Arnold-Avez, Godbillon, Guillemin-Sternberg, Siegel-Moser, and Souriau, there have been many research articles published. Two good collections are "Symposia Mathematica," vol. XIV, and "Géométrie Symplectique el Physique Mathématique," CNRS, Colloque Internationaux, no. 237. There are also important survey articles, such as Weinstein [1977b]. The text and bibliography contain many of the important new references we are aware of. We have continued to find the classic works, especially Whittaker [1959], invaluable.
The basic audience for the book remains the same: mathematicians, physicists, and engineers interested in geometrical methods in mechanics, assuming a background in calculus, linear algebra, some classical analysis, and point set topology. We include most of the basic results in manifold theory, as well as some key facts from point set topology and Lie group theory. Other things used without proof are clearly noted.
We have updated the material on symmetry groups and qualitative theory, added new sections on the rigid body, topology and mechanics, and quantization, and other topics, and have made numerous corrections and additions. In fact, some of the results in this edition are new.
We have made two major changes in notation: we now use f^* for pull-back (the first edition used f[sub]*), in accordance with standard usage, and have adopted the "Bourbaki" convention for wedge product. The latter eliminates many annoying factors of 2.
A. N. Kolmogorov's address at the 1954 International Congress of Mathematicians marked an important historical point in the development of the theory, and is reproduced as an appendix. The work of Kolmogorov, Arnold, and Moser and its application to Laplace's question of stability of the solar system remains one of the goals of the exposition. For complete details of all tbe theorems needed in this direction, outside references will have to be consulted, such as Siegel-Moser [1971] and Moser [1973a].
We are pleased to acknowledge valuable assistance from Paul Chernoff, Wlodek Tulczyjew, Morris Hirsh, Alan Weinstein, and our invaluable assistant authors, Richard Cushman and Tudor Ratiu, who all contributed some of their original material for incorporation into the text.
Also, we are grateful to Ethan Akin, Kentaro Mikami, Judy Arms, Harold Naparst, Michael Buchner, Ed Nelson, Robert Cahn, Sheldon Newhouse, Emil Chorosoff, George Oster, André Deprit, Jean-Paul Penot, Bob Devaney, Joel Robbin, Hans Duistermaat, Clark Robinson, John Guckenheimer, David Rod, Martin Gutzwiller, William Satzer, Richard Hansen, Dieter Schmidt, Morris Kirsch, Mike Shub, Michael Hoffman, Steve Smale, Andrei Iacob, Rich Spencer, Robert Jantzen, Mike Spivak, Therese Langer, Dan Sunday, Ken Meyer, Floris Takens, [and] Randy Wohl for contributions, remarks, and corrections which we have included in this edition.
Further, we express our gratitude to Chris Shaw, who made exceptional efforts to transfom our sketches into the graphics which illustrate the text, to Peter Coha for his assistance in organizing the Museum and Bibliography, and to Ruthie Cephas, Jody Hilbun, Marnie McElhiney, Ruth (Bionic Fingers) Suzuki, and Ikuko Workman for their superb typing job.
Theoretical mechanics is an ever-expanding subject. We will appreciate comments from readers regarding new results and shortcomings in this edition.
RALPH ABRAHAM
JERROLD E. MARSDEN View Show abstract Stochastic broadening of the separatrix of a tokamak divertor Article Jan 1993 PHYS REV LETT Alkesh Punjabi Arun Verma Allen H Boozer The plasma in a modern tokamak is bounded by a separatrix between magnetic field lines that form toroidal magnetic surfaces, on which the plasma is confined, and open field lines that divert the plasma exhaust to so-called divertor plates. This separatrix is sharp in an ideal tokamak, but we show that magnetic perturbations create a stochastic region of open field lines inside the ideal separatrix which contains approximately 6 times the magnetic flux as does the strike points of these lines on the divertor plates. Since magnetic field lines are a 11/2 degree of freedom Hamiltonian system, the behavior of the field lines in a tokamak divertor is archetypal for the similar Hamiltonian systems. View Show abstract The Dynamics of Runge-Kutta Methods Article Jun 1992 INT J BIFURCAT CHAOS Julyan Cartwright Oreste Piro The first step in investigating the dynamics of a continuous-time system described by an ordinary differential equation is to integrate to obtain trajectories. In this paper, we attempt to elucidate the dynamics of the most commonly used family of numerical integration schemes, Runge–Kutta methods, by the application of the techniques of dynamical systems theory to the maps produced in the numerical analysis. View Show abstract
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The Project Gutenberg eBook of The Oversight, by Miles J. Breuer.
The Project Gutenberg eBook of The Oversight, by Miles J. Breuer
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Title: The Oversight
Author: Miles J. Breuer
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*** START OF THE PROJECT GUTENBERG EBOOK THE OVERSIGHT ***
THE OVERSIGHT
by MILES J. BREUER
Time Accomplishes Progress On Earth.
[Transcriber's Note: This etext was produced from
Comet December 40.
Extensive research did not uncover any evidence that
the U.S. copyright on this publication was renewed.]
John C. Hastings, senior medical student in the Nebraska State
University Medical School at Omaha, looked out of the window of the
Packard sedan he was driving down the road along the top of the bluff,
and out in the middle of the Missouri River he saw a Roman galley,
sweeping down midstream with three tiers of huge oars.
A pang of alarm shot through him. The study of medicine is a terrible
grind; he had been working hard. In a recent psychiatry class they
had touched upon hysterical delusions and illusions. Was his mind
slipping? Or was this some sort of optical delusion? He had stolen away
from Omaha with Celestine Newbury to enjoy the green and open freshness
of the country like a couple of stifled city folks. Perhaps the nearest
he had come to foolishness had been when the stars had looked like her
eyes and he had pointed out Mars and talked of flying with her to visit
that mysterious red planet.
"Do you see it too?" he gasped at Celestine.
She saw it, too, and heard the creak of oars and the thumping of
a drum; there floated up to them a hoarse chant, rhythmic but not
musical, broken into by rough voices that might have been cursing.
It was a clumsy vessel, built of heavy timbers, with a high-beaked
prow. There was a short mast and a red-and-yellow sail that bulged in
the breeze. The long oars looked tremendously heavy and unwieldy, and
swung in long, slow strokes, swirling up the muddy water and throwing
up a yellow bow-wave. The decks were crowded with men, from whom came
the gleam of metal shields, swords, and helmets.
"Some advertising scheme I suppose," muttered John cynically.
"Or some traveling show, trying to be original," Celestine suggested.
But the thing looked too grim and clumsy for either of these things.
There was a total lack of modern touch about it. Nor was there a
word or sign of advertising anywhere on it. They stopped the car and
watched. As it slowly drew nearer they could see that the men were
coarse, rowdy, specimens; and that the straining of human muscles at
the oars was too real to be any kind of play.
Then there were shots below them. Someone at the foot of the bluff was
blazing away steadily at the galley. On board the latter, a commotion
arose. Men fell. Then voices out on the road in front of them became
more pressing than either of these things.
"A young fellow and a girl," someone said; "big, fast car. Omaha
license number. They'll do."
"Hey!" a voice hailed them.
In front, on the road, were a dozen men. Some were farmers, some were
Indians. One or two might have been bank clerks or insurance salesmen.
All were heavily armed, with shotguns, rifles, and pistols. They looked
haggard and sullen.
"Take us to Rosalie, and then beat it for Omaha and tell them what you
saw," one of the men ordered gruffly. "The newspapers and the commander
at Fort Crook."
This was strange on a peaceful country road, but John could see no
other course than to comply with their request. He turned the car back
to Rosalie, the Indian Reservation town, and the men were crowded
within it and hung all over the outside. Even the powerful Packard
found it a heavy burden. In the direction of Rosalie, the strangest
sight of all awaited them.
Before they saw the town, they found a huge wall stretching across the
road. Beyond it rose blunt shapes, the tops of vast low buildings. What
a tremendous amount of building! the thought struck John at once. For,
they had driven this way just three days before, and there had been
no sign of it; only the wide green fields and the slumbering little
village.
The armed men became excited and furious when they saw the wall. They
broke out into exclamations which were half imprecations and half
explanatory.
"They put these things down on our land. Ruined our farms. God knows
what's become of the town. Squeezed us out. Must be a good many dead.
We have telephoned Lincoln and Washington, but they are slow. They
can't wake up. Maybe they don't believe us." There were curses.
John could see great numbers of armed men gathering from all
directions. There was no order or discipline about them, except the
one uniting cause of their fury against this huge thing that had so
suddenly arisen. Far in the distance, countless little groups were
emerging from behind trees and around bends in the road or driving
up in cars; and nearby there were hundreds more arriving with every
conceivable firearm. The last man in the countryside must have been
aroused.
The men climbed out of John's car and repeated their order that he
drive to Omaha and tell what he saw.
A ragged skirmish line was closing in rapidly toward the big gray
wall, that stretched for a mile from north to south. Along the top of
it, after the manner of sentries, paced little dark figures. John and
Celestine were amazed to see that they, too, were Roman soldiers. The
sunlight glinted from their armor; the plumes on their helmets stood
out against the sky; their shield and short swords were picturesque,
but, against the rifles below, out of place.
There came a shot, and another from the approaching attackers, and a
figure on top of the wall toppled and fell sprawling to its foot and
lay still on the ground. Hoarse shouts arose. A dense knot of Roman
soldiers gathered on top of the wall. A fusillade of shots broke out
from below, men running frantically to get within close range. The
group on the wall melted away, many crashing down on the outside, and
a heap remaining on top. The wall was completely deserted. The wind
wafted a sulphurous odor to the nostrils of the two young people in the
Packard.
Then followed a horrible spectacle. John, hardened to gruesome sights
in the course of his medical work, came away from it trembling,
wondering how Celestine would react.
A huge gate swung wide in the wall, and a massed army of Roman soldiers
marched out. Bare thighs and bronze greaves, and strips of armor over
their shoulders, plumed helmets, small, heavy shields; one company
with short swords, the next with long spears; one solid company after
another poured out of the gates and marched forth against their
attackers.
The Farmers and Indians and other dispossessed citizens opened fire on
the massed troops with deadly effect. Soldiers fell by the hundreds;
huge gaps appeared in the ranks; whole companies were wiped out. But,
with precise and steady discipline, others marched in their places.
Blood soaked the ground and smeared the trees and shrubbery. Piles
of dead were heaped up in long windrows, with twitching and crawling
places in them. New ranks climbed over them and marched into the blaze
of lead, only to fall and be replaced by others. The peaceful Nebraska
prairie was strewn with thousands of armed corpses.
Terror gripped the hearts of the couple in the Packard. The firing
began to halt. It became scattered here and there as ammunition became
scarce. As the troops poured out in unlimited numbers, men in overalls,
sweaters, and collars and shirt sleeves began to retreat. The grim
ranks closed upon the nearest ones. Swords rose and fell, spears
thrust, clubbed rifles were borne down. There was more blood, and the
bodies of American citizens littered the ground that they themselves
had owned and tried to defend.
John and Celestine, paralyzed by the spectacle, came to with a jerk.
"It's time to move," John said.
He swung the car around just as, with a rattle and a roar, a score of
chariots dashed out of the great gates and the horses came galloping
down the road. The ranks of the infantry opened to permit pursuit of
the retreating skirmishers. The clumsy vehicles rattled and bumped
behind flying hoofs at a rapid clip, the men in them hanging on to
the reins and keeping their footing by a miracle. Gay cloaks streamed
backward in the wind, and gold gleamed on the horses' harness.
Roman soldiers, armor glistening in the sun! Chariots! Galleys! They came in endless columns, fearless....
John bore down on the accelerator pedal, and the car leaped ahead with
a roar, a scattered string of chariots swinging in behind it. He headed
down the road and, once the Packard got a proper start, it left its
pursuers ridiculously behind. Celestine shrieked and pointed ahead.
"Look!"
A group of Roman soldiers with drawn swords were formed on the road
ahead, and more were swarming out of the shrubbery.
An officer waved a sword and shouted a sharp word.
"Stop, nothing!" John said through gritted teeth, remembering bloody
overalls and sprawling limbs gripping battered rifles.
He put his full weight on the accelerator pedal and the huge machine
throbbed and rumbled into life, a gleaming, roaring gray streak.
"Duck down below the windshield, dear," he said to Celestine. Never
before had he used that word, though he had often felt like it.
The Roman soldiers quailed as they saw the big car hurtling toward
them, but they had no time to retreat. The bumper struck the mass of
men with a thud and a crash of metal. Dark spatters appeared on the
windshield and things crunched sickeningly. The car swerved and swung,
dizzily, and John's forehead bumped against the glass ahead of him, but
his hands hung to the wheel. The fenders crumpled and the wheels bumped
over soft things. Just as he thought the car would overturn, he found
himself flying smoothly down a clear road; in his windshield mirror a
squirming mass on the road was becoming rapidly too small to see.
He laughed a hard laugh.
"They didn't know enough to jab a sword into a tire," he said grimly.
And, there to their left, was the tiresome galley, sliding down the
river. The countryside was green and peaceful; in a moment even
the galley was out of sight. Except for the crumpled fenders and
the leaking radiator it seemed that they had just awakened from an
unpleasant dream and found that it had not been true.
They talked little on the way to Omaha; but they could not help talking
some. Who were these men? Where did they come from? What did it mean,
the piles of dead, the sickening river of blood?
They must hurry with the news, so that help would be sent to the
stricken area.
The hum of the motor became a song that ate up miles. John worried
about tires. A blowout before he reached the army post at Fort Crook
might cost many lives. There was no time to waste.
Just as the roof-covered hills of Omaha appeared in the distance, two
motorcycles dashed forward to meet the car and signalled a stop. The
khaki clad police riders eyed the bloody radiator and nodded their
heads together.
"You've been there?" they asked. John nodded.
"You've been there?" he queried in return.
"The telephone and telegraph wires are hot."
"They need help—," John began.
"Are you good for a trip back there in a plane, to guide an observer?"
the officer asked. "We'll see the lady home."
So John found himself dashing to the landing field on a motorcycle,
and then in an Army plane, a telephone on his ears connected with the
lieutenant in front of him. It was all a mad, dizzy, confused dream. He
had never been up in a plane before, and the novelty and anxiety of it
fought with his tense observation of the sliding landscape below. But
there was the galley on the river, and three more following it in the
distance. There was an army marching along the top of the bluffs down
the river, a countless string of densely packed companies with horsemen
and chariots swarming around. There were the huge flat buildings in the
walled enclosure where Rosalie had stood. Out of the buildings and out
of the enclosures, marched more and more massed troops, all heading
toward Omaha.
Then they were back in the City Hall, he and the lieutenant, and facing
them were the chief of police and an Army colonel. There was talk of
the Governor and General Paul of the State Militia due to arrive from
Lincoln any moment in an airplane; and the National Guard mobilizing
all over the state, and trucks and caissons and field guns already en
route from Ashland with skeletonized personnel. Secretaries dashed out
with scribbled messages and in with yellow telegrams. A terrific war
was brewing, and what was it all about?
The lieutenant stepped up to the colonel and saluted.
"If you please, sir, the galleys on the river—"
"Yes?" asked the worried colonel.
"They've got to be sunk."
"We have no bombs," the colonel answered. "We're just a toy army here,
in the middle of the continent."
"No bombs!" The lieutenant was nonplussed for a moment, and hung his
head in study. "Will you leave it to me, sir? Somehow—"
"Good fellow. Thank you," said the colonel, very much relieved. "Your
orders are, then, to sink the galleys."
"Come!" The lieutenant said to John.
"Me?" gasped John.
"Don't you want to?" the lieutenant asked. "Men are scarce. I need
help. You're the closest. And you've got a level head."
"Just give me a chance," John said eagerly.
The lieutenant spent fifteen minutes in a telephone booth. Then they
dashed in a motorcycle to the city landing field where the plane lay.
They made the short hop to the Army flying field. This all took time;
but when they taxied towards the Army hangars, there stood men ready
to load things into the plane. A stack of kegs labeled "Dynamite" and
white lengths of fuse did not look very military, and their source was
indicated by the departing delivery truck of a hardware firm. The men
knocked the stoppers out of the kegs and wadded the fuses into the
bungholes with paper.
"Bombs!" The lieutenant spread his hands in a proud gesture. "The
Q.M.G. in Washington ought to see this. Maybe he'd trust us with real
ones some day."
He turned to John.
"We'll use a cigarette-lighter down in the cockpit, and heave them over
the side."
Out over the city they flew, and up the river. The trireme was steadily
approaching, and the lieutenant flew his plane a hundred feet above the
ship. They could see gaping mouths and goggling whites of eyes turned
up at them. The decks were a mass of coarse looking faces.
"Hate to do it," remarked the lieutenant, looking down on the decks
packed with living men. "But, Lord, it seems to be the game, so light
up!" he ordered sharply.
As John applied the cigarette-lighter and the fuse began to fizzle, the
lieutenant circled about and again flew over the creeping galley.
"Now!" He shouted, and John rolled the keg over the side. It turned
over and over endwise as it fell, and left a sputtering trail of smoke
in the air.
It fell on the deck and knocked over several men. The lieutenant was
putting height and distance between themselves and the galley as
rapidly as possible, and rightly. In another moment there was a burst
of flame and black smoke. Blotches of things flew out sidewards from
it, and a dull roar came up to them. For a few minutes a mangled
mass of wreckage continued the galley's course down the river. Then
it slowed and drifted sidewise, and flames licked over it. Struggling
figures stirred the water momentarily and sank. Not a swimmer was left;
bronze armor does not float on muddy Missouri River water.
Above the second galley they were met by a flight of arrows, and the
lieutenant hurriedly performed some dizzy gyrations with the plane to
get out of bowshot, but not before several barbed shafts struck through
the wings and thumped against the bottom. So they lit their fuse and
passed low over the galley at full speed. There was less regret and
more thrill as they rolled the keg with its sputtering tail over
the side; the humming arrows made the game less one-sided. The high
speed of the plane spoiled the aim, and the keg of dynamite plumped
harmlessly into the water just ahead of the galley. The second time
they figured a little more closely, and before very long, all four of
the galleys were a mass of scattered, blackened wreckage.
John leaned back in the seat.
"Terrible way to squander human beings," he said.
The lieutenant's teeth were set.
"You haven't seen anything yet," he said to John. "We've got two more
kegs of dynamite and no orders to the contrary. Let's go back to the
front lines."
"Front lines!" exclaimed John.
The lieutenant smiled.
"You've studied medicine; I've studied war. It is two and a half hours
since we left the meeting. The Roman—or whatever the blank they
are—infantry has made ten miles south and west. Our troops from the
Fort have easily made thirty or forty in their trucks, and started
digging trenches and emplacing guns. That would mean that there must be
fighting north and west of here. Isn't that so?"
"I hadn't thought of it," John admitted.
"Also by this time there must be two or three regiments of State
militia on trucks and bound in this direction; and the artillery and
machine-guns from Ashland ought to be ready any minute. We've got two
more kegs. Are you game?"
As if in answer, a dull boom sounded from the northwest, followed by
another; and in five minutes the banging was almost continuous.
John nodded his head. The lieutenant swung the plane around, and it was
less than ten minutes before they saw the trenches of the Fort Crook
troops spread below them; and from far into the north there poured
column upon column of densely formed Roman troops, with the gleam of
the afternoon sun upon the metal of their armor and swords. On the
eastern end of the line the Roman infantry had reached the trenches and
a sickening carnage was taking place. As they advanced steadily toward
the trenches, the Roman troops were mowed down by the machine-guns of
the Federal soldiers and the Omaha police, in swaths like meadow-grass
laid flat by the blade of the scythe. During the period of a few
minutes as they looked down they saw thousands of men fall; great heaps
of twitching and bloody dead in armor and plumes were piled before the
thin line of khaki.
"They don't need us much, but here goes!"
Far back over the enemy's lines, where the troops were massed the
densest, they sailed, and dropped their black and smoking blasts and
scattered several companies of bewildered soldiers. But others took
their places and pressed steadily on.
"If we only had a few fighting planes and some ammunition for
them—wouldn't we clean up the place!" gloated the lieutenant. "But
there isn't a plane with a machine-gun on it in this division, and not
an aerial bomb except some dummies for practice. The War Department
isn't ever so very fast, and this certainly came suddenly. However,
I'm sure that they must be getting busy sending things over by now.
Let's look westward."
The line was flung a dozen miles west of the Missouri River, and
gradually was crawling still further west. The artillery from Ashland
had stopped ten miles southwest of the place where fighting first
began, and by now had set up their pieces and gotten the range with the
aid of a commandeered, tri-motored, passenger plane; they were banging
shells at the rate of one every three seconds into the thickest of
the troops. Even at the height of three thousand feet, the sight was
horrible; there were red areas against the green of the landscape, and
red areas on the piled up heaps that twitched and gleamed with spots of
metal; the heaps piled up and grew into hills, between the gaping holes
that the shells dug into the wheatfields.
"Ha! Look!"
The lieutenant pointed near the line at the middle.
"An artillery captain is looking for prisoners."
The barrage of one of the batteries was laying flat a wide area, but
preserving a little circle intact in the middle of it. On this island,
among a sea of smoky holes, stood a huddled group of Roman soldiers.
One by one they fell, for flying fragments of high-explosive shell
traveled far, and they did not know enough to fall flat on their faces.
Then the barrage stopped and a platoon of men in khaki with rifles
crept toward them.
The lieutenant looked like a man on the side-lines of a football game.
He flew his plane low and gazed breathlessly at the combat below. For
it was an exciting one.
The khaki-clad soldiers wanted prisoners alive. But the Roman soldiers
understood nothing of the threat of the gun. Rifles and pistols were
leveled, but served in no wise to stop them from making a fierce attack
on the Americans with swords and spears. To save their own lives, the
latter had to stop and shoot the Romans down.
All but a half a dozen armored men now lay flat on the ground. These
gathered together for a moment's council, adjusted their shields, and
balanced their swords and spears. They were preparing a charge.
The lieutenant on the ground obviously had orders to get live
prisoners. He also knew his battle psychology well.
He formed his men in line; bayonets flashed out of scabbards and in
a moment a serried line of them bristled forward on the ends of the
rifles. The khaki-clad line started first. The men on the flanks ran
as fast as they could go and dodged through shell-holes. The Romans
started slowly toward the thin looking center of the American line.
The aviation lieutenant rose in his seat and dropped the stick of the
plane for a moment in his excitement. The plane veered and the fight
below was lost to view for a moment. By the time he had swung the
plane back, the circle of khaki had almost closed around the Romans.
The latter stood back to back, spears straight out in front of them.
It must have taken nerve to face that circle of advancing bayonets,
outnumbering them six to one. They held, stolid as a rock wall, and
John was almost beginning to think that they would fight to the death
and kill a few American soldiers. But, just as the ring of bayonets was
within a foot of the ends of their spears, they suddenly dropped their
weapons on the ground, and held their hands in the age-old gesture,
straight above their heads.
The men in khaki pushed them apart with their bayonets, and two to a
prisoner, marched them back to the line; others stopping to pick up
weapons. For the first time John noted that these men were all giants;
even from the altered perspective of the aeroplane it was clear that
they were six and a half to seven feet tall, and burly.
"We'll go back and report, then get a rest," the aviation lieutenant
said, heading the plane toward the Army field. There he shook hands
with John, and arranged to meet in the morning for further work.
After a telephone conversation with Celestine, and a meal, John settled
down in his room and turned on the radio. Program material had been
crowded off all stations by the news of the war.
"The front lines are now fully equipped with portable searchlights and
flares. But the Roman soldiers have quit coming. Apparently there will
be no fighting during the night."
There followed a resume of happenings with which John was already
familiar, and he shut the instrument off. Just as he was beginning to
doze, his telephone rang. It was the pathologist at the Medical School.
"Hello, Hastings," he said. "You have been in on this from the start,
and I thought you would be interested in our prisoners."
John hurried over to the hospital, where in one of the wards there
was a squad of soldiers with fixed bayonets, and two of the giants
on the beds. One had a shoulder wound and one a thigh wound from
high-explosive fragments. Both wounds were very slight.
"Mr. Hastings," said the pathologist, presenting him to a man bending
over one of the prisoners, "Professor Haven is from Creighton
University, and is the head of the Latin Department. He is trying to
talk to these men."
Professor Haven shook his head.
"These men speak Latin but I don't," he sighed. "I've studied it a
lifetime, but I can't speak it. And they speak a very impure, corrupted
Latin. But, I'm making out, somehow."
He spoke slowly, in ponderous syllables to the prisoner. The man
grumbled surlily. In the meantime, the pathologist called John away.
"One of the prisoners died," he said, "and we are doing a post-mortem.
Just a slight flesh-wound; no reason under the sun why it shouldn't
heal easily. He seemed to have no vitality, no staying power."
The post-mortem failed to make clear what had been the cause of death;
the slight bullet wound in the shoulder could not have caused it. No
other abnormality was found. They went back to the ward, and found
another of the prisoners dead.
"Strange," the pathologist muttered. "They can't resist anything. And
there is some odd quality about their tissues, both anatomical and
physiological, that I can't put my finger on. But they're different."
"They're certainly stupid," the Latin professor said. "I have succeeded
in making myself understood to this man. I asked him, who are they,
what they wanted, why they were fighting us, where they come from. He
does not know. '
Non scio, non scio, non scio!
' That's all I got out
of either one of them, except that they are hungry and would prefer to
lie on the floor rather than on the bed. They give me the impression of
being feeble-minded."
"Good fighting machines," John remarked.
When he got back to his room, the radio was urging everybody to go
to sleep and rest. There were guards detailed for necessary night
work, and there was no danger. Freshness and strength would be needed
tomorrow. But John was too excited following his strenuous day, and
knew that sleep would be impossible. He kept on listening to the news
from the radio, which was trying to solve the mystery of these Roman
hordes.
"Who are they?" the announcer asked rhetorically. "Where are they
from? What do they want?" His questions were asked but not answered.
He reported that during the afternoon the entire world had been
searched by cable and radio, and nowhere was there any trace of the
departure of such vast numbers of men. Italy and Russia were especially
suspected; but it was out of the question that such hundreds of
thousands could have been transported without leaving some evidence.
How had they reached the middle of the North American continent? No
railroad knew anything about them; there had been no unusual number
of airships observed in any direction. One was tempted to think that
they came out of the ground. Someone proposed the idea, based on the
popularity of Einstein's recent conceptions, that these men had somehow
crossed the time dimension from Julius Caesar's time; a fold in the
continuum might readily bring the period of the Roman Senate in contact
with the period of radio and automobiles.
A few minutes later the announcer stated that he had received a dozen
contemptuous and scornful messages about the idea from scientists and
historians. If these troops had come from Caesar's time, their sudden
disappearance would certainly have caused enough sensation to be
recorded; and no such record existed. If they came from such a period,
they must have disappeared from the sight of the people who lived then;
otherwise one must assume that they went on existing in their own time
as well as the present day. The idea was rent to bits. The announcer
went on with rhetorical questions:
How many more men were there? What would happen tomorrow? At least
there were comforting reports that in the morning the sky would be
crowded with planes bearing tons of high-explosive bombs. It could not
last long.
Suddenly John slapped his thigh. He went to the telephone and called up
the aviation lieutenant.
"Hello!" he said. "Did I get you out of bed? Well, it looks as though
neither one of us is so bright about war."
"Now what?" the lieutenant asked.
"Those last two kegs of dynamite that you dropped on Caesar's army—"
"Yes?" the lieutenant asked.
"They ought to have been dumped on the buildings on the Indian
Reservation, what?"
A faint oath came over the phone.
"Say, Hastings, I feel like resigning my commission and getting a job
selling bananas. But, what do you say to correcting the oversight? At
once?"
"I'm there. But wait. I'm getting positively brilliant tonight. Why not
get the Latin prof to go with us and see what we can find out?"
"If I could slap you on the back by phone, I'd do it. I'm waiting for
you with the ship. Hurry."
Professor Haven was delighted at the opportunity; the wizened little
fellow seemed oblivious to the dangers of the undertaking. They put
rifles in the plane, and two forty-fives apiece in their belts.
The walled enclosure was visible to the plane from a distance, because
of a strange reddish glow that came up from it. The glow enabled
the lieutenant to note that a long, flat-roofed building offered a
far better opportunity for a landing than did the ground, which was
systematically spaced with guards. He shut off his motor several miles
away, and managed his landing with marvelous skill and silence. Only
the landing-wheels, bumping over the rough places on the roof, made any
sound. They waited for thirty minutes in silence, and as no further
sounds came from the camp, they crept out of the cockpit and stole
along the roof.
The guards pacing about below seemed not to have noticed their landing.
Ahead of them was a large, square affair like a chimney, with a red
glow coming out of it. But, it was not a chimney, for no heat came from
it. It might have been a ventilator; in fact as they approached they
found that a strong current of air drew
downward
into it. They could
lean over the edge and see a large, bright room immediately below them.
It was certainly no crude Roman room. It was a scientific laboratory,
crowded with strange and delicate apparatus. Most of it was quite
unfamiliar to John in use or nature, despite the fact that he was well
posted on modern scientific matters, and could make intelligent guesses
about scientific things or equipment even out of his own line. He could
make nothing out of the things he saw below.
Just beneath them stood a huge Roman officer; the numerous gold
insignia on his chest indicated high rank. He stood in front of a glass
jar about four feet high, from which numerous cords led to a table full
of intricate apparatus. Inside the jar there was something that looked
like a piece of seaweed. It was hard, tough, leathery. In the bright
light, it might have been a sort of a branching cactus. But it moved
about within its jar. It gestured with one of its branches. It pointed
at the Roman soldier, and nodded a large, head-like portion. A rapid
rattle of words in a foreign tongue came up to them, and Haven, the
Latin professor, craned his neck. John recognized a Latin word here and
there, but could make out no meaning. Haven later translated what he
had heard. The first words he distinguished were those of the big Roman
general.
"We need fifty more legions of men by morning," he said apologetically.
"Why not?" a metallic voice replied. It continued monotonously, with
scant intonation. "I'll start them at once and have them ready by
daylight." There was a quick gesture of the leathery thing in the jar.
Little groups of long, red thorns scattered over it.
The general went on.
"These people are good fighters. They may conquer us. We haven't a
thousand soldiers left."
The metallic voice that replied conveyed no emotion, but the gesture of
the cactus-like thing in the jar was eloquent of deprecation.
"To our science they are but a puff of wind," the droning voice said.
"I can destroy them all by pressing a button. Do you think I have
studied the earth and its beast-like men for ages in vain? But, I want
sport. I've been bored for too many centuries. So, to entertain me you
shall have your five hundred companies of soldiers tomorrow morning.
Now go. I must be alone."
The general saluted with an arm straight forward and upward, turned
about, and walked out of the field of view, muttering something
dubiously under his breath. For a long time, all was silent. Then the
metallic voice spoke:
"Earth men, I perceive you up on the roof about the ventilator." The
leathery thing in the jar stirred and the machinery on the table
clicked.
The group on the roof started in alarm, but the wizened little Haven
regained his composure first.
"Who and what are you?" he exclaimed.
"You ask as though you had a right to demand," the metallic voice
droned. "But it pleases me to inform you, earth men, that I am a being
of the planet Mars. Tired of the monotony of life in our dull world, I
decided to emigrate. I came peacefully."
"
Peacefully!
" exclaimed the lieutenant, but the metallic voice went
on as though he had not spoken:
"I harmed no one until your people attacked my walled enclosure and
destroyed my defenders. They have suffered. I am sorry. Let me alone,
and I shall not molest you. I wish you no harm."
"But!" exclaimed Haven, "you cannot take possession of a hundred acres
of land that belongs to other people, and lay waste to thousands more.
That is their land. They will fight for it. How can they let you alone?"
"It is better for you not to bother me. The science of Mars is still
millions of years ahead of yours—"
There arose a shouting and a clatter among the guards below. Their
suspicions had been aroused by sounds on the roof. A trampling of
feet toward the building increased in volume. The trio hurried to
their plane, swung it about by the tail, and jumping in, took off with
a roar, leaving a band of gaping legionnaires below. John eventually
found himself in his bed at about three o'clock in the morning, and
even then too exhausted to sleep. Questions kept running through his
mind.
The creature's claim that it was a Martian, made things more mysterious
instead of less so. It was not possible to transport these hundreds of
thousands of men from Mars. And the buildings and chariots and horses.
It would have taken an enormous tonnage of vessels, whose arrival
certainly would have been noticed. And to think that Mars was inhabited
by Roman soldiers was a most preposterous and childish notion. And if
the Martians were as far advanced in science as they claimed, why did
they use the military methods of ancient Rome? Certainly there was
still plenty about this that had not been explained.
John slept late and awoke exhausted by his previous day's unwonted
stress. But the thundering of guns would let him sleep no longer.
The radio told him that fighting was going on up around Sioux City
and westward toward Fremont and Norfolk. Always the reports carried
the same statements of the incredible slaughter of innumerable Roman
soldiers by the modern engines of war against which their swords and
shields meant nothing. It was an unbelievable nightmare, creepy,
horrible destruction of life and a soaking of the earth with blood, and
piling up of mounds of dead bodies scores of feet high on the green and
peaceful prairies. The reports ended up with an optimistic note that
aeroplanes with high-explosive bombs were due to arrive from the East
at any moment.
Then his telephone rang. It was his dean calling him to a conference
with the Commanding Officer of the area. The smiling aviation
lieutenant was also present. They were discussing the advisability of
destroying the Martian in his building, and thus stamping out the rest
of the trouble.
"It might not necessarily stop all trouble, you know," the medical dean
said; "those curious men are still loose in large numbers. I think that
the creature, instead of being destroyed, ought to be captured and
studied."
The dean's view finally prevailed, and it was decided to avoid
destroying the spot on which the Martian stood. The adjutant was
already busy directing. Army and Navy planes were now arriving in
swarms from East and West. Arrangements were made to bomb all around
the Martian's retreat, and then raid it with a small party when
everything was clear.
Grimly, methodically, the Army and Navy fliers went about their tasks.
They systematically covered the entire contested territory with
high-explosive bombs. In three hours, a Nebraska county was a field
plowed by a giant, in which persisted one little island, the long house
in the walled enclosure, with its red-glowing chimney. Airplanes landed
a platoon of the National Guard on the river, and these marched to the
surviving building and searched it thoroughly. With them was John and
his friend the aviation lieutenant; and also the dean and the Latin
professor. They found nothing anywhere, except in the room below the
ventilator, where the Martian was still sealed in his glass jar.
"Earth men!" the metallic voice said suddenly, and the leathery body
jerked in surprise. "
Homines terrae!
"
Professor Haven spoke in Latin. He was imbued with the educated
person's ideal of courtesy in the victor.
"I have been watching you," the metallic voice said. Its tones conveyed
no feeling, but the attitude of the branched body was weary. "I am
surprised I must have missed something."
"Eh? What's that?"
"I must have missed something in my observations. After all, your
fighting machines are very simple. I could have destroyed them in a
breath, only, I did not know you had such things. I cannot understand
why I did not find them before."
The men stood in silence, looking at the dry, hard looking thing, not
knowing what to say. Finally the metallic speaking began again. John
noted that the voice came from a metal diaphragm among the apparatus on
the table, to which the cords led from the creature in the jar.
"I cannot understand it. When I planned to migrate to the Earth, I came
here and remained many years, studying many men, their bodies, their
language, their methods of fighting—fighting was something new to me,
and I enjoyed it; we do not have fighting on Mars. I took all necessary
observations so that I might prepare to live among them.
"Then I went back home and spent sufficient time in research to make
everything perfect. Of course it took a long time. I devised a suit in
which I could stand in your atmospheric pressure, heat, and moisture;
methods of transporting the nuclei of my apparatus to the Earth and
growing them into proper bulk when I arrived, so that I might carry
only very little with me. I was especially interested in devising
methods of growing human beings on suitable culture media. I developed
men who were just a little larger and a little stronger than yours; yet
not too much so, because I wanted to see good sport, though remaining
sure of winning you over in the end—"
"Cultured these men!" Professor Haven exclaimed. He lagged a little in
using his Latin words. "You mean you grow them like we grow bacteria in
test-tubes?" He got his meaning across by many words and much effort.
"I grew these soldiers on culture media," the metallic voice answered,
and a shriveled arm gestured in a circle. "With a forced supply of air
for carbon, oxygen, and nitrogen, and water for hydrogen, I can grow a
man in a few hours; or as many men at once as I have culture medium and
containers for. They grow by simultaneous fission of all somatic cells."
"So they are not really human?" Haven seemed much relieved at the idea
that the destruction might not have been that of human life.
"That depends on what you mean by human," the dried-up Martian said, by
means of his machine. "To me, it means nothing."
"That accounts for the queer differences our pathologist found," the
dean observed when the fact had been translated to him that these
hordes of men were cultured in a laboratory.
"Now that you have me in your power," the Martian continued, "please
explain to me how you kept all your destructive engines hidden when I
was here on my preparatory observation trip."
The dean of the Medical School touched Haven on the shoulder.
"Ask him how long ago he was here."
"It took me," the machine said, "just about a thousand years (our year
is twice as long as yours) to work out my methods of transportation,
maintenance, and culture, and to make a voice instrument with which to
talk to these culture-soldiers."
The dean turned toward the Commanding Officer.
"Two thousand years ago," he said. "The Romans were just about at the
height of their military glory. Explain that to him, and how the world
and its people have changed since."
The queer, seaweed-like creature nodded in comprehension and settled
itself down in its jar in resignation.
"That is the point I overlooked. For millions of years, the Martians,
at the zenith of scientific knowledge, have remained stable. The idea
of human change, of progress in civilization, had slipped my mind. Our
race has forgotten it. Your race progressed, and left me behind."
A little discussion arose among them. All agreed that it would be most
interesting and valuable to preserve the Martian carefully in some
museum. A great deal of useful information could be obtained from him.
Many benefits would accrue to humanity from his knowledge.
"Only," reminded the Commanding Officer, "how much power does he still
have left for doing harm?"
The dean was interested, and bent close to the jar to have a better
look. He put his hand on the glass.
There was a quick rush and a crash of furniture. The big Roman general
leaped up from beneath a couch, where he had been concealed. With sword
upraised he dashed at the dean.
"Look out!" shouted John.
The Roman general gave a hoarse cry. Fortunately it took a goodly
number of seconds for him to cross the room. The Commanding Officer was
tugging at his pistol holder. His automatic came out fairly quickly and
banged twice. The Roman came rushing on almost to within a foot of the
muzzle.
Then his sword dropped with a clatter on the floor, his helmet rolling
several feet away. The case tipped. It toppled. It looked almost as
though it would go over.
Then it settled back; but a crackling sound came from it. A crack
appeared in the glass, and wound spirally around it. There was a sizzle
of air going into the jar. Machinery clicked and sparks crackled.
The creature inside jerked convulsively, and then was still. In a few
minutes it began to bloat, and a red mold spread rapidly over it.
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(PDF) Rapid Metabolism of Glucose Detected with FRET Glucose Nanosensors in Epidermal Cells and Intact Roots of Arabidopsis RNA-Silencing Mutants
PDF | Genetically encoded glucose nanosensors have been used to measure steady state glucose levels in mammalian cytosol, nuclei, and endoplasmic... | Find, read and cite all the research you need on ResearchGate
Rapid Metabolism of Glucose Detected with FRET Glucose Nanosensors in Epidermal Cells and Intact Roots of Arabidopsis RNA-Silencing Mutants
October 2006
The Plant Cell 18(9):2314-25
DOI: 10.1105/tpc.106.044073
Authors:
Abstract and Figures
Genetically encoded glucose nanosensors have been used to measure steady state glucose levels in mammalian cytosol, nuclei, and endoplasmic reticulum. Unfortunately, the same nanosensors in Arabidopsis thaliana transformants manifested transgene silencing and undetectable fluorescence resonance energy transfer changes. Expressing nanosensors in sgs3 and rdr6 transgene silencing mutants eliminated silencing and resulted in high fluorescence levels. To measure glucose changes over a wide range (nanomolar to millimolar), nanosensors with higher signal-to-noise ratios were expressed in these mutants. Perfusion of leaf epidermis with glucose led to concentration-dependent ratio changes for nanosensors with in vitro K(d) values of 600 microM (FLIPglu-600 microDelta13) and 3.2 mM (FLIPglu-3.2 mDelta13), but one with 170 nM K(d) (FLIPglu-170 nDelta13) showed no response. In intact roots, FLIPglu-3.2 mDelta13 gave no response, whereas FLIPglu-600 microDelta13, FLIPglu-2 microDelta13, and FLIPglu-170 nDelta13 all responded to glucose. These results demonstrate that cytosolic steady state glucose levels depend on external supply in both leaves and roots, but under the conditions tested they are lower in root versus epidermal and guard cells. Without photosynthesis and external supply, cytosolic glucose can decrease to <90 nM in root cells. Thus, observed gradients are steeper than expected, and steady state levels do not appear subject to tight homeostatic control. Nanosensor-expressing plants can be used to assess glucose flux differences between cells, invertase-mediated sucrose hydrolysis in vivo, delivery of assimilates to roots, and glucose flux in mutants affected in sugar transport, metabolism, and signaling.
Expression of Nanosensors in Arabidopsis Wild Type and Silencing Mutants. …
Construct Maps and in Vitro Saturation Curves for FLIPglu- D 13. …
Glucose-Induced FRET Changes in the Cytosol of Leaf Epidermal Cells. …
Isotherms for Glucose Binding Proteins Fused to the Codon-Modified eCFP and Venus Encoding Ares and Aphrodite Genes. …
Supplementary resources (2)
Synthetic construct yellow fluorescent protein aphrodite gene, complete cds
Nucleotide Sequence
April 2006
K. Deuschle · W.B. Frommer
Synthetic construct cyan fluorescent protein ares gene, complete cds
K. Deuschle · W.B. Frommer
... FRET-based nanosensors can be genetically encoded NM-based, using NMs, molecular ligands, proteins, or protein domains that moderate the distance in the middle of the acceptor, donor, and fluorescent areas of double fluorophores . Applying FRET sensors to plants is difficult, mainly due to gene silencing (Chaudhuri et al., 2011;
Deuschle et al., 2006)
. However, studies have shown that nanosensors, derived by mutant plants missing gene can be used to measure steady-state sucrose or glucose levels in the cytosol of epidermal leaf cells and complete roots of soil-grown plants (Chaudhuri et al., 2008;Deuschle et al., 2006). ...
... Applying FRET sensors to plants is difficult, mainly due to gene silencing (Chaudhuri et al., 2011;Deuschle et al., 2006). However, studies have shown that nanosensors, derived by mutant plants missing gene can be used to measure steady-state sucrose or glucose levels in the cytosol of epidermal leaf cells and complete roots of soil-grown plants (Chaudhuri et al., 2008;
Deuschle et al., 2006)
. NM-based FRET sensors use various NMs including lanthanide-doped up conversion NMs (UCNMs) and semiconductor quantum dots (QDs), as one of two quenchers or a FRET donor . ...
... Inherently, nanosensors are matched for in vivo research of cellular signaling by their ease of setting them into plant tissues . FRET-based saccharide sensors have been used in plants to screen comparative changes in sugar levels of the steady state in a subcellular section (Chaudhuri et al., 2008;
Deuschle et al., 2006;
Lager et al., 2006). These analyses are complex due to different plant cells displaying different responses. ...
... Successful gene codification and expression of FLIPs in plants have allowed the identification of new SWEET transporters involved in the carbohydrate uptake in roots
[15]
, sucrose transport into phloem cells [60], translocation of sucrose into seeds [107], production of floral nectar [108], and the resistance against pathogens [18]. Nevertheless, some FLIP variants did not show any FRET signal in cytoplasmic conditions [15]. ...
... Successful gene codification and expression of FLIPs in plants have allowed the identification of new SWEET transporters involved in the carbohydrate uptake in roots [15], sucrose transport into phloem cells [60], translocation of sucrose into seeds [107], production of floral nectar [108], and the resistance against pathogens [18]. Nevertheless, some FLIP variants did not show any FRET signal in cytoplasmic conditions
[15]
. Furthermore, signal transduction in sucrose FLIPs by FRET appears to be limited to LOD of µM concentrations [14], which may be insufficient to quantify some biochemical processes where sugar concentrations have been below 90 nM [15]. ...
... Nevertheless, some FLIP variants did not show any FRET signal in cytoplasmic conditions [15]. Furthermore, signal transduction in sucrose FLIPs by FRET appears to be limited to LOD of µM concentrations [14], which may be insufficient to quantify some biochemical processes where sugar concentrations have been below 90 nM
[15]
. ...
Molecular Level Sucrose Quantification: A Critical Review
Sucrose is a primary metabolite in plants, a source of energy, a source of carbon atoms for growth and development, and a regulator of biochemical processes. Most of the traditional analytical chemistry methods for sucrose quantification in plants require sample treatment (with consequent tissue destruction) and complex facilities, that do not allow real-time sucrose quantification at ultra-low concentrations (nM to pM range) under in vivo conditions, limiting our understanding of sucrose roles in plant physiology across different plant tissues and cellular compartments. Some of the above-mentioned problems may be circumvented with the use of bio-compatible ligands for molecular recognition of sucrose. Nevertheless, problems such as the signal-noise ratio, stability, and selectivity are some of the main challenges limiting the use of molecular recognition methods for the in vivo quantification of sucrose. In this review, we provide a critical analysis of the existing analytical chemistry tools, biosensors, and synthetic ligands, for sucrose quantification and discuss the most promising paths to improve upon its limits of detection. Our goal is to highlight the criteria design need for real-time, in vivo, highly sensitive and selective sucrose sensing capabilities to enable further our understanding of living organisms, the development of new plant breeding strategies for increased crop productivity and sustainability, and ultimately to contribute to the overarching need for food security.
... showed significant emission ratio changes to NO 3 − in roots ( Fig. 2D; quantification in Fig. 2E), indicating that NiMet3.0 can specifically detect NO 3 − in plants. For the generation of high-sensitivity FRET sensors, many parameters are critical, such as sensory domain for affinity and specificity, fluorescent proteins for brightness and ligand-induced FRET changes, and linkers for the effect on sensor responses (16,24,
25)
. Here, we successfully engineered NiMet1.0 responses to NO 3 − and further optimized the sensor to create NiMet2.0 and NiMet3.0. ...
... Constructs were inserted by Gateway LR reactions into the yeast expression vectors pDRFlip30, pDRFlip39, pDRFlip42-linker, and pDRFlip-GW (Gateway). The pDRFlip30 vector sandwiches the insert between an N-terminal AFPt9 variant
(25)
, with nine amino acids truncated off the C terminus, and a C-terminal mCer (51). pDRFlip39 sandwiches the inserted polypeptide between an N-terminal enhanced dimer Aphrodite t9 (edAFPt9) and C-terminal fluorescent protein enhanced dimer, with seven amino acids and nine amino acids truncated from the N terminus and the C terminus of eCyan (t7.ed.eCFPt9), respectively. ...
... expression clones. Transgenic plant lines were generated using the Agrobacterium floral dip method as described previously
(25)
. Transformants were selected on agar plates containing 1 / 2 strength MS medium with vitamins (PhytoTech Labs, M519) and with kanamycin. ...
In vivo visualization of nitrate dynamics using a genetically encoded fluorescent biosensor
Nitrate (NO3-) uptake and distribution are critical to plant life. Although the upstream regulation of NO3- uptake and downstream responses to NO3- in a variety of cells have been well studied, it is still not possible to directly visualize the spatial and temporal distribution of NO3- with high resolution at the cellular level. Here, we report a nuclear-localized, genetically encoded fluorescent biosensor, which we named NitraMeter3.0, for the quantitative visualization of NO3- distribution in Arabidopsis thaliana. This biosensor tracked the spatiotemporal distribution of NO3- along the primary root axis and disruptions by genetic mutation of transport (low NO3- uptake) and assimilation (high NO3- accumulation). The developed biosensor effectively monitors NO3- concentrations at the cellular level in real time and spatiotemporal changes during the plant life cycle.
... However, protocols exist to overcome this limitation [55,56]. Additionally, the implementation of FRET-based nanosensors in plants has proven difficult due to gene silencing [42,
57]
. The expression of FRET-based nanosensors in mutant plants deficient in gene silencing has overcome this problem and allowed the monitoring of metabolite levels in the cytosol of epidermal leaf cells and roots of plants [9,57]. ...
... Additionally, the implementation of FRET-based nanosensors in plants has proven difficult due to gene silencing [42,57]. The expression of FRET-based nanosensors in mutant plants deficient in gene silencing has overcome this problem and allowed the monitoring of metabolite levels in the cytosol of epidermal leaf cells and roots of plants [9,
57]
. Genetically encoded FRET-based nanosensors have been used to detect protein interactions with nucleic acids [41,58], to sense reactive oxygen species [59], and to monitor levels of ions or metabolites [43,60]. ...
... Notably, singleorescent protein biosensors can also be ratiometric when the fluorescent protein has excitation wavelengths that respond differentially to an analyte, for example, the pl optimised pH-sensitive green florescent protein (pHGFP [51]; based on the pH-sensi pHluorin [52]) and redox-oxidation sensitive green fluorescent proteins (roGFPs) [53 A disadvantage of FRET-based nanosensors that use fluorescent proteins is the overla emission wavelength with chlorophyll autofluorescence (ex 410-460 nm, em 600-700 and the fluorescence of cell wall components (ex 235-475 nm, em 400-500 nm) and sta However, protocols exist to overcome this limitation [55,56]. Additionally, the implem tation of FRET-based nanosensors in plants has proven difficult due to gene silen [42,
57]
. The expression of FRET-based nanosensors in mutant plants deficient in gen lencing has overcome this problem and allowed the monitoring of metabolite levels in cytosol of epidermal leaf cells and roots of plants [9,57]. ...
Nanosensor Applications in Plant Science
Plant science is a major research topic addressing some of the most important global challenges we face today, including energy and food security. Plant science has a role in the production of staple foods and materials, as well as roles in genetics research, environmental management, and the synthesis of high-value compounds such as pharmaceuticals or raw materials for energy production. Nanosensors—selective transducers with a characteristic dimension that is nanometre in scale—have emerged as important tools for monitoring biological processes such as plant signalling pathways and metabolism in ways that are non-destructive, minimally invasive, and capable of real-time analysis. A variety of nanosensors have been used to study different biological processes; for example, optical nanosensors based on Förster resonance energy transfer (FRET) have been used to study protein interactions, cell contents, and biophysical parameters, and electrochemical nanosensors have been used to detect redox reactions in plants. Nanosensor applications in plants include nutrient determination, disease assessment, and the detection of proteins, hormones, and other biological substances. The combination of nanosensor technology and plant sciences has the potential to be a powerful alliance and could support the successful delivery of the 2030 Sustainable Development Goals. However, a lack of knowledge regarding the health effects of nanomaterials and the high costs of some of the raw materials required has lessened their commercial impact.
... Advances in flexible electronic devices, microfluidics, and nanofabrication technologies have combined with the emergence of the internet of things paradigm to achieve continuous, minimally invasive or noninvasive, long-term and real-time high-throughput plant physiological and chemical phenotypic trait detection (Han et al. 2017;Byun et al. 2019). Implantable nanosensors have been successfully applied to measure plant reactive oxygen species (Fichman et al. 2019), wound-induced H 2 O 2 waves (Lew et al. 2020), glucose
(Deuschle et al. 2006;
Zhu et al. 2017), sucrose (Chaudhuri et al. 2008), Ca 2+ (Krebs et al. 2012;Matsuda et al. 2013), nitric oxide (Giraldo et al. 2015), ethylene (Esser et al. 2012), jasmonic acid (Larrieu et al. 2015), methyl salicylate (Li et al. 2018b), abscisic acid (Jones et al. 2014;Waadt et al. 2014), and pH (Fasano et al. 2001). Sensors that make it possible to precisely and accurately monitor the onset of stress in individual plants will promote the enhancement of plant phenotyping approaches for plant breeding programs, utilizing high-throughput measurements of physiological and biochemical traits of stress-tolerant plant varieties in the future. ...
Role of the Genomics–Phenomics–Agronomy Paradigm in Plant Breeding
Plant breeding primarily focuses on improving agronomy traits, e.g. yield, quality, host plant resistance to pathogens and pests, and abiotic stress tolerance; however, the methods for their genetic improvement are being rapidly enhanced through genomics and phenomics. In the Genomics–Phenomics–Agronomy (G‐P‐A) paradigm, diverse research approaches have been conducted to bridge any two of these elements, and recently, all of them together. This review first highlights the progress to link (1) genomics to agronomy, (2) genomics to phenomics, and (3) phenomics to agronomy. Secondly, the G‐P‐A domain is dissected into different layers, each addressing the three elements simultaneously. These layers include genetic dissection through gene mapping using genome‐wide association studies and genomic selection using best linear unbiased prediction, Bayesian approaches, and machine learning. The objective of the review is to help readers to grasp the core developments among the exponentially growing literature in each of these fields. Through this review, the connections among the three elements of the G‐P‐A paradigm are coherently integrated toward the prospect of sustainable development of agronomy traits through both genomics and phenomics.
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Show abstract
... expression clones. Transgenic plant lines were generated using the Agrobacterium floral dip method as described previously
(28)
. Transformants were selected on agar plates containing ½ × Murashige Skoog (MS) medium with Kanamycin. ...
In vivo visualization of nitrate dynamics using a genetically encoded biosensor
Nitrate (NO 3 ⁻ ) uptake and distribution are critical to plant life. Although the upstream regulation of nitrate uptake and downstream responses to nitrate in a variety of cells have been well-studied, it is still not possible to directly visualize the spatial and temporal distribution of nitrate with high resolution at the cellular level. Here, we report a nuclear-localized, genetically encoded biosensor, nlsNitraMeter3.0, for the quantitative visualization of nitrate distribution in Arabidopsis thaliana . The biosensor tracked the spatiotemporal distribution of nitrate along the primary root axis and disruptions by genetic mutation of transport (low nitrate uptake) and assimilation (high nitrate accumulation). The developed biosensor effectively monitors nitrate concentrations at cellular level in real time and spatiotemporal changes during the plant life cycle.
One-Sentence Summary
A genetically encoded biosensor for in vivo visualization of spatiotemporal nitrate levels at a cellular resolution.
Non-invasive in-vivo glucose-based stress monitoring in plants
Plant stress responses involve a suite of genetically encoded mechanisms triggered by real-time interactions with their surrounding environment. Although sophisticated regulatory networks maintain proper homeostasis to prevent damage, the tolerance thresholds to these stresses vary significantly among organisms. Current plant phenotyping techniques and observables must be better suited to characterize the real-time metabolic response to stresses. This impedes practical agronomic intervention to avoid irreversible damage and limits our ability to breed improved plant organisms. Here, we introduce a sensitive, wearable electrochemical glucose-selective sensing platform that addresses these problems. Glucose is a primary plant metabolite, a source of energy produced during photosynthesis, and a critical molecular modulator of various cellular processes ranging from germination to senescence. The wearable-like technology integrates a reverse iontophoresis glucose extraction capability with an enzymatic glucose biosensor that offers a sensitivity of 22.7 nA/(μM·cm2), a limit of detection (LOD) of 9.4 μM, and a limit of quantification (LOQ) of 28.5 μM. The system's performance was validated by subjecting three different plant models (sweet pepper, gerbera, and romaine lettuce) to low-light and low-high temperature stresses and demonstrating critical differential physiological responses associated with their glucose metabolism. This technology enables non-invasive, non-destructive, real-time, in-situ, and in-vivo identification of early stress response in plants and provides a unique tool for timely agronomic management of crops and improving breeding strategies based on the dynamics of genome-metabolome-phenome relationships.
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Glucose sensing by regulator of G protein signaling 1 (RGS1) plays a crucial role in coordinating defense in response to environmental variation in tomato
• Low light intensities affect the outbreak of plant diseases. However, the underlying molecular mechanisms remain poorly understood. • HPLC analysis of tomato (Solanum lycopersicum) revealed that apoplastic glucose (Glc) levels decreased in response to low light. Conversely, low light-induced susceptibility to Pseudomonas syringae pv. tomato (Pst) DC3000 was significantly alleviated by exogenous Glc treatment. Using cell-based biolayer interferometry assays, we found that Glc specifically binds to the tomato regulator of G protein signaling 1 (RGS1). Laser scanning confocal microscopy imaging revealed that Glc triggers RGS1 endocytosis, which influences the uncoupling of the RGS1-Gα (GPA1) and GPA1-Gβ (SlGB1) proteins, in a dose- and duration-dependent manner. • Analysis of G protein single and double mutants revealed that RGS1 negatively regulates disease resistance under low light and is required for Glc-enhanced defense. Downstream of RGS1-Glc binding, GPA1 negatively mediates the light intensity-regulated defense, while SlGB1 positively regulates this process. • These results reveal a novel light intensity-responsive defense system that is mediated by a Glc-RGS1-G protein signaling pathway. This information will be critical for future investigations of how plant cells sense extracellular sugars and adjust defense under different environments, as well as genetic engineering approaches to improve stress resilience.
Strategies of nanotechnology as a defense system in plants
Today, the potential uses and benefits of nanotechnology are enormous, but little is known about the safety aspects of the application of nanotechnologies in crop production. Bipolymeric materials are important in agriculture. The unique properties of these materials at the nanoscale level make them essential and important. Organic farming changes to technology, biotechnology, and ultimately to bionanotechnology. Hence, in the present pandemic scenario, it is a great challenge to reduce toxicity from nature and enhance natural resources using nanotechnology. The “nano” would be a bigger economic force than software. In this chapter, we will see the unique potential of the nanotechnology business and its risky path. Its multidisciplinary approaches and the overall impact on potentially improve food production are also highlighted here. The defense mechanisms that counteract nanotoxicity and the role of nanoencapsulation, nanohybrid, nanosensor, and metal-based nanoparticles as well as antioxidant mechanisms are elaborated in this chapter.
| https://www.researchgate.net/publication/6852556_Rapid_Metabolism_of_Glucose_Detected_with_FRET_Glucose_Nanosensors_in_Epidermal_Cells_and_Intact_Roots_of_Arabidopsis_RNA-Silencing_Mutants |
Thurman v. United States | Ninth Circuit | 02-19-1970 | www.anylaw.com
Research the case of Thurman v. United States, from the Ninth Circuit, 02-19-1970. AnyLaw is the FREE and Friendly legal research service that gives you unlimited access to massive amounts of valuable legal data.
Thurman v. United States
THOMPSON, District Judge:
The District Court denied Appellant Thurman's motion to vacate judgment and sentence (28 U.S.C. § 2255).
In June, 1961, Thurman was indicted on two charges, conspiracy (18 U.S.C. § 371) and armed postal robbery with life in jeopardy (18 U.S.C. § 2114). After a jury trial, he was convicted and sentenced to five years on the conspiracy count and twenty-five years (mandatory) on the robbery count. The sentences were ordered to run concurrently. Subsequently, the conviction was reversed and a new trial ordered. Thurman v. United States, 316 F.2d 205 (9th Cir. 1963).
On August 8, 1963, Thurman was in Court with retained counsel. He withdrew his pleas of not guilty and entered pleas of guilty to both counts. On the following day, Thurman was sentenced to five years' imprisonment on the conspiracy count and to twenty-five years' imprisonment on the postal robbery count, to run consecutively, but the Court suspended execution of the twenty-five year sentence and placed him on probation for five years to commence on expiration of the five year sentence. The term of probation commenced on January 25, 1966 on Thurman's release from prison. In 1968, Thurman was arrested as a probation violator and after extensive hearings, his probation was revoked on October 15, 1968.
In the meantime, i.e., on June 25, 1968, Thurman filed the Section 2255 motion from the denial of which the instant appeal is taken. With one exception, the contentions on appeal are frivolous. The argument that a more severe sentence was imposed after reversal of the original judgment by the Court of Appeals, because the sentences on the two counts were ordered to run consecutively rather than concurrently, does have a surface allure.
In North Carolina v. Pearce, 395 U.S. 711, 89 S. Ct. 2072, 23 L. Ed. 2d 656 (1969), it was decided that upon resentencing after vacation of the initial sentence, "a more severe" sentence cannot constitutionally be imposed unless reasons based on objective information of identifiable conduct by the defendant after the original sentencing are made a part of the record. No such reasons are recited in this record. We must determine whether the second sentence against Thurman was in fact a more severe sentence in violation of due process.
This inquiry cannot be answered by a dicta that consecutive sentences are necessarily more severe than concurrent sentences. The totality of the impact of the sentence on the defendant must be considered.
On March 19, 1962, at the original sentencing after the Court imposed the sentence of five years on Count I and twenty-five years on Count II, to run concurrently, defendant's attorney suggested that execution of the twenty-five year sentence should be suspended. The colloquy between Court and counsel is copied in the margin. 1
When Thurman was resentenced on August 9, 1963, he had been interviewed by the probation officer on the previous afternoon, who had reported to the Court. The colloquy at resentencing is quoted in the margin. 2
Patently, an argument that a twenty-five year term concurrent with a five year term is less severe than a five year term followed by five years' probation under an unexecuted twenty-five year sentence exalts form over substance. Thurman did not consider it so, nor did his attorney, nor did the Court. Everyone thought he was receiving lenient treatment rather than a more severe sentence. There is no basis for a charge of vindictiveness or of apprehension of retaliatory motivation which influenced the Court in Pearce, supra, to find a deprivation of due process.
Affirmed.
Disposition
Affirmed.
* Hon. Bruce R. Thompson, United States District Judge, Reno, Nevada, sitting by designation.
1. "MR. MULL: Yes. Well, I am very happy if that does apply. "There's one other thing I'd like to call the Court's attention to, or just suggest to the Court, that before this Court some years ago there was a case, United States v. John Breckenridge in which a similar offense was charged, first count, second count, the same as in this charge. In that case after three trials the Defendant was convicted and he was given probation on the second count and on the first count he was given five years. "THE COURT: I am mindful of that also, Mr. Mull. "MR. MULL: The Court's mindful of that case also? "THE COURT: Yes. I am mindful of that, and I have thought of that, but in going over Mr. Thurman's -- he's hurt people. He's hurt people. In looking over his record Mr. Thurman has hurt people. That is all there is to it. It's not only that he's committed a crime against the United States in these two instances, in the opinion of the Court the evidence was overwhelming of his guilt of this crime although I tried my best and, well, anyway, let it go at that. There is no question that the evidence was very ample to sustain the verdict reached by the Jury in this matter. But in addition to this I feel in looking over his past record -- the whole thing there is almost ten pages -- it is a case of his hurting people, and this man, in my opinion, has got -- he's come to the point of reckoning. This is the beginning of the time when he has to start paying back to society for what he has done previously, and that's the reason for my sentence. And the two are to run concurrently. I hope by sentencing him under 4208(a) (2) that some good will come from such a sentence. "That's my sentence. Thank you, Mr. Mull."
2. "THE COURT: Mr. Thurman, is there anything that you desire to say before judgment is pronounced in this case? "THE DEFENDANT: No, sir. "THE COURT: Mr. Thurman, I have read this report and your case, obviously, is something out of the ordinary. It is not the usual case that gets before me here. You have already been in prison for what, about 19 months, isn't it? "THE DEFENDANT: Yes, sir. "THE COURT: Well, you made a suggestion as to what you think I ought to do in this matter here, and I am going to assume that 19 months imprisonment has sort of gotten you straightened around so that you know where you are going and what you are going to do. "If I go along with your suggestion in this matter are you going to let me down or are you going to get straightened around and behave yourself from here on out? "THE DEFENDANT: I will straighten around, I guess. "THE COURT: Well, you ought to know by now that that is no place to be, up there. The best prison in the world is not as good as being out here broke on the street. "THE DEFENDANT: That is correct. "THE COURT: Well, I am going to go along with what you have to suggest in this matter here on the basis of, as I say, this is an unusual case. I have a strong feeling in criminal cases you can't say everybody gets ten days in jail or everybody gets fined $50, because that doesn't make any sense at all. If you fined everybody $50 it may mean the last dime in the world that one man has got and the other man $50 doesn't mean a thing to. It is just like taking a cigarette away from him. So I try to handle each ase (sic) on an individual basis. "In this case it is the judgment of the Court and the sentence of the law that for the offense to which you have pled guilty in Count 1 you be imprisoned in a federal penitentiary for a term of five years. As to the offense set forth in Count 2 of the indictment you be imprisoned in a federal penitentiary for a term of 25 years. These terms are to be consecutive, but the execution of this sentence on Count 2 is suspended and you will be placed on probation at the expiration of the term on Count 1, so that when you have completed your sentence there you will be on probation. "Now, is this in line with what you thought you were suggesting to me? "THE DEFENDANT: Yes, sir. "THE COURT: Are you satisfied now that you have gotten a fair shake as far as I am concerned? "THE DEFENDANT: I was hoping I might get something on the 19th months, but I realize -- "THE COURT: You told the probation officer, though, that you were willing to forget that. "THE DEFENDANT: Yes, I am. "THE COURT: All right. In other words, you are getting just what you asked for, aren't you? "THE DEFENDANT: Yes."
| https://www.anylaw.com/case/thurman-v-united-states/ninth-circuit/02-19-1970/6IfSP2YBTlTomsSB0f3E |
London Borough of Croydon v K-A (SEN) - Case Law - VLEX 925871439
0: [object Object]. 1: [object Object]. 2: [object Object]. 3: [object Object]. 4: [object Object]. 5: [object Object]
London Borough of Croydon v K-A (SEN)
Jurisdiction UK Non-devolved Court Upper Tribunal (Administrative Appeals Chamber) Judge Judge Wikeley Neutral Citation [2022] UKUT 106 (AAC) Subject Matter Special educational needs - special educational provision - naming school,Special educational needs - special educational provision - naming school or other institution in EHC plan,Tribunal procedure,practice - precedence of decisions,Wikeley,N Published date 24 May 2022
London Borough of Croydon v K.-A.
[2022] UKUT 106 (AAC)
1
IN THE UPPER TRIBUNAL Appeal No. UA -2021- 00 1986- HS
ADMINISTRATIVE APPEALS CHAMBER
On appeal from the First-tier Tribunal (HESC Chamber)
Between: London Borough of Croydon Appellant
- v –
S. K- A. Respondent
Before: Upper Tribunal Judge Wikeley
Hearing date: 6 April 2022
Decision date: 20 April 2022
Representation:
Appellant: Ms Amelia Walker of Counsel, instructed by the London Borough
of Croydon
Respondent: Ms Alice de Coverley of Counsel, instructed by the Coram
Children’s Legal Centre
DECISION
The decision of the Upper Tribunal is to dismiss the Local Author ity’s appeal.
The decision of the First-tier Tribunal dated 14 April 2021 under file number
EH 306 /20/00 032 was not in error of law (section 11 of the Tribunals, Courts and
Enforcement Act 2007 ).
ORDER UNDER RULE 14
Pursuant to rule 14(1) of the Tribunal Procedure (Upper Tribunal) Rules 2008, it is
prohibited for any person to disclose or publish any matter likely to lead members of
the public to identify the young person in these proceedings. This order does not
apply to (a) the young person’s parent (s); (b) any person to whom the young
person’s parent (s), in d ue exercise of their parental responsibility, disclose such a
matter or who learns of it through publication by either parent, where such publication
is a due exercise of parental responsibility; (c) any person exercising statutory
(including judicial) functions in relation to the young person where knowledge of the
matter is reasonably necessary for the proper exercise of the functions.
London Borough of Croydon v K.-A. [2022] UKUT 106 (AAC)
Case no: UA - 202 1- 00 1986- HS
2
REASONS FOR DECISION
Th e legal issue raised by this appeal to the Upper Tribunal
1. Th is appeal by the London Borough of Croydon (‘the local authority ’ or ‘the LA’ )
against the decision of the First- tier Tribunal (‘the Tribunal’) concerns the proper
interpretation and application of section 9 of the Education Act 1996. This
section (as amended) provides as follows:
Pupils to be educated in acco rdance with parents’ wishes
9. In exercising or performing all their respective powers and duties under
the Education Acts, the Secretary of State and local authorities shall have
regard to the general principle that pupils are to be educated in
accordance with the wishes of their p arents, so far as that is compatible
with the provision of efficient instruction and training and the avoidance of
unreasonable public expenditure.
2. It is not in dispute that section 9 also applies to the Tribunal insofar as it stands
in the shoes of a local authority in deciding matters on appeal. It is also
common ground that section 9 does not impose a duty to act in accordance with
the parental preference, but rather to have regard to it.
The background to this case
3. This case concerns a young boy who I shall simply call J, in order to protect his
privacy and anonymity, as well as that of his family. At the time of the Tribunal
hearing, J was aged 13. He has a diagnosis of severe bilateral spastic
quadriplegia form of Cerebral Palsy. J is non-verbal, doubly incontinent, non-
ambulant and a full-time wheelchair user, who requires hoisting for all transfers
during the day. He has serious respiratory problems and profound and multiple
learning difficulties. He is, inevitably, reliant on adults for all his personal care
and mobility needs.
4. That summary is doubtless wholly inadequate in conveying the challenges
faced both b y J a nd by his mother on his behalf. I apologise in advance for the
inordinate length of this decision, which may seem somewhat de tached from
the real life issues they face, but the appeal raises a wider point of legal
principle that may affect other children with special educational needs.
The proceedings before the First-tier Tribunal
5. In February 2020 the local authority decided to make and maintain an
Education Health and Care ( ‘ EHC ’ ) Plan for J. By the time the matter came
before the Tribunal, the local authority had accepted that J needed a 52 -week
per year residential placement. It proposed (in Section I o f t he E HC Plan) a
placement for J at a school I will simply ca ll ‘the Manor’, an independent special
school. J’s mother felt that he needed to be at a diffe rent residential school (‘the
Trust’) , a non-maintained special school. In fact as it happened J had already
been placed at the Trust for post -operative recuperation, but had then remained
there in the light of the national lockdown caused by the Covid-19 pandemic.
6. J’s mother accordingly appe al ed to the Tribunal under section 51 of the
Children and Families Act 2014, against the contents of the EHC Plan made by
the local authority for her son. At the Tribunal hearing the live issues in dispute
| https://vlex.co.uk/vid/london-borough-of-croydon-925871439 |
Percutaneous Coronary Intervention With the Angiolite Drug-eluting Stent: an Optical Cohenrece Tomography Study - Full Text View - ClinicalTrials.gov
Percutaneous Coronary Intervention With the Angiolite Drug-eluting Stent: an Optical Cohenrece Tomography Study
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government.
Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02776267 Recruitment Status :
Completed First Posted : May 18, 2016 Last Update Posted : July 17, 2018
Sponsor:
iVascular
Information provided by (Responsible Party):
Josep Rodes-Cabau, Centre de Recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Quebec
Study Details
Study Description
Brief Summary:
The purpose of this study is to perform a first-in-man assessment of feasibility, exploratory efficacy and clinical performance of the novel Angiolite drug-eluting stent (iVascular, Barcelona, Spain) utilizing intracoronary optical coherence tomography (OCT).
Condition or disease Intervention/treatment Phase Coronary Heart Disease Device: Angiolite stent Not Applicable
Detailed Description:
This is a prospective registry including patient scheduled for a clinically-indicated percutaneous coronary intervention (PCI) of a de novo epicardial lesion with indication for drug-eluting stent implantation. Following study enrolment and PCI/stent with the Angiolite DES, patients will be scheduled for follow-up surveillance coronary angiography and OCT with the C7-XRTM Fourier Domain OCT system with C7 DragonflyTM catheter (St Jude Medical, Minneapolis, MN) or with the Terumo LunawayTM OCT system with fastview catheter (Terumo Medical Corporation, Tokyo, Japan). An adaptive design component of the study will randomize patients to either 3-month or 6-month angio/OCT follow-up. Clinical follow-up will occur at 30 days, 3 months, 6 months, 12 months and 24 months post PCI.
Study Design
Layout table for study information Study Type : Interventional
(Clinical Trial) Estimated Enrollment : 100 participants Allocation: Randomized Intervention Model: Parallel Assignment Masking: None (Open Label) Primary Purpose: Treatment Official Title: Percutaneous Coronary Intervention With the ANgiolite Drug-Eluting Stent: an Optical CoHerence TOmogRaphy Study. The ANCHOR Study Study Start Date : May 2015 Actual Primary Completion Date : June 2017 Actual Study Completion Date : June 2018
Arms and Interventions
Arm Intervention/treatment Experimental: Angiolite stent - 3-month angiogram/OCT Patients scheduled for PCI (and whot meet pre-specified inlcusion criteria) are enrolled to receive the Angiolite DES. They will undergo a scheduled repeat coronary angiogram and OCT evaluation at 3-month post index PCI. Device: Angiolite stent Following index PCI, patients will be followed via scheduled clinic and/or phone contact at 1-, 3-, 6-, 12- and 24-month. Patient will be randomized to undergo a scheduled repeat coronary angiogram and OCT evaluation at either at 3- or 6-month post index PCI. Other Name: (Angiolite CE Mark reference number: 2014 12 0833 ED) Experimental: Angiolite stent - 6-month angiogram/OCT Patients scheduled for PCI (and whot meet pre-specified inlcusion criteria) are enrolled to receive the Angiolite DES. They will undergo a scheduled repeat coronary angiogram and OCT evaluation at 6-month post index PCI. Device: Angiolite stent Following index PCI, patients will be followed via scheduled clinic and/or phone contact at 1-, 3-, 6-, 12- and 24-month. Patient will be randomized to undergo a scheduled repeat coronary angiogram and OCT evaluation at either at 3- or 6-month post index PCI. Other Name: (Angiolite CE Mark reference number: 2014 12 0833 ED)
Outcome Measures
Primary Outcome Measures
:
Neo-intimal coverage [ Time Frame: 6-month ]
Strut-based analysis: % of covered struts. Cross-sectional analysis: number of cross-sections with RUTTS (Rate of uncovered to total number of struts) score>30%.
Measured by an independant OCT laboratory
Neo-intimal obstruction [ Time Frame: 6-month ]
Strut-based analysis: mean neointimal thickness (µm). Cross-sectional analysis: neointimal volume obstruction (%). Measured by an independant OCT laboratory
Secondary Outcome Measures
:
Neo-intimal coverage [ Time Frame: 3-month ]
Strut-based analysis: % of covered struts. Cross-sectional analysis: number of cross-sections with RUTTS (Rate of uncovered to total number of struts) score>30%.
Measured by an independant OCT laboratory.
Neo-intimal obstruction [ Time Frame: 3-month ]
Strut-based analysis: mean neointimal thickness (µm). Cross-sectional analysis: neointimal volume obstruction (%). Measured by an independant OCT laboratory.
Apposition [ Time Frame: 3- and 6-month ]
Strut-based analysis: incomplete strut apposition (ISA) rate. Cross-sectional analysis: % frames with ISA. Measured by an independant OCT laboratory.
In-stent angiographic late lumen in mm [ Time Frame: 6-month ]
Confirmed by Imaging and measured by an independant QCA laboratory
In-stent and in-segment restenosis [ Time Frame: 6-month ]
Confirmed by Imaging and measured by an independant QCA laboratory (Reduction in percent diameter stenosis of stented segment of >= 50%
CV death [ Time Frame: 6-month and 1-year ]
Death from any known cardiovascular etiology
Myocardial infarction [ Time Frame: Peri-procedural, spontaneous ]
Peri-procedural myocardial infarction will be defined according to the 3rd universal definition of MI Following PCI, myocardial infarction will be defined according to the specific clinical situation of the patient.
Target-lesion revascularization [ Time Frame: 24 months ]
Any repeat revascularization du to a restenosis within the DES-treated segment
Binary restenosis [ Time Frame: 24 months ]
Reduction in percent diameter stenosis of stented segment of < vs.>= 50%
Eligibility Criteria
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Information from the National Library of Medicine
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
Layout table for eligibility information Ages Eligible for Study: 18 Years to 85 Years (Adult, Older Adult) Sexes Eligible for Study: All Accepts Healthy Volunteers: No
Criteria
Inclusion Criteria:
Patients scheduled for clinically-indicated PCI of a de nove epicardial lesion, including those with chronic stable angina, ACS (defined as NSTEMI or ACS with negative cardiac enzymes) or in the setting of elective PCI.
Indication for DES implantation
Target lesion must have visually estimated stenosis ≥50% and one of the following: stenosis ≥70% or evidence of ischemia
Strong preference for single stent coverage per lesion, but if unexpected clinically indicated second stent placement with overlap is needed, these patients will not be excluded from optical coherence tomographic follow-up
Target lesion, if possible, should be predilated/pretreated
Exclusion Criteria:
Age >85 years
Acute ST segment elevation MI (STEMI)
Cardiogenic shock
Known left ventricular ejection fraction <30%
Contraindication for dual antiplatelet therapy (DAPT) for at least 6-month duration
Iodinated contrast allergy
Renal impairment with serum creatinine >2.0 mg/dL
Anticipated medical non-compliance
Life-expectancy <12 months
Chronic total occlusion (CTO) in the target vessel
Bifurcation lesion requiring a two-stent strategy
In-stent restenosis
Severe lesion/segment angulation/tortuosity
Severe vessel/lesion calcification
Simultaneous PCI within the same or different vessel during the same procedure
Lesion unsuitable for OCT (proximal lesions <10 mm from ostium of left main or right coronary arteries)
Lesion length >18 mm
Stent length >24 mm
Stent diameter ≤2.5 mm and > 4.0 mm
Unprotected left main coronary artery disease (≥50% diameter stenosis)
>1 lesion
Planned use of 2 overlapping stents
Contacts and Locations
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02776267
Locations
Layout table for location information Spain Hospital Vall D'Hebron Barcelona, Spain Hospital Universitario de Leon Leon, Spain Hospital Clinico San Carlos Madrid, Spain Hospital Universitario Marqués de Valdecilla Santander, Spain
Sponsors and Collaborators
Josep Rodes-Cabau
iVascular
Investigators
Layout table for investigator information Principal Investigator: Josep Rodes-Cabau, MD Institut universitaire de cardiologie et de pneumologie de Québec, University Laval
More Information
Publications:
Farooq V, Gogas BD, Serruys PW. Restenosis: delineating the numerous causes of drug-eluting stent restenosis. Circ Cardiovasc Interv. 2011 Apr 1;4(2):195-205. doi: 10.1161/CIRCINTERVENTIONS.110.959882. No abstract available.
Garg S, Serruys PW. Coronary stents: current status. J Am Coll Cardiol. 2010 Aug 31;56(10 Suppl):S1-42. doi: 10.1016/j.jacc.2010.06.007.
Daemen J, Wenaweser P, Tsuchida K, Abrecht L, Vaina S, Morger C, Kukreja N, Juni P, Sianos G, Hellige G, van Domburg RT, Hess OM, Boersma E, Meier B, Windecker S, Serruys PW. Early and late coronary stent thrombosis of sirolimus-eluting and paclitaxel-eluting stents in routine clinical practice: data from a large two-institutional cohort study. Lancet. 2007 Feb 24;369(9562):667-78. doi: 10.1016/S0140-6736(07)60314-6.
Nakazawa G, Finn AV, Joner M, Ladich E, Kutys R, Mont EK, Gold HK, Burke AP, Kolodgie FD, Virmani R. Delayed arterial healing and increased late stent thrombosis at culprit sites after drug-eluting stent placement for acute myocardial infarction patients: an autopsy study. Circulation. 2008 Sep 9;118(11):1138-45. doi: 10.1161/CIRCULATIONAHA.107.762047. Epub 2008 Aug 25.
Serruys PW, Ormiston JA, Onuma Y, Regar E, Gonzalo N, Garcia-Garcia HM, Nieman K, Bruining N, Dorange C, Miquel-Hebert K, Veldhof S, Webster M, Thuesen L, Dudek D. A bioabsorbable everolimus-eluting coronary stent system (ABSORB): 2-year outcomes and results from multiple imaging methods. Lancet. 2009 Mar 14;373(9667):897-910. doi: 10.1016/S0140-6736(09)60325-1.
Prati F, Guagliumi G, Mintz GS, Costa M, Regar E, Akasaka T, Barlis P, Tearney GJ, Jang IK, Arbustini E, Bezerra HG, Ozaki Y, Bruining N, Dudek D, Radu M, Erglis A, Motreff P, Alfonso F, Toutouzas K, Gonzalo N, Tamburino C, Adriaenssens T, Pinto F, Serruys PW, Di Mario C; Expert's OCT Review Document. Expert review document part 2: methodology, terminology and clinical applications of optical coherence tomography for the assessment of interventional procedures. Eur Heart J. 2012 Oct;33(20):2513-20. doi: 10.1093/eurheartj/ehs095. Epub 2012 May 31. No abstract available.
Tearney GJ, Regar E, Akasaka T, Adriaenssens T, Barlis P, Bezerra HG, Bouma B, Bruining N, Cho JM, Chowdhary S, Costa MA, de Silva R, Dijkstra J, Di Mario C, Dudek D, Falk E, Feldman MD, Fitzgerald P, Garcia-Garcia HM, Gonzalo N, Granada JF, Guagliumi G, Holm NR, Honda Y, Ikeno F, Kawasaki M, Kochman J, Koltowski L, Kubo T, Kume T, Kyono H, Lam CC, Lamouche G, Lee DP, Leon MB, Maehara A, Manfrini O, Mintz GS, Mizuno K, Morel MA, Nadkarni S, Okura H, Otake H, Pietrasik A, Prati F, Raber L, Radu MD, Rieber J, Riga M, Rollins A, Rosenberg M, Sirbu V, Serruys PW, Shimada K, Shinke T, Shite J, Siegel E, Sonoda S, Suter M, Takarada S, Tanaka A, Terashima M, Thim T, Uemura S, Ughi GJ, van Beusekom HM, van der Steen AF, van Es GA, van Soest G, Virmani R, Waxman S, Weissman NJ, Weisz G; International Working Group for Intravascular Optical Coherence Tomography (IWG-IVOCT). Consensus standards for acquisition, measurement, and reporting of intravascular optical coherence tomography studies: a report from the International Working Group for Intravascular Optical Coherence Tomography Standardization and Validation. J Am Coll Cardiol. 2012 Mar 20;59(12):1058-72. doi: 10.1016/j.jacc.2011.09.079. Erratum In: J Am Coll Cardiol. 2012 May 1;59(18):1662. Dudeck, Darius [corrected to Dudek, Darius]; Falk, Erlin [corrected to Falk, Erling]; Garcia, Hector [corrected to Garcia-Garcia, Hector M]; Sonada, Shinjo [corrected to Sonoda, Shinjo]; Troels, Thim [corrected to Thim, Troels]; van Es, Gerrit-Ann [correct.
Suzuki Y, Ikeno F, Koizumi T, Tio F, Yeung AC, Yock PG, Fitzgerald PJ, Fearon WF. In vivo comparison between optical coherence tomography and intravascular ultrasound for detecting small degrees of in-stent neointima after stent implantation. JACC Cardiovasc Interv. 2008 Apr;1(2):168-73. doi: 10.1016/j.jcin.2007.12.007.
Murata A, Wallace-Bradley D, Tellez A, Alviar C, Aboodi M, Sheehy A, Coleman L, Perkins L, Nakazawa G, Mintz G, Kaluza GL, Virmani R, Granada JF. Accuracy of optical coherence tomography in the evaluation of neointimal coverage after stent implantation. JACC Cardiovasc Imaging. 2010 Jan;3(1):76-84. doi: 10.1016/j.jcmg.2009.09.018. Epub 2010 Jan 12.
Templin C, Meyer M, Muller MF, Djonov V, Hlushchuk R, Dimova I, Flueckiger S, Kronen P, Sidler M, Klein K, Nicholls F, Ghadri JR, Weber K, Paunovic D, Corti R, Hoerstrup SP, Luscher TF, Landmesser U. Coronary optical frequency domain imaging (OFDI) for in vivo evaluation of stent healing: comparison with light and electron microscopy. Eur Heart J. 2010 Jul;31(14):1792-801. doi: 10.1093/eurheartj/ehq168. Epub 2010 Jun 5.
Gutierrez-Chico JL, van Geuns RJ, Regar E, van der Giessen WJ, Kelbaek H, Saunamaki K, Escaned J, Gonzalo N, di Mario C, Borgia F, Nuesch E, Garcia-Garcia HM, Silber S, Windecker S, Serruys PW. Tissue coverage of a hydrophilic polymer-coated zotarolimus-eluting stent vs. a fluoropolymer-coated everolimus-eluting stent at 13-month follow-up: an optical coherence tomography substudy from the RESOLUTE All Comers trial. Eur Heart J. 2011 Oct;32(19):2454-63. doi: 10.1093/eurheartj/ehr182. Epub 2011 Jun 9.
Toledano Delgado FJ, Alvarez-Ossorio MP, de Lezo Cruz-Conde JS, Bellido FM, Romero Moreno MA, Fernandez-Aceytuno AM, de Lezo Herrerosde Tejada JS, Pineda SO, Saint-Gerons JM, Pavlovic D. Optical coherence tomography evaluation of late strut coverage patterns between first-generation drug-eluting stents and everolimus-eluting stent. Catheter Cardiovasc Interv. 2014 Nov 1;84(5):720-6. doi: 10.1002/ccd.25235. Epub 2013 Oct 31.
Kim JS, Jang IK, Kim JS, Kim TH, Takano M, Kume T, Hur NW, Ko YG, Choi D, Hong MK, Jang Y. Optical coherence tomography evaluation of zotarolimus-eluting stents at 9-month follow-up: comparison with sirolimus-eluting stents. Heart. 2009 Dec;95(23):1907-12. doi: 10.1136/hrt.2009.167759. Epub 2009 Jun 16.
Chieffo A, Buchanan GL, Parodi G, Versaci F, Bianchi RM, Valenti R, Sacca S, Mongiardo A, Span S, Migliorini A, Spaccarotella C, Reimers B, Antoniucci D, Indolfi C, Ferrari A, Maehara A, Mintz GS, Colombo A. Drug-eluting stent implantation in patients with acute coronary syndrome - the Activity of Platelets after Inhibition and Cardiovascular Events: Optical Coherence Tomography (APICE OCT) study. EuroIntervention. 2014 Dec;10(8):916-23. doi: 10.4244/EIJY14M06_10.
Verheye S, Ormiston JA, Stewart J, Webster M, Sanidas E, Costa R, Costa JR Jr, Chamie D, Abizaid AS, Pinto I, Morrison L, Toyloy S, Bhat V, Yan J, Abizaid A. A next-generation bioresorbable coronary scaffold system: from bench to first clinical evaluation: 6- and 12-month clinical and multimodality imaging results. JACC Cardiovasc Interv. 2014 Jan;7(1):89-99. doi: 10.1016/j.jcin.2013.07.007. Epub 2013 Oct 16.
Kim JS, Jang IK, Fan C, Kim TH, Kim JS, Park SM, Choi EY, Lee SH, Ko YG, Choi D, Hong MK, Jang Y. Evaluation in 3 months duration of neointimal coverage after zotarolimus-eluting stent implantation by optical coherence tomography: the ENDEAVOR OCT trial. JACC Cardiovasc Interv. 2009 Dec;2(12):1240-7. doi: 10.1016/j.jcin.2009.10.006.
Qian J, Zhang YJ, Xu B, Yang YJ, Yan HB, Sun ZW, Zhao YL, Tang YD, Gao Z, Chen J, Cui JG, Mintz GS, Gao RL. Optical coherence tomography assessment of a PLGA-polymer with electro-grafting base layer versus a PLA-polymer sirolimus-eluting stent at three-month follow-up: the BuMA-OCT randomised trial. EuroIntervention. 2014 Nov;10(7):806-14. doi: 10.4244/EIJY14M07_17.
Prati F, Romagnoli E, Valgimigli M, Burzotta F, De Benedictis M, Ramondo A, Mehran R, Stella PR. Randomized comparison between 3-month Cre8 DES vs. 1-month Vision/Multilink8 BMS neointimal coverage assessed by OCT evaluation: the DEMONSTRATE study. Int J Cardiol. 2014 Oct 20;176(3):904-9. doi: 10.1016/j.ijcard.2014.08.031. Epub 2014 Aug 13.
Mauri L, Kereiakes DJ, Yeh RW, Driscoll-Shempp P, Cutlip DE, Steg PG, Normand SL, Braunwald E, Wiviott SD, Cohen DJ, Holmes DR Jr, Krucoff MW, Hermiller J, Dauerman HL, Simon DI, Kandzari DE, Garratt KN, Lee DP, Pow TK, Ver Lee P, Rinaldi MJ, Massaro JM; DAPT Study Investigators. Twelve or 30 months of dual antiplatelet therapy after drug-eluting stents. N Engl J Med. 2014 Dec 4;371(23):2155-66. doi: 10.1056/NEJMoa1409312. Epub 2014 Nov 16.
Colombo A, Chieffo A, Frasheri A, Garbo R, Masotti-Centol M, Salvatella N, Oteo Dominguez JF, Steffanon L, Tarantini G, Presbitero P, Menozzi A, Pucci E, Mauri J, Cesana BM, Giustino G, Sardella G. Second-generation drug-eluting stent implantation followed by 6- versus 12-month dual antiplatelet therapy: the SECURITY randomized clinical trial. J Am Coll Cardiol. 2014 Nov 18-25;64(20):2086-97. doi: 10.1016/j.jacc.2014.09.008. Epub 2014 Sep 15.
Thygesen K, Alpert JS, Jaffe AS, Simoons ML, Chaitman BR, White HD; Joint ESC/ACCF/AHA/WHF Task Force for Universal Definition of Myocardial Infarction; Authors/Task Force Members Chairpersons; Thygesen K, Alpert JS, White HD; Biomarker Subcommittee; Jaffe AS, Katus HA, Apple FS, Lindahl B, Morrow DA; ECG Subcommittee; Chaitman BR, Clemmensen PM, Johanson P, Hod H; Imaging Subcommittee; Underwood R, Bax JJ, Bonow JJ, Pinto F, Gibbons RJ; Classification Subcommittee; Fox KA, Atar D, Newby LK, Galvani M, Hamm CW; Intervention Subcommittee; Uretsky BF, Steg PG, Wijns W, Bassand JP, Menasche P, Ravkilde J; Trials & Registries Subcommittee; Ohman EM, Antman EM, Wallentin LC, Armstrong PW, Simoons ML; Trials & Registries Subcommittee; Januzzi JL, Nieminen MS, Gheorghiade M, Filippatos G; Trials & Registries Subcommittee; Luepker RV, Fortmann SP, Rosamond WD, Levy D, Wood D; Trials & Registries Subcommittee; Smith SC, Hu D, Lopez-Sendon JL, Robertson RM, Weaver D, Tendera M, Bove AA, Parkhomenko AN, Vasilieva EJ, Mendis S; ESC Committee for Practice Guidelines (CPG); Bax JJ, Baumgartner H, Ceconi C, Dean V, Deaton C, Fagard R, Funck-Brentano C, Hasdai D, Hoes A, Kirchhof P, Knuuti J, Kolh P, McDonagh T, Moulin C, Popescu BA, Reiner Z, Sechtem U, Sirnes PA, Tendera M, Torbicki A, Vahanian A, Windecker S; Document Reviewers; Morais J, Aguiar C, Almahmeed W, Arnar DO, Barili F, Bloch KD, Bolger AF, Botker HE, Bozkurt B, Bugiardini R, Cannon C, de Lemos J, Eberli FR, Escobar E, Hlatky M, James S, Kern KB, Moliterno DJ, Mueller C, Neskovic AN, Pieske BM, Schulman SP, Storey RF, Taubert KA, Vranckx P, Wagner DR. Third universal definition of myocardial infarction. J Am Coll Cardiol. 2012 Oct 16;60(16):1581-98. doi: 10.1016/j.jacc.2012.08.001. Epub 2012 Sep 5. No abstract available.
| https://clinicaltrials.gov/ct2/show/NCT02776267 |
ST. CHARLES CABLE TV v. E | 664 F.Supp. 824 (1987) | upp82411328 | Leagle.com
OPINION MacMAHON District Judge. Invoking diversity jurisdiction plaintiffs brought this action against defendant Eagle Comtronics...upp82411328
ST. CHARLES CABLE TV v. EAGLE COMTRONICS, INC.
No. 83 Civ. 7126 (LFM).
View Case
Cited Cases
Citing Case
664 F.Supp. 824 (1987)
ST. CHARLES CABLE TV, INC., Alexandra Realty Corporation, Energistics, Inc., GPA-CATV, Inc., Delta Telecommunications, a Limited Partnership, and Robert Broz, Plaintiffs,
v.
EAGLE COMTRONICS, INC., Defendant.
United States District Court, S.D. New York. https://leagle.com/images/logo.png
July 16, 1987.
July 16, 1987.
Attorney(s) appearing for the Case
Bloch, Graff, Danzig & Jelline by Howard Graff and Laura J. Kahn, New York City, for plaintiffs.
Scolaro, Shulman, Cohen Lawler & Burstein, P.C. by Walter D. Kogut and Ted Williams, Syracuse, N.Y., for defendant.
United States District Court, S.D. New York.
OPINION
MacMAHON, District Judge.
Invoking diversity jurisdiction, plaintiffs brought this action against defendant Eagle Comtronics, Inc. ("Eagle") to recover damages allegedly caused by defective equipment purchased from Eagle for use in the St. Charles Parish, Louisiana, community antenna television system ("cable system"). Contending that both plaintiff, St. Charles Cable TV, Inc. ("SCC") and Eagle are citizens of the State of New York, Eagle moves to dismiss this action for lack of diversity, and for failure to join Cable Holdings, Inc. ("Cable Holdings"), a New York company which is affiliated with SCC, as an indispensable party. Eagle also seeks sanctions against SCC. SCC opposes Eagle's motions and moves for sanctions against Eagle and its counsel.
We held an evidentiary hearing on March 2, 1987 to resolve the underlying issues of fact pertinent to the motions. After carefully considering the exhibits, hearing and observing the witnesses, and weighing all of the evidence and the arguments of counsel, we find the following facts:
[664 F.Supp. 826]
FACTS
SCC is a corporation organized under the laws of the State of Louisiana, 1with a registered office in New Orleans. 2According to its by-laws, SCC's annual shareholders' meetings to elect directors "shall be held in the City of New York, State of New York;" 3its special shareholders' meetings, other than to elect directors, "may be held ... within or without the State of Louisiana;" 4and all of its board of directors' meetings "may be held either within or without the State of Louisiana." 5All of SCC's "first directors," as well as its incorporators, were New York citizens. 6
The Parish of St. Charles, Louisiana, by agreement dated November 13, 1981, granted SCC "the right, privilege and franchise to construct, operate, modify and maintain a Cable System in the West Bank area of the Parish of St. Charles, Louisiana" until 1995, subject to various conditions ("the franchise"). 7Donald Behrman, 8the individual "responsible for the design of the [St. Charles Parish cable] system, the selection of its equipment and ... its ultimate construction," 9testified that such a franchise is necessary to operate a cable system in Louisiana; 10that SCC holds franchises only from St. Charles Parish and neighboring Lafourche Parish, Louisiana; 11and that SCC has never sought a franchise outside of Louisiana. 12
In September 1982, SCC began selling fractional interests in the franchise to Delta Telecommunications Limited, 13Energistics, Inc., 14GPA-CATV, Inc., 15and Robert Broz 16(collectively referred to as "the owners"). None of these owners had "experience in the operation and management of [cable] systems...." 17Thus, contemporaneous with their purchase agreements with SCC, the owners entered into "management contract[s]" with SCC 18under which they retained SCC to operate and maintain the cable system for them. 19
In compliance with the requirements of the franchise 20and the management contracts, 21SCC maintains an office in St. Charles Parish, Louisiana, with a manager 22and "six or eight" employees. 23This office serves as "the headquarters for the maintenance crews and the people who install service to subscribers, the people who have contact with the subscribers either in person coming into the office or by telephone." 24
[664 F.Supp. 827]
According to Behrman, SCC's "day-to-day business decisions" are made "[f]or the most part" by its Louisiana staff, 25 which also compiles billing information for use by an independent billing agency, Cable Data, Inc. of Sacramento, California. 26 The subscribers, however, pay directly to SCC's St. Charles Parish office. 27 Their remissions, the sole source of revenue generated by the cable system, 28 are deposited into SCC's Luling, Louisiana, bank account. 29
In addition to its Louisiana office, SCC maintains an office at 745 Fifth Avenue in New York City, 30in the same building as an SCC affiliated corporation, 31Cable Holdings. 32There is no evidence, however, that SCC is a subsidiary of Cable Holdings or that Cable Holdings has any ownership interest in SCC. Richard Treibick is an officer and majority shareholder of both SCC 33and Cable Holdings. 34He testified that "all of the companies which [he controls] ... are pretty much the same. They are slightly interchangeable." 35Cable Holdings provides a variety of "essentially administrative services" to SCC, 36and Treibick, from his New York City office, makes basically all of SCC's executive decisions. 37In light of the evidence concerning the number of SCC's Louisiana employees and the day-to-day operations and functions which they perform there, we reject defendant's contention that Treibick makes "all" of SCC's decisions from New York.
Cable Holdings also provides book-keeping 38and payment 39services to SCC. SCC transfers the funds generated by the St. Charles Parish cable system from its Luling, Louisiana, bank account to an omnibus bank account in New York City, 40and, through Cable Holdings, pays all of the vendors of the St. Charles Parish cable system. 41Cable Holdings also provides payroll services to SCC through Automatic Data Processing of New Jersey. 42This service involves using funds deposited into another account, maintained by Cable Holdings Finance Corporation at Manufacturers Hanover Trust. 43Cable Holdings also provides SCC with engineering services. 44
[664 F.Supp. 828]
In October 1982, defendant Eagle, a New York corporation, 45 agreed to sell equipment for use in the St. Charles Parish cable system. 46 The sales orders and invoices memorializing the sale of the equipment 47 show that Eagle would "BILL TO:"
CABLE HOLDINGS, INC. 745 FIFTH AVE STE 405 NEW YORK, N.Y. 10022
but that Eagle would "SHIP TO:"
CABLE HOLDINGS/ST CHARLES INC48
1500 PAUL MAILLARD ROAD LULING, LA 70070
Although somewhat evasive, Joseph Ostuni, Eagle's vice-president, 49testified that, although Eagle was billing Cable Holdings for the equipment, it was not shipping the equipment to Cable Holdings but "to somebody else" in Luling. 50Behrman testified that the equipment was in fact shipped to St. Charles Parish and that it was used solely to construct the St. Charles Parish cable system. 51
According to Ostuni, Eagle requested and received a good faith payment of $50,000.00 "[t]o be applied for [the] equipment that was shipped to St. Charles...." 52This payment was made by check, dated March 1, 1983, drawn on the Bank of New York, 53and bearing at the top a handwritten notation "Cable Holdings of St. Charles, Inc." 54This notation, according to Ostuni, could simply reflect which of the various accounts of Cable Holdings should be credited. 55On the other hand, this notation is also consistent with Cable Holdings' payment services to SCC, 56or may indicate that SCC paid Eagle directly for the equipment. At this stage of this action, however, we need not determine "who paid" for the equipment. 57
DISCUSSION
Subject Matter Jurisdiction
Eagle contends that diversity jurisdiction is lacking because both it and SCC are citizens of New York.
58
We are satisfied, however, that SCC has demonstrated by competent proof
59
that its principal place
[664 F.Supp. 829]
of business and place of incorporation is Louisiana, and that we, therefore, have diversity — subject matter — jurisdiction.
Two tests have evolved for determining the location of a corporation's principal place of business. 60On the one hand, a corporation which has its operations spread across numerous states has its principal place of business at "`the nerve center from which it radiates out to its constituent parts and from which its officers direct, control and coordinate all activities without regard to locale, in the furtherance of the corporate objective.'" 61On the other hand, a corporation which does not have its operations spread across numerous states, but is centralized, has its principal place of business where it "has its most extensive contacts with, or greatest impact on, the general public." 62
In R.G. Barry Corp. v. Mushroom Makers, Inc.,612 F.2d 651(2d Cir.1979), the court held that Mushroom Makers, which was incorporated in Mississippi and had extensive contacts there, was also a citizen of New York for jurisdictional purposes. Mushroom Makers was affiliated 63with a Mississippi-based holding company. Although the overall policies for Mushroom Makers were set in Mississippi and much of its administrative and manufacturing requirements were contracted out to affiliated Mississippi firms, the court held that it had its most extensive contacts with the public in New York and, therefore, had its principal place of business in New York. This decision was based on the fact that New York was where Mushroom Makers' line of clothing was designed, the fabrics for its garments selected and purchased, its finished product advertised and sold, and its accounts receivable financed. 64
Like Mushroom Makers, which had its principal place of business in New York, although its overall policies were set in Mississippi, SCC receives numerous executive and administrative services from New York, primarily through Cable Holdings, an affiliated corporation. 65Nevertheless, SCC's primary function is to service the St. Charles Parish cable system. To this end, SCC's Louisiana employees run the cable system's day-to-day operations, such as maintaining the equipment, handling subscriber complaints, and receiving subscriber payments. In short, SCC's operations are not spread across numerous states, but are centralized in Louisiana. Indeed, Eagle concedes that SCC is not a "far-flung corporation." 66SCC's most extensive contacts with and greatest impact on the public are in Louisiana, which is not only the place of its incorporation, but also its principal place of business. SCC is a citizen only of Louisiana, thereby satisfying diversity jurisdiction.
Eagle also moves to dismiss this action pursuant to Fed.R.Civ.P. 12(h)(3), contending that plaintiffs, other than SCC, which were recently joined as parties pursuant to a stipulation and order, "have not provided jurisdictional allegations with regard to their respective residences."
67
Although afforded the opportunity to raise this contention at the March 2, 1987 hearing, Eagle failed to do so but seeks to raise it now for
[664 F.Supp. 830]
the first time in its post-hearing memorandum of law.
On February 6, 1987, we signed a stipulation and order adding as party plaintiffs in this action Alexandra Realty, Inc., Energistics, Inc., Delta Telecommunications Limited Partnership, and Robert Broz, all of whom, with the exception of Alexandra Realty, Inc., previously submitted affidavits "ratifying" this litigation and setting forth Connecticut as their state of citizenship. 68Moreover, the evidence at the hearing corroborates the fact that Connecticut is the state of citizenship for Energistics Inc., 69Delta Telecommunications Limited Partnership, 70and Robert Broz. 71Behrman's uncontroverted testimony established that Alexandra Realty, Inc. was located "[i]n Greenwich, Connecticut." 72In the absence of any evidence to the contrary, these averments are sufficient. We hereby dismiss GPA-CATV, Inc., however, as a party plaintiff, pursuant to Rule 21, Fed.R.Civ.P., without prejudice to reinstatement upon motion or stipulation, because GPA-CATV, Inc., which has attempted to join this litigation, was not a party to the February 6, 1987 stipulation and order.
Rule 19, Fed.R.Civ.P.
Eagle also moves to dismiss this action on the ground that SCC has failed to join an indispensable party, Cable Holdings. In essence, Eagle contends that Cable Holdings is an indispensable party because it was an agent for an undisclosed principal — SCC — during the purchase of the cable equipment from Eagle. Thus, Eagle argues that Cable Holdings is liable to it on the sales contracts. 73Regardless of whether Eagle knew, when selling the cable equipment at issue here, that SCC was Cable Holdings' principal, Cable Holdings is not an indispensable party to this action.
Determining indispensability is a procedural matter governed by Rule 19, Fed.R. Civ.P. 74In a diversity action such as this, however, we must apply the standards of Rule 19 to rights and interests that are derived from and defined by the laws of the State of New York. 75
Under New York law, an agent for a disclosed principal is not liable for contracts entered into between its principal and a third party, absent "clear and explicit" evidence of the agent's intention to substitute or superadd its personal liability for, or to, that of its principal. 76If we assume, without deciding, that SCC was Cable Holdings' disclosed principal, then Cable Holdings would not be contractually liable to Eagle because there is no evidence from which we can infer Cable Holdings' intention to incur personal liability on the contracts. Hence, Cable Holdings would be neither an indispensable nor a proper party to this action.
Conversely, if we assume, without deciding, that Eagle was unaware that SCC was Cable Holdings' principal, then we reach the same result.
77
Under New York law, when an agent for an undisclosed principal contracts with a third party, both the agent and the principal are jointly and severally
[664 F.Supp. 831]
liable to the third party, provided the agent acted according to his authority, or the principal subsequently ratifies and confirms the agent's acts. 78 Here, there is no evidence to suggest that Cable Holdings exceeded its authority in dealing with Eagle. Moreover, even if it did, SCC's use of the cable equipment in the St. Charles Parish cable system is evidence that SCC ratified or confirmed Cable Holdings' purchase of the equipment from Eagle. Thus, if we assume, without deciding, that SCC was Cable Holdings' undisclosed principal, then SCC and Cable Holdings would still be jointly and severally liable to Eagle. 79 Therefore, Cable Holdings would not be an indispensable party because parties which are jointly and severally liable are not "indispensable" within the meaning of Rule 19. 80
Sanctions
SCC moves for sanctions against Eagle and its counsel pursuant to our inherent equitable powers, Rule 11, Fed.R. Civ.P., and 28 U.S.C. § 1927, and bases its motion on two grounds: (1) Eagle should have renewed its motion to dismiss for lack of subject matter jurisdiction during the prior proceedings before the Special Master, and (2) Eagle failed to confront legal precedent in its motion to dismiss. Eagle, on the other hand, moves for sanctions against SCC, alleging that SCC's motion for sanctions is frivolous.
It would have been preferable for Eagle to move to dismiss, pursuant to Rule 12(b)(1), Fed.R.Civ.P., during the proceedings conducted by the Special Master so that he could frame the jurisdictional issue for us. However, a motion to dismiss for lack of subject matter jurisdiction may be made by anyone at any time and may be raised by us sua sponte. 81We, therefore, will not impose sanctions upon Eagle or its counsel for failure to renew the jurisdictional objection prior to March 2, 1987. SCC also moves for sanctions on the ground that Eagle, in its motion to dismiss, neglected to distinguish the facts of this action from precedent, such as, R.G. Barry Corp. v. Mushroom Makers, Inc., supra.The better practice would have been for Eagle to attempt, from the outset, to distinguish contrary precedent. However, we are unwilling to declare that Eagle's reliance on other cases, which apply the "nerve center" test for jurisdictional purposes, rises to the level of bad faith, vexatious, or wanton litigation. Indeed, the jurisdictional question in this action is one on which there is substantial ground for difference of opinion. We, therefore, deny SCC's motion for sanctions. 82Likewise, we deny Eagle's motion for sanctions because it is without basis. 83
Certification for Interlocutory Appeal
This interlocutory order involves controlling questions of law concerning
[664 F.Supp. 832]
subject matter jurisdiction and joinder of parties. These questions, if determined otherwise, may result in the immediate termination of this action. We, therefore, certify that this order involves controlling questions of law as to which there is substantial ground for difference of opinion, and that an immediate appeal may materially advance the ultimate termination of the litigation. 84 In the event that any of the parties desires to appeal from this order, an appropriate petition for permission to appeal, in accordance with Rule 5, Fed. R.App.P., shall be filed with the United States Court of Appeals for the Second Circuit within ten (10) days after the entry of this order. 85
CONCLUSION
The foregoing constitutes our findings of fact and conclusions of law, pursuant to Rule 52, Fed.R.Civ.P.
Accordingly:
(1) We deny defendant's motion to dismiss this action pursuant to Rule 12(b)(1), Fed.R.Civ.P., for lack of diversity jurisdiction;
(2) We dismiss, sua sponte,GPA-CATV, Inc. as a party plaintiff, without prejudice to reinstatement upon motion or stipulation, pursuant to Rule 21, Fed.R.Civ.P., for failure to join this action properly;
(3) We deny defendant's motion to dismiss this action pursuant to Rule 12(b)(7), Fed.R.Civ.P., for failure to join an indispensable party;
(4) We deny all motions for sanctions; and
(5) We certify that this order involves controlling questions of law as to which there is substantial ground for difference of opinion, and that an immediate appeal may materially advance the ultimate termination of the litigation.
So ordered.
FootNotes
1. Exhibit ("Ex. ___") PP. At the time of its incorporation, SCC was known as "Cable Holdings of St. Charles, Inc." Trial Transcript ("Tr. ___") at 4; Ex. SSSS at p. 7; Ex. ZZZZ.
2. Ex. QQ, Art. I, § 1.
3. Id., Art. II, § 1.
4. Id., Art. III, § 1.
5. Id., Art. VI, § 1.
6. Ex. PP.
7. Ex. 34 at § 4; Tr. 15.
8. Behrman is Chief Engineer for Cable Holdings, Inc. Tr. 13, 22.
9. Tr. 14;
see also
Tr. 22-23. Behrman also acknowledged that he had the primary responsibility for negotiating the contracts to purchase the equipment at issue in this case. Tr. 27-29.
10. Tr. 14-15.
11. Tr. 15.
12. Id.
13. Exs. RR-3, RR-4.
14. Exs. VV-3, VV-4.
15. Ex. WW-2.
16. Ex. XX-2.
17. ¶ 2 of Exs. RR-5, RR-6, VV-5, VV-6, WW-3 and XX-3.
18. Exs. RR-5, RR-6 (Delta Telecommunications Limited); Exs. VV-5, VV-6 (Energistics, Inc.); Ex. WW-3 (GPA-CATV, Inc.); and Ex. XX-3 (Robert Broz).
19. ¶ 2 of each exhibit referred to in note 18, supra.
20. Ex. 34 at § 29; Tr. 17.
21. ¶ 2(d) of each exhibit referred to in note 18, supra.
22. Tr. 17.
23. Tr. 20.
24. Tr. 17. Defense counsel acknowledged that "[w]hat is done in Louisianna (sic) [by SCC] is ... the blue collar work of interfacing with subscribers, and installing whatever equipment is done there...." Tr. 11.
25. Tr. 20.
26. Tr. 17-18; Ex. SSSS at p. 17. Behrman also testified that he negotiated the most recent contract with Cable Data, Inc. on behalf of SCC. Tr. 30.
27. Tr. 18; Ex. SSSS at p. 15.
28. Tr. 16.
29. Ex. SSSS at pp. 14-15.
30. Exs. UUU, RR-5 at ¶ 9, RR-6 at ¶ 9, VV-5 at ¶ 9, VV-6 at ¶ 9, WW-3 at ¶ 9, and XX-3 at ¶ 9. Additionally, SCC lists a New York City post office box as its return address on its 1981 federal income tax return. Ex. ZZZZ.
31. See Ex. SSSS at pp. 3-18. Indeed, Eagle consistently has referred to SCC as an "affiliate" of Cable Holdings.
See
¶ 10 of Amended Answer to Second Amended Complaint; Defendant's Memorandum of Law in Support of Motion to Dismiss at p. 3; and Defendant's Proposed Findings of Fact at ¶ 6.
32. Tr. 21-22.
33. Ex. SSSS at pp. 3, 6. Additionally, Treibick also holds a voting trust for all of the other shares, thereby making him "the sole stockholder for voting purposes."
Id.
at p. 6.
34. Id. at pp. 5-6. Treibick also testified that he is paid only by Cable Holdings and one of its affiliates, Alexandra Realty Corporation. Id. at pp. 3, 18.
35. Id. at p. 4.
36. Id. at p. 10; see also Tr. 26.
37. See Tr. 18, 20-21.
38. Ex. SSSS at p. 17. Treibick described Cable Holdings' bookkeeping services as "[p]ayables, ledgers, reconciliations, everything." Id.
39.
Id.
at pp. 11-14. Treibick also testified that withdrawal authority on SCC's local account, in which SCC does not maintain "any meaningful balances," is limited to himself, Robert Broz, and Eli Haber.
Id.
at pp. 12-13.
40. Id. at pp. 11-12. This omnibus account is maintained at the Bank of New York by Alexandra Realty Corporation. Id. at p. 12.
41. Id. at p. 11.
42. Id. at pp. 16-17.
43. Id. at p. 17. Treibick is also an officer and director of Cable Holdings Finance Corporation. Id.
44. Id. at p. 10. See also note 8, supra, and accompanying text.
45. ¶ 4 of Second Amended Complaint; ¶ 1 of Amended Answer to Second Amended Complaint.
46. SCC contends that it entered into the sales agreement with Eagle. ¶ 9 of Second Amended Complaint. Eagle, however, refutes this contention and asserts that the sales order was placed by Cable Holdings. ¶ 4 of Amended Answer to Second Amended Complaint.
47. Exs. L, N, O, P, Q, R and S.
48. Some of the sales orders and invoices add "P.O. BOX 62" to this address.
49. Tr. 33.
50. Tr. 46. See also Tr. 37.
51. Tr. 18-20. Ostuni testified that he was aware of the St. Charles Parish cable system and knew that the equipment was to be used in it. Tr. 37.
52. Tr. 38.
53. Ex. 3. Treibick testified that the omnibus bank account from which Cable Holdings renders payment services to SCC is maintained at the Bank of New York. Ex. SSSS at pp. 11-12.
54. Ex. 3. "Cable Holdings of St. Charles, Inc." is SCC's former name. See note 1, supra.
55. Tr. 38.
56. See note 41, supra, and accompanying text.
57. Another check made payable to Eagle and drawn on the Bank of New York, dated December 30, 1982, in the amount of $12,547.00, was received in evidence. Ex. 79. There is, however, no evidence that Eagle ever received this check. Thus, we are not considering this exhibit in deciding the issues here.
58.
See Strawbridge v. Curtiss,
7 U.S. (3 Cranch) 267, 2 L.Ed. 435 (1806).
For purposes of diversity jurisdiction, a corporation is deemed a citizen of the state of its incorporation and of the state where it has its principal place of business. 28 U.S.C. § 1332(c); R.G. Barry Corp. v. Mushroom Makers, Inc.,612 F.2d 651, 654 (2d Cir.1979). There is no dispute that Eagle is a citizen of New York and that SCC was incorporated in Louisiana. Seepp. 2, 5, supra.Thus, we need only determine the location of SCC's principal place of business.
59. See, e.g., McNutt v. General Motors Acceptance Corp., 298 U.S. 178 , 189, 56 S.Ct. 780, 785, 80 L.Ed. 1135 (1936).
60. R.G. Barry Corp. v. Mushroom Makers, Inc., supra, 612 F.2d at 654-55.
61. Id., 612 F.2d at 655 (quoting Scot Typewriter Co. v. Underwood Corp., 170 F.Supp. 862 , 865 (S.D.N.Y.1959)).
62.
R.G. Barry Corp. v. Mushroom Makers, Inc., supra,
612 F.2d at 655;
Inland Rubber Corp. v. Triple A Tire Serv., Inc.,
220 F.Supp. 490
(S.D.N. Y.1963).
63. The court used the term "affiliate" to denote corporations which "are commonly owned and managed by the same individuals."
R.G. Barry Corp. v. Mushroom Makers, Inc., supra,
612 F.2d at 656 n. 8. The evidence here discloses a similar affiliation between SCC and Cable Holdings.
See
note 31,
supra,
and accompanying text.
64. R.G. Barry Corp. v. Mushroom Makers, Inc., supra, 612 F.2d at 655-57.
65.
See
p. 4,
supra.
The parent-subsidiary cases on which Eagle relies are inapposite because the evidence discloses only that SCC and Cable Holdings are affiliated corporations. There is no proof that Cable Holdings possesses any ownership interest in SCC.
66. Tr. 51.
67. Eagle's Memorandum of Law at p. 4.
68. See Ex. C to Graff Affidavit of March 26, 1987.
69. Exs. VV-3, VV-4, VV-5, VV-6.
70. Exs. RR-3, RR-4, RR-5, RR-6.
71. Exs. XX-2, XX-3.
72. Tr. 25.
73. Eagle, in its post-hearing memorandum of law, argues: "Cable Holdings should not be permitted to evade responsibility on this contract by the mere fact that the goods were shipped to [SCC], a corporation with no assets." Eagle's Memorandum of Law at p. 6.
See also
Tr. 57-58.
74. Provident Tradesmens Bank & Trust Co. v. Patterson, 390 U.S. 102 , 88 S.Ct. 733, 19 L.Ed.2d 936 (1968).
75.
Jones Knitting Corp. v. A.M. Pullen & Co.,
50 F.R.D. 311, 314 (S.D.N.Y.1970) (footnote omitted).
See also
3A J. Moore, Moore's Federal Practice ¶ 19.01-1[4] at 19-28 to 19-29 (2d ed. 1985).
76. Savoy Record Co. v. Cardinal Export Corp., 15 N.Y.2d 1 , 4, 203 N.E.2d 206, 207, 254 N.Y.S.2d 521, 523 (1964).
77. See also 3A J. Moore, Moore's Federal Practice ¶ 19.10, at 19-200 to 19-201 & footnote 11. (2d ed. 1985).
78.
Industrial Mfrs., Inc. v. Bangor Mills, Inc.,
283 A.D. 113
, 117, 126 N.Y.S.2d 508, 512 (1st Dep't 1953),
aff'd,
307 N.Y. 746
, 121 N.E.2d 552 (1954); N.Y.CPLR § 3002(b) (McKinney 1974).
79. N.Y.CPLR § 3002(b) (McKinney 1974). The practice commentary to § 3002(b) states that this "provision is procedural only."
See
N.Y. CPLR § 3002(b), Practice Commentary § 3002:21, at 540 (McKinney 1974). Although we have found no federal case applying § 3002(b), we do not believe that the commentator intended this statement to mean that § 3002(b) is procedural for purposes of analysis under
Erie R. Co. v. Tompkins,
304 U.S. 64
, 58 S.Ct. 817, 82 L.Ed. 1188 (1938). Therefore, notwithstanding the practice commentary, we will apply § 3002(b) in order to determine whether Cable Holdings is an indispensable party to this action.
See Hanna v. Plumer,
380 U.S. 460
, 85 S.Ct. 1136, 14 L.Ed.2d 8 (1965);
Phillips v. Smith,
717 F.2d 44
, 49 (2d Cir.1983) ("Comity requires that federal courts respect state procedural rules to the extent those rules do not unjustly extinguish rights guaranteed by the federal Constitution."),
cert. denied,
465 U.S. 1027, 104 S.Ct. 1287, 79 L.Ed.2d 689 (1984).
See also Lipsky v. Commonwealth United Corp.,
551 F.2d 887
, 895 (2d Cir.1976) (we "stand in the shoes of a state court judge" when ruling on contract issues in a diversity case).
80.
Kerr v. Compagnie De Ultramar,
250 F.2d 860
, 863 (2d Cir.1958);
Fradkin Bros. Furniture Village, Inc. v. Bradford Trust Co.,
89 F.R.D. 667, 671 (S.D.N.Y.1981);
Jones Knitting Corp. v. A.M. Pullen & Co., supra,
50 F.R.D. at 315.
81. Air Cargo, Inc. v. Local Union 851, 733 F.2d 241 , 247 n. 5 (2d Cir.1984).
82. See, e.g., Oliveri v. Thompson, 803 F.2d 1265 (2d Cir.1986).
83. Id.
84. 28 U.S.C. § 1292(b);
English v. Seaboard Coast Line R. Co.,
465 F.2d 43
(5th Cir.1972) (interlocutory appeal permitted in order to determine joinder of parties question);
Movielab, Inc. v. Berkey Photo, Inc.,
452 F.2d 662
(2d Cir.1971) (interlocutory appeal permitted in order to determine subject matter jurisdiction question);
Brown v. Bullock,
294 F.2d 415
, 417 (2d Cir.1961);
State Teachers Retirement Bd. v. Fluor Corp.,
84 F.R.D. 38, 39 (S.D.N.Y.1979); 9 J. Moore, Moore's Federal Practice ¶ 110.22 at pp. 256-67 (2d ed. 1985).
85. 28 U.S.C. § 1292(b).
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North America (NAFTA) Insurance - Market Summary, Competitive Analysis and Forecast, 2016-2025
North America (NAFTA) Insurance - Market Summary, Competitive Analysis and Forecast, 2016-2025 North America (NAFTA) Insurance - Market Summary, Competitive Analysis and Forecast, 2016-2025 Summary The NAFTA - Market research report and industry analysis - 30916129
North America (NAFTA) Insurance - Market Summary, Competitive Analysis and Forecast, 2016-2025
Best Price Guarantee Price from $795 Length 114 Pages Publisher MarketLine Published Date January, 2022 SKU MTLN17001004
Table of Contents
Description
North America (NAFTA) Insurance - Market Summary, Competitive Analysis and Forecast, 2016-2025 SummaryThe NAFTA Insurance industry profile provides top-line qualitative and quantitative summary information including: market share, market size (value 2016-20, and forecast to 2025). The profile also contains descriptions of the leading players including key financial metrics and analysis of competitive pressures within the market. Key Highlights
The North American Free Trade Agreement (NAFTA) is a trade agreement between the countries in North America: the US, Canada and Mexico. The insurance industry within the NAFTA countries had a total market value of $2,688.7 billion in 2020.The Mexico was the fastest growing country, with a CAGR of 7.4% over the 2016-20 period.
Within the insurance industry, the US is the leading country among the NAFTA bloc, with market revenues of $2,530.6 billion in 2020. This was followed by Canada and Mexico, with a value of $130.4 and $27.7 billion, respectively.
The US is expected to lead the insurance industry in the NAFTA bloc, with a value of $2,978.9 billion in 2025, followed by Canada and Mexico with expected values of $160.9 and $34.1 billion, respectively.
Scope
Save time carrying out entry-level research by identifying the size, growth, major segments, and leading players in the NAFTA insurance market
Use the Five Forces analysis to determine the competitive intensity and therefore attractiveness of the NAFTA insurance market
Leading company profiles reveal details of key insurance market players’ NAFTA operations and financial performance
Add weight to presentations and pitches by understanding the future growth prospects of the NAFTA insurance market with five year forecasts
Compares data from the US, Canada and Mexico, alongside individual chapters on each country
Reasons to Buy
What was the size of the NAFTA insurance market by value in 2020?
What will be the size of the NAFTA insurance market in 2025?
What factors are affecting the strength of competition in the NAFTA insurance market?
How has the market performed over the last five years?
Who are the top competitors in the NAFTA insurance market?
Companies MentionedIntact Financial CorpKnights of ColumbusAssurant IncGlobe Life IncGrupo Nacional Provincial SABChubb LtdAXA SAQualitas Controladora SAB de CVState Farm Mutual Automobile Insurance CoBerkshire Hathaway IncNew York Life Insurance CoThe Progressive Corp
1 Introduction
1.1. What is this report about?
1.2. Who is the target reader?
1.3. How to use this report
1.4. Definitions
2 NAFTA Insurance
2.1. Industry Outlook
3 Insurance in Canada
3.1. Market Overview
3.2. Market Data
3.3. Market Segmentation
3.4. Market outlook
3.5. Five forces analysis
4 Macroeconomic Indicators
4.1. Country data
5 Insurance in Mexico
5.1. Market Overview
5.2. Market Data
5.4. Market outlook
5.5. Five forces analysis
6 Macroeconomic Indicators
6.1. Country data
7 Insurance in The United States
7.1. Market Overview
7.2. Market Data
7.3. Market Segmentation
7.4. Market outlook
7.5. Five forces analysis
8 Macroeconomic Indicators
8.1. Country data
9 Company Profiles
9.1. Intact Financial Corp
9.2. Knights of Columbus
9.3. Assurant Inc
9.4. Globe Life Inc
9.5. Grupo Nacional Provincial SAB
9.6. Chubb Ltd
9.7. AXA SA
9.8. Qualitas Controladora SAB de CV
9.9. State Farm Mutual Automobile Insurance Co
9.11. New York Life Insurance Co
9.12. The Progressive Corp
10 Appendix
10.1. Methodology
10.2. About MarketLine
List of Tables
Table 1: NAFTA countries insurance industry, revenue ($bn), 2016-25
Table 2: NAFTA countries insurance industry, revenue ($bn), 2016-20
Table 3: NAFTA countries insurance industry forecast, revenue ($bn), 2020-25
Table 4: Canada insurance market value: $ billion, 2016–20
Table 5: Canada insurance market category segmentation: $ billion, 2020
Table 6: Canada insurance market geography segmentation: $ billion, 2020
Table 7: Canada insurance market share: % share, by value, 2020
Table 8: Canada insurance market value forecast: $ billion, 2020–25
Table 9: Canada size of population (million), 2016–20
Table 10: Canada gdp (constant 2005 prices, $ billion), 2016–20
Table 11: Canada gdp (current prices, $ billion), 2016–20
Table 12: Canada inflation, 2016–20
Table 13: Canada consumer price index (absolute), 2016–20
Table 14: Canada exchange rate, 2016–20
Table 15: Mexico insurance market value: $ billion, 2016–20
Table 16: Mexico insurance market category segmentation: $ billion, 2020
Table 17: Mexico insurance market geography segmentation: $ billion, 2020
Table 18: Mexico insurance market share: % share, by value, 2020
Table 19: Mexico insurance market value forecast: $ billion, 2020–25
Table 20: Mexico size of population (million), 2016–20
Table 21: Mexico gdp (constant 2005 prices, $ billion), 2016–20
Table 22: Mexico gdp (current prices, $ billion), 2016–20
Table 23: Mexico inflation, 2016–20
Table 24: Mexico consumer price index (absolute), 2016–20
Table 25: Mexico exchange rate, 2016–20
Table 26: United States insurance market value: $ billion, 2016–20
Table 27: United States insurance market category segmentation: $ billion, 2020
Table 28: United States insurance market geography segmentation: $ billion, 2020
Table 29: United States insurance market share: % share, by value, 2020
Table 30: United States insurance market value forecast: $ billion, 2020–25
Table 31: United States size of population (million), 2016–20
Table 32: United States gdp (constant 2005 prices, $ billion), 2016–20
Table 33: United States gdp (current prices, $ billion), 2016–20
Table 34: United States inflation, 2016–20
Table 35: United States consumer price index (absolute), 2016–20
Table 36: United States exchange rate, 2016–20
Table 37: Intact Financial Corp: key facts
Table 38: Intact Financial Corp: Annual Financial Ratios
Table 39: Intact Financial Corp: Key Employees
Table 40: Intact Financial Corp: Key Employees Continued
Table 41: Knights of Columbus: key facts
Table 42: Knights of Columbus: Key Employees
Table 43: Assurant Inc: key facts
Table 44: Assurant Inc: Annual Financial Ratios
Table 45: Assurant Inc: Key Employees
Table 46: Assurant Inc: Key Employees Continued
Table 47: Globe Life Inc: key facts
Table 48: Globe Life Inc: Annual Financial Ratios
Table 49: Globe Life Inc: Key Employees
Table 50: Globe Life Inc: Key Employees Continued
Table 51: Grupo Nacional Provincial SAB: key facts
Table 52: Grupo Nacional Provincial SAB: Annual Financial Ratios
Table 53: Grupo Nacional Provincial SAB: Key Employees
Table 54: Chubb Ltd: key facts
Table 55: Chubb Ltd: Annual Financial Ratios
Table 56: Chubb Ltd: Key Employees
Table 57: Chubb Ltd: Key Employees Continued
Table 58: Chubb Ltd: Key Employees Continued
Table 59: Chubb Ltd: Key Employees Continued
Table 60: AXA SA: key facts
Table 61: AXA SA: Annual Financial Ratios
Table 62: AXA SA: Key Employees
Table 63: AXA SA: Key Employees Continued
Table 64: AXA SA: Key Employees Continued
Table 65: Qualitas Controladora SAB de CV: key facts
Table 66: Qualitas Controladora SAB de CV: Annual Financial Ratios
Table 67: Qualitas Controladora SAB de CV: Key Employees
Table 68: State Farm Mutual Automobile Insurance Co: key facts
Table 69: State Farm Mutual Automobile Insurance Co: Key Employees
Table 70: Berkshire Hathaway Inc: key facts
Table 71: Berkshire Hathaway Inc: Annual Financial Ratios
Table 72: Berkshire Hathaway Inc: Key Employees
Table 73: Berkshire Hathaway Inc: Key Employees Continued
Table 74: New York Life Insurance Co: key facts
Table 75: New York Life Insurance Co: Key Employees
Table 76: New York Life Insurance Co: Key Employees Continued
Table 77: The Progressive Corp: key facts
Table 78: The Progressive Corp: Annual Financial Ratios
Table 79: The Progressive Corp: Key Employees
Table 80: The Progressive Corp: Key Employees Continued
List of Figures
Figure 1: NAFTA countries insurance industry, revenue ($bn), 2016-25
Figure 2: NAFTA countries insurance industry, revenue ($bn), 2016-20
Figure 3: NAFTA countries insurance industry forecast, revenue ($bn), 2020-25
Figure 4: Canada insurance market value: $ billion, 2016–20
Figure 5: Canada insurance market category segmentation: % share, by value, 2020
Figure 6: Canada insurance market geography segmentation: % share, by value, 2020
Figure 7: Canada insurance market share: % share, by value, 2020
Figure 8: Canada insurance market value forecast: $ billion, 2020–25
Figure 9: Forces driving competition in the insurance market in Canada, 2020
Figure 10: Drivers of buyer power in the insurance market in Canada, 2020
Figure 11: Drivers of supplier power in the insurance market in Canada, 2020
Figure 12: Factors influencing the likelihood of new entrants in the insurance market in Canada, 2020
Figure 13: Factors influencing the threat of substitutes in the insurance market in Canada, 2020
Figure 14: Drivers of degree of rivalry in the insurance market in Canada, 2020
Figure 15: Mexico insurance market value: $ billion, 2016–20
Figure 16: Mexico insurance market category segmentation: % share, by value, 2020
Figure 17: Mexico insurance market geography segmentation: % share, by value, 2020
Figure 18: Mexico insurance market share: % share, by value, 2020
Figure 19: Mexico insurance market value forecast: $ billion, 2020–25
Figure 20: Forces driving competition in the insurance market in Mexico, 2020
Figure 21: Drivers of buyer power in the insurance market in Mexico, 2020
Figure 22: Drivers of supplier power in the insurance market in Mexico, 2020
Figure 23: Factors influencing the likelihood of new entrants in the insurance market in Mexico, 2020
Figure 24: Factors influencing the threat of substitutes in the insurance market in Mexico, 2020
Figure 25: Drivers of degree of rivalry in the insurance market in Mexico, 2020
Figure 26: United States insurance market value: $ billion, 2016–20
Figure 27: United States insurance market category segmentation: % share, by value, 2020
Figure 29: United States insurance market share: % share, by value, 2020
Figure 30: United States insurance market value forecast: $ billion, 2020–25
Figure 31: Forces driving competition in the insurance market in the United States, 2020
Figure 32: Drivers of buyer power in the insurance market in the United States, 2020
Figure 33: Drivers of supplier power in the insurance market in the United States, 2020
Figure 34: Factors influencing the likelihood of new entrants in the insurance market in the United States, 2020
Figure 35: Factors influencing the threat of substitutes in the insurance market in the United States, 2020
Figure 36: Drivers of degree of rivalry in the insurance market in the United States, 2020
North America (NAFTA) Life Insurance - Market Summary, Competitive Analysis and Forecast, 2016-2025
North America (NAFTA) Non-Life Insurance - Market Summary, Competitive Analysis and Forecast, 2016-2025
North America (NAFTA) Haircare (NAFTA) - Market Summary, Competitive Analysis and Forecast, 2016-2025
North America (NAFTA) Meat - Market Summary, Competitive Analysis and Forecast, 2016-2025
North America (NAFTA) Utilities - Market Summary, Competitive Analysis and Forecast, 2016-2025
North America (NAFTA) Suncare - Market Summary, Competitive Analysis and Forecast, 2016-2025
| https://www.marketresearch.com/MarketLine-v3883/North-America-NAFTA-Insurance-Summary-30916129/ |
Difference between revisions of "Lafayette County, Arkansas Genealogy" • FamilySearch
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Difference between revisions of "Lafayette County, Arkansas Genealogy"
Revision as of 12:03, 4 March 2022 ( view source ) Batsondl ( talk | contribs ) m (Text replacement - "FamilySearch Places]:Cities and Towns- How to Use FS Places " to "FamilySearch Places]: Map of cities and towns in this county - How to Use FS Places ") ← Older edit Revision as of 08:59, 3 April 2022 ( view source ) Fieldinggarydelynn1 ( talk | contribs ) ( →Court Records : Adding FS Catalog entries project ) Newer edit → Line 235: Line 235: === Court Records === === Court Records === {{AR Court Intro|Lafayette}} {{AR Court Intro|Lafayette}} + * '''1828-1875''' {{FHL|1018569|item|disp=Circuit Court record, 1828-1875}}(*); Arkansas. Circuit Court (Lafayette County) at FamilySearch Catalog — Index and images + * '''1838-1875''' {{FHL|351493|item|disp=County Court records, 1838-1875}}(*); Arkansas. County Court (Lafayette County) at FamilySearch Catalog — images + * '''1840-1878''' {{FHL|343013|item|disp=Circuit Court records, 1840-1878}}(*); Arkansas. Chancery Court (Lafayette County) at FamilySearch Catalog — Index and images + * '''1879-1955''' {{FHL|741561|item|disp=Chancery records, 1879-1955}}(*); Arkansas. Chancery Court (Lafayette County) at FamilySearch Catalog — images === Directories === === Directories ===
Revision as of 08:59, 3 April 2022
United States
Arkansas
Lafayette County
Guide to Lafayette County, Arkansas ancestry, genealogy and family history, birth records, marriage records, death records, census records, family history, and military records.
County Facts County seat: Lewisville Organized: October 15, 1827 Parent County(s): Hempstead [1] Neighboring Counties Bossier (LA) • Caddo (LA) • Columbia • Hempstead • Miller • Nevada • Webster (LA) See County Maps Courthouse _link_ Location Map _link_ Adoption This page is available for adoption
Red River meanders in Lafayette and Miller Counties, Arkansas
Contents
1 County Information
1.1 Description
1.2 County Courthouse
1.3 Lafayette County, Arkansas
1.4 Record Loss
1.5 Boundary Changes
1.6 Populated Places
1.7 History Timeline
2 Resources
2.1 Bible Records
2.2 Biographies
2.3 Business, Commerce, and Occupations
2.4 Cemeteries
2.5 Census Records
2.6 Church Records
2.7 Court Records
2.8 Directories
2.9 Emigration and Immigration
2.10 Ethnic, Political, and Religious Groups
2.10.1 African Americans
2.11 Funeral Homes
2.12 Genealogies
2.13 Guardianship
2.14 Land and Property Records
2.15 Local Histories
2.16 Maps and Gazetteers
2.17 Migration
2.18 Military Records
2.18.1 Civil War
2.19 Naturalization and Citizenship
2.20 Newspapers
2.21 Obituaries
2.22 Other Records
2.23 Periodicals
2.24 Probate Records
2.25 School Records
2.26 Social Security Records
2.27 Tax Records
2.28 Vital Records
2.28.1 Birth
2.28.2 Marriage
2.28.3 Death
2.28.4 Divorce
2.29 Voter Records
3 Research Facilities
3.1 Archives
3.2 Family History Centers
3.3 Libraries
3.4 Museums
4 Societies
5 Websites
6 Research Guides
7 References
County Information [ edit | edit source ]
Description [ edit | edit source ]
The county was named for or the Marquis de Lafayette, who came from France and fought on the side of the Americans in the Revolutionary war. It is located in the southwest corner of the state. [2]
County Courthouse [ edit | edit source ]
Lafayette County Courthouse2 Courthouse SquareLewisville, AR 71845Phone: 870.921.4633Lafayette County WebsiteCounty Clerk has marriage records from 1848 and probate records;Clerk Circuit Court has divorce and land records. [3]
Lafayette County, Arkansas [ edit | edit source ]
Information for this chart was taken from various sources, often containing conflicting dates. This information should be taken as a guide and should be verified by contacting the county and/or the state government agency.
Known Beginning Dates for Major Records [4] Birth* Marriage Death* Court Land Probate Census 1914 1828 1914 1828 1828 1828 1830 *State birth and death records began in 1914. Limited compliance until the 1920s
Record Loss [ edit | edit source ]
There is no known history of courthouse disasters in this county.
Boundary Changes [ edit | edit source ]
1827-- Lafayette County was created 15 October 1827 from Hempstead County. County seat: Lewisville [5] For animated maps illustrating Arkansas county boundary changes,"Rotating Formation Arkansas County Boundary Maps"(1813-1925) may be viewed for free at the MapofUS.org website.
Populated Places [ edit | edit source ]
For a complete list of populated places, including small neighborhoods and suburbs, visitHometown Locator.
The following are the most historically and genealogically relevant populated places in this county: [6]
Towns Bradley Buckner Lewisville Stamps Townships Baker (most of Stamps ) French Hadley ( Buckner , small part of Stamps ) La Grange (small part of Lewisville ) Mars Hill Roane ( Bradley ) Russell Steel (most of Lewisville ) Walker Creek
History Timeline [ edit | edit source ]
Emphasis for this timeline is on events that affected migration, records, or record-keeping. Unless otherwise mentioned, the events below were taken from the Lafayette County page on the website,The Encyclopedia of Arkansas History and Culture. [7]
1800s (early) - Identification of specific European explorers and settlers in the future Lafayette County area of the Louisiana Purchase is difficult.
1815 - The New Madrid Earthquakes and the War of 1812 prompted President James Monroe to survey and offer lands from the Louisiana Purchase to veterans and displaced farmers.
1826 - The first years for the settlers on Long Prairie were especially difficult with uncomfortable wilderness conditions afflicting the community. Many pulled up stakes and move 100 miles to the east.
1827 October 15 - Lafayette County was organized.
1861-1865 - Like most areas in the South, Lafayette County was devastated by the Civil War.
1865-1877 - The most significant change during this period may have been the proliferation of family farms.
1880s - Another dramatic change of the era was the arrival of the railroad.
1900-1940s - The first four decades of the twentieth century saw both prosperity and depression. Banks failed, mortgagers foreclosed, properties were lost, and crop values plummeted.
1930-2010 - The population of Lafayettte County hit its high mark in 1930 at 16,900 and is now (2010) at less than half that number at 7,600
Resources [ edit | edit source ]
Bible Records [ edit | edit source ]
Biographies [ edit | edit source ]
Business, Commerce, and Occupations [ edit | edit source ]
Cemeteries [ edit | edit source ]
Cemeteries of Lafayette, Arkansas online and in print Tombstone Transcriptions Online Find A Grave BillionGraves USGW Tombstone Transcription Project Interment.net Arkansas Gravestones Tombstone Transcriptions in Print ( Often more complete ) FamilySearch Catalog WorldCat.org List of Cemeteries in the County Find A Grave BillionGraves FamilySearch Places See Arkansas Cemeteries for more information
Census Records [ edit | edit source ]
Historical populations Census Pop. %± 1830 748 — 1840 2,200 194.1% 1850 5,220 137.3% 1860 8,464 62.1% 1870 9,139 8.0% 1880 5,730 −37.3% 1890 7,700 34.4% 1900 10,594 37.6% 1910 13,741 29.7% 1920 15,522 13.0% 1930 16,934 9.1% 1940 16,851 −0.5% 1950 13,203 −21.6% 1960 11,030 −16.5% 1970 10,018 −9.2% 1980 10,213 1.9% 1990 9,643 −5.6% 2000 8,559 −11.2% 2010 7,645 −10.7% Source: "Wikipedia.org".
Church Records [ edit | edit source ]
List of Churches and Church Parishes
FamilySearch Places
1875-1899 - Nebraska, Church Records, 1875-1899 at FamilySearch — index - How to Use this Collection
Court Records [ edit | edit source ]
1828-1875 Circuit Court record, 1828-1875 (*) ; Arkansas. Circuit Court (Lafayette County) at FamilySearch Catalog — Index and images
1838-1875 County Court records, 1838-1875 (*) ; Arkansas. County Court (Lafayette County) at FamilySearch Catalog — images
1840-1878 Circuit Court records, 1840-1878 (*) ; Arkansas. Chancery Court (Lafayette County) at FamilySearch Catalog — Index and images
1879-1955 Chancery records, 1879-1955 (*) ; Arkansas. Chancery Court (Lafayette County) at FamilySearch Catalog — images
Directories [ edit | edit source ]
Emigration and Immigration [ edit | edit source ]
Ethnic, Political, and Religious Groups [ edit | edit source ]
African Americans [ edit | edit source ]
1866-1868 — Freedmen's Bureau Field Office Records, Lewisville at FamilySearch.org — browsable images only; letters
Funeral Homes [ edit | edit source ]
A.O. Smith Funeral Homes, Inc in Stamps
Hamilton-Davis Funeral Home in Stamps
Genealogies [ edit | edit source ]
Guardianship [ edit | edit source ]
Probate Records 1828-1925
Lafayette County portion of the collection:
Arkansas Probate Records, 1817-1979
:
Arkansas Probate Records, 1817-1979
FamilySearch Historical Collections (Free, browse images) -
How to Use this Collection
Includes Administration bonds 1859-1905; Letters of administration and guardianship 1859-1906; Miscellaneous probate records 1844-1858; Probate records 1828-1897; Wills 1846-1925.
Land and Property Records [ edit | edit source ]
Local Histories [ edit | edit source ]
Local histories are available for Lafayette County. They may include biographies, church, school and government history, and military information. For more about local histories, seeArkansas Local Histories.
Biographical and Historical Memoirs of Southern Arkansas. 2 volumes. 1890. Chicago, IL, USA: Goodspeed Publishing. Online at: Vol. 1 - FamilySearch Digital Library , Vol. 2 - FamilySearch Digital Library , Vol. 1 - Internet Archive , Vol. 2 - Internet Archive , Google Books , Ancestry ($) ; At various libraries (WorldCat) . Lafayette County history begins on Page 347 in Vol. 1.
Maps and Gazetteers [ edit | edit source ]
Maps of Arkansas (1813-1925)
FamilySearch Places : Map of cities and towns in this county - How to Use FS Places
Migration [ edit | edit source ]
Military Records [ edit | edit source ]
Civil War [ edit | edit source ]
Regiments.Men in Lafayette County served in various regiments and companies. Those listed below were specifically formed in this county:
- 6th Regiment, Arkansas Infantry (Confederate)
- 19th Regiment, Arkansas Infantry (Dockery's) (Confederate)
- 20th Regiment, Arkansas Infantry (Confederate) , Company K
- 26th Regiment, Arkansas Infantry (Confederate) , Company G
- Abraham's Company, Arkansas Mounted Volunteers (State Troops) (Confederate)
- 3rd Regiment, Arkansas Cavalry (Union) [8] , Company I
Online Records
1861-1865 - Arkansas Civil War Service Records of Union Soldiers, 1861-1865 at FamilySearch — index - How to Use this Collection
1890-1963 - Arkansas Confederate Soldier Home,1890-1963 at FamilySearch — index and images - How to Use this Collection
1891-1939 - Arkansas Ex-Confederate Pension Records, 1891-1939 at FamilySearch — index and images - How to Use this Collection
1901-1929 - Arkansas Confederate Pensions, 1901-1929 at FamilySearch — index and images - How to Use this Collection
Naturalization and Citizenship [ edit | edit source ]
Newspapers [ edit | edit source ]
Finding More Arkansas NewspapersAdditional newspapers abstracts can sometimes be found using search phrases such as Lafayette newspapersin online catalogs like:
WorldCat
FamilySearch. Do a Lafayette County, Arkansas Genealogy Place-name search for these and other records in the FamilySearch Catalog (For instructions see, FamilySearch Catalog Places Search ).
Fayetteville Democrat at Ancestry.com ($)
Fayetteville Daily Democrat at Ancestry.com ($)
Daily Fayetteville Democrat at Ancestry.com ($)
Northwest Arkansas Times at Ancestry.com ($)
Courier Times at Ancestry.com ($)
1800s-1999 U.S., Newspapers.com Marriage Index, 1800s-1999 at Ancestry - index ($)
Obituaries [ edit | edit source ]
Other Records [ edit | edit source ]
Periodicals [ edit | edit source ]
Probate Records [ edit | edit source ]
Online Probate Indexes and Records
1783-1998 Arkansas Wills and Probate Records 1783-1998 at Ancestry.com — index and images ($)
1817-1979 Arkansas Probate Records, 1817-1979 (*) at FamilySearch — How to Use this Collection ; images
1828-1905 Probate Records, 1828-1905 (*) ; Probate Court at FamilySearch Catalog — index & images
1846-1925 Will Record, v. B-C, 1846-1925 (*) ; County Court at FamilySearch Catalog — images
School Records [ edit | edit source ]
Social Security Records [ edit | edit source ]
1935-2014 United States Social Security Death Index at FamilySearch - How to use this collection ; index. Also at Ancestry , findmypast , Fold3 , GenealogyBank , MyHeritage , and Steve Morse . Click here for more information .
1936-2007 U.S., Social Security Applications and Claims Index, 1936-2007 at Ancestry ($) — index, click here for more information .
Tax Records [ edit | edit source ]
Vital Records [ edit | edit source ]
Birth [ edit | edit source ]
Birth Records reveal Y es or M aybe ⇒ Y M Name of Child _link_ Birth Date and Place _link_ Parent's Names _link_ Mother's Maiden Name _link_ Parent's Ages _link_ Father's Occupation _link_ Current Residence _link_ Name of Doctor or Midwife _link_
In 1877, a few county and city clerks [9]started keeping birth and death records.
In 1914, the state law required all county clerks to record births and forward them to the state.
Arkansas Births and Christenings, 1812-1965
Marriage [ edit | edit source ]
1779-1966 - Arkansas, United States Marriages at FindMyPast — index $
1828 - 1952 - Lafayette County Marriage Books 1-2, C-Z, A2-G2 Index 1828-1952 in Arkansas, County Marriages, 1837-1957 at FamilySearch - free. [10] - How to Use this Collection
1828 - 1921 - Lafayette County Marriage Books 1-2, C-S Index 1828-1921 in International Genealogical Index at FamilySearch - free. [11]
1917-1969 Arkansas, Marriage Certificates, 1917-1969 at Ancestry.com - index and images ($)
Death [ edit | edit source ]
1914-1969 Arkansas, Death Certificates, 1914-1969 at Ancestry.com - index and images ($)
Lafayette County, Arkansas Obituary Collection From GenealogyBuff.com ~ Free. From Various Funeral Homes around Stamps, Lewisville, Bradley, and Buckner, Arkansas.
1935-1961 Arkansas, Death Index, 1935-1961 at MyHeritage - index and images ($)
Divorce [ edit | edit source ]
1923-1969 Arkansas, Divorces, 1923-1969 at Ancestry.com - index ($)
Voter Records [ edit | edit source ]
1868-1910 - Arkansas, County Voter Registration Records, 1868-1910 at FamilySearch — index and images - How to Use this Collection
Research Facilities [ edit | edit source ]
Archives [ edit | edit source ]
Listed below are archives in Lafayette County. For state-wide archival repositories, seeArkansas Archives and Libraries.
Family History Centers [ edit | edit source ]
FamilySearch Center and Affiliate Library Locator map- search for local FamilySearch Centers or Affiliate Libraries
FamilySearch Centers provide one-on-one assistance, free access to center-only databases, and to premium genealogical websites.
FamilySearch Affiliate Libraries have access to most center-only databases, but may not always have full services normally provided by a FamilySearch center.
Local Centers and Affiliate Libraries
Libraries [ edit | edit source ]
Listed below are libraries in Lafayette County. For state-wide library facilities, seeArkansas Archives and Libraries.
Museums [ edit | edit source ]
Societies [ edit | edit source ]
Listed below are societies in Lafayette County. For state-wide genealogical societies, seeArkansas Societies.
Websites [ edit | edit source ]
USGenWeb Archives . Free. Data may be submitted by individuals or may be complete transcriptions
RootsWeb . Free. Data may be submitted by individuals or may be complete transcriptions
Linkpendium . Free. Click links. Some sites they link to may have fees ($)
CyndisList . Free. Click links. Some sites they link to may have fees ($)
FamilySearch Catalog - The FamilySearch catalog contains descriptions and access information for all genealogical materials (including books, online materials, microfilm, microfiche, and publications) in their collection. Use Historical Records to search for specific individuals in genealogical records
Research Guides [ edit | edit source ]
References [ edit | edit source ]
↑ The Handybook for Genealogists: United States of America ,10th ed. (Draper, UT: Everton Publishers, 2002).
↑ Genealogy Trails History Group, “Lafayette County, Arkansas Genealogy and History”, http://genealogytrails.com/ark/lafayette/
↑ The Handybook for Genealogists: United States of America ,10th ed. (Draper, UT: Everton Publishers, 2002).
↑ Handybook for Genealogists: United States of America , 10th ed. (Draper, Utah: Everton Pub., 2002), Lafayette County, Arkansas. Page 68 At various libraries (WorldCat) ; FHL Book 973 D27e 2002 ; Alice Eichholz, ed. Ancestry’s Red Book: American State, County, and Town Sources, Third ed. (Provo, Utah: Ancestry, 2004), 66.
↑ The Handybook for Genealogists: United States of America ,10th ed. (Draper, UT: Everton Publishers, 2002).
↑ Wikipedia contributors, "Lafayette County, Arkansas," in Wikipedia: the Free Encyclopedia , https://en.wikipedia.org/wiki/Lafayette_County,_Arkansas , accessed 28 August 2018.
↑ Glynn McCalman, The Encyclopedia of Arkansas History & Culture, ( http://www.encyclopediaofarkansas.net/encyclopedia/entry-detail.aspx?entryID=781&type=Category&item=Counties&parent=Counties%2c+Cities%2c+and+Towns&grandparent= : accessed January 14, 2016), “Lafayette County.”
↑ Desmond Walls Allen, Third Arkansas Union Cavalry, (Conway, Arkansas: Arkansas Research, c1987), p. 33-92. FHL book 976.7 M28dc
↑ such as Sebastian County (Fort Smith) and Pulaski County (Little Rock) (No entry in FamilySearch Catalog found for Pulaski County nor for Little Rock, Aug 2014)
↑ FamilySearch Wiki contributors, " Arkansas County Marriages - FamilySearch Historical Records ," in FamilySearch Wiki.
↑ Genealogical Society of Utah, Parish and Vital Records List (July 1998). Microfiche. Digital version at https://www.familysearch.org/wiki/en/images/0/0d/Igiarkansasem.pdf .
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Re: [802SEC] +++10 Day EC Email Ballot (Closes no later than 22 January
Re: [802SEC] +++10 Day EC Email Ballot (Closes no later than 22 January 2007)+++Motion regarding IEEE 802 reciprocal voting rights+++
To: [email protected]
Subject: Re: [802SEC] +++10 Day EC Email Ballot (Closes no later than 22 January 2007)+++Motion regarding IEEE 802 reciprocal voting rights+++
From: "Shellhammer, Steve" <[email protected]>
Date: Fri, 12 Jan 2007 14:44:43 -0800
Approved-By: [email protected]
In-Reply-To: A<001A8FDFE3AC804CB035C540210AF0940F759139@zrtphxm1.corp.nortel.com>
List-Help: <http://listserv.ieee.org/cgi-bin/wa?LIST=STDS-802-SEC>, <mailto:[email protected]?body=INFO STDS-802-SEC>
List-Owner: <mailto:[email protected]>
List-Subscribe: <mailto:[email protected]>
List-Unsubscribe: <mailto:[email protected]>
Reply-To: "Shellhammer, Steve" <[email protected]>
Sender: ***** IEEE 802 Executive Committee List ***** <[email protected]>
Thread-Index: Acc2cs4+UGOU5ws6QfS+6okruocVPgAAGI3wAAgxFnAAAKlM0AABJDKg
Thread-Topic: [802SEC] +++10 Day EC Email Ballot (Closes no later than 22 January 2007)+++Motion regarding IEEE 802 reciprocal voting rights+++
John,
See my suggested wording in the email in response to Mike. I
think it will work for you.
Regards,
Steve
-----Original Message-----
From: ***** IEEE 802 Executive Committee List *****
[
mailto:[email protected]
] On Behalf Of John Hawkins
Sent: Friday, January 12, 2007 2:15 PM
To: [email protected]
Subject: Re: [802SEC] +++10 Day EC Email Ballot (Closes no later than 22
January 2007)+++Motion regarding IEEE 802 reciprocal voting rights+++
A slight wrinkle/technicality arises in that not all "members of the EC"
are WG chairs, so there is no means of reciprocity in all cases. So this
motion may need to be re-worded somewhat to be directed at 802 WG
chairs, not "members of the EC." I would appreciate being afforded
membership/voting status in the WGs, but alas I cannot return the favor
(ok, maybe a few extra cookies for WG chairs? :-).
john
-----Original Message-----
From: ***** IEEE 802 Executive Committee List *****
[
mailto:[email protected]
] On Behalf Of Shellhammer, Steve
Sent: Friday, January 12, 2007 5:01 PM
To: [email protected]
Subject: Re: [802SEC] +++10 Day EC Email Ballot (Closes no later than 22
January 2007)+++Motion regarding IEEE 802 reciprocal voting rights+++
EC Members,
Mike and I discussed this a while back. I believe Mike has no
intention of creating a "new class of voting voters." I agree 100% that
we do not want to do that. Current the text states "That all voting
members of the 802 EC shall have voting rights in all IEEE 802 WGs and
TAGs." If that implies a new class of voting members we could consider
new text that states "That all voting members of the 802 EC shall be
members of all IEEE 802 WGs and TAGs." Roger, does this address you
concern about "a new class of voting members?"
My personal opinion is that I am okay with conditioning it on a
mutual agreement between the WG/TAG chairs. I believe if there is a
legitimate reason to exchange voting rights then the WG/TAG chairs would
agree to exchange voting rights. And if there is no reason to exchange
voting rights it limits the additional members who are likely not to
attend.
Regards,
Steve
-----Original Message-----
From: ***** IEEE 802 Executive Committee List *****
[
mailto:[email protected]
] On Behalf Of Michael Lynch
Sent: Friday, January 12, 2007 10:03 AM
To: [email protected]
Subject: Re: [802SEC] +++10 Day EC Email Ballot (Closes no later than 22
January 2007)+++Motion regarding IEEE 802 reciprocal voting rights+++
Roger,
The "802.18 Motion to SEC" is what was on the original proposal in
November.
One reason for the rule change is to provide a basis for allowing the
voting. Some participants within the various WGs/TGs may view granting
of voting rights to a chair or EC member as being irregular.
I expect to be offline until sometime Saturday afternoon London time.
Regards from DFW,
Mike
+1 972 814 4901 Mobile
-----Original Message-----
From: Roger B. Marks [
mailto:[email protected]
]
Sent: Friday, January 12, 2007 11:55
To: Lynch, Michael (RICH1:2H50)
Cc: [email protected]
Subject: Re: [802SEC] +++10 Day EC Email Ballot (Closes no later than 22
January 2007)+++Motion regarding IEEE 802 reciprocal voting rights+++
Mike,
I vote Disapprove, because:
(a) The motion is inappropriate according to the P&P. We don't have the
right to pass a motion that would specify that material "be included in
the next revision of the LMSC P&P". That's not the procedure for
changing the P&P.
(b) We can't by simple motion temporarily override the P&P, which is
what the motion is trying to do.
(c) Although you tried to avoid creating "a new class of voters", this
language would do so. The P&P do not specify a class of people with WG
voting rights; they specify the class of people who are WG members.
Voting is one right held by those members. This language would create an
additional class.
I generally like the idea you are proposing, but I remain concerned that
it would seriously impact quorum requirements in the smaller groups. I
would prefer a rule that would offer such reciprocal membership not
automatically but only upon request. I would support the initiation of
P&P change ballot along these lines.
P.S. I don't understand the labeling of the slide. In what sense is this
an "802.18 Motion to SEC"?
Roger
On Jan 12, 2007, at 10:12 AM, Michael Lynch wrote:
> Dear EC members,
>
> During the November Plenary meeting I presented to the EC a motion on
> reciprocal voting rights. There was discussion of the motion and some
> edits were suggested. It was decided that there should be further work
> on the motion. That motion, now modified, is being submitted here for
> EC ballot.
>
> During the revision to the original motion it was considered that
> those with reciprocal voting rights would not be considered in
> determining quorums. After discussion that was dropped since it seemed
> to create a new class of voters.
>
> Next week's Joint Interim meeting will provide an opportunity for some
> of the EC to have face-to-face discussions of this motion and of
> course we can discuss it here. Next Tuesday evening will be the RR-TAG
> hosted meeting to determine if IEEE 802 will submit an input to ITU-R
> WP8F on IMT requirements. It is possible that IMT requirements may be
> the first of several IEEE 802 inputs to WP8F. If the work method
> involves developing the response(s) within individual TGs and bringing
> those results to the RR-TAG then having reciprocal voting rights
> should prove useful to that work.
>
> Motion: Moved by Mike Lynch, seconded by Steve Shellhammer
>
> The text of the motion is attached.
>
> Informative: This document informs ITU-R WP8F of a new project being
> started in IEEE.
>
> This ballot opens at midnight CT Friday 12 January and closes at 11:59
> p.m. CT Monday 22 January 2007.
>
> Regards,
>
> Mike
>
> +1 972 814 4901 Mobile
>
> <<18-06-0077-r4-0000_RR-TAG_Reciprocal_Voting_Nov06.ppt>>
>
>
> ----------
> This email is sent from the 802 Executive Committee email reflector.
> This list is maintained by Listserv.
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Follow-Ups
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Re: [802SEC] +++10 Day EC Email Ballot (Closes no later than 22 January 2007)+++Motion regarding IEEE 802 reciprocal voting rights+++
From:Pat Thaler <[email protected]>
Re: [802SEC] +++10 Day EC Email Ballot (Closes no later than 22 January 2007)+++Motion regarding IEEE 802 reciprocal voting rights+++
From:"Bob O'Hara (boohara)" <[email protected]>
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Re: [802SEC] +++10 Day EC Email Ballot (Closes no later than 22 January 2007)+++Motion regarding IEEE 802 reciprocal voting rights+++
From:John Hawkins <[email protected]>
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Genes | Free Full-Text | Whole Exome Sequencing to Find Candidate Variants for the Prediction of Kidney Transplantation Efficacy
Introduction: Kidney transplantation is the optimal treatment strategy for some end-stage renal disease (ESRD); however, graft survival and the success of the transplantation depend on several elements, including the genetics of recipients. In this study, we evaluated exon loci variants based on a high-resolution Next Generation Sequencing (NGS) method. Methods: We evaluated whole-exome sequencing (WES) of transplanted kidney recipients in a prospective study. The study involved a total of 10 patients (5 without a history of rejection and 5 with). About five milliliters of blood were collected for DNA extraction, followed by whole-exome sequencing based on molecular inversion probes (MIPs). Results: Sequencing and variant filtering identified nine pathogenic variants in rejecting patients (low survival). Interestingly, in five patients with successful kidney transplantation, we found 86 SNPs in 63 genes 61 were variants of uncertain significance (VUS), 5 were likely pathogenic, and five were likely benign/benign. The only overlap between rejecting and non-rejecting patients was SNPs rs529922492 in rejecting and rs773542127 in non-rejecting patients’ MUC4 gene. Conclusions: Nine variants of rs779232502, rs3831942, rs564955632, rs529922492, rs762675930, rs569593251, rs192347509, rs548514380, and rs72648913 have roles in short graft survival.
Seyed Mohammad Kazem Aghamir 1 ,
Hassan Roudgari 2,3 ,
Hassan Heidari 1 ,
Mohammad Salimi Asl 1 ,
Yousef Jafari Abarghan 4 ,
Venous Soleimani 1 ,
Rahil Mashhadi 1 and
Fatemeh Khatami 1,*,†
1
Urology Research Center, Tehran University of Medical Sciences, Tehran P94V+8MF, Iran
2
Genomic Research Centre (GRC), Shahid Beheshti University of Medical Sciences (SBMU), Tehran 1416634793, Iran
3
Department of Applied Medicine, Medical School, Aberdeen University, Aberdeen AB24 3FX, UK
4
Deparment of Molecular Genetics, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad 1696700, Iran
*
Author to whom correspondence should be addressed.
†
Mailing Address: Urology Research Center, Sina Hospital, Hassan Abad Sq., Imam Khomeini Ave., Tehran 1136746911, Iran.
Genes 2023 , 14 (6), 1251; https://doi.org/10.3390/genes14061251
Received: 11 March 2023 / Revised: 4 April 2023 / Accepted: 6 April 2023 / Published: 11 June 2023
(This article belongs to the Special Issue Cancer Systems Biology and Genomics )
Abstract
Introduction: Kidney transplantation is the optimal treatment strategy for some end-stage renal disease (ESRD); however, graft survival and the success of the transplantation depend on several elements, including the genetics of recipients. In this study, we evaluated exon loci variants based on a high-resolution Next Generation Sequencing (NGS) method. Methods: We evaluated whole-exome sequencing (WES) of transplanted kidney recipients in a prospective study. The study involved a total of 10 patients (5 without a history of rejection and 5 with). About five milliliters of blood were collected for DNA extraction, followed by whole-exome sequencing based on molecular inversion probes (MIPs). Results: Sequencing and variant filtering identified nine pathogenic variants in rejecting patients (low survival). Interestingly, in five patients with successful kidney transplantation, we found 86 SNPs in 63 genes 61 were variants of uncertain significance (VUS), 5 were likely pathogenic, and five were likely benign/benign. The only overlap between rejecting and non-rejecting patients was SNPs rs529922492 in rejecting and rs773542127 in non-rejecting patients’ MUC4 gene. Conclusions: Nine variants of rs779232502, rs3831942, rs564955632, rs529922492, rs762675930, rs569593251, rs192347509, rs548514380, and rs72648913 have roles in short graft survival.
Keywords:
whole-exome sequencing
;
single nucleotide polymorphisms
;
kidney transplant
;
exonic/intronic
1. Introduction
Kidney transplantation is the optimal treatment strategy for end-stage kidney disease; however, its complications may cause morbidity and mortality in transplant recipients [ 1 ]. Prediction of transplant rejection is essential and requires accurate, time-sensitive, and noninvasive biomarker platforms. The traditional method of monitoring allograft rejection using the elevated level of serum creatinine cannot precisely represent ongoing immunologic rejection [ 2 ]. These days, the genes that govern the acceptance or rejection of a transplant are at the center of attention. Several studies have shown that proteins, DNA, and RNA could be promising candidate biomarkers for monitoring renal transplantation rejection [ 3 , 4 , 5 , 6 , 7 ]. The putative genes that play a role in the survival of transplanted cells, tissues, or organs belong to a family called the major histocompatibility complex (MHC) [ 8 ]. The Cross Match is more important, followed by knowledge of the differences in HLA typing between the donor and the recipient. Host–donor matching is hugely related to the human leukocyte antigen (HLA) molecule. Class I HLA molecules are expressed in nucleated cells, and class II HLA molecules are expressed in antigen-presenting cells. These molecules play an essential role in kidney and bone marrow transplantation, where matching HLA-A , -B , and -DR loci are important [ 9 ]. There is still acute kidney transplant rejection, despite a higher chance of successful transplantation by HLA typing and matching. Therefore, it is believed that more genetic loci can be checked for higher success. This research highlighted critical exonic mutations and polymorphisms that could contribute to the destiny of kidney transplantation using next-generation sequencing (NGS).
2. Materials and Methods
2.1. Patients and Samples
This study was granted a permit by the Tehran University of Medical Sciences Ethics Committee (IR.TUMS.MEDICINE.REC.1400.149). All participants agreed to enter the study by signing a written informed consent. A total of 10 transplant patients were recruited from the urology research center, Tehran University of Medical Sciences, between 1 January 2019 and 31 December 2020. Detailed clinical and family histories of patients were provided through questionnaires. First, HLA typing is done, and then transplantation is scheduled based on the HLA matching result. HLA typing is necessary in kidney transplantation, as detection of foreign HLA by receiver T lymphocytes induces an immune response, leading to graft rejection. T lymphocyte activation starts a serial reaction of mediators that end in the immune system against the allograft. HLA laboratories currently perform serologic and molecular typing methods. After transplantation, the rejection and nonrejection genomes were sequenced separately to find possible polymorphisms with an impact on transplant rejection (
Figure 1
).
Figure 1. Graphical abstract of the research procedure.
All five rejecting patients had mixed cellular and antibody-mediated rejection. They had chronic rejection, which occurs months after organ or tissue transplantation (rejection between 3 and 6 months considered in this study). First, we administered a triple immunosuppression scheme (tacrolimus, mycophenolate mofetil, and corticosteroids). Then, we evaluated patients for Polyomavirus-BK (BK) and cytomegalovirus (CMV) infections for additional treatment strategies.
About 5 milliliters of blood were collected at the time of recruitment. Serum creatinine and the CKD-EPI Creatinine Equation (2021) were used to estimate the GFR at the time of recruitment. DNA was harvested from blood samples using the QIAamp DNA Micro Kit (Cat# 56304).
2.2. Whole Exome Sequencing
Untargeted whole exome sequencing (WES) was used to study genetic variations in 10 recipients of transplanted kidneys. Samples were fragmented using a Covaris S2 ultrasonicator (Covaris, Woburn, MA, USA) and trained for sequencing on an Illumina HiSeq2500 using a custom DNA library preparation protocol established on the method described by Rohland et al. [ 10 ]. The end result read out was aligned to the human reference genome from 2013 (GRCh38/hg38) Sentieon BWA (Sentieon, Mountain View, CA, USA). The final reads and variant labeling were valued using the Sentieon DNAseq pipeline [ 11 ].
2.3. Analysis of Variants
All final labeled variants were annotated by ANNOVAR [ 12 ] and filtered according to variant function (nonsynonymous, stop gain/loss, splicing, frameshift insertion/deletion, and in-frame insertion/deletion variants) and minor allele frequencies (MAF; <0.1% global population MAF) in the Genome Aggregation Database (gnomAD) [ 13 ] and a population-level database of genomic variant frequencies derived from large-scale exome and genome sequencing data. The medical implications of functional variants were clarified using InterVar based on the Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG-AMP) [ 14 , 15 ]. Finally, variants were categorized as “pathogenic” or “likely pathogenic”, and the inheritance prototype (dominant or recessive) was considered. In addition, several computational prediction algorithms, including SIFT, Polyphen2 (Polyphen2_HDIV and Polyphen2_HVAR), Mutation Taster, M-CAP, and LRT, were used to support the understanding of nonsynonymous variants categorized as “variants of unknown significance” (VUSs) according to ACMG-AMP guidelines [ 16 ]. Additional data of pathogenicity was checked for VUSs if at least 5 of these six prediction methods were in agreement with pathogenicity [ 16 ]. Furthermore, we presented copy-number variant (CNV) analysis via Atlas-CNV, a system for distinguishing and selecting high-confidence CNVs from targeted NGS data. Entirely listed CNVs were visualized using the Integrative Genomics Viewer software program and subsequently double-checked manually.
2.4. Statistical Analysis
Continuous data are usually shown as the median, and discontinuous data are shown as n (%). Differences between the rejecting and non-rejecting transplant groups were measured by χ2 tests, and then Fisher’s exact test (or test for trend) was used for discontinuous variables. The unpaired t -tests from STATA software version 17.0 were used to compare the continuous data. The SNP-set (Sequence) Kernel Association Test (SKAT) was used to assess the gene-based rare variant association burden [ 17 ]. Two-tailed p -values < 0.05 were considered statistically significant.
3. Results
Ten kidney transplantation patients from the Urology Research Center were enrolled in this study, including five rejections of transplants and five sex- and age-matched non-rejecting cases. Then, all patients were genetically sequenced for genetic alterations. Demographic information is presented in Table 1 .
Table 1. Demographic information of the study subjects.
The median age was 37 and 36 in rejecting and non-rejecting patients. Most patients in our rejecting group were not diabetic.
Using an untargeted sequencing panel, we identified 194 rare but functional variants (including nonsynonymous, stop gain/loss, splicing, frameshift insertion/deletion, and in-frame insertion/deletion variants) in 10 patients ( Supplementary File S1 ). Among the 10 patients included in this study, we found 610 variants, which were already recorded in exonic, exonic splicing, intergenic, intronic, non-coding RNA exonic, splicing, untranslated upstream region, and one untranslated region.
There were no putative variants among the five transplant rejecting patients; however, there were nine variants from six genes that could be suggested to have a role in graft rejection in four patients (
Table 2
). All SNPs were categorized as pathogenic or likely pathogenic based on ACMG-AMP guidelines; another was classified as variants of uncertain significance “VUSs”. To distinguish between benign and pathogen variants, we used three famous sites, including Varsome (
https://varsome.com/
, accessed on 1 August 2022), Intervar (
https://wintervar.wglab.org/
, accessed on 1 August 2022), and Frankin (
https://franklin.genoox.com/
, accessed on 1 August 2022). Two variants were reported as likely pathogenic, including rs779232502 in
Asporin (ASPN
) and rs3831942 in
Potassium Calcium-Activated Channel Subfamily N Member 3 (KCNN3)
. Six variants were reported as likely benign, including rs564955632, rs529922492, rs762675930, rs569593251, rs192347509, and rs548514380. The only SNP reported as benign was rs72648913 on
Titin (TTN).
Table 2. The characteristics of 9 variants from six known genes with possible role in graft rejection.
In five patients with successful kidney transplantation (meaning no rejection for more than five years), interestingly, alterations in 63 known genes were found ( Table 3 ). Out of the 86 SNPs identified in those 63 genes, 61 SNPs were VUS, five were likely pathogenic, and another five were likely benign. All variants were located on the exonic region, the coding part of a gene, but there was one variant from Acyl-CoA Synthetase Family Member 3 (ACSF3), consisting of four inserted nucleotides (GGAG) in a splicing site.
Table 3. The characteristics of 90 variants of 63 common genes with a possible role in preventing graft rejection.
Mutation in the LVRN gene (one of those 63 genes that produces a protein called Laeverin) is associated with a disease that causes Astigmatism. This one, in fact, contributes to metallopeptidase activity, which in turn affects placentation by regulating the biological activity of the critical peptides at the embryo-maternal interface.
The
MUC4
gene (Mucin c, which is linked to pancreatic adenocarcinoma) is the principal constituent of mucus. This glycoprotein has essential functions in the protection of epithelial cells by maintaining membrane integration and has been observed to contribute to epithelial renewal and differentiation. The MUC4 gene has a coding sequence with a variable number (>100) of 48 nucleotide tandem repeats, which contributes to the O-linked glycosylation pathway, so defective C1GALT1C1 causes Tn poly agglutination syndrome (TNPS).
TTN
(Titin) encodes a large protein for striated muscles with two ends called an N-terminal I-band and a C-terminal A-band as the elastic part of the molecule. It contains two regions of tandem immunoglobulin domains on either side of a PEVK region that is rich in proline, glutamate, valine, and lysine. The rs762675930 of TTN contains an exonic and missense replacement of Asn > Asp on amino acid 5165. Titin also includes binding sites for serving as an adhesion template to build up the contractile machinery inside muscle cells. Mutations in this gene might be associated with familial hypertrophic cardiomyopathy nine and/or the production of autoantibodies against Titin, especially in Scleroderma. The gene ontology (GO) annotations for this gene include calcium ion binding and chromatin binding.
Asporin
(
ASPN
) is an extracellular cartilage protein from a small leucine-rich proteoglycan family. This protein can regulate chondrogenesis by inhibiting the expression of the transforming growth factor-beta gene in cartilage.
The last one is Potassium
Calcium-Activated Channel Subfamily N Member 3
(
KCNN3
), which belongs to the
KCNN
family of potassium channels and includes two CAG repeat regions that increase susceptibility to disease. There are some spliced transcript variants that encode different isoforms of this gene.
There was no report in ClinVar for variant rs564955632 (Missense Variant), rs529922492 (Missense Variant), rs762675930 (Missense Variant), rs72648913 (Missense Variant), rs192347509 (Missense Variant), rs548514380 (Missense Variant), and rs779232502 (Missense Variant). The rs569593251 variant of the
TTN
gene is reported by ClinVar as likely benign for interpreted conditions, such as Myopathy myofibrillar with early respiratory failure. rs3831942 is an in-frame deletion, which plays a role in Pyloric stenosis and Esophageal atresia.
These pathogenic or likely pathogenic single nucleotide and insertion/deletion variants were detected in 3 genes, including
ZNF806
,
HYDIN
, and
ATXN3
. There were another five benign or likely benign single-nucleotide and insertion/deletion variants detected in 5 genes, too, including
FAM104B
, of
MUC12
,
ARMC9
,
ZNF717
, and
MUC4
, the only gene shared between both rejecting and the non-rejecting groups was
MUC4
; however, the variants were different, including rs529922492 in the rejecting group and rs773542127 in the non-rejecting group. The medications used for patients were the same between rejecting and non-rejecting patients regardless of the variants (
Table 4
).
Table 4. Detailed information on medications in five rejecting (columns 1 to 5) and five non-rejecting patients (columns 6 to 10).
4. Discussion
Using next-generation sequencing (NGS) technology, we successfully identified nine variants that could predict kidney transplantation rejection and 86 variants that might play a protective role. Genetic testing for managing chronic kidney disease and transplantation is rapidly developing. Available guidelines from the OPTN (Organ Procurement and Transplantation Network) and KDIGO (KDIGO Clinical Practice Guideline on the Evaluation and Management of Candidates for Kidney Transplantation) imply that genetic testing in a renal transplant should become more widespread [ 18 , 19 , 20 , 21 ]. We found nine polymorphisms from 6 genes as promoting and 86 protective variants for rejection of kidney transplants. These six genes and their related proteins are shown in Figure 2 .
Figure 2. The protein interaction network of six target genes with other genes based on GeneMANIA.
These genes co-occur with the biological term “kidney transplant” in the GeneRIF Biological Term Annotations dataset. They are from different genes, including Adiponectin, C1Q, and collagen domain-containing (ADIPOQ) and cytochrome P450, family 3, subfamily A, polypeptide 5 (CYP3A5). ( https://maayanlab.cloud/Harmonizome/gene_set/kidneytransplant/GeneRIF+Biological+Term+Annotations , accessed on 1 August 2022).
It has been recently published by Mann et al. that nearly one-third of pediatric renal transplant recipients had a genetic cause of their kidney disease identified by WES [ 22 ]. For the first time, Mota-Zamorano and colleagues found that some variants in the LEPR and ADIPOQ genes of donors and recipients might affect the outcome of kidney transplantation [ 23 ]. Later, it was observed in several studies that ADIPOQ played an essential role in patients with post-transplant diabetes mellitus [ 24 , 25 , 26 , 27 , 28 ].
We detected pathogenic variants in three genes, including
ZNF806
,
HYDIN
, and
ATXN3.
The only variant that we found in
KCNN3
was the insertion of fifteen nucleotides (GCTGCTGCTGCTGCT) that led to a frameshift mutation resulting in a nonfunctional protein.
KCNN3
plays a role in different pathways, so changes in its activity can affect some physiological mechanisms. Calcium-activated K+ via its specific channels promotes action potential (AP) repolarization; accordingly, some
KCNN2
and
KCNN3
variants are associated with increased atrial fibrillation (AF) risk. In addition, histone deacetylase-related epigenetic mechanisms have been found to affect AP regulation [
29
]. Thus, epigenetic change of
KCNN3
was reported in new-onset diabetes after kidney transplant (NODAT), which had an adverse impact on kidney allograft and patient survival [
30
]. Myeloid-derived suppressor cells (MDSC) form a heterogeneous population of immature myeloid cells that increasingly proliferate in inflammatory conditions, including transplantations, and KCNN3 is top listed among the 50 genes involved in the migration of MDSCs [
31
]. A large-scale study also identified a relationship between
KCNN3
and
IL6R
genes and AP [
32
].
LVRN (Laeverin) encodes a cell surface aminopeptidase that is involved in embryonic signaling pathways. LVRN belongs to the M1 peptidase family, also called ‘aminopeptidase Q’ [ 33 , 34 ]. Primate LVRN has a unique peptide-binding motif (HXMEN), where the first glycine (Gly) residue is substituted by histidine (His), inducing significant changes in end-product peptide hormones. However, there are no previous studies on the role of LVRN in kidney transplantation; for the very first time, we suggest that LVRN plays an essential role in the rejection of kidney transplants.
The TTN we studied is rs762675930, an exonic and missense alteration affecting amino acid 5165 (Asn > Asp). Previously, TTN was also evaluated for its role in cardiac arrhythmias, cardiomyopathies, and sudden death [ 35 ].
The
MUC4
gene is the only gene shared between rejecting and non-rejecting groups. However, the detected variants were different (rs529922492 in rejecting and rs773542127 in non-rejecting). There are eight well-known human epithelial mucin genes [
36
] that several studies have implied have roles in transplantation. In 2003, Wasserberg and colleagues suggested that early transplant rejection could be associated with increased MUC2, MUC4, IFN-gamma, and TNF-alpha expression [
37
], so they can be used as predictive markers in combination with histopathologic examination for assessment of the risk of graft rejection. A study by Shamloo and colleagues on MHC Class I and II mismatch using a mouse model suggested a role for mucins in the pathogenesis of dry eye-associated with graft versus host disease. MUC4 has also been reported as an ERK signaling pathway activator in epithelial cells. An animal study suggested a role for MUC4 and ERK signaling pathways in oxidative stress and CaOx crystal formation in renal tubular epithelial cell [
38
].
The rs192347509 of
SVEP1
was identified in two Short segment Hirschsprung disease patients [
39
]. The
SVEP1
gene encodes a large extracellular matrix protein with sushi (complement control protein), von Willebrand factor type A, epidermal growth factor-like (EGF), and pentraxin domains (PMID: 11062057, PMID: 16206243), so its deficiency leads to increased plasma levels of Cxcl1, which is an expansion of plaque inflammatory leukocytes that in turn promotes atherosclerotic plaque formation. Coxam and colleagues reported that
SVEP1
plays the role of a modulator for vessel anastomosis during developmental angiogenesis in zebrafish embryos, so the loss of SVEP1 followed by a decrease in blood flow together contributes to a defective anastomosis of intersegmental vessels [
40
]. Accordingly, we assume that the inhibition of the degradation of
SVEP1
gene products using products may offer a therapeutic strategy to prevent kidney transplant rejection [
41
].
ASPN encodes a protein that belongs to a family of leucine-rich repeat (LRR) proteins that exist in the cartilage matrix. The name asporin shows the exceptional aspartate-rich N terminus and its connection to decorin [ 42 ]. Studies on ASPN have found a promotional role for ASPN in epithelial and mesenchymal transformation and in invasion, migration, and metastasis of several malignancies via activating the CD44-AKT/ERK-NF-kappaB pathway [ 43 , 44 , 45 ]. Several studies have found the periodontal ligament-associated protein-1 ( PLAP-1 )/ asporin ’s susceptibility gene for osteoarthritis. PLAP-1 / asporin negatively regulates TLR2- and TLR4-induced inflammatory responses through direct molecular interactions [ 46 ]. Iida and coworkers found a SNP that maps within a 33.4-kb genomic region covering ASPN [ 47 ]. Sakashita and colleagues showed that the absence of PLAP-1 could inhibit high-fat diet-induced metabolic syndrome and bone resorption in vivo, and adipocyte differentiation resulting in an extracellular matrix change. Studying PLAP-1 represents the correlation between diabetes and periodontal disease [ 48 ]. Mice lacking PLAP-1 / asporin responds to extraordinary fat diet-induced metabolic disorder and alveolar bone loss by using adipose tissue expansion [ 48 ].
The presence of the C allele of rs1044250 and the G allele of rs2278236 in the
ANGPTL4
gene is linked to the developed risk of moderate/severe proteinuria in renal transplant patients [
49
], but this was not the case in our study. We found pathogenic single nucleotide and insertion/deletion variants in
ZNF806
,
HYDIN
, and
ATXN3
genes among non-rejecting patients; however, none of the previous studies could see these three genes’ role in transplant rejection. Some investigators suggested a higher incidence of
ZNF 469
gene variants in fast progressive advanced keratoconus patients who had surgery by the age of 30 compared to its frequency in the average Turkish population [
50
].
ZNF
genes have been shown to act as potential molecular biomarkers involved in RCC carcinogenesis. The limitations of this research include the very small number of patients who were studied.
5. Conclusions
It is quite applicable to use the WES test to predict the survival of kidney transplantation. Moreover, nine variants rs779232502, rs3831942, rs564955632, rs529922492, rs762675930, rs569593251, rs192347509, rs548514380, and rs72648913 of six genes, LVRN, MUC4, TTN, SVEP1, ASPN, and KCNN3, have possible roles in graft rejection that are suggested to be checked in graft recipients.
Supplementary Materials
The following supporting information can be downloaded at: https://www.mdpi.com/article/10.3390/genes14061251/s1 , see Supplementary File S1.
Author Contributions
S.M.K.A. and H.R. were the principal investigators, H.H. edited manuscript, M.S.A. and Y.J.A. analyzed the data, R.M. and V.S. provided data and data curation, and F.K. wrote the manuscript. All authors have read and agreed to the published version of the manuscript.
Funding
This research received no external funding.
Institutional Review Board Statement
The study was granted a permit by the Tehran University of Medical Sciences Ethics Committee (IR.TUMS.MEDICINE.REC.1400.149). All participants agreed to enter the study by signing a written informed consent.
Informed Consent Statement
All participants agreed to enter the study by signing a written informed consent.
Data Availability Statement
All necessary data are submitted through manuscript. Detailed data will be available on request.
Acknowledgments
Special thanks to the urology research center, Tehran University of Medical Sciences, and National Institute for Medical.
Conflicts of Interest
All authors declare that there is not any conflict of interest for this publication.
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Figure 1. Graphical abstract of the research procedure.
Figure 2. The protein interaction network of six target genes with other genes based on GeneMANIA.
Table 1. Demographic information of the study subjects.
Variable Group p -Value Rejecting Non-Rejecting Sex (male), n (%) 4 (80%) 4 (80%) 1.000 Education (BSc), n (%) 1 (20%) 3 (60%) 0.524 Age (year), median (IQR) 37 (36–43) 36 (34–42) 0.459 Creatinine, median (IQR) 5 (3.6–6) 1.3 (1.2–1.3) 0.009 Weight, median (IQR) 76 (70–76) 65 (65–87) 0.750 Height, median (IQR) 170 (168–170) 168 (168–168) 0.142 BMI, median (IQR) 24.8 (24.0–26.3) 23.9 (23.0–30.4) 0.917 DM (yes), n (%) 2 (40%) 1 (20%) 0.500 DM family history (yes), n (%) 2 (40%) 1 (20%) 0.500
Table 2. The characteristics of 9 variants from six known genes with possible role in graft rejection.
Gene Exonic/ Intronic SNP Pathogenicity Cytoband Start End REF Sequence ALT Sequence Depth 1 LVRN Exonic rs564955632 VUS 5q23.1 115320380 115320380 G A 78 2 MUC4 Exonic rs529922492 VUS 3q29 195510751 195510751 G T 455 3 TTN Intron rs762675930 VUS 2q31.2 179611634 179611634 C T 199 4 TTN Exonic rs569593251 VUS 2q31.2 179406087 179406087 G A 105 5 TTN Exonic rs72648913 Benign 2q31.2 179610967 179610967 C T 166 6 SVEP1 Exonic rs192347509 Likely Benign 9q31.3 113170636 113170636 C T 98 7 SVEP1 Exonic rs548514380 VUS 9q31.3 113261413 113261413 C T 146 8 ASPN Intronic rs779232502 VUS 9q22.31 95236968 95236968 A G 33 9 KCNN3 Exonic rs3831942 Likely Benign 1q21.3 154842199 154842199 - GCTGCTGCTGCTGCT (insertion) 80
Table 3. The characteristics of 90 variants of 63 common genes with a possible role in preventing graft rejection.
Gene Exonic/Intronic SNP Pathogenicity Cytoband Start End REF Sequence ALT Sequence Depth 1 ACSF3 Splicing - - 16q24.3 89167068 89167068 - GGAG 44 2 ANKRD36 Exonic rs71329611 VUS 2q11.2 97864333 97864334 CC AT 36 3 ANKRD36C Exonic rs78179792 VUS 2q11.1 96616504 96616504 C A 103 4 ANKRD36C Exonic rs78178577 VUS 2q11.1 96521640 96521640 C T 211 5 ANKRD36C Exonic rs76276218 VUS 2q11.1 96517474 96517474 G A 130 6 ANKRD36C Exonic rs200183690 VUS 2q11.1 96521090 96521090 T C 108 7 ANKRD36C Exonic rs77124870 VUS 2q11.1 96517471 96517471 A G 128 8 ATXN3 Exonic;splicing rs748879218 Likely Pathogenic 14q32.12 92537397 92537397 T - 73 9 CDC27 Exonic rs111227623 VUS 17q21.32 45216162 45216162 A C 94 10 CDC27 Exonic rs76836152 VUS 17q21.32 45216172 45216172 A G 94 11 CDC27 Exonic rs62075657 VUS 17q21.32 45216132 45216132 T G 93 12 CDC27 Exonic rs796538886 VUS 17q21.32 45219329 45219329 A C 87 13 CTDSP2 Exonic rs74343811 VUS 12q14.1 58220841 58220841 C T 168 14 CTDSP2 Exonic rs111346934 VUS 12q14.1 58220823 58220823 C T 165 15 CTDSP2 Exonic rs76940645 VUS 12q14.1 58220816 58220816 A G 165 16 CTDSP2 Exonic rs75591888 VUS 12q14.1 58220844 58220844 C T 168 17 CTDSP2 Exonic rs74554628 VUS 12q14.1 58240210 58240210 G T 115 18 DSPP Exonic - - 4q22.1 88537133 88537133 G A 38 19 FAM104B Exonic rs1047037 Likely Benign Xp11.21 55172687 55172687 T C 213 20 FRG1BP; FRG1DP Exonic rs867116961 VUS Xp11.21 29612099 29612099 G A 151 21 FRG1DP; FRG1BP Exonic rs1047037 VUS Xp11.21 29612103 29612103 T C 203 22 FRG2C Exonic rs2118760 VUS 3p12.3 75715099 75715099 T A 235 23 HLA-A Exonic - - 6p22.1 29911260 29911261 AC CG 116 24 HLA-B Exonic - - 6p21.33 31324887 31324888 GG CT 73 25 HLA-DQA1 Exonic rs386699859 VUS 6p21.32 33037639 33037640 GC AT 38 26 HLA-DQB1 Exonic - - 6p21.32 32632659 32632660 CT TG 57 27 HLA-DRB1 Exonic rs796196270 VUS 6p21.32 32551957 32551958 GC TT 82 28 HLA-DRB1 Exonic rs796846373 VUS 6p21.32 32551938 32551939 GG AT 79 29 HYDIN Exonic rs375727122 - 16q22.2 70954704 70954718 GCGCTCCTTCTCCGT - 182 30 HYDIN Exonic rs11337008 Likely Pathogenic 16q22.2 70896016 70896016 A - 111 31 IGSF3 Exonic rs75947003 VUS 1p13.1 117142700 117142700 C A 107 32 IGSF3 Exonic rs61786651 VUS 1p13.1 117156459 117156459 C T 117 33 KRTAP9-1 Exonic rs76389571 VUS 17q21.2 39346578 39346578 C G 68 34 MUC2 Exonic - - 11p15.5 1093483 1093484 GT AC 302 35 MUC3A Exonic rs113251740 VUS 2q21.2 100551133 100551133 C T 513 36 MUC3A Exonic rs72494466 VUS 7q22.1 100551122 100551122 T G 448 37 MUC3A Exonic rs760637480 VUS 7q22.1 100551094 100551094 G A 423 38 MUC3A Exonic rs771974573 VUS 7q22.1 100551092 100551092 G C 158 39 MUC3A Exonic rs749410668 VUS 7q22.1 100551082 100551082 C T 170 40 MUC3A Exonic rs141925032 VUS 7q22.1 100550704 100550704 C A 139 41 MUC4 Exonic rs773542127 Likely Benign 3q29 195510254 195510254 C G 160 42 MUC6 Exonic rs374545453 VUS 11p15.5 1017239 1017240 CG TA 263 43 OR2L8 Exonic rs34851853 VUS 1q44 248112762 248112763 TG CA 78 44 PCM1 Exonic rs754721723 VUS 8p22 17796382 17796383 AC GT 69 45 PLIN4 Exonic - - 19p13.3 4513143 4513144 CA TG 107 46 PSG3 Exonic rs34721205 VUS 19q13.2 43243217 43243218 AA GG 85 47 TEX11 Exonic rs386825673 VUS Xq13.1 69749852 69749853 AT GA 43 48 ZNF717 Exonic rs796081257 VUS 3p12.3 rs796081257 rs796081257 CA GG 144 49 PRB3 Exonic - - 12p13.2 11420495 11420496 GG AA 53 50 RP1L1 Exonic rs747592079 VUS 8p23.1 10466686 10466686 G A 103 51 SLC35G4 Exonic rs386801281 VUS 18p11.21 11609903 11609904 CA GG 150 52 ZNF705E Exonic - - 1q13.4 71527895 71527896 CG TA 162 53 ZNF717 Exonic rs77322475 Likely Benign 3p12.3 75787159 75787159 C T 325 54 ZNF806 Exonic rs11491243 VUS 2q21.2 133075612 133075612 C T 181 55 ZNF806 Exonic rs113311843 Likely Pathogenic 2q21.2 133075904 133075904 - A 154 56 ZNF806 Exonic rs111405036 Likely Pathogenic 2q21.2 133076118 133076118 A - 146 57 ZNF806 Exonic rs111944984 Likely Pathogenic 2q21.2 133075479 133075479 C - 221 58 ARHGEF26 Exonic rs386667246 VUS 3q25.2 153839959 153839960 CT TC 87 59 ARMC9 Exonic rs386656198 Likely Benign 2q37.1 232087474 232087475 AT GA 66 60 MYG1, MYG1-AS1, PFDN5 Exonic rs71453838 VUS 12q13.13 53693532 53693533 AA GC 43 61 DUSP5 Exonic rs35834951 VUS 10q25.2 112266822 112266823 GC AT 62 62 FCGBP Exonic rs796880559 VUS 19q13.2 40368498 40368499 AA CC 71 63 GTF2IRD2; GTF2IRD2B Exonic rs370642824 VUS 7q11.23 74558397 74558397 C A 24 64 HLA-C Exonic rs796075923 VUS 6p21.33 31238009 31238010 TT CG 31 65 IP6K3 Exonic rs34332988 VUS 6p21.33 33690796 33690797 CA TG 87 66 KLRC3 Exonic rs796361824 VUS 12p13.2 10573094 10573095 CA GG 16 67 KRTAP10-6 Exonic - - 21q22.3 46012181 46012182 CG TA 49 68 MPP2 Exonic rs70964679 VUS 17q21.31 41960633 41960634 CG GC 83 69 MUC12 Exonic rs763405288 Likely Benign 7q22.1 100639418 100639419 CG AA 50 70 OR2L8 Exonic rs34851853 VUS 1q44 248112762 248112763 TG CA 102 71 OR2T35 Exonic - - 1q44 248801610 248801611 GC AT 35 OR9G1; OR9G9 Exonic rs71458233 VUS 11q12.1 56468047 56468048 AC GT 278 72 PCM1 Exonic rs754721723 VUS 8p22 17796382 17796383 AC GT 71 73 PSG3 Exonic rs34721205 VUS 19q13.2 43243217 43243218 AA GG 98 74 RGPD5 Exonic - - 2q13 110593536 110593536 C A 14 75 RNF212 Exonic - - 4p16.3 1087329 1087329 - TGGAGCCAGCCAT 44 76 SCARF2 Exonic rs70944210 VUS 22q11.21 20779946 20779947 CG GC 37 77 SPIB Exonic rs113934432 VUS 19q13.33 50926264 50926265 TG CC 40 78 TCF15 Exonic rs71212728 VUS 20p13 590542 590543 CG GC 55 79 TRIM50 Exonic rs71517080 VUS 7q11.23 72738762 72738763 CA TG 65 80 VCX2 Exonic Xp22.31 8138170 8138171 CT GC 19 81 PCDHA9 Exonic rs35021536 VUS 5q31.3 140230370 140230371 AA CC 115 82 MUC5B Exonic - - 11p15.5 1258240 1258241 CA TG 158 83 OR4C3 Exonic rs386753295 VUS 11p11.2 48346961 48346962 AA TG 174 84 KRTAP12-2 Exonic rs35163632 VUS 21q22.3 46086757 46086758 GC AT 83 85 PIGZ Exonic rs71611508 VUS 3q29 196674972 196674973 CT TC 69 86 PRIM2 Exonic - - 6p11.2 57512796 57512796 - CA 86
VUS: variants of uncertain significance.
Table 4. Detailed information on medications in five rejecting (columns 1 to 5) and five non-rejecting patients (columns 6 to 10).
Patient Code 1 2 3 4 5 6 7 8 9 10 Mediation B1 100 Vit B6 Rocatrol Rocatrol Vit B6 Rocatrol Metoral Metoral Rocatrol Nistatine Metoral Amilodip Amilodip Amilodip Prazosin Calcium D A.S.A A.S.A Calcium D A.S.A Amilodip Ranitiine NEFROVIT NEFROVIT Nistatine VALCYTE Vit B6 Vit B6 Carvedilol Vit B6 Nistatine Metoral Allopurinol Metoral Rocatrol Vit B6 Pantamine Pantamine Cinacalcet Carvedilol Rocatrol Nistatine Tacrolimus Nistatine Amilodip Amilodip Pantaprozol Pantaprozol Diltiazem Ranitiine Sevelamer Pantaprozol Losartan Pantaprozol Calcium D Nistatine CellCept CellCept Losartan Rocatrol VALCYTE VALCYTE Omeprazole VALCYTE VALCYTE Allopurinol Clotrimazole Clotrimazole Metformin VALCYTE Levofloxacin Insulin Atorvastatin Insulin Pantaprozol Isoniazid Folic Acid Folic Acid Pantamine Furosemide Pantaprozol Allopurinol CellCept Allopurinol Atorvastatin Pantaprozol Prednisolone Prednisolone Pantaprozol Metformin Clotrimazole CellCept Co-trimoxazole CellCept CellCept Atorvastatin Rocatrol Rocatrol Amlopidine Pantaprozol NEFROVIT Clotrimazole Folic Acid Clotrimazole Clotrimazole CellCept Persulfate Tamsulosin Prednisolone Folic Acid Hydrochlorothiazide Folic Acid Folic Acid Clotrimazole NEFROVIT CellCept Sandimmune Prednisolone Prednisolone Prednisolone Prednisolone Folic Acid Omeprazole Clotrimazole Rocaltrol Sandimmune Rocaltrol Prednisolone Atorvastatin Folic Acid Sandimmune Sandimmune Sandimmune CellCept Prednisolone Clotrimazole Prednisolone
MDPI and ACS Style
Aghamir, S.M.K.; Roudgari, H.; Heidari, H.; Salimi Asl, M.; Jafari Abarghan, Y.; Soleimani, V.; Mashhadi, R.; Khatami, F.
Whole Exome Sequencing to Find Candidate Variants for the Prediction of Kidney Transplantation Efficacy. Genes 2023, 14, 1251.
https://doi.org/10.3390/genes14061251
AMA Style
Aghamir SMK, Roudgari H, Heidari H, Salimi Asl M, Jafari Abarghan Y, Soleimani V, Mashhadi R, Khatami F.
Whole Exome Sequencing to Find Candidate Variants for the Prediction of Kidney Transplantation Efficacy. Genes. 2023; 14(6):1251.
https://doi.org/10.3390/genes14061251
Chicago/Turabian Style
Aghamir, Seyed Mohammad Kazem, Hassan Roudgari, Hassan Heidari, Mohammad Salimi Asl, Yousef Jafari Abarghan, Venous Soleimani, Rahil Mashhadi, and Fatemeh Khatami.
2023. "Whole Exome Sequencing to Find Candidate Variants for the Prediction of Kidney Transplantation Efficacy" Genes14, no. 6: 1251.
https://doi.org/10.3390/genes14061251
Article Metrics
Aghamir, S.M.K.; Roudgari, H.; Heidari, H.; Salimi Asl, M.; Jafari Abarghan, Y.; Soleimani, V.; Mashhadi, R.; Khatami, F.
Whole Exome Sequencing to Find Candidate Variants for the Prediction of Kidney Transplantation Efficacy. Genes 2023, 14, 1251.
https://doi.org/10.3390/genes14061251
| https://www.mdpi.com/2073-4425/14/6/1251 |
prctl(2) - Linux manual page
prctl(2) — Linux manual page
PRCTL(2) Linux Programmer's Manual PRCTL(2)
NAME top
prctl - operations on a process or thread
SYNOPSIS top
#include <sys/prctl.h> int prctl(int option , unsigned long arg2 , unsigned long arg3 , unsigned long arg4 , unsigned long arg5 );
DESCRIPTION top
prctl
() manipulates various aspects of the behavior of the
calling thread or process.
Note that careless use of some
prctl
() operations can confuse the
user-space run-time environment, so these operations should be
used with care.
prctl
() is called with a first argument describing what to do
(with values defined in
<linux/prctl.h>
), and further arguments
with a significance depending on the first one. The first
argument can be:
PR_CAP_AMBIENT
(since Linux 4.3)
Reads or changes the ambient capability set of the calling
thread, according to the value of
arg2
, which must be one
of the following:
PR_CAP_AMBIENT_RAISE
The capability specified in
arg3
is added to the
ambient set. The specified capability must already
be present in both the permitted and the
inheritable sets of the process. This operation is
not permitted if the
SECBIT_NO_CAP_AMBIENT_RAISE
securebit is set.
PR_CAP_AMBIENT_LOWER
The capability specified in
arg3
is removed from
the ambient set.
PR_CAP_AMBIENT_IS_SET
The
prctl
() call returns 1 if the capability in
arg3
is in the ambient set and 0 if it is not.
PR_CAP_AMBIENT_CLEAR_ALL
All capabilities will be removed from the ambient
set. This operation requires setting
arg3
to zero.
In all of the above operations,
arg4
and
arg5
must be
specified as 0.
Higher-level interfaces layered on top of the above
operations are provided in the
libcap(3)
library in the
form of
cap_get_ambient(3)
,
cap_set_ambient(3)
, and
cap_reset_ambient(3)
.
PR_CAPBSET_READ
(since Linux 2.6.25)
Return (as the function result) 1 if the capability
specified in
arg2
is in the calling thread's capability
bounding set, or 0 if it is not. (The capability
constants are defined in
<linux/capability.h>
.) The
capability bounding set dictates whether the process can
receive the capability through a file's permitted
capability set on a subsequent call to
execve(2)
.
If the capability specified in
arg2
is not valid, then the
call fails with the error
EINVAL
.
A higher-level interface layered on top of this operation
is provided in the
libcap(3)
library in the form of
cap_get_bound(3)
.
PR_CAPBSET_DROP
(since Linux 2.6.25)
If the calling thread has the
CAP_SETPCAP
capability
within its user namespace, then drop the capability
specified by
arg2
from the calling thread's capability
bounding set. Any children of the calling thread will
inherit the newly reduced bounding set.
The call fails with the error:
EPERM
if the calling thread
does not have the
CAP_SETPCAP
;
EINVAL
if
arg2
does not
represent a valid capability; or
EINVAL
if file
capabilities are not enabled in the kernel, in which case
bounding sets are not supported.
A higher-level interface layered on top of this operation
is provided in the
libcap(3)
library in the form of
cap_drop_bound(3)
.
PR_SET_CHILD_SUBREAPER
(since Linux 3.4)
If
arg2
is nonzero, set the "child subreaper" attribute of
the calling process; if
arg2
is zero, unset the attribute.
A subreaper fulfills the role of
init(1)
for its
descendant processes. When a process becomes orphaned
(i.e., its immediate parent terminates), then that process
will be reparented to the nearest still living ancestor
subreaper. Subsequently, calls to
getppid(2)
in the
orphaned process will now return the PID of the subreaper
process, and when the orphan terminates, it is the
subreaper process that will receive a
SIGCHLD
signal and
will be able to
wait(2)
on the process to discover its
termination status.
The setting of the "child subreaper" attribute is not
inherited by children created by
fork(2)
and
clone(2)
.
The setting is preserved across
execve(2)
.
Establishing a subreaper process is useful in session
management frameworks where a hierarchical group of
processes is managed by a subreaper process that needs to
be informed when one of the processes—for example, a
double-forked daemon—terminates (perhaps so that it can
restart that process). Some
init(1)
frameworks (e.g.,
systemd(1)
) employ a subreaper process for similar
reasons.
PR_GET_CHILD_SUBREAPER
(since Linux 3.4)
Return the "child subreaper" setting of the caller, in the
location pointed to by
(int *) arg2
.
PR_SET_DUMPABLE
(since Linux 2.3.20)
Set the state of the "dumpable" attribute, which
determines whether core dumps are produced for the calling
process upon delivery of a signal whose default behavior
is to produce a core dump.
In kernels up to and including 2.6.12,
arg2
must be either
0 (
SUID_DUMP_DISABLE
, process is not dumpable) or 1
(
SUID_DUMP_USER
, process is dumpable). Between kernels
2.6.13 and 2.6.17, the value 2 was also permitted, which
caused any binary which normally would not be dumped to be
dumped readable by root only; for security reasons, this
feature has been removed. (See also the description of
/proc/sys/fs/suid_dumpable
in
proc(5)
.)
Normally, the "dumpable" attribute is set to 1. However,
it is reset to the current value contained in the file
/proc/sys/fs/suid_dumpable
(which by default has the value
0), in the following circumstances:
* The process's effective user or group ID is changed.
* The process's filesystem user or group ID is changed
(see
credentials(7)
).
* The process executes (
execve(2)
) a set-user-ID or set-
group-ID program, resulting in a change of either the
effective user ID or the effective group ID.
* The process executes (
execve(2)
) a program that has
file capabilities (see
capabilities(7)
), but only if
the permitted capabilities gained exceed those already
permitted for the process.
Processes that are not dumpable can not be attached via
ptrace(2)
PTRACE_ATTACH
; see
ptrace(2)
for further
details.
If a process is not dumpable, the ownership of files in
the process's
/proc/[pid]
directory is affected as
described in
proc(5)
.
PR_GET_DUMPABLE
(since Linux 2.3.20)
Return (as the function result) the current state of the
calling process's dumpable attribute.
PR_SET_ENDIAN
(since Linux 2.6.18, PowerPC only)
Set the endian-ness of the calling process to the value
given in
arg2
, which should be one of the following:
PR_ENDIAN_BIG
,
PR_ENDIAN_LITTLE
, or
PR_ENDIAN_PPC_LITTLE
(PowerPC pseudo little endian).
PR_GET_ENDIAN
(since Linux 2.6.18, PowerPC only)
Return the endian-ness of the calling process, in the
location pointed to by
(int *) arg2
.
PR_SET_FP_MODE
(since Linux 4.0, only on MIPS)
On the MIPS architecture, user-space code can be built
using an ABI which permits linking with code that has more
restrictive floating-point (FP) requirements. For
example, user-space code may be built to target the O32
FPXX ABI and linked with code built for either one of the
more restrictive FP32 or FP64 ABIs. When more restrictive
code is linked in, the overall requirement for the process
is to use the more restrictive floating-point mode.
Because the kernel has no means of knowing in advance
which mode the process should be executed in, and because
these restrictions can change over the lifetime of the
process, the
PR_SET_FP_MODE
operation is provided to allow
control of the floating-point mode from user space.
The
(unsigned int) arg2
argument is a bit mask describing
the floating-point mode used:
PR_FP_MODE_FR
When this bit is
unset
(so called
FR=0
or
FR0
mode), the 32 floating-point registers are 32 bits
wide, and 64-bit registers are represented as a
pair of registers (even- and odd- numbered, with
the even-numbered register containing the lower 32
bits, and the odd-numbered register containing the
higher 32 bits).
When this bit is
set
(on supported hardware), the
32 floating-point registers are 64 bits wide (so
called
FR=1
or
FR1
mode). Note that modern MIPS
implementations (MIPS R6 and newer) support
FR=1
mode only.
Applications that use the O32 FP32 ABI can operate
only when this bit is
unset
(
FR=0
; or they can be
used with FRE enabled, see below). Applications
that use the O32 FP64 ABI (and the O32 FP64A ABI,
which exists to provide the ability to operate with
existing FP32 code; see below) can operate only
when this bit is
set
(
FR=1
). Applications that use
the O32 FPXX ABI can operate with either
FR=0
or
FR=1
.
PR_FP_MODE_FRE
Enable emulation of 32-bit floating-point mode.
When this mode is enabled, it emulates 32-bit
floating-point operations by raising a reserved-
instruction exception on every instruction that
uses 32-bit formats and the kernel then handles the
instruction in software. (The problem lies in the
discrepancy of handling odd-numbered registers
which are the high 32 bits of 64-bit registers with
even numbers in
FR=0
mode and the lower 32-bit
parts of odd-numbered 64-bit registers in
FR=1
mode.) Enabling this bit is necessary when code
with the O32 FP32 ABI should operate with code with
compatible the O32 FPXX or O32 FP64A ABIs (which
require
FR=1
FPU mode) or when it is executed on
newer hardware (MIPS R6 onwards) which lacks
FR=0
mode support when a binary with the FP32 ABI is
used.
Note that this mode makes sense only when the FPU
is in 64-bit mode (
FR=1
).
Note that the use of emulation inherently has a
significant performance hit and should be avoided
if possible.
In the N32/N64 ABI, 64-bit floating-point mode is always
used, so FPU emulation is not required and the FPU always
operates in
FR=1
mode.
This option is mainly intended for use by the dynamic
linker (
ld.so(8)
).
The arguments
arg3
,
arg4
, and
arg5
are ignored.
PR_GET_FP_MODE
(since Linux 4.0, only on MIPS)
Return (as the function result) the current floating-point
mode (see the description of
PR_SET_FP_MODE
for details).
On success, the call returns a bit mask which represents
the current floating-point mode.
The arguments
arg2
,
arg3
,
arg4
, and
arg5
are ignored.
PR_SET_FPEMU
(since Linux 2.4.18, 2.5.9, only on ia64)
Set floating-point emulation control bits to
arg2
. Pass
PR_FPEMU_NOPRINT
to silently emulate floating-point
operation accesses, or
PR_FPEMU_SIGFPE
to not emulate
floating-point operations and send
SIGFPE
instead.
PR_GET_FPEMU
(since Linux 2.4.18, 2.5.9, only on ia64)
Return floating-point emulation control bits, in the
location pointed to by
(int *) arg2
.
PR_SET_FPEXC
(since Linux 2.4.21, 2.5.32, only on PowerPC)
Set floating-point exception mode to
arg2
. Pass
PR_FP_EXC_SW_ENABLE
to use FPEXC for FP exception enables,
PR_FP_EXC_DIV
for floating-point divide by zero,
PR_FP_EXC_OVF
for floating-point overflow,
PR_FP_EXC_UND
for floating-point underflow,
PR_FP_EXC_RES
for floating-
point inexact result,
PR_FP_EXC_INV
for floating-point
invalid operation,
PR_FP_EXC_DISABLED
for FP exceptions
disabled,
PR_FP_EXC_NONRECOV
for async nonrecoverable
exception mode,
PR_FP_EXC_ASYNC
for async recoverable
exception mode,
PR_FP_EXC_PRECISE
for precise exception
mode.
PR_GET_FPEXC
(since Linux 2.4.21, 2.5.32, only on PowerPC)
Return floating-point exception mode, in the location
pointed to by
(int *) arg2
.
PR_SET_IO_FLUSHER
(since Linux 5.6)
If a user process is involved in the block layer or
filesystem I/O path, and can allocate memory while
processing I/O requests it must set
arg2
to 1. This will
put the process in the IO_FLUSHER state, which allows it
special treatment to make progress when allocating memory.
If
arg2
is 0, the process will clear the IO_FLUSHER state,
and the default behavior will be used.
The calling process must have the
CAP_SYS_RESOURCE
capability.
arg3
,
arg4
, and
arg5
must be zero.
The IO_FLUSHER state is inherited by a child process
created via
fork(2)
and is preserved across
execve(2)
.
Examples of IO_FLUSHER applications are FUSE daemons, SCSI
device emulation daemons, and daemons that perform error
handling like multipath path recovery applications.
PR_GET_IO_FLUSHER (Since Linux 5.6)
Return (as the function result) the IO_FLUSHER state of
the caller. A value of 1 indicates that the caller is in
the IO_FLUSHER state; 0 indicates that the caller is not
in the IO_FLUSHER state.
The calling process must have the
CAP_SYS_RESOURCE
capability.
arg2
,
arg3
,
arg4
, and
arg5
must be zero.
PR_SET_KEEPCAPS
(since Linux 2.2.18)
Set the state of the calling thread's "keep capabilities"
flag. The effect of this flag is described in
capabilities(7)
.
arg2
must be either 0 (clear the flag)
or 1 (set the flag). The "keep capabilities" value will
be reset to 0 on subsequent calls to
execve(2)
.
PR_GET_KEEPCAPS
(since Linux 2.2.18)
Return (as the function result) the current state of the
calling thread's "keep capabilities" flag. See
capabilities(7)
for a description of this flag.
PR_MCE_KILL
(since Linux 2.6.32)
Set the machine check memory corruption kill policy for
the calling thread. If
arg2
is
PR_MCE_KILL_CLEAR
, clear
the thread memory corruption kill policy and use the
system-wide default. (The system-wide default is defined
by
/proc/sys/vm/memory_failure_early_kill
; see
proc(5)
.)
If
arg2
is
PR_MCE_KILL_SET
, use a thread-specific memory
corruption kill policy. In this case,
arg3
defines
whether the policy is
early kill
(
PR_MCE_KILL_EARLY
),
late
kill
(
PR_MCE_KILL_LATE
), or the system-wide default
(
PR_MCE_KILL_DEFAULT
). Early kill means that the thread
receives a
SIGBUS
signal as soon as hardware memory
corruption is detected inside its address space. In late
kill mode, the process is killed only when it accesses a
corrupted page. See
sigaction(2)
for more information on
the
SIGBUS
signal. The policy is inherited by children.
The remaining unused
prctl
() arguments must be zero for
future compatibility.
PR_MCE_KILL_GET
(since Linux 2.6.32)
Return (as the function result) the current per-process
machine check kill policy. All unused
prctl
() arguments
must be zero.
PR_SET_MM
(since Linux 3.3)
Modify certain kernel memory map descriptor fields of the
calling process. Usually these fields are set by the
kernel and dynamic loader (see
ld.so(8)
for more
information) and a regular application should not use this
feature. However, there are cases, such as self-modifying
programs, where a program might find it useful to change
its own memory map.
The calling process must have the
CAP_SYS_RESOURCE
capability. The value in
arg2
is one of the options
below, while
arg3
provides a new value for the option.
The
arg4
and
arg5
arguments must be zero if unused.
Before Linux 3.10, this feature is available only if the
kernel is built with the
CONFIG_CHECKPOINT_RESTORE
option
enabled.
PR_SET_MM_START_CODE
Set the address above which the program text can
run. The corresponding memory area must be
readable and executable, but not writable or
shareable (see
mprotect(2)
and
mmap(2)
for more
information).
PR_SET_MM_END_CODE
Set the address below which the program text can
run. The corresponding memory area must be
readable and executable, but not writable or
shareable.
PR_SET_MM_START_DATA
Set the address above which initialized and
uninitialized (bss) data are placed. The
corresponding memory area must be readable and
writable, but not executable or shareable.
PR_SET_MM_END_DATA
Set the address below which initialized and
uninitialized (bss) data are placed. The
corresponding memory area must be readable and
writable, but not executable or shareable.
PR_SET_MM_START_STACK
Set the start address of the stack. The
corresponding memory area must be readable and
writable.
PR_SET_MM_START_BRK
Set the address above which the program heap can be
expanded with
brk(2)
call. The address must be
greater than the ending address of the current
program data segment. In addition, the combined
size of the resulting heap and the size of the data
segment can't exceed the
RLIMIT_DATA
resource limit
(see
setrlimit(2)
).
PR_SET_MM_BRK
Set the current
brk(2)
value. The requirements for
the address are the same as for the
PR_SET_MM_START_BRK
option.
The following options are available since Linux 3.5.
PR_SET_MM_ARG_START
Set the address above which the program command
line is placed.
PR_SET_MM_ARG_END
Set the address below which the program command
line is placed.
PR_SET_MM_ENV_START
Set the address above which the program environment
is placed.
PR_SET_MM_ENV_END
Set the address below which the program environment
is placed.
The address passed with
PR_SET_MM_ARG_START
,
PR_SET_MM_ARG_END
,
PR_SET_MM_ENV_START
, and
PR_SET_MM_ENV_END
should belong to a process stack
area. Thus, the corresponding memory area must be
readable, writable, and (depending on the kernel
configuration) have the
MAP_GROWSDOWN
attribute set
(see
mmap(2)
).
PR_SET_MM_AUXV
Set a new auxiliary vector. The
arg3
argument
should provide the address of the vector. The
arg4
is the size of the vector.
PR_SET_MM_EXE_FILE
Supersede the
/proc/pid/exe
symbolic link with a
new one pointing to a new executable file
identified by the file descriptor provided in
arg3
argument. The file descriptor should be obtained
with a regular
open(2)
call.
To change the symbolic link, one needs to unmap all
existing executable memory areas, including those
created by the kernel itself (for example the
kernel usually creates at least one executable
memory area for the ELF
.text
section).
In Linux 4.9 and earlier, the
PR_SET_MM_EXE_FILE
operation can be performed only once in a process's
lifetime; attempting to perform the operation a
second time results in the error
EPERM
. This
restriction was enforced for security reasons that
were subsequently deemed specious, and the
restriction was removed in Linux 4.10 because some
user-space applications needed to perform this
operation more than once.
The following options are available since Linux 3.18.
PR_SET_MM_MAP
Provides one-shot access to all the addresses by
passing in a
struct prctl_mm_map
(as defined in
<linux/prctl.h>
). The
arg4
argument should provide
the size of the struct.
This feature is available only if the kernel is
built with the
CONFIG_CHECKPOINT_RESTORE
option
enabled.
PR_SET_MM_MAP_SIZE
Returns the size of the
struct prctl_mm_map
the
kernel expects. This allows user space to find a
compatible struct. The
arg4
argument should be a
pointer to an unsigned int.
This feature is available only if the kernel is
built with the
CONFIG_CHECKPOINT_RESTORE
option
enabled.
PR_MPX_ENABLE_MANAGEMENT
,
PR_MPX_DISABLE_MANAGEMENT
(since Linux
3.19, removed in Linux 5.4; only on x86)
Enable or disable kernel management of Memory Protection
eXtensions (MPX) bounds tables. The
arg2
,
arg3
,
arg4
, and
arg5
arguments must be zero.
MPX is a hardware-assisted mechanism for performing bounds
checking on pointers. It consists of a set of registers
storing bounds information and a set of special
instruction prefixes that tell the CPU on which
instructions it should do bounds enforcement. There is a
limited number of these registers and when there are more
pointers than registers, their contents must be "spilled"
into a set of tables. These tables are called "bounds
tables" and the MPX
prctl
() operations control whether the
kernel manages their allocation and freeing.
When management is enabled, the kernel will take over
allocation and freeing of the bounds tables. It does this
by trapping the #BR exceptions that result at first use of
missing bounds tables and instead of delivering the
exception to user space, it allocates the table and
populates the bounds directory with the location of the
new table. For freeing, the kernel checks to see if
bounds tables are present for memory which is not
allocated, and frees them if so.
Before enabling MPX management using
PR_MPX_ENABLE_MANAGEMENT
, the application must first have
allocated a user-space buffer for the bounds directory and
placed the location of that directory in the
bndcfgu
register.
These calls fail if the CPU or kernel does not support
MPX. Kernel support for MPX is enabled via the
CONFIG_X86_INTEL_MPX
configuration option. You can check
whether the CPU supports MPX by looking for the
mpx
CPUID
bit, like with the following command:
cat /proc/cpuinfo | grep ' mpx '
A thread may not switch in or out of long (64-bit) mode
while MPX is enabled.
All threads in a process are affected by these calls.
The child of a
fork(2)
inherits the state of MPX
management. During
execve(2)
, MPX management is reset to
a state as if
PR_MPX_DISABLE_MANAGEMENT
had been called.
For further information on Intel MPX, see the kernel
source file
Documentation/x86/intel_mpx.txt
RETURN VALUE top
On success, PR_CAP_AMBIENT + PR_CAP_AMBIENT_IS_SET , PR_CAPBSET_READ , PR_GET_DUMPABLE , PR_GET_FP_MODE , PR_GET_IO_FLUSHER , PR_GET_KEEPCAPS , PR_MCE_KILL_GET , PR_GET_NO_NEW_PRIVS , PR_GET_SECUREBITS , PR_GET_SPECULATION_CTRL , PR_SVE_GET_VL , PR_SVE_SET_VL , PR_GET_TAGGED_ADDR_CTRL , PR_GET_THP_DISABLE , PR_GET_TIMING , PR_GET_TIMERSLACK , and (if it
returns) PR_GET_SECCOMP return the nonnegative values described
above. All other option values return 0 on success. On error,
-1 is returned, and errno is set to indicate the error.
ERRORS top
EACCES option is PR_SET_SECCOMP and arg2 is SECCOMP_MODE_FILTER ,
but the process does not have the CAP_SYS_ADMIN capability
or has not set the no_new_privs attribute (see the
discussion of PR_SET_NO_NEW_PRIVS above). EACCES option is PR_SET_MM , and arg3 is PR_SET_MM_EXE_FILE , the
file is not executable. EBADF option is PR_SET_MM , arg3 is PR_SET_MM_EXE_FILE , and the
file descriptor passed in arg4 is not valid. EBUSY option is PR_SET_MM , arg3 is PR_SET_MM_EXE_FILE , and this
the second attempt to change the /proc/pid/exe symbolic
link, which is prohibited. EFAULT arg2 is an invalid address. EFAULT option is PR_SET_SECCOMP , arg2 is SECCOMP_MODE_FILTER , the
system was built with CONFIG_SECCOMP_FILTER , and arg3 is
an invalid address. EFAULT option is PR_SET_SYSCALL_USER_DISPATCH and arg5 has an
invalid address. EINVAL The value of option is not recognized, or not supported on
this system. EINVAL option is PR_MCE_KILL or PR_MCE_KILL_GET or PR_SET_MM , and
unused prctl () arguments were not specified as zero. EINVAL arg2 is not valid value for this option . EINVAL option is PR_SET_SECCOMP or PR_GET_SECCOMP , and the kernel
was not configured with CONFIG_SECCOMP . EINVAL option is PR_SET_SECCOMP , arg2 is SECCOMP_MODE_FILTER , and
the kernel was not configured with CONFIG_SECCOMP_FILTER . EINVAL option is PR_SET_MM , and one of the following is true
* arg4 or arg5 is nonzero;
* arg3 is greater than TASK_SIZE (the limit on the size
of the user address space for this architecture);
* arg2 is PR_SET_MM_START_CODE , PR_SET_MM_END_CODE , PR_SET_MM_START_DATA , PR_SET_MM_END_DATA , or PR_SET_MM_START_STACK , and the permissions of the
corresponding memory area are not as required;
* arg2 is PR_SET_MM_START_BRK or PR_SET_MM_BRK , and arg3 is less than or equal to the end of the data segment or
specifies a value that would cause the RLIMIT_DATA resource limit to be exceeded. EINVAL option is PR_SET_PTRACER and arg2 is not 0, PR_SET_PTRACER_ANY , or the PID of an existing process. EINVAL option is PR_SET_PDEATHSIG and arg2 is not a valid signal
number. EINVAL option is PR_SET_DUMPABLE and arg2 is neither SUID_DUMP_DISABLE nor SUID_DUMP_USER . EINVAL option is PR_SET_TIMING and arg2 is not PR_TIMING_STATISTICAL . EINVAL option is PR_SET_NO_NEW_PRIVS and arg2 is not equal to 1
or arg3 , arg4 , or arg5 is nonzero. EINVAL option is PR_GET_NO_NEW_PRIVS and arg2 , arg3 , arg4 , or arg5 is nonzero. EINVAL option is PR_SET_THP_DISABLE and arg3 , arg4 , or arg5 is
nonzero. EINVAL option is PR_GET_THP_DISABLE and arg2 , arg3 , arg4 , or arg5 is nonzero. EINVAL option is PR_CAP_AMBIENT and an unused argument ( arg4 , arg5 , or, in the case of PR_CAP_AMBIENT_CLEAR_ALL , arg3 )
is nonzero; or arg2 has an invalid value; or arg2 is PR_CAP_AMBIENT_LOWER , PR_CAP_AMBIENT_RAISE , or PR_CAP_AMBIENT_IS_SET and arg3 does not specify a valid
capability. EINVAL option was PR_GET_SPECULATION_CTRL or PR_SET_SPECULATION_CTRL and unused arguments to prctl ()
are not 0. EINVAL option is PR_PAC_RESET_KEYS and the
arguments are invalid or unsupported. See the description
of PR_PAC_RESET_KEYS above for details. EINVAL option is PR_SVE_SET_VL and the arguments are invalid or
unsupported, or SVE is not available on this platform.
See the description of PR_SVE_SET_VL above for details. EINVAL option is PR_SVE_GET_VL and SVE is not available on this
platform. EINVAL option is PR_SET_SYSCALL_USER_DISPATCH and one of the
following is true:
* arg2 is PR_SYS_DISPATCH_OFF and the remaining arguments
are not 0;
* arg2 is PR_SYS_DISPATCH_ON and the memory range
specified is outside the address space of the process.
* arg2 is invalid. EINVAL option is PR_SET_TAGGED_ADDR_CTRL and the arguments are
invalid or unsupported. See the description of PR_SET_TAGGED_ADDR_CTRL above for details. EINVAL option is PR_GET_TAGGED_ADDR_CTRL and the arguments are
invalid or unsupported. See the description of PR_GET_TAGGED_ADDR_CTRL above for details. ENODEV option was PR_SET_SPECULATION_CTRL the kernel or CPU does
not support the requested speculation misfeature. ENXIO option was PR_MPX_ENABLE_MANAGEMENT or PR_MPX_DISABLE_MANAGEMENT and the kernel or the CPU does
not support MPX management. Check that the kernel and
processor have MPX support. ENXIO option was PR_SET_SPECULATION_CTRL implies that the
control of the selected speculation misfeature is not
possible. See PR_GET_SPECULATION_CTRL for the bit fields
to determine which option is available. EOPNOTSUPP option is PR_SET_FP_MODE and arg2 has an invalid or
unsupported value. EPERM option is PR_SET_SECUREBITS , and the caller does not have
the CAP_SETPCAP capability, or tried to unset a "locked"
flag, or tried to set a flag whose corresponding locked
flag was set (see capabilities(7) ). EPERM option is PR_SET_SPECULATION_CTRL wherein the speculation
was disabled with PR_SPEC_FORCE_DISABLE and caller tried
to enable it again. EPERM option is PR_SET_KEEPCAPS , and the caller's SECBIT_KEEP_CAPS_LOCKED flag is set (see capabilities(7) ). EPERM option is PR_CAPBSET_DROP , and the caller does not have
the CAP_SETPCAP capability. EPERM option is PR_SET_MM , and the caller does not have the CAP_SYS_RESOURCE capability. EPERM option is PR_CAP_AMBIENT and arg2 is PR_CAP_AMBIENT_RAISE ,
but either the capability specified in arg3 is not present
in the process's permitted and inheritable capability
sets, or the PR_CAP_AMBIENT_LOWER securebit has been set. ERANGE option was PR_SET_SPECULATION_CTRL and arg3 is not PR_SPEC_ENABLE , PR_SPEC_DISABLE , PR_SPEC_FORCE_DISABLE ,
nor PR_SPEC_DISABLE_NOEXEC .
VERSIONS top
The prctl () system call was introduced in Linux 2.1.57.
CONFORMING TO top
This call is Linux-specific. IRIX has a prctl () system call
(also introduced in Linux 2.1.44 as irix_prctl on the MIPS
architecture), with prototype ptrdiff_t prctl(int option , int arg2 , int arg3 ); and options to get the maximum number of processes per user, get
the maximum number of processors the calling process can use,
find out whether a specified process is currently blocked, get or
set the maximum stack size, and so on.
HTML rendering created 2022-12-18
byMichael Kerrisk,
author of The Linux Programming Interface,
maintainer of theLinux man-pagesproject.For details of in-depthLinux/UNIX system programming training coursesthat I teach, lookhere.Hosting byjambit GmbH.
| https://man7.org/linux/man-pages/man2/prctl.2.html |
Coatings | Free Full-Text | Characteristics of Corrosion Products of Friction-Type High-Strength Bolted Joints of Steel Bridge: A Case Study
The contact surface corrosion of friction high-strength bolt (FHSB) joints was analyzed to examine the characteristics of corrosion products and influence factors in steel bridges. Samples were selected from the Dongying Shengli Yellow River Bridge, which has been in service for 33 years. Scanning electron microscope (SEM), energy dispersive spectroscopy (EDS), and X-ray diffraction (XRD) were utilized to analyze the microscopic morphology and chemical composition of the corroded surface of the samples. The study identifies that construction quality issues accelerate corrosion of the contact surface and that the contact surface of the aluminum spraying layer transforms from rugged and dense to smooth and porous as corrosion increases. The findings also suggest that the friction coefficient of the FHSB connection node initially decreases and then increases as the corroded surface changes. Corrosion products contained S, Cl, Mn, Si, FeS, and their oxides, indicating that atmospheric, industrial, and Yellow River soil environments contribute to joint corrosion. The study proposes sandblasting and coating the corroded contact surface and deck steel plate with inorganic zinc-rich paint to prevent media penetration and delay substrate corrosion. Adopting ultra-high-performance concrete (UHPC) as the deck structure is also recommended to reduce top plate tensile stress, deck cracking, and media invasion. This study provides insights into the characteristics and mechanisms of FHSB joint corrosion to aid the maintenance, repair, and protection of steel bridges.
Characteristics of Corrosion Products of Friction-Type High-Strength Bolted Joints of Steel Bridge: A Case Study
by Gangnian Xu 1 , Wenpeng Xu 1 , Xu Dong 1,* , Shengwei Fan 1 and Xianggang Wang 2
1
School of Transportation and Civil Engineering, Shandong Jiaotong University, Jinan 250357, China
2
China National Chemical Communications Construction Group Co., Ltd., Jinan 250102, China
*
Author to whom correspondence should be addressed.
Coatings 2023 , 13 (6), 1023; https://doi.org/10.3390/coatings13061023
Abstract
The contact surface corrosion of friction high-strength bolt (FHSB) joints was analyzed to examine the characteristics of corrosion products and influence factors in steel bridges. Samples were selected from the Dongying Shengli Yellow River Bridge, which has been in service for 33 years. Scanning electron microscope (SEM), energy dispersive spectroscopy (EDS), and X-ray diffraction (XRD) were utilized to analyze the microscopic morphology and chemical composition of the corroded surface of the samples. The study identifies that construction quality issues accelerate corrosion of the contact surface and that the contact surface of the aluminum spraying layer transforms from rugged and dense to smooth and porous as corrosion increases. The findings also suggest that the friction coefficient of the FHSB connection node initially decreases and then increases as the corroded surface changes. Corrosion products contained S, Cl, Mn, Si, FeS, and their oxides, indicating that atmospheric, industrial, and Yellow River soil environments contribute to joint corrosion. The study proposes sandblasting and coating the corroded contact surface and deck steel plate with inorganic zinc-rich paint to prevent media penetration and delay substrate corrosion. Adopting ultra-high-performance concrete (UHPC) as the deck structure is also recommended to reduce top plate tensile stress, deck cracking, and media invasion. This study provides insights into the characteristics and mechanisms of FHSB joint corrosion to aid the maintenance, repair, and protection of steel bridges.
Keywords:
steel bridge
;
connection node
;
friction type high-strength bolt
;
corrode
;
SEM
;
EDS
;
XRD
1. Introduction
The friction high-strength bolt (FHSB) connection functions primarily by clamping the connecting plate through the strong clamping force generated by bolt fastening and transferring the shear force perpendicular to the bolt axis through the friction force generated by the indirect contact surface of the connecting plate. FHSB is extensively used in steel structure bridges due to advantages such as high connection strength, simple and convenient construction, and the ability to directly bear dynamic and fatigue loads [ 1 , 2 , 3 ].
Compared with other steel bridge components, FHSB connection nodes are more prone to corrosion and deterioration, which is primarily reflected in their inherent structural characteristics and the role of surrounding corrosive media [ 4 , 5 , 6 , 7 , 8 ]. Because of frequent gaps between FHSB connectors of steel bridges, water and gases containing corrosive ions can easily invade node components and cause corrosion. Due to the concealed nature of FHSB joint diseases and the complexity of removing the joints, analysis of corroded joint components is mainly based on laboratory testing. Using X-ray diffraction (XRD), scanning electron microscopy (SEM), electrochemical technology, and alternate dry and wet corrosion testing, many studies have examined the corrosion behavior and rust formation mechanism of steel plates in different atmospheric corrosive environments [ 9 , 10 ]. Air pollutants, potential of hydrogen (pH) value, and wet time greatly influence the formation of the steel surface protective layer [ 11 , 12 ]. For high-strength bolts, a study by Daniel et al. examined the characteristics of corrosion products formed in the contact and exposed areas of bolts and nut fasteners [ 13 ]. A study by Wen et al. examined the causes of fracture failure of high-strength bolts of steel bridges in subtropical humid climates, and the results showed that corrosive environment and stress accelerated impact on fracture failure [ 14 ]. Compared with industrial atmospheric environments, high-strength bolts showed higher corrosion sensitivity in marine atmospheric environments, which led to bolt loosening and fatigue crack of bolt thread [ 15 , 16 ]. Therefore, the corrosive environment caused severe corrosion behavior in the raw materials of steel bridges, which is one of the main factors affecting the performance degradation of FHSB connection joints of steel structures [ 17 , 18 , 19 ]. In an effort to suppress steel corrosion, many researchers have reported various results annually on corrosion inhibitors, including their preparation or extraction, as well as the mechanism of classification and inhibition [ 20 , 21 , 22 , 23 , 24 ]. However, due to the structural characteristics of the FHSB joint and the long-term anti-corrosion requirements, this method still has certain limitations.
In summary, due to the different corrosive environments of FHSB connection nodes of steel bridges, their corrosion behaviors and corrosion products also differ. Therefore, studying the characteristics of corrosion products of nodes on actual bridges and influencing factors in complex environmental corrosive conditions, such as wet, industrial, and dusty climates, is of great value.
This study first analyzed the primary diseases of the FHSB connection nodes of the Dongying Shengli Yellow River Bridge, which has been in operation for 33 years. Then, after selecting seven representative FHSB connection sub-samples and eight steel plate samples, SEM, EDS, and XRD were utilized to analyze the microscopic morphology and chemical composition of corrosion products on the sample surfaces. Finally, this study examines the relationship between the corroded sample surfaces and environmental corrosion, aiming to identify the main causes and propose scientific anti-corrosion protection measures for nodes in aging steel bridges in the future. By clarifying the factors that contribute to corrosion in these structures, this research can help inform the development of effective strategies for preventing corrosion and extending the lifespan of steel bridges.
2. Node Diseases
The Shengli Yellow River Bridge is the first cable-stayed bridge with a steel box girder and orthogonal special-shaped plates built in China. Located in Kenli County, Dongying City, the bridge was completed and opened to traffic in October 1987. With a main bridge span of (60.5 + 136.5 + 288 + 136.5 + 60.5) m, the main beam has 57 steel box sections and 56 transverse joints in total. Its cross-section is a separated double-sided rectangular box. Six orthotropic bridge decks are symmetrically arranged in the middle of the cross-section, with two in upstream and downstream box girders, respectively, and four between the box girders. The top and bottom plates are U-shaped closed ribbed orthotropic plates, most of which are 12 mm thick.
Figure 1
shows the schematic diagram of FHSB connection nodes for transverse joints. The transverse joint nodes of the whole bridge are connected by more than 110,000 sets of 10.9 M22 FHSB, and the diameter of the bolt opening is 24.5 mm. The seam between the steel box sections is 6 mm wide, and the splice plate is 10 mm thick. The design value of the friction coefficient of the aluminum spraying contact surface is 0.45, and the longitudinal joint connection is field groove welding. The pavement is composed of an epoxy resin coal tar anti-skid layer, a 40 mm bottom layer, and a 30 mm surface layer of rubber asphalt.
Figure 2
shows the schematic diagram of the components of the FHSB connection node.
Figure 1. Schematic diagram of transverse joint FHSB connection node.
Figure 2. Schematic diagram of components of FHSB connection node.
Figure 3
displays some typical diseases of the transverse joint FHSB connection node. Due to exposure of the top plate of the box girder at the lower-part sidewalk and cracking of the pavement, the nodes were corroded by rain and corrosive gas year-round, resulting in severe corrosion of the nodes, with some nut thicknesses reduced by up to 65%. In addition, the longitudinal ribs of the top and bottom plates at the FHSB nodes of the transverse joints had open butt welds, severely weakening the rigidity of the bridge deck, and resulting in different polishing degrees among the joint connecting components. The primary diseases of FHSB connection nodes of transverse joints included coating peeling, corrosion of connection components, and polishing of section plate joints and bolt holes. Investigation and analysis found that 9.62% of bolt holes were not expanded according to specifications. Some gusset plate bolt holes were polished around, generally in a circle of the varying area with an average diameter of 11 mm. Polished bolt holes accounted for 15.22% of the total. Construction quality issues such as nonstandard hole expansion, staggered slab joints, and contact surface pollution led to poor tightness of FHSB connection joint contact surfaces, accelerating corrosion of joint contact surfaces.
Figure 3. Illustration of common issues observed in transverse joint FHSB connection nodes.
3. Analysis of Node Corrosion Products
3.1. Samples of Test Pieces
In order to examine the surface characteristics of the FHSB connection node assembly, fifteen representative samples at different positions of the node were selected. Table 1 describes the sample material, sampling location, and surface corrosion degrees. A total of seven samples were selected from the surface of the high-strength bolt connection pair, with three (Head-1~Head-3) from the bolt head, two nuts (Nut-1 and Nut-2), and two gaskets (Washer-1 and Washer-2). Among these samples, three (Head-1, Nut-1, and Nut-2) were in direct contact with the atmosphere, two (Head-2 and Head-3) were in contact with the gasket, and two (Washer-1 and Washer-2) were in contact with the upper splice plate. A total of eight samples were selected from the surface of the connecting steel plate assembly, with two (Plate-1 and Plate-2) from the contact surface of the lower splice plate, five (Plate-3Plate-7) from the contact surface of the upper splice plate, and one (Plate-8) from the contact surface of the roof. Among these samples, five (Plate-1, Plate-2, and Plate-4~Plate-6) were in contact with the roof, and three (Plate-3, Plate-7, and Plate-8) were in direct contact with the atmosphere. Notably, six samples (Plate-1~Plate-6) were primarily used to examine the characteristics of corrosion products of aluminum-sprayed steel plate contact surfaces with different corrosion degrees. In Table 1 , the solid samples include Head-2~3, Washer-1~2, Plate-1~5 and Plate-7, the powder samples include Head-1, Nut-1~2, Plate-6 and Plate-8. The materials used for the screw and steel plate in this study were 40B and 16Mnq, respectively. These materials are known as SWRCHB and SM50-B.C in Japan, 50B40 for bolt heads in the United States, and 38B and ST52-3 in Germany [ 25 , 26 , 27 ]. The legend for the sample selection positions can be found in Figure 4 .
Figure 4. Sample selection position legend.
Table 1. Description of sample material, sampling location, and surface corrosion degrees [ 25 , 26 , 27 ].
The instruments utilized in this analysis included a ZEISS SIGMA 500 field emission scanning electron microscope (SEM) from ZEISS, Oberkochen, Germany, which was used to observe the surface morphology of the samples and analyze the chemical composition of both the substrate and corrosion layer using energy spectrum. The material structure of the corrosion products was analyzed using a German D8 ADVANCE A25 X-ray powder diffractometer, Bruker, Billerica, MA, USA. The powdery substances were ground into a fine powder of less than 200 mesh in an agate mortar and placed on the sample tank for testing, while the measured surface of blocky substances was made as flat and smooth as possible to ensure that the sample could be loaded into the φ 25 mm × 3 mm sample tank. The wire-cutting machine used was a Hai DK7735 from Changwei, Jiangsu, China, with an average cutting speed of 60–90 mm 2 /min. An ultrasonic cleaner (Model: Xinzhi-SB-5200DT, Xinzhi, Ningbo, China) with a power of 360 W was employed, along with an electric thermostatic drier (Model: Shangcheng-101, Shangcheng, Shaoxing, China) with a voltage/power of 220 V/500 W and a temperature range of 10–300 °C. The ZEISS SIGMA 500 field emission SEM had a resolution ratio of 0.8 [email protected] kV STEM, 0.8 [email protected] kV, 1.4 [email protected] kV, and a magnification range of 10–1,000,000×. The X-ray powder diffractometer used was a D8 ADVANCE A25 from Germany, with an angle measurement range of 10–90 degrees, a Cu target, and a scanning speed of 0.2/step [ 14 , 28 ]. Figure 5 shows a schematic diagram illustrating the experimental setup used in the study.
Figure 5. Schematic diagram illustrating the experimental setup used in the study.
3.2. Micromorphology
Figure 6
displays the microscopic morphology of the sample surfaces. SEM analysis found that the corrosion products on the surface of the bolt head (Head-1) were mostly scaly and loose. The corrosion products on Head-2 were mostly clastic, with a loose structure, smooth local areas, and obvious boundaries. Head-3 had a compact structure, smooth local areas, and obvious boundaries. The corrosion products of Nut-1 and Nut-2 were mainly needle-shaped, as well as scaly and spiky. The micromorphology of the gasket surface was basically similar to that of Head-2 and Head-3. The surface of Plate-1 aluminum spraying layer was uneven and in a dense granular shape, without visible rust. The surface of the Plate-2 and Plate-5 aluminum spray coating was slightly rusted and dark gray, with layered and cracked corrosion products. The Plate-6 aluminum spraying layer was severely rusted, smooth, porous, and had white powder and a loose surface structure. After the aluminum coating on the contact surface was completely corroded, and the steel plate substrate gradually rusted, the corrosion products of Plate-3 and Plate-4 were reddish-brown, mostly massive, and spherical with obvious cracks. The surface protective layer of Plate-7 and Plate-8 in contact with the atmosphere had basically fallen off, with clustered corrosion products on Plate-7’s surface and dense massive corrosion products on Plate-8’s surface, though with many cracks and obvious delamination.
Figure 6. Micromorphology of sample surface.
In general, the micromorphology of the corrosion products on the surfaces of each sample in contact with the atmosphere was relatively rich, related to the complex corrosive environment of the connecting nodes. Debris accumulation occurred near polished areas formed by the contact surface, likely due to fretting and sliding of the connecting nodes. As the corrosion degree increased, the contact surface of the aluminum spray coating on the steel plate gradually changed from an uneven and dense state to a smooth, porous, powdery state. Once the steel plate substrate gradually rusted, the corrosion product became fluffy and cracked red rust. With insufficient oxygen in the plate seam, the rust gradually turned from red to brown, and the surface bonded. Therefore, the uneven “biting” state of the aluminum sprayed steel plate contact surface was constantly changing. It is deduced that the friction coefficient of the contact surface decreased first and then increased. Furthermore, polishing around the bolt hole likely changed the roughness and bonding state of the uneven contact surface, reducing the friction coefficient of the contact surface.
3.3. Chemical Composition
Table 2
displays the specification values of the main elements in the sample matrix and EDS results of the corroded surfaces and Yellow River soil. The results showed that the elements mainly originated from the sample elements themselves and corrosive ions in the environment. The surface material of the high-strength bolt connection pair sample comprised the primary elements (Fe, O, and C) and minor elements (Mn, S, Mg, Ti, Ca, Al, Si, P, Cl, Zn, K, Na, etc.). The surface material of the steel plate sample comprised the primary elements (Al, Fe, O, and C) and minor elements (Mn, S, Mg, Ti, Ca, Si, P, Cl, Zn, K, Na, etc.). Several elements (S, Mg, Ca, Si, Cl, and Na) were detected on the surfaces of Plate-1P~late-2 and Plate-4~Plate-6 samples. Multiple elements (Mn, Mg, Ca, Al, Cl, K, and Na) were detected on the surfaces of Plate-3, Plate-7, and Plate-8 samples in contact with the atmosphere.
Table 2. Specification values of main elements in the sample matrix and the EDS results of surface corrosion products and Yellow River soil [ 25 , 26 , 27 ].
According to the literature, the sample matrix contained minor amounts of elements such as C, Mn, S, Si, and P [
25
,
26
,
27
]. Dongying is an industrial oil refining city in China that produces large amounts of nitrogen oxides, sulfur dioxide, and chloride ions, resulting in frequent acid rain in this region. Significant amounts of S and Cl were detected in the corrosion products of the samples. The sample corrosion may have been related to atmospheric corrosion (acid rain). Test results showed that the solid suspended particles in the atmosphere around the Dongying Shengli Yellow River Bridge were primarily composed of Mg, Ca, Al, Si, K, and Na, consistent with the elements of Yellow River soil. Therefore, it is speculated that the Mg, Ca, Si, K, and Na elements present in the corrosion products of the samples may have been related to the inclusion of Yellow River soil.
3.4. Phase Analysis
Figure 7 displays the XRD pattern of corrosion products on the sample surfaces. Analysis results showed that the corrosion products of the bolt head, nut, gasket, and outer surface of the steel plate were primarily iron and silicon oxides. Additionally, the corrosion products of Head-1 contained FeS. Those of Nut-1 and Nut-2 contained MnO 2 and FeOOH. Those of Plate-7 and Plate-8 contained Mn 2 O 3 and FeOOH. The corrosion products of the steel plate contact surface samples were primarily aluminum and iron oxides, mostly Al 2 O 3 , Fe 2 O 3 , and Fe 3 O 4 .
Figure 7. The XRD pattern of sample.
Table 3
displays the XRD results of the primary corrosion products on the sample surfaces. As shown in the table, the corrosion products of most steel plate contact surface samples were Al
2
O
3
. Fe
2
O
3
and Fe
3
O
4
were also detected in severely corroded samples. When the corrosive ions, oxygen, water, and dust invaded the joint, the aluminum layer on the joint contact surface was sprayed for oxidation first, and white powder gradually formed as the block fell off. The corrosion product was primarily Al
2
O
3
. With corrosion of the steel plate substrate, the surface corrosion products were primarily Fe
2
O
3
and Fe
3
O
4
. XRD phase analysis results showed that the samples also contained oxides of Mn, Si, and other elements, as well as FeS. It is speculated that node corrosion was also related to atmospheric (acid rain) and industrial dust and other corrosive environments. Additionally, the XRD pattern of silty yellow soil showed that SiO
2
, Al
2
O
3
, and Fe
2
O
3
were the primary oxide components, and nearly all samples detected the SiO
2
component of Yellow River soil. Because silty yellow river soil was easily adsorbed onto node components after being blown up, the wet yellow river environment year-round may have accelerated node corrosion.
Table 3. XRD results showing the main corrosion products present on the surface of the sample.
Moreover, this study is in agreement with earlier studies (Refs. [
9
,
28
]) that attribute the corrosion of FHSB joints to electrochemical processes.
Table 3
shows that the samples contained SiO
2
, Mg, Ca, K, Na, and other elements that are typical components of Yellow River soil. This indicates that the aging and cracking of the asphalt pavement and anti-slip layer are the main paths for corrosive agents and Yellow River soil to penetrate the FHSB joints. To prevent such infiltration, the bridge deck structure should be modified. Construction issues, such as non-standard hole expansion, staggered segmental plate joints, and surface pollution, can also lead to inadequate tightness of the FHSB joint contact surfaces, thereby accelerating corrosion.
4. Corrosion Causes and Prevention
4.1. Corrosion Causes
Pavement design and joint construction quality play a significant role in the corrosion of FHSB joints. Almost all samples detected SiO
2
from Yellow River soil, as well as elements such as Mg, Ca, K, and Na, which are consistent with the composition of Yellow River soil. The deterioration and cracking of asphalt pavement and anti-slip layers enable corrosive media and soil to infiltrate the joints. Construction issues such as improper hole expansion, misaligned segmental plates, and contaminated contact surfaces reduce the tightness of the joints, accelerating corrosion. Pavement design and joint construction quality play a significant role in the corrosion of FHSB joints. Almost all samples detected SiO
2
from Yellow River soil, as well as elements such as Mg, Ca, K, and Na (
Table 2
), which are consistent with the composition of Yellow River soil. The deterioration and cracking of asphalt pavement and anti-slip layers enable corrosive media and soil to infiltrate the joints. Construction issues such as improper hole expansion, misaligned segmental plates, and contaminated contact surfaces reduce the tightness of the joints, accelerating corrosion.
The analysis of the Yellow River soil holds significant value as it allows us to gain insights into its composition and its infiltration into the FHSB board joints. The presence of SiO
2
, observed in most specimens, is particularly noteworthy as it strongly supports the aforementioned conclusion. However, the compounds identified in the Yellow River soil align closely with the main compounds found in the FHSB joint specimen of the node plate. This suggests that only a small fraction of the compound composition and elements can be attributed to the invasion of the Yellow River soil, while the majority are formed as a result of electrochemical corrosion within the specimen itself.
In the early stages of corrosion, specimens in direct contact with the atmosphere form Fe (II) hydrate complexes due to the presence of abundant corrosive H
+
in the acid rain environment. This substance is oxidized by dissolved oxygen in water, eventually forming FeOOH. In the later stages, the reaction between FeOOH and Fe
2+
generated by the anodic reaction results in the formation of a significant amount of brown corrosion product Fe
3
O
4
. The surface gradually transitions from a wet to a dry state during sunlight exposure, and because FeOOH is an electrochemically active substance, some cluster-like corrosion products FeOOH are prone to dehydration, forming brownish-black products Fe
2
O
3
. As a result, flake-like corrosion products appear on the outer structure of the corrosion products. The electrochemical corrosion process on the surface of the aluminum spray layer occurs by conducting electricity outside the water film, internal and external ions, and the aluminum alloy matrix, forming an electrochemical circuit. This leads to corrosion of the aluminum spray layer and ultimately generates Al
2
O
3
. The anodic chemical reaction is Al − 3e → Al
3+
, and the cathode is O
2
+ 2H
2
O + 4e → 4OH
−
. The longer the aluminum alloy is covered by a water film in a humid air environment, the more severe the corrosion becomes due to the extended corrosion reaction time.
4.2. Corrosion Prevention
The bridge employs inorganic zinc-rich paint spraying after sandblasting the corroded joint contact surface and bridge deck plate, as it offers superior adhesion and anti-slip friction coefficient compared to the aluminum spraying process. The use of highly metallic zinc as the joint allows the matrix iron to be protected from corrosion due to its high potential; furthermore, the corrosion products of zinc have a dense structure and deposit in the coating’s pores, which can block and seal the pores, preventing the penetration of corrosive media, reducing iron corrosion, and improving the friction coefficient of the contact surface. Additionally, the bridge deck reinforcement uses UHPC as the structural layer to participate in the joint stress, significantly reducing the tensile stress of the box girder top plate and minimizing the risk of UHPC bridge deck cracking and corrosion medium invasion.
Consequently, the primary steps of the corroded FHSB joints repair and bridge deck reinforcement construction process are as follows: milling the original pavement layer → removing bolt groups → sandblasting the contact surface → spraying inorganic zinc-rich paint → re-bolting the splicing plate → overall sandblasting and rust removal of the steel bridge deck → spraying inorganic zinc-rich paint → welding shear nails and arranging steel bars → paving a 55 mm thick UHPC bridge deck and 30 mm thick asphalt concrete.
5. Conclusions
This study investigated the characteristics and influencing factors of corrosion products in FHSB connection joints. First, the primary damage modes of joints in the Dongying Shengli Yellow River Bridge were analyzed. Then, seven representative FHSB connection sub-samples and eight steel plate samples were selected. Scanning electron microscopy, energy dispersive spectroscopy, and X-ray diffraction were used to analyze the microscopic morphology and chemical composition of corrosion products on the sample surfaces. Finally, the relationship between corrosion products and environmental corrosion was discussed. The main findings are as follows:
(1)
After the aluminum coating corroded, the contact surface changed from uneven and dense to smooth and powdery. As the steel substrate corroded further, the contact surface transformed from fluffy and stratified to surface-bonded. These changes in the corroded contact surface significantly impacted the slip-bearing capacity of the FHSB joint by altering the friction coefficient;
(2)
Almost all samples detected SiO 2 from Yellow River soil as well as elements such as Mg, Ca, K, and Na, largely matching Yellow River soil composition. Cracking of asphalt pavement and anti-slip layers allowed corrosive media and soil to invade the joints. Joint tightness was impaired by construction issues, accelerating corrosion;
(3)
Corrosion products contained large amounts of S and Cl as well as oxides of Mn, Si, and other elements and FeS, indicating atmospheric corrosion (e.g., acid rain) and industrial dust contributed to joint corrosion;
(4)
Sandblasting and coating the corroded contact surface and deck steel plate with inorganic zinc-rich paint prevented media penetration and delayed substrate corrosion. Adopting UHPC as the deck structure reduced top plate tensile stress, deck cracking, and media invasion.
Going forward, corrosion behavior and mechanisms in simulated environments will be examined to propose methods to delay corrosion rates and extend joint service life. The effects of corrosion on friction coefficients and clamping forces will be studied to reveal joint anti-slip force degradation mechanisms.
Author Contributions
Conceptualization, G.X., W.X. and X.D.; methodology, G.X. and W.X.; validation, G.X., W.X., X.D., S.F. and X.W.; formal analysis, X.D.; investigation, G.X.; resources, G.X.; writing—original draft preparation, G.X. and W.X.; writing—review and editing, X.D. and S.F.; visualization, G.X.; supervision, G.X.; project administration, G.X.; funding acquisition, G.X. and X.W. All authors have read and agreed to the published version of the manuscript.
Funding
This work is supported by (a) the National Natural Science Foundation of China (No. 51578325), (b) the Youth Foundation of Shandong Natural Science Foundation of China (No. ZR2021QE279), and (c) the Open Project of Key Laboratory of Transportation Industry (Beijing) for Old Bridge Detection and Reinforcement Technology (No. 2021-JQKFKT-3).
Institutional Review Board Statement
Not applicable.
Informed Consent Statement
Not applicable.
Data Availability Statement
Not applicable.
Conflicts of Interest
The authors declare no conflict of interest.
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Figure 1. Schematic diagram of transverse joint FHSB connection node.
Figure 2. Schematic diagram of components of FHSB connection node.
Figure 3. Illustration of common issues observed in transverse joint FHSB connection nodes.
Figure 4. Sample selection position legend.
Figure 5. Schematic diagram illustrating the experimental setup used in the study.
Figure 6. Micromorphology of sample surface.
Table 1. Description of sample material, sampling location, and surface corrosion degrees [ 25 , 26 , 27 ].
Joint Components Specimen ID Material Selection Position Contact Medium Description of Surface Features FHSB connection pair Head-1 40B Bolt head Atmosphere With the anti-corrosion coating falling off, the surface is slightly rusted and red. Head-2 Washer No rust is found by naked eye, and local parts are polished and shiny. Head-3 Washer No rust is found by naked eye, and local polishing is shiny, with obvious boundary. Nut-1 45 Nut Atmosphere The outer layer of the nut is severely rusted and reddish brown. Nut-2 Atmosphere The inner layer of the nut is severely rusted and brown-black. Washer-1 Washer Upper splice plate Slightly rusted, partially polished, and shiny. Washer-2 Upper splice plate No rust is found with naked eye, and there is obvious boundary. Steel plate Plate-1 16Mnq Lower splice plate Roof No rust is found by naked eye, and the aluminum coating is shiny. Plate-2 Roof The aluminum coating is slightly rusted and gray. Plate-3 Upper splice plate Atmosphere The aluminum spraying layer is severely rusted and reddish brown. Plate-4 Roof The aluminum spraying layer is severely rusted and reddish brown. Plate-5 Roof The aluminum coating is slightly rusted and gray. Plate-6 Roof The aluminum spraying layer is severely rusted and has gray-white powder. Plate-7 Atmosphere With the anti-corrosion coating falling off, the surface is slightly rusted, and red. Plate-8 Top plate Atmosphere Severely rusted, and brown-black.
Table 2. Specification values of main elements in the sample matrix and the EDS results of surface corrosion products and Yellow River soil [ 25 , 26 , 27 ].
Specimen Fe O C Mn S Mg Ti Ca Al Si P Cl Zn K Na Standard 0.37~0.44 0.60~0.90 0.20~0.40 Head-1 52.79~93.69 3.33~38.84 1.70~9.43 0.41~0.75 0.13~0.55 0.36~0.72 0.16~0.34 0.08~1.10 0.20~1.05 0.11~0.28 0.24~0.36 1.11~2.37 Head-2 41.29~86.89 32.62~34.31 11.21~18.07 0.67~0.83 0.19~0.38 0.27~0.32 0.25~0.94 0.23~1.70 0.37~2.90 0.26~2.62 2.34~2.53 Head-3 48.62~64.35 10.40~32.18 8.14~22.56 0.45~0.58 0.28~1.30 0.25~0.34 0.94~1.95 Standard 0.42~0.50 0.50~0.80 ≤0.04 0.17~0.37 ≤0.04 Nut-1 54.96~60.08 36.40~37.27 2.97~5.71 0.55~1.80 0.15~0.27 0.17~0.24 0.14~0.37 0.38~0.51 0.85~2.54 Nut-2 57.11~63.11 32.79~37.14 3.69~5.01 0.41~0.74 0.14~0.32 0.13~0.21 Standard 0.42~0.50 0.50~0.80 ≤0.04 0.17~0.37 ≤0.04 Washer-1 6.01~26.69 14.23~28.51 53.50~54.51 0.23~1.38 0.51~0.86 0.87~2.61 0.53~2.37 0.57~1.87 0.42~1.75 0.39~1.99 0.11~1.46 0.30~0.40 0.46~1.28 Washer-2 14.89~25.26 17.53~24.53 44.43~56.46 0.39~0.79 0.26~0.54 0.28~2.32 3.01~4.56 0.76~2.29 0.16~0.53 Standard ≤0.20 1.20~1.35 ≤0.004 1.20~1.35 ≤0.015 Plate-1 3.51~3.99 3.93~5.86 0.18~0.64 88.09~90.05 0.35~0.84 Plate-2 6.52~15.62 7.92~21.21 1.64~4.30 0.44~0.65 0.08~0.13 1.25~2.00 11.31~42.51 2.76~3.61 0.73~1.12 Plate-3 42.42~88.59 7.19~46.19 2.87~6.27 0.24~0.31 0.32~1.43 0.37~1.75 0.98~5.13 0.83~1.29 Plate-4 25.16~56.62 23.88~35.11 4.64~5.63 0.61~2.34 0.42~0.94 0.41~0.84 1.32~2.41 1.20~3.24 0.58~1.17 0.78~1.77 0.78~1.37 0.53~1.95 0.99~4.99 0.56~2.03 Plate-5 0.85~4.95 34.38~54.53 4.71~10.83 0.16~0.61 0.29~0.79 0.15~0.26 0.42~3.45 5.10~39.09 0.34~2.02 0.12~0.16 1.24~3.65 0.28~1.16 0.13~4.10 Plate-6 54.33~62.83 4.61~7.49 0.57~0.81 1.88~2.35 26.74~36.72 0.26~1.42 Plate-7 67.81~87.48 7.94~26.31 1.36~3.48 0.43~1.40 0.18~0.22 0.17~1.27 0.35~1.64 0.35~2.36 0.67~1.62 Plate-8 61.56~80.96 16.52~32.86 1.82~4.34 0.60~1.73 0.10~0.82 0.15~0.21 1.42~3.05 Soil 0.96~2.08 45.31~51.02 8.84~10.95 0.36~0.53 0.44~3.29 0.84~1.50 23.62~32.84 0.41~4.33 2.24~4.62
Table 3. XRD results showing the main corrosion products present on the surface of the sample.
Specimen Contact Medium Products This Study Ref. [ 9 ] Ref. [ 28 ] Head Atmosphere Fe 2 O 3 , FeS, SiO 2 / / Nut Atmosphere Fe 2 O 3 , MnO 2 , FeOOH, SiO 2 / / Washer Interface Fe 2 O 3 , Fe 3 O 4 , SiO 2 / / Plate Interface Al 2 O 3 , Fe 3 O 4 , SiO 2 / / Atmosphere Al 2 O 3 , Fe 2 O 3 , Fe 3 O 4 , Mn 2 O 3 , FeOOH, SiO 2 Fe 2 O 3 , Fe 3 O 4 , FeOOH Fe 3 O 4 , FeOOH
Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here .
| https://www.mdpi.com/2079-6412/13/6/1023/xml |
Global Interactive Kisok Market Size, Trends and Growth Opportunity, By Component (Hardware,Software And Service), By End-User (Retail, BFSI, Food & Beverages, Healthcare, Government, Travel & Tourism and Others) By Type (Automated Teller Machine, Retail S
Global Interactive Kisok Market Size, Trends and Growth Opportunity, By Component (Hardware,Software And Service), By End-User (Retail, BFSI, Food & Beverages, Healthcare, Government, Travel & Tourism - Market research report and industry analysis - 33082203
Global Interactive Kisok Market Size, Trends and Growth Opportunity, By Component (Hardware,Software And Service), By End-User (Retail, BFSI, Food & Beverages, Healthcare, Government, Travel &Tourism and Others) By Type (Automated Teller Machine, Retail S
Best Price Guarantee Price from $3,950 Publisher QualiKet Research Published Date December, 2022 SKU QUA17624018
Table of Contents
Description
Global Interactive Kisok Market Size, Trends and Growth Opportunity, By Component (Hardware, Software And Service), By End-User (Retail, BFSI, Food & Beverages, Healthcare, Government, Travel & Tourism and Others) By Type (Automated Teller Machine, Retail Self-Checkout Kiosks, Self-Service Kiosks, Vending Kiosks) By Region and Forecast Till 2027.Global Interactive Kiosk MarketThe Global Interactive Kiosk market was valued at US$ 19.6 billion in 2021 and it is expected to reachat US$ 32.3 billion in 2027 at a CAGR of 9.2% during forecast period 2022-2027.A self-service kiosk or computer terminal known as an interactive kiosk is used in the public sector toenable users to interact with digital information and data through user-friendly interfaces. Retailsales, payment services, navigational, information sharing, and tourism all employ interactive kiosks.Since they make it simple for users to provide personal information, these kiosks are utilized in awide range of contexts, including the healthcare and travel industries.Market DriversBy minimizing operating costs and equipment requirements, interactive kiosks benefit serviceproviders in a variety of ways and optimise corporate costs overall. Customers can obtain a serviceindependently and without the intervention of direct service personnel due to self-servicetechnologies. By giving customers power over their purchase decisions, this elevates their level ofsatisfaction. These major factors have led customers in urban areas to adopt self-service interactivekiosks on a wide scale.Market RestraintIf maintained or rules are not followed, interactive kiosks are vulnerable to theft and security issues.To use the kiosk payments, a validated identity proof of the user is needed because there is a chancethat a third party could misuse the data. Due to the rise in cybercrimes, many people are reluctantto use the kiosks for financial transactions or to provide their bank account credentials which act as arestraining factor in this segment.COVID-19 Impact on Interactive Kiosk MarketAs a result of the outbreak, interactive kiosk vendors have had the opportunity to extend thembusinesses and diversify their product lines, with a primary aim of minimizing client interaction whileyet providing for their needs and improving serviceability. By assisting customers without requiringthem to speak with coordinators or salespeople, self-service kiosks limit contact and maintain socialdistance rules. The market won& be as negatively impacted by COVID-19 as other industries. Amoderate effect will be felt by the market.Market SegmentationThe global interactive kiosk market segmented on the basis of component, end-user, and type. Onthe basis of component it segmented into hardware, software and service. On the basis of type, itsegmented into automated teller machine, retail self-checkout kiosks, self-service kiosks, vendingkiosks. On the basis of end use retail, BFSI, food & beverages, healthcare, government, travel &tourism and others.Regional AnalysisThe global interactive kiosk market segmented into five regions North America, Europe, LatinAmerica, Asia Pacific, Middle East and Africa. North America is one of the regions that are likely tocontinue this trend in the years to come. Positive indications for firms include the growing marketdemand. The industry participants are now focusing on bringing ideas into action to meet theexpectations of the tech-savvy clients. The market expansion in the Asia Pacific region is beingfuelled by the increasing popularity of kiosk offerings, a sizeable client base, and technologicaladvancements emerging in nations like China and India which witnessing a significant growth of thisregion.Key PlayersVarious key players are listed in this report such as KIOSK Information Systems, Olea Kiosks Inc.,Frank Mayer and Associates, Inc., Source Technologies, NCR Corporation, Glory Limited, DieboldNixdorf, Embross, Meridian Kiosk, RedYREF Interactive Kiosks.Market TaxonomyBy Component
Hardware
Software
Service
By End-User
Retail
BFSI
Food & Beverages
Healthcare
Government
Travel & Tourism
Others
By Type
Automated teller machine
Retail self-checkout kiosks
Self-service kiosks
Vending kiosks
By Region
North America
Latin America
Europe
Asia Pacific
Middle East & Africa
1 Introduction
1.1 Objective of the Study
1.2 Market definition
1.3 Market Scope
2 Research Methodology
2.1 Data Mining
2.2 Validation
2.3 Primary Interviews
2.4 List of Data Sources
3 Executive Summary
4 Global Interactive Kiosk Market Outlook
4.2.1 Drivers
4.2.2 Restraints
4.2.3 Opportunities
4.3 Porters Five Force Model
4.4 Value Chain Analysis
5 Global Interactive Kiosk Market, By Component
5.1 Y-o-Y Growth Comparison, By Component
5.2 Global Interactive Kiosk Market Share Analysis, By Component
5.3 Global Interactive Kiosk Market Size and Forecast, By Component
5.3.1 Hardware
5.3.2 Software
5.3.3 Service
6 Global Interactive Kiosk Market, By End-User
6.1 Y-o-Y Growth Comparison, By End-User
6.2 Global Interactive Kiosk Market Share Analysis, By End-User
6.3 Global Interactive Kiosk Market Size and Forecast, By End-User
6.3.1 Retail
6.3.2 BFSI
6.3.3 Food & Beverages
6.3.4 Healthcare
6.3.5 Government
7 Global Interactive Kiosk Market, By Type
7.1 Y-o-Y Growth Comparison, By Type
7.2 Global Interactive Kiosk Market Share Analysis, By Type
7.3 Global Interactive Kiosk Market Share Analysis, By Type
7.3.1 Automated Teller Machine
7.3.2 Retail Self-Checkout Kiosk
7.3.3 Self Service Kiosk
7.3.4 Vending Kiosk
8 Global Interactive Kiosk Market, By Region
8.1 Global Interactive Kiosk Market Share Analysis, By Region
8.2 Global Interactive Kiosk Market Share Analysis, By Region
9 North America Interactive Kiosk Analysis and Forecast (2022-2027)
9.1 Introduction
9.2 North America Interactive Kiosk Market Share Analysis, By Component
9.3 North America Interactive Kiosk Market Size and Forecast, By End-User
9.4 North America Interactive Kiosk Market Size and Forecast, By Type
9.5 North America Interactive Kiosk Market Size and Forecast, By Country
9.5.1 U.S
9.5.2 Canada
9.5.3 Mexico
10 Europe Interactive Kiosk Market Analysis and Forecast (2022-2027)
10.1 Introduction
10.2 Europe Interactive Kiosk Market Share Analysis, By Component
10.3 Europe Interactive Kiosk Market Size and Forecast, By End-User
10.4 Europe Interactive Kiosk Market Size and Forecast, By Type
10.5 Europe Interactive Kiosk Market Size and Forecast, By Country
10.5.1 Germany
10.5.2 France
10.5.3 UK
10.5.4 Rest of Europe
11 Asia Pacific Interactive Kiosk Market Analysis and Forecast (2022-2027)
11.1 Introduction
11.2 Asia-Pacific Interactive Kiosk Market Size and Forecast, By Component
11.3 Asia-Pacific Interactive Kiosk Market Size and Forecast, By End-User
11.4 Asia-Pacific Interactive Kiosk Market Size and Forecast, By Type
11.5 Asia-Pacific Interactive Kiosk Market Size and Forecast, By Country
11.5.1 China
11.5.2 Japan
11.5.3 India
11.5.4. Rest of Asia Pacific
12 Latin America Interactive Kiosk Market Analysis and Forecast (2022-2027)
12.1 Introduction
12.2 Latin America Interactive Kiosk Market Size and Forecast, By Component
12.3 Latin America Interactive Kiosk Market Size and Forecast, By End-User
12.4 Latin America Interactive Kiosk Market Size and Forecast, By Type
12.5 Latin America Interactive Kiosk Market Size and Forecast, By Country
12.5.1 Brazil
12.5.2. Rest of Latin America
13 Middle East High-Intensity Market Analysis and Forecast (2022-2027)
13.1 Introduction
13.2 Middle East Interactive Kiosk Market Share Analysis, By Component
13.3 Middle East Interactive Kiosk Market Size and Forecast, By End-User
13.4 Middle East Interactive Kiosk Market Size and Forecast, By Type
13.5 Middle East Interactive Kiosk Market Size and Forecast, By Country
13.5.1. Saudi Arabia
13.5.2. UAE
13.5.3. Egypt
13.5.4. Kuwait
13.5.5. South Africa
14 Competitive Analysis
14.1 Competition Dashboard
14.2 Market share Analysis of Top Vendors
14.3 Key Development Strategies
15 Company Profiles
15.1. KIOSK Information Systems
15.1.1 Overview
15.1.2 Offerings
15.1.3 Key Financials
15.1.4 Business Segment & Geographic Overview
15.1.5 Key Market Developments
15.1.6 Key Strategies
15.2. Olea Kiosks Inc.
15.2.1 Overview
15.2.2 Offerings
15.2.3 Key Financials
15.2.4 Business Segment & Geographic Overview
15.2.5 Key Market Developments
15.2.6 Key Strategies
15.3. Frank Mayer and Associates, Inc.
15.3.1 Overview
15.3.2 Offerings
15.3.3 Key Financials
15.3.4 Business Segment & Geographic Overview
15.3.5 Key Market Developments
15.3.6 Key Strategies
15.4. Source Technologies
15.4.1 Overview
15.4.2 Offerings
15.4.3 Key Financials
15.4.4 Business Segment & Geographic Overview
15.4.5 Key Market Developments
15.4.6 Key Strategies
15.5. NCR Corporation
15.5.1 Overview
15.5.2 Offerings
15.5.3 Key Financials
15.5.4 Business Segment & Geographic Overview
15.5.5 Key Market Developments
15.5.6 Key Strategies
15.6. Glory Limited
15.1 Overview
15.6.2 Offerings
15.6.3 Key Financials
15.6.4 Business Segment & Geographic Overview
15.6.5 Key Market Developments
15.6.6 Key Strategies
15.7. Diebold Nixdorf
15.7.1 Overview
15.7.2 Offerings
15.7.3 Key Financials
15.7.4 Business Segment & Geographic Overview
15.7.5 Key Market Developments
15.7.6 Key Strategies
15.8.2 Offerings
15.8.3 Key Financials
15.8.4 Business Segment & Geographic Overview
15.8.5 Key Market Developments
15.8.6 Key Strategies
15.9. Meridian Kiosk
15.9.1 Overview
15.9.2 Offerings
15.9.3 Key Financials
15.9.4 Business Segment & Geographic Overview
15.9.5 Key Market Developments
15.9.6 Key Strategies
15.10. RedYREF Interactive Kiosks
15.10.1 Overview
15.10.2 Offerings
15.10.3 Key Financials
15.10.4 Business Segment & Geographic Overview
15.10.5 Key Market Developments
15.10.6 Key Strategies
Kiosk [Self-service/Interactive Kiosk] Market (Product Type: Food Kiosks, Beverage Kiosks, Retail Kiosks, Parking Kiosks, Electric Vehicle Charging Kiosks, Patient Interactive Kiosks, Information Kiosks, Employment Kiosks, Check-in Kiosks, Automated Teller Machines Kiosks, and Others) - Global Industry Analysis, Size, Share, Growth, Trends, and Forecast, 2022-2031
Kiosk Market, by Type (Vending Machine (Drink Vending Machine, Food Vending Machine, Photo Vending Machine, DVD Rental), Self-service Kiosk / Interactive Kiosk (Information Kiosk, Ticketing Kiosk, Patient Interactive Kiosk, Check-in Kiosk, Employment Kios
Interactive Kiosk Market (Product Type: ATMs, Self-checkout Kiosks, Self-service Kiosks, Vending Kiosks, and Others; Mounting Type: Floor Standing, Wall Mount, and Others) - Global Industry Analysis, Size, Share, Growth, Trends, and Forecast, 2022-2031
Interactive Kiosk Market Analysis, By Type (Bank Kiosk, Vending Kiosk, Self-service Kiosks), By Offering (Hardware, Software, Services), By Location (Indoor Interactive Kiosk, Outdoor Interactive Kiosk), By Panel Size (17”–32” Display Interactive Kiosk, Above 32” Display Interactive Kiosk) - Global Market Insights 2021 to 2031
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Sapulpa Daily Herald (Sapulpa, Okla.), Vol. 73, No. 264, Ed. 1 Sunday, July 19, 1987
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<summary type =" html " >
<p><a href="https://gateway.okhistory.org/ark:/67531/metadc1502145/"><img alt="Sapulpa Daily Herald (Sapulpa, Okla.), Vol. 74, No. 31, Ed. 1 Monday, October 19, 1987" title="Sapulpa Daily Herald (Sapulpa, Okla.), Vol. 74, No. 31, Ed. 1 Monday, October 19, 1987" src="https://gateway.okhistory.org/ark:/67531/metadc1502145/small/"/></a></p><p>Daily newspaper from Sapulpa, Oklahoma that includes local, state, and national news along with advertising.</p>
</summary >
<media:thumbnail url =" https://gateway.okhistory.org/ark:/67531/metadc1502145/small/ " />
</entry >
<entry >
<title >
Sapulpa Daily Herald (Sapulpa, Okla.), Vol. 73, No. 291, Ed. 1 Wednesday, August 19, 1987
</title >
<link href =" https://gateway.okhistory.org/ark:/67531/metadc1502161/ " rel =" alternate " />
<published > 2019-06-07T17:52:35-05:00 </published >
<id >
https://gateway.okhistory.org/ark:/67531/metadc1502161/
</id >
<summary type =" html " >
<p><a href="https://gateway.okhistory.org/ark:/67531/metadc1502161/"><img alt="Sapulpa Daily Herald (Sapulpa, Okla.), Vol. 73, No. 291, Ed. 1 Wednesday, August 19, 1987" title="Sapulpa Daily Herald (Sapulpa, Okla.), Vol. 73, No. 291, Ed. 1 Wednesday, August 19, 1987" src="https://gateway.okhistory.org/ark:/67531/metadc1502161/small/"/></a></p><p>Daily newspaper from Sapulpa, Oklahoma that includes local, state, and national news along with advertising.</p>
</summary >
<media:thumbnail url =" https://gateway.okhistory.org/ark:/67531/metadc1502161/small/ " />
</entry >
<entry >
<title >
Sapulpa Daily Herald (Sapulpa, Okla.), Vol. 73, No. 239, Ed. 1 Friday, June 19, 1987
</title >
<link href =" https://gateway.okhistory.org/ark:/67531/metadc1504209/ " rel =" alternate " />
<published > 2019-06-07T17:52:35-05:00 </published >
<id >
https://gateway.okhistory.org/ark:/67531/metadc1504209/
</id >
<summary type =" html " >
<p><a href="https://gateway.okhistory.org/ark:/67531/metadc1504209/"><img alt="Sapulpa Daily Herald (Sapulpa, Okla.), Vol. 73, No. 239, Ed. 1 Friday, June 19, 1987" title="Sapulpa Daily Herald (Sapulpa, Okla.), Vol. 73, No. 239, Ed. 1 Friday, June 19, 1987" src="https://gateway.okhistory.org/ark:/67531/metadc1504209/small/"/></a></p><p>Daily newspaper from Sapulpa, Oklahoma that includes local, state, and national news along with advertising.</p>
</summary >
<media:thumbnail url =" https://gateway.okhistory.org/ark:/67531/metadc1504209/small/ " />
</entry >
<entry >
<title >
Sapulpa Daily Herald (Sapulpa, Okla.), Vol. 73, No. 212, Ed. 1 Tuesday, May 19, 1987
</title >
<link href =" https://gateway.okhistory.org/ark:/67531/metadc1503342/ " rel =" alternate " />
<published > 2019-06-07T17:52:35-05:00 </published >
<id >
https://gateway.okhistory.org/ark:/67531/metadc1503342/
</id >
<summary type =" html " >
<p><a href="https://gateway.okhistory.org/ark:/67531/metadc1503342/"><img alt="Sapulpa Daily Herald (Sapulpa, Okla.), Vol. 73, No. 212, Ed. 1 Tuesday, May 19, 1987" title="Sapulpa Daily Herald (Sapulpa, Okla.), Vol. 73, No. 212, Ed. 1 Tuesday, May 19, 1987" src="https://gateway.okhistory.org/ark:/67531/metadc1503342/small/"/></a></p><p>Daily newspaper from Sapulpa, Oklahoma that includes local, state, and national news along with advertising.</p>
</summary >
<media:thumbnail url =" https://gateway.okhistory.org/ark:/67531/metadc1503342/small/ " />
</entry >
<entry >
<title >
Sapulpa Daily Herald (Sapulpa, Okla.), Vol. 73, No. 186, Ed. 1 Sunday, April 19, 1987
</title >
<link href =" https://gateway.okhistory.org/ark:/67531/metadc1505012/ " rel =" alternate " />
<published > 2019-06-07T17:52:35-05:00 </published >
<id >
https://gateway.okhistory.org/ark:/67531/metadc1505012/
</id >
<summary type =" html " >
<p><a href="https://gateway.okhistory.org/ark:/67531/metadc1505012/"><img alt="Sapulpa Daily Herald (Sapulpa, Okla.), Vol. 73, No. 186, Ed. 1 Sunday, April 19, 1987" title="Sapulpa Daily Herald (Sapulpa, Okla.), Vol. 73, No. 186, Ed. 1 Sunday, April 19, 1987" src="https://gateway.okhistory.org/ark:/67531/metadc1505012/small/"/></a></p><p>Daily newspaper from Sapulpa, Oklahoma that includes local, state, and national news along with advertising.</p>
</summary >
<media:thumbnail url =" https://gateway.okhistory.org/ark:/67531/metadc1505012/small/ " />
</entry >
<entry > ... </entry >
<entry >
<title >
Sapulpa Daily Herald (Sapulpa, Okla.), Vol. 73, No. 109, Ed. 1 Monday, January 19, 1987
</title >
<link href =" https://gateway.okhistory.org/ark:/67531/metadc1501404/ " rel =" alternate " />
<published > 2019-06-07T17:52:35-05:00 </published >
<id >
https://gateway.okhistory.org/ark:/67531/metadc1501404/
</id >
<summary type =" html " >
<p><a href="https://gateway.okhistory.org/ark:/67531/metadc1501404/"><img alt="Sapulpa Daily Herald (Sapulpa, Okla.), Vol. 73, No. 109, Ed. 1 Monday, January 19, 1987" title="Sapulpa Daily Herald (Sapulpa, Okla.), Vol. 73, No. 109, Ed. 1 Monday, January 19, 1987" src="https://gateway.okhistory.org/ark:/67531/metadc1501404/small/"/></a></p><p>Daily newspaper from Sapulpa, Oklahoma that includes local, state, and national news along with advertising.</p>
</summary >
<summary type =" html " > ... </summary >
<media:thumbnail url =" https://gateway.okhistory.org/ark:/67531/metadc1501404/small/ " />
</entry >
<entry > ... </entry >
<entry >
<title >
Sapulpa Daily Herald (Sapulpa, Okla.), Vol. 73, No. 160, Ed. 1 Thursday, March 19, 1987
</title >
<link href =" https://gateway.okhistory.org/ark:/67531/metadc1501259/ " rel =" alternate " />
<published > 2019-06-07T17:52:35-05:00 </published >
<id >
https://gateway.okhistory.org/ark:/67531/metadc1501259/
</id >
<summary type =" html " >
<p><a href="https://gateway.okhistory.org/ark:/67531/metadc1501259/"><img alt="Sapulpa Daily Herald (Sapulpa, Okla.), Vol. 73, No. 160, Ed. 1 Thursday, March 19, 1987" title="Sapulpa Daily Herald (Sapulpa, Okla.), Vol. 73, No. 160, Ed. 1 Thursday, March 19, 1987" src="https://gateway.okhistory.org/ark:/67531/metadc1501259/small/"/></a></p><p>Daily newspaper from Sapulpa, Oklahoma that includes local, state, and national news along with advertising.</p>
</summary >
<summary type =" html " > ... </summary >
<media:thumbnail url =" https://gateway.okhistory.org/ark:/67531/metadc1501259/small/ " />
</entry >
<entry > ... </entry >
<entry >
<title >
Sapulpa Daily Herald (Sapulpa, Okla.), Vol. 73, No. 136, Ed. 1 Thursday, February 19, 1987
</title >
<link href =" https://gateway.okhistory.org/ark:/67531/metadc1501774/ " rel =" alternate " />
<published > 2019-06-07T17:52:35-05:00 </published >
<id >
https://gateway.okhistory.org/ark:/67531/metadc1501774/
</id >
<id > ... </id >
<summary type =" html " >
<p><a href="https://gateway.okhistory.org/ark:/67531/metadc1501774/"><img alt="Sapulpa Daily Herald (Sapulpa, Okla.), Vol. 73, No. 136, Ed. 1 Thursday, February 19, 1987" title="Sapulpa Daily Herald (Sapulpa, Okla.), Vol. 73, No. 136, Ed. 1 Thursday, February 19, 1987" src="https://gateway.okhistory.org/ark:/67531/metadc1501774/small/"/></a></p><p>Daily newspaper from Sapulpa, Oklahoma that includes local, state, and national news along with advertising.</p>
</summary >
<summary type =" html " > ... </summary >
<media:thumbnail url =" https://gateway.okhistory.org/ark:/67531/metadc1501774/small/ " />
</entry >
<entry > ... </entry >
<entry >
<title >
Sapulpa Daily Herald (Sapulpa, Okla.), Vol. 74, No. 58, Ed. 1 Thursday, November 19, 1987
</title >
<link href =" https://gateway.okhistory.org/ark:/67531/metadc1501801/ " rel =" alternate " />
<published > 2019-06-07T17:52:35-05:00 </published >
<id >
https://gateway.okhistory.org/ark:/67531/metadc1501801/
</id >
<id > ... </id >
<summary type =" html " >
<p><a href="https://gateway.okhistory.org/ark:/67531/metadc1501801/"><img alt="Sapulpa Daily Herald (Sapulpa, Okla.), Vol. 74, No. 58, Ed. 1 Thursday, November 19, 1987" title="Sapulpa Daily Herald (Sapulpa, Okla.), Vol. 74, No. 58, Ed. 1 Thursday, November 19, 1987" src="https://gateway.okhistory.org/ark:/67531/metadc1501801/small/"/></a></p><p>Daily newspaper from Sapulpa, Oklahoma that includes local, state, and national news along with advertising.</p>
</summary >
<summary type =" html " > ... </summary >
<media:thumbnail url =" https://gateway.okhistory.org/ark:/67531/metadc1501801/small/ " />
</entry >
<entry > ... </entry >
<entry >
<title >
Student News Network (Tulsa, Okla.), Vol. 1, No. 17, Ed. 1 Thursday, February 19, 1987
</title >
<title > ... </title >
<link href =" https://gateway.okhistory.org/ark:/67531/metadc1805979/ " rel =" alternate " />
<published > 2021-05-24T00:50:20-05:00 </published >
<id >
https://gateway.okhistory.org/ark:/67531/metadc1805979/
</id >
<id > ... </id >
<summary type =" html " >
<p><a href="https://gateway.okhistory.org/ark:/67531/metadc1805979/"><img alt="Student News Network (Tulsa, Okla.), Vol. 1, No. 17, Ed. 1 Thursday, February 19, 1987" title="Student News Network (Tulsa, Okla.), Vol. 1, No. 17, Ed. 1 Thursday, February 19, 1987" src="https://gateway.okhistory.org/ark:/67531/metadc1805979/small/"/></a></p><p>Weekly student newspaper from Tulsa, Oklahoma that includes educational articles, interviews, cartoons, and puzzles.</p>
</summary >
<summary type =" html " > ... </summary >
<media:thumbnail url =" https://gateway.okhistory.org/ark:/67531/metadc1805979/small/ " />
</entry >
<entry > ... </entry >
<entry >
<title >
Student News Network (Tulsa, Okla.), Vol. 1, No. 21, Ed. 1 Thursday, March 19, 1987
</title >
<title > ... </title >
<link href =" https://gateway.okhistory.org/ark:/67531/metadc1805984/ " rel =" alternate " />
<published > 2021-05-24T00:50:34-05:00 </published >
<id >
https://gateway.okhistory.org/ark:/67531/metadc1805984/
</id >
<id > ... </id >
<summary type =" html " >
<p><a href="https://gateway.okhistory.org/ark:/67531/metadc1805984/"><img alt="Student News Network (Tulsa, Okla.), Vol. 1, No. 21, Ed. 1 Thursday, March 19, 1987" title="Student News Network (Tulsa, Okla.), Vol. 1, No. 21, Ed. 1 Thursday, March 19, 1987" src="https://gateway.okhistory.org/ark:/67531/metadc1805984/small/"/></a></p><p>Weekly student newspaper from Tulsa, Oklahoma that includes educational articles, interviews, cartoons, and puzzles.</p>
</summary >
<summary type =" html " > ... </summary >
<media:thumbnail url =" https://gateway.okhistory.org/ark:/67531/metadc1805984/small/ " />
</entry >
<entry > ... </entry >
<entry >
<title >
The Oklahoma Eagle (Tulsa, Okla.), Vol. 66, No. 8, Ed. 1 Thursday, February 19, 1987
</title >
<link href =" https://gateway.okhistory.org/ark:/67531/metadc1806734/ " rel =" alternate " />
<published > 2021-05-24T09:32:54-05:00 </published >
<id >
https://gateway.okhistory.org/ark:/67531/metadc1806734/
</id >
<summary type =" html " >
<p><a href="https://gateway.okhistory.org/ark:/67531/metadc1806734/"><img alt="The Oklahoma Eagle (Tulsa, Okla.), Vol. 66, No. 8, Ed. 1 Thursday, February 19, 1987" title="The Oklahoma Eagle (Tulsa, Okla.), Vol. 66, No. 8, Ed. 1 Thursday, February 19, 1987" src="https://gateway.okhistory.org/ark:/67531/metadc1806734/small/"/></a></p><p>Weekly newspaper from Tulsa, Oklahoma that includes local, state, and national news along with advertising.</p>
</summary >
<media:thumbnail url =" https://gateway.okhistory.org/ark:/67531/metadc1806734/small/ " />
</entry >
<entry >
<title >
The Oklahoma Eagle (Tulsa, Okla.), Vol. 66, No. 12, Ed. 1 Thursday, March 19, 1987
</title >
<link href =" https://gateway.okhistory.org/ark:/67531/metadc1806737/ " rel =" alternate " />
<published > 2021-05-24T09:33:52-05:00 </published >
<id >
https://gateway.okhistory.org/ark:/67531/metadc1806737/
</id >
<summary type =" html " >
<p><a href="https://gateway.okhistory.org/ark:/67531/metadc1806737/"><img alt="The Oklahoma Eagle (Tulsa, Okla.), Vol. 66, No. 12, Ed. 1 Thursday, March 19, 1987" title="The Oklahoma Eagle (Tulsa, Okla.), Vol. 66, No. 12, Ed. 1 Thursday, March 19, 1987" src="https://gateway.okhistory.org/ark:/67531/metadc1806737/small/"/></a></p><p>Weekly newspaper from Tulsa, Oklahoma that includes local, state, and national news along with advertising.</p>
</summary >
<summary type =" html " > ... </summary >
<media:thumbnail url =" https://gateway.okhistory.org/ark:/67531/metadc1806737/small/ " />
</entry >
<entry > ... </entry >
<entry >
<title >
The Oklahoma Eagle (Tulsa, Okla.), Vol. 66, No. 47, Ed. 1 Thursday, November 19, 1987
</title >
<link href =" https://gateway.okhistory.org/ark:/67531/metadc1806772/ " rel =" alternate " />
<published > 2021-05-24T09:45:08-05:00 </published >
<id >
https://gateway.okhistory.org/ark:/67531/metadc1806772/
</id >
<summary type =" html " >
<p><a href="https://gateway.okhistory.org/ark:/67531/metadc1806772/"><img alt="The Oklahoma Eagle (Tulsa, Okla.), Vol. 66, No. 47, Ed. 1 Thursday, November 19, 1987" title="The Oklahoma Eagle (Tulsa, Okla.), Vol. 66, No. 47, Ed. 1 Thursday, November 19, 1987" src="https://gateway.okhistory.org/ark:/67531/metadc1806772/small/"/></a></p><p>Weekly newspaper from Tulsa, Oklahoma that includes local, state, and national news along with advertising.</p>
</summary >
<media:thumbnail url =" https://gateway.okhistory.org/ark:/67531/metadc1806772/small/ " />
</entry >
<entry > ... </entry >
<entry >
<title >
The Muskogee - Okmulgee Oklahoma Eagle (Muskogee and Okmulgee, Okla.), Vol. 12, No. 47, Ed. 1 Thursday, February 19, 1987
</title >
<link href =" https://gateway.okhistory.org/ark:/67531/metadc1810478/ " rel =" alternate " />
<published > 2021-05-30T16:34:23-05:00 </published >
<id >
https://gateway.okhistory.org/ark:/67531/metadc1810478/
</id >
<summary type =" html " >
<p><a href="https://gateway.okhistory.org/ark:/67531/metadc1810478/"><img alt="The Muskogee - Okmulgee Oklahoma Eagle (Muskogee and Okmulgee, Okla.), Vol. 12, No. 47, Ed. 1 Thursday, February 19, 1987" title="The Muskogee - Okmulgee Oklahoma Eagle (Muskogee and Okmulgee, Okla.), Vol. 12, No. 47, Ed. 1 Thursday, February 19, 1987" src="https://gateway.okhistory.org/ark:/67531/metadc1810478/small/"/></a></p><p>Weekly newspaper from Muskogee and Okmulgee, Oklahoma that includes local, state, and national news along with advertising.</p>
</summary >
<media:thumbnail url =" https://gateway.okhistory.org/ark:/67531/metadc1810478/small/ " />
</entry >
<entry > ... </entry >
<entry >
<title >
The Muskogee - Okmulgee Oklahoma Eagle (Muskogee and Okmulgee, Okla.), Vol. 12, No. 51, Ed. 1 Thursday, March 19, 1987
</title >
<link href =" https://gateway.okhistory.org/ark:/67531/metadc1810482/ " rel =" alternate " />
<published > 2021-05-30T16:34:38-05:00 </published >
<id >
https://gateway.okhistory.org/ark:/67531/metadc1810482/
</id >
<summary type =" html " >
<p><a href="https://gateway.okhistory.org/ark:/67531/metadc1810482/"><img alt="The Muskogee - Okmulgee Oklahoma Eagle (Muskogee and Okmulgee, Okla.), Vol. 12, No. 51, Ed. 1 Thursday, March 19, 1987" title="The Muskogee - Okmulgee Oklahoma Eagle (Muskogee and Okmulgee, Okla.), Vol. 12, No. 51, Ed. 1 Thursday, March 19, 1987" src="https://gateway.okhistory.org/ark:/67531/metadc1810482/small/"/></a></p><p>Weekly newspaper from Muskogee and Okmulgee, Oklahoma that includes local, state, and national news along with advertising.</p>
</summary >
<media:thumbnail url =" https://gateway.okhistory.org/ark:/67531/metadc1810482/small/ " />
</entry >
<entry >
<title >
The Muskogee - Okmulgee Oklahoma Eagle (Muskogee and Okmulgee, Okla.), Vol. 13, No. 33, Ed. 1 Thursday, November 19, 1987
</title >
<link href =" https://gateway.okhistory.org/ark:/67531/metadc1810529/ " rel =" alternate " />
<published > 2021-05-30T16:37:49-05:00 </published >
<id >
https://gateway.okhistory.org/ark:/67531/metadc1810529/
</id >
<summary type =" html " >
<p><a href="https://gateway.okhistory.org/ark:/67531/metadc1810529/"><img alt="The Muskogee - Okmulgee Oklahoma Eagle (Muskogee and Okmulgee, Okla.), Vol. 13, No. 33, Ed. 1 Thursday, November 19, 1987" title="The Muskogee - Okmulgee Oklahoma Eagle (Muskogee and Okmulgee, Okla.), Vol. 13, No. 33, Ed. 1 Thursday, November 19, 1987" src="https://gateway.okhistory.org/ark:/67531/metadc1810529/small/"/></a></p><p>Weekly newspaper from Muskogee and Okmulgee, Oklahoma that includes local, state, and national news along with advertising.</p>
</summary >
<summary type =" html " > ... </summary >
<media:thumbnail url =" https://gateway.okhistory.org/ark:/67531/metadc1810529/small/ " />
</entry >
<entry >
<title >
The Oklahoma Daily (Norman, Okla.), Vol. 73, No. 92, Ed. 1 Monday, January 19, 1987
</title >
<link href =" https://gateway.okhistory.org/ark:/67531/metadc1822143/ " rel =" alternate " />
<published > 2021-07-11T11:39:13-05:00 </published >
<id >
https://gateway.okhistory.org/ark:/67531/metadc1822143/
</id >
<summary type =" html " >
<p><a href="https://gateway.okhistory.org/ark:/67531/metadc1822143/"><img alt="The Oklahoma Daily (Norman, Okla.), Vol. 73, No. 92, Ed. 1 Monday, January 19, 1987" title="The Oklahoma Daily (Norman, Okla.), Vol. 73, No. 92, Ed. 1 Monday, January 19, 1987" src="https://gateway.okhistory.org/ark:/67531/metadc1822143/small/"/></a></p><p>Student newspaper of the University of Oklahoma in Norman, Oklahoma that includes national, local, and campus news along with advertising.</p>
</summary >
<media:thumbnail url =" https://gateway.okhistory.org/ark:/67531/metadc1822143/small/ " />
</entry >
<entry > ... </entry >
<entry >
<title >
The Oklahoma Daily (Norman, Okla.), Vol. 73, No. 115, Ed. 1 Thursday, February 19, 1987
</title >
<title > ... </title >
<link href =" https://gateway.okhistory.org/ark:/67531/metadc1822166/ " rel =" alternate " />
<published > 2021-07-11T11:43:58-05:00 </published >
<id >
https://gateway.okhistory.org/ark:/67531/metadc1822166/
</id >
<id > ... </id >
<summary type =" html " >
<p><a href="https://gateway.okhistory.org/ark:/67531/metadc1822166/"><img alt="The Oklahoma Daily (Norman, Okla.), Vol. 73, No. 115, Ed. 1 Thursday, February 19, 1987" title="The Oklahoma Daily (Norman, Okla.), Vol. 73, No. 115, Ed. 1 Thursday, February 19, 1987" src="https://gateway.okhistory.org/ark:/67531/metadc1822166/small/"/></a></p><p>Student newspaper of the University of Oklahoma in Norman, Oklahoma that includes national, local, and campus news along with advertising.</p>
</summary >
<media:thumbnail url =" https://gateway.okhistory.org/ark:/67531/metadc1822166/small/ " />
</entry >
<entry > ... </entry >
<entry >
<title >
The Oklahoma Daily (Norman, Okla.), Vol. 73, No. 130, Ed. 1 Thursday, March 19, 1987
</title >
<link href =" https://gateway.okhistory.org/ark:/67531/metadc1822181/ " rel =" alternate " />
<published > 2021-07-11T11:48:00-05:00 </published >
<id >
https://gateway.okhistory.org/ark:/67531/metadc1822181/
</id >
<summary type =" html " >
<p><a href="https://gateway.okhistory.org/ark:/67531/metadc1822181/"><img alt="The Oklahoma Daily (Norman, Okla.), Vol. 73, No. 130, Ed. 1 Thursday, March 19, 1987" title="The Oklahoma Daily (Norman, Okla.), Vol. 73, No. 130, Ed. 1 Thursday, March 19, 1987" src="https://gateway.okhistory.org/ark:/67531/metadc1822181/small/"/></a></p><p>Student newspaper of the University of Oklahoma in Norman, Oklahoma that includes national, local, and campus news along with advertising.</p>
</summary >
<media:thumbnail url =" https://gateway.okhistory.org/ark:/67531/metadc1822181/small/ " />
</entry >
<entry > ... </entry >
<entry >
<title >
The Oklahoma Daily (Norman, Okla.), Vol. 73, No. 44, Ed. 1 Monday, October 19, 1987
</title >
<title > ... </title >
<link href =" https://gateway.okhistory.org/ark:/67531/metadc1822261/ " rel =" alternate " />
<published > 2021-07-11T12:08:19-05:00 </published >
<id >
https://gateway.okhistory.org/ark:/67531/metadc1822261/
</id >
<id > ... </id >
<summary type =" html " >
<p><a href="https://gateway.okhistory.org/ark:/67531/metadc1822261/"><img alt="The Oklahoma Daily (Norman, Okla.), Vol. 73, No. 44, Ed. 1 Monday, October 19, 1987" title="The Oklahoma Daily (Norman, Okla.), Vol. 73, No. 44, Ed. 1 Monday, October 19, 1987" src="https://gateway.okhistory.org/ark:/67531/metadc1822261/small/"/></a></p><p>Student newspaper of the University of Oklahoma in Norman, Oklahoma that includes national, local, and campus news along with advertising.</p>
</summary >
<summary type =" html " > ... </summary >
<media:thumbnail url =" https://gateway.okhistory.org/ark:/67531/metadc1822261/small/ " />
</entry >
<entry > ... </entry >
<entry >
<title >
The Oklahoma Daily (Norman, Okla.), Vol. 73, No. 70, Ed. 1 Thursday, November 19, 1987
</title >
<title > ... </title >
<link href =" https://gateway.okhistory.org/ark:/67531/metadc1822287/ " rel =" alternate " />
<published > 2021-07-11T12:14:25-05:00 </published >
<id >
https://gateway.okhistory.org/ark:/67531/metadc1822287/
</id >
<id > ... </id >
<summary type =" html " >
<p><a href="https://gateway.okhistory.org/ark:/67531/metadc1822287/"><img alt="The Oklahoma Daily (Norman, Okla.), Vol. 73, No. 70, Ed. 1 Thursday, November 19, 1987" title="The Oklahoma Daily (Norman, Okla.), Vol. 73, No. 70, Ed. 1 Thursday, November 19, 1987" src="https://gateway.okhistory.org/ark:/67531/metadc1822287/small/"/></a></p><p>Student newspaper of the University of Oklahoma in Norman, Oklahoma that includes national, local, and campus news along with advertising.</p>
</summary >
<summary type =" html " > ... </summary >
<media:thumbnail url =" https://gateway.okhistory.org/ark:/67531/metadc1822287/small/ " />
</entry >
<entry > ... </entry >
<entry >
<title >
The Oklahoma Daily (Norman, Okla.), Vol. 73, No. 179, Ed. 1 Friday, June 19, 1987
</title >
<title > ... </title >
<link href =" https://gateway.okhistory.org/ark:/67531/metadc1830267/ " rel =" alternate " />
<published > 2021-08-02T11:47:05-05:00 </published >
<id >
https://gateway.okhistory.org/ark:/67531/metadc1830267/
</id >
<id > ... </id >
<summary type =" html " >
<p><a href="https://gateway.okhistory.org/ark:/67531/metadc1830267/"><img alt="The Oklahoma Daily (Norman, Okla.), Vol. 73, No. 179, Ed. 1 Friday, June 19, 1987" title="The Oklahoma Daily (Norman, Okla.), Vol. 73, No. 179, Ed. 1 Friday, June 19, 1987" src="https://gateway.okhistory.org/ark:/67531/metadc1830267/small/"/></a></p><p>Student newspaper of the University of Oklahoma in Norman, Oklahoma that includes national, local, and campus news along with advertising.</p>
</summary >
<summary type =" html " > ... </summary >
<media:thumbnail url =" https://gateway.okhistory.org/ark:/67531/metadc1830267/small/ " />
</entry >
<entry > ... </entry >
<entry >
<title >
The Oklahoma Daily (Norman, Okla.), Vol. 74, No. 1, Ed. 1 Wednesday, August 19, 1987
</title >
<title > ... </title >
<link href =" https://gateway.okhistory.org/ark:/67531/metadc1830297/ " rel =" alternate " />
<published > 2021-08-02T11:49:37-05:00 </published >
<id >
https://gateway.okhistory.org/ark:/67531/metadc1830297/
</id >
<id > ... </id >
<summary type =" html " >
<p><a href="https://gateway.okhistory.org/ark:/67531/metadc1830297/"><img alt="The Oklahoma Daily (Norman, Okla.), Vol. 74, No. 1, Ed. 1 Wednesday, August 19, 1987" title="The Oklahoma Daily (Norman, Okla.), Vol. 74, No. 1, Ed. 1 Wednesday, August 19, 1987" src="https://gateway.okhistory.org/ark:/67531/metadc1830297/small/"/></a></p><p>Student newspaper of the University of Oklahoma in Norman, Oklahoma that includes national, local, and campus news along with advertising.</p>
</summary >
<summary type =" html " > ... </summary >
<media:thumbnail url =" https://gateway.okhistory.org/ark:/67531/metadc1830297/small/ " />
</entry >
<entry > ... </entry >
<entry >
<title >
Chickasha Daily Express (Chickasha, Okla.), Vol. 95, No. 326, Ed. 1 Monday, January 19, 1987
</title >
<title > ... </title >
<link href =" https://gateway.okhistory.org/ark:/67531/metadc1871568/ " rel =" alternate " />
<published > 2021-12-19T16:39:29-06:00 </published >
<id >
https://gateway.okhistory.org/ark:/67531/metadc1871568/
</id >
<id > ... </id >
<summary type =" html " >
<p><a href="https://gateway.okhistory.org/ark:/67531/metadc1871568/"><img alt="Chickasha Daily Express (Chickasha, Okla.), Vol. 95, No. 326, Ed. 1 Monday, January 19, 1987" title="Chickasha Daily Express (Chickasha, Okla.), Vol. 95, No. 326, Ed. 1 Monday, January 19, 1987" src="https://gateway.okhistory.org/ark:/67531/metadc1871568/small/"/></a></p><p>Daily newspaper from Chickasha, Oklahoma that includes local, state, and national news along with advertising.</p>
</summary >
<summary type =" html " > ... </summary >
<media:thumbnail url =" https://gateway.okhistory.org/ark:/67531/metadc1871568/small/ " />
</entry >
<entry > ... </entry >
<entry >
<title >
Chickasha Daily Express (Chickasha, Okla.), Vol. 95, No. 353, Ed. 1 Thursday, February 19, 1987
</title >
<title > ... </title >
<link href =" https://gateway.okhistory.org/ark:/67531/metadc1871595/ " rel =" alternate " />
<published > 2021-12-19T16:45:18-06:00 </published >
<id >
https://gateway.okhistory.org/ark:/67531/metadc1871595/
</id >
<id > ... </id >
<summary type =" html " >
<p><a href="https://gateway.okhistory.org/ark:/67531/metadc1871595/"><img alt="Chickasha Daily Express (Chickasha, Okla.), Vol. 95, No. 353, Ed. 1 Thursday, February 19, 1987" title="Chickasha Daily Express (Chickasha, Okla.), Vol. 95, No. 353, Ed. 1 Thursday, February 19, 1987" src="https://gateway.okhistory.org/ark:/67531/metadc1871595/small/"/></a></p><p>Daily newspaper from Chickasha, Oklahoma that includes local, state, and national news along with advertising.</p>
</summary >
<summary type =" html " > ... </summary >
<media:thumbnail url =" https://gateway.okhistory.org/ark:/67531/metadc1871595/small/ " />
</entry >
<entry > ... </entry >
<entry >
<title >
Chickasha Daily Express (Chickasha, Okla.), Vol. 96, No. 67, Ed. 1 Thursday, March 19, 1987
</title >
<title > ... </title >
<link href =" https://gateway.okhistory.org/ark:/67531/metadc1871619/ " rel =" alternate " />
<published > 2021-12-19T16:50:19-06:00 </published >
<id >
https://gateway.okhistory.org/ark:/67531/metadc1871619/
</id >
<id > ... </id >
<summary type =" html " >
<p><a href="https://gateway.okhistory.org/ark:/67531/metadc1871619/"><img alt="Chickasha Daily Express (Chickasha, Okla.), Vol. 96, No. 67, Ed. 1 Thursday, March 19, 1987" title="Chickasha Daily Express (Chickasha, Okla.), Vol. 96, No. 67, Ed. 1 Thursday, March 19, 1987" src="https://gateway.okhistory.org/ark:/67531/metadc1871619/small/"/></a></p><p>Daily newspaper from Chickasha, Oklahoma that includes local, state, and national news along with advertising.</p>
</summary >
<summary type =" html " > ... </summary >
<media:thumbnail url =" https://gateway.okhistory.org/ark:/67531/metadc1871619/small/ " />
</entry >
<entry > ... </entry >
<entry >
<title >
Chickasha Daily Express (Chickasha, Okla.), Vol. 96, No. 93, Ed. 1 Sunday, April 19, 1987
</title >
<title > ... </title >
<link href =" https://gateway.okhistory.org/ark:/67531/metadc1871644/ " rel =" alternate " />
<published > 2021-12-19T16:55:49-06:00 </published >
<id >
https://gateway.okhistory.org/ark:/67531/metadc1871644/
</id >
<id > ... </id >
<summary type =" html " >
<p><a href="https://gateway.okhistory.org/ark:/67531/metadc1871644/"><img alt="Chickasha Daily Express (Chickasha, Okla.), Vol. 96, No. 93, Ed. 1 Sunday, April 19, 1987" title="Chickasha Daily Express (Chickasha, Okla.), Vol. 96, No. 93, Ed. 1 Sunday, April 19, 1987" src="https://gateway.okhistory.org/ark:/67531/metadc1871644/small/"/></a></p><p>Daily newspaper from Chickasha, Oklahoma that includes local, state, and national news along with advertising.</p>
</summary >
<summary type =" html " > ... </summary >
<media:thumbnail url =" https://gateway.okhistory.org/ark:/67531/metadc1871644/small/ " />
</entry >
<entry > ... </entry >
<entry >
<title >
Chickasha Daily Express (Chickasha, Okla.), Vol. 96, No. 119, Ed. 1 Tuesday, May 19, 1987
</title >
<title > ... </title >
<link href =" https://gateway.okhistory.org/ark:/67531/metadc1871669/ " rel =" alternate " />
<published > 2021-12-19T17:02:23-06:00 </published >
<id >
https://gateway.okhistory.org/ark:/67531/metadc1871669/
</id >
<id > ... </id >
<summary type =" html " >
<p><a href="https://gateway.okhistory.org/ark:/67531/metadc1871669/"><img alt="Chickasha Daily Express (Chickasha, Okla.), Vol. 96, No. 119, Ed. 1 Tuesday, May 19, 1987" title="Chickasha Daily Express (Chickasha, Okla.), Vol. 96, No. 119, Ed. 1 Tuesday, May 19, 1987" src="https://gateway.okhistory.org/ark:/67531/metadc1871669/small/"/></a></p><p>Daily newspaper from Chickasha, Oklahoma that includes local, state, and national news along with advertising.</p>
</summary >
<summary type =" html " > ... </summary >
<media:thumbnail url =" https://gateway.okhistory.org/ark:/67531/metadc1871669/small/ " />
</entry >
<entry > ... </entry >
<entry >
<title >
Chickasha Daily Express (Chickasha, Okla.), Vol. 96, No. 146, Ed. 1 Friday, June 19, 1987
</title >
<title > ... </title >
<link href =" https://gateway.okhistory.org/ark:/67531/metadc1871696/ " rel =" alternate " />
<published > 2021-12-19T17:09:04-06:00 </published >
<id >
https://gateway.okhistory.org/ark:/67531/metadc1871696/
</id >
<id > ... </id >
<summary type =" html " >
<p><a href="https://gateway.okhistory.org/ark:/67531/metadc1871696/"><img alt="Chickasha Daily Express (Chickasha, Okla.), Vol. 96, No. 146, Ed. 1 Friday, June 19, 1987" title="Chickasha Daily Express (Chickasha, Okla.), Vol. 96, No. 146, Ed. 1 Friday, June 19, 1987" src="https://gateway.okhistory.org/ark:/67531/metadc1871696/small/"/></a></p><p>Daily newspaper from Chickasha, Oklahoma that includes local, state, and national news along with advertising.</p>
</summary >
<summary type =" html " > ... </summary >
<media:thumbnail url =" https://gateway.okhistory.org/ark:/67531/metadc1871696/small/ " />
</entry >
<entry > ... </entry >
<entry >
<title >
Chickasha Daily Express (Chickasha, Okla.), Vol. 96, No. 171, Ed. 1 Sunday, July 19, 1987
</title >
<title > ... </title >
<link href =" https://gateway.okhistory.org/ark:/67531/metadc1871721/ " rel =" alternate " />
<published > 2021-12-19T17:15:26-06:00 </published >
| https://gateway.okhistory.org/explore/collections/ODNP/feed/?fq=str_day%3A19&fq=str_year%3A1987&sort=added_a |
Bill Seurer (POWER8) - Results for 7.0.0 20160425 (experimental) [trunk revision 235406] (GCC)
Results for 7.0.0 20160425 (experimental) [trunk revision 235406] (GCC) testsuite on powerpc64le-unknown-linux-gnu
From : "Bill Seurer (POWER8)" <seurer at linux dot vnet dot ibm dot com>
To : gcc-testresults at gcc dot gnu dot org
Date : Mon, 25 Apr 2016 04:19:41 -0500
Subject : Results for 7.0.0 20160425 (experimental) [trunk revision 235406] (GCC) testsuite on powerpc64le-unknown-linux-gnu
Authentication-results : sourceware.org; auth=none
Linux 3.13.0-35-generic ppc64le
GNU C Library (Ubuntu EGLIBC 2.19-0ubuntu6.6) stable release version 2.19
GNU ld (GNU Binutils for Ubuntu) 2.24
GNU assembler (GNU Binutils for Ubuntu) 2.24
GNU Make 3.81
DejaGnu:
Expect version is 5.45
Tcl version is 8.6
Framework version is 1.5
64-bit
LAST_UPDATED: Mon Apr 25 08:05:31 UTC 2016 (revision 235406)
Native configuration is powerpc64le-unknown-linux-gnu
=== g++ tests ===
Running target unix
FAIL: c-c++-common/asan/null-deref-1.c -O2 output pattern test, is ASAN:DEADLYSIGNAL
FAIL: c-c++-common/asan/null-deref-1.c -O2 -flto -fno-use-linker-plugin -flto-partition=none output pattern test, is ASAN:DEADLYSIGNAL
FAIL: c-c++-common/asan/null-deref-1.c -O2 -flto -fuse-linker-plugin -fno-fat-lto-objects output pattern test, is ASAN:DEADLYSIGNAL
FAIL: c-c++-common/asan/null-deref-1.c -O3 -g output pattern test, is ASAN:DEADLYSIGNAL
FAIL: g++.dg/cpp1y/vla-initlist1.C -std=gnu++11 execution test
FAIL: g++.dg/cpp1y/vla-initlist1.C -std=gnu++14 execution test
XPASS: g++.dg/tls/thread_local-order2.C -std=c++11 execution test
XPASS: g++.dg/tls/thread_local-order2.C -std=c++14 execution test
=== g++ Summary ===
# of expected passes 100094
# of unexpected failures 6
# of unexpected successes 2
# of expected failures 306
# of unsupported tests 3987
/home/gccbuild/build/nightly/build-gcc-trunk/gcc/testsuite/g++/../../xg++ version 7.0.0 20160425 (experimental) [trunk revision 235406] (GCC)
=== gcc tests ===
Running target unix
FAIL: c-c++-common/asan/misalign-1.c -O0 output pattern test, is =================================================================
FAIL: c-c++-common/asan/misalign-1.c -O1 output pattern test, is =================================================================
FAIL: c-c++-common/asan/misalign-1.c -O2 output pattern test, is =================================================================
FAIL: c-c++-common/asan/misalign-1.c -O2 -flto -fno-use-linker-plugin -flto-partition=none output pattern test, is =================================================================
FAIL: c-c++-common/asan/misalign-1.c -O2 -flto -fuse-linker-plugin -fno-fat-lto-objects output pattern test, is =================================================================
FAIL: c-c++-common/asan/misalign-1.c -O3 -g output pattern test, is =================================================================
FAIL: c-c++-common/asan/misalign-1.c -Os output pattern test, is =================================================================
FAIL: c-c++-common/asan/misalign-2.c -O0 output pattern test, is =================================================================
FAIL: c-c++-common/asan/misalign-2.c -O1 output pattern test, is =================================================================
FAIL: c-c++-common/asan/misalign-2.c -O2 output pattern test, is =================================================================
FAIL: c-c++-common/asan/misalign-2.c -O2 -flto -fno-use-linker-plugin -flto-partition=none output pattern test, is =================================================================
FAIL: c-c++-common/asan/misalign-2.c -O2 -flto -fuse-linker-plugin -fno-fat-lto-objects output pattern test, is =================================================================
FAIL: c-c++-common/asan/misalign-2.c -O3 -g output pattern test, is =================================================================
FAIL: c-c++-common/asan/misalign-2.c -Os output pattern test, is =================================================================
FAIL: c-c++-common/asan/null-deref-1.c -O0 output pattern test, is ASAN:DEADLYSIGNAL
FAIL: c-c++-common/asan/null-deref-1.c -O1 output pattern test, is ASAN:DEADLYSIGNAL
FAIL: c-c++-common/asan/null-deref-1.c -O2 output pattern test, is ASAN:DEADLYSIGNAL
FAIL: c-c++-common/asan/null-deref-1.c -O2 -flto -fno-use-linker-plugin -flto-partition=none output pattern test, is ASAN:DEADLYSIGNAL
FAIL: c-c++-common/asan/null-deref-1.c -O2 -flto -fuse-linker-plugin -fno-fat-lto-objects output pattern test, is ASAN:DEADLYSIGNAL
FAIL: c-c++-common/asan/null-deref-1.c -O3 -g output pattern test, is ASAN:DEADLYSIGNAL
FAIL: c-c++-common/asan/null-deref-1.c -Os output pattern test, is ASAN:DEADLYSIGNAL
FAIL: gcc.dg/loop-8.c scan-rtl-dump-times loop2_invariant "Decided" 1
FAIL: gcc.dg/sms-4.c scan-rtl-dump-times sms "SMS succeeded" 1
XPASS: gcc.dg/guality/example.c -O0 execution test
XPASS: gcc.dg/guality/example.c -O1 execution test
XPASS: gcc.dg/guality/guality.c -O0 execution test
XPASS: gcc.dg/guality/guality.c -O1 execution test
XPASS: gcc.dg/guality/guality.c -O2 execution test
XPASS: gcc.dg/guality/guality.c -O2 -flto -fno-use-linker-plugin -flto-partition=none execution test
XPASS: gcc.dg/guality/guality.c -O2 -flto -fuse-linker-plugin -fno-fat-lto-objects execution test
XPASS: gcc.dg/guality/guality.c -O3 -g execution test
XPASS: gcc.dg/guality/guality.c -Os execution test
XPASS: gcc.dg/guality/inline-params.c -O2 execution test
XPASS: gcc.dg/guality/inline-params.c -O2 -flto -fno-use-linker-plugin -flto-partition=none execution test
XPASS: gcc.dg/guality/inline-params.c -O3 -g execution test
XPASS: gcc.dg/guality/inline-params.c -Os execution test
FAIL: gcc.dg/guality/pr36728-1.c -O2 line 18 y == 2
FAIL: gcc.dg/guality/pr36728-1.c -O2 -flto -fno-use-linker-plugin -flto-partition=none line 18 y == 2
FAIL: gcc.dg/guality/pr36728-1.c -O2 -flto -fuse-linker-plugin -fno-fat-lto-objects line 16 y == 2
FAIL: gcc.dg/guality/pr36728-1.c -O3 -g line 16 y == 2
FAIL: gcc.dg/guality/pr36728-1.c -O3 -g line 18 y == 2
FAIL: gcc.dg/guality/pr36728-2.c -O2 line 18 *x == (char) 25
FAIL: gcc.dg/guality/pr36728-2.c -O2 -flto -fno-use-linker-plugin -flto-partition=none line 18 *x == (char) 25
FAIL: gcc.dg/guality/pr36728-2.c -O2 -flto -fuse-linker-plugin -fno-fat-lto-objects line 16 arg1 == 1
FAIL: gcc.dg/guality/pr36728-2.c -O2 -flto -fuse-linker-plugin -fno-fat-lto-objects line 16 arg2 == 2
FAIL: gcc.dg/guality/pr36728-2.c -O2 -flto -fuse-linker-plugin -fno-fat-lto-objects line 16 arg3 == 3
FAIL: gcc.dg/guality/pr36728-2.c -O2 -flto -fuse-linker-plugin -fno-fat-lto-objects line 16 arg4 == 4
FAIL: gcc.dg/guality/pr36728-2.c -O2 -flto -fuse-linker-plugin -fno-fat-lto-objects line 16 arg5 == 5
FAIL: gcc.dg/guality/pr36728-2.c -O2 -flto -fuse-linker-plugin -fno-fat-lto-objects line 16 arg6 == 6
FAIL: gcc.dg/guality/pr36728-2.c -O2 -flto -fuse-linker-plugin -fno-fat-lto-objects line 16 arg7 == 30
FAIL: gcc.dg/guality/pr36728-2.c -O2 -flto -fuse-linker-plugin -fno-fat-lto-objects line 16 y == 2
FAIL: gcc.dg/guality/pr36728-2.c -O2 -flto -fuse-linker-plugin -fno-fat-lto-objects line 18 arg1 == 1
FAIL: gcc.dg/guality/pr36728-2.c -O2 -flto -fuse-linker-plugin -fno-fat-lto-objects line 18 arg2 == 2
FAIL: gcc.dg/guality/pr36728-2.c -O2 -flto -fuse-linker-plugin -fno-fat-lto-objects line 18 arg3 == 3
FAIL: gcc.dg/guality/pr36728-2.c -O2 -flto -fuse-linker-plugin -fno-fat-lto-objects line 18 arg4 == 4
FAIL: gcc.dg/guality/pr36728-2.c -O2 -flto -fuse-linker-plugin -fno-fat-lto-objects line 18 arg5 == 5
FAIL: gcc.dg/guality/pr36728-2.c -O2 -flto -fuse-linker-plugin -fno-fat-lto-objects line 18 arg6 == 6
FAIL: gcc.dg/guality/pr36728-2.c -O2 -flto -fuse-linker-plugin -fno-fat-lto-objects line 18 arg7 == 30
FAIL: gcc.dg/guality/pr36728-2.c -O3 -g line 16 arg1 == 1
FAIL: gcc.dg/guality/pr36728-2.c -O3 -g line 16 arg2 == 2
FAIL: gcc.dg/guality/pr36728-2.c -O3 -g line 16 arg3 == 3
FAIL: gcc.dg/guality/pr36728-2.c -O3 -g line 16 arg4 == 4
FAIL: gcc.dg/guality/pr36728-2.c -O3 -g line 16 arg5 == 5
FAIL: gcc.dg/guality/pr36728-2.c -O3 -g line 16 arg6 == 6
FAIL: gcc.dg/guality/pr36728-2.c -O3 -g line 16 arg7 == 30
FAIL: gcc.dg/guality/pr36728-2.c -O3 -g line 16 y == 2
FAIL: gcc.dg/guality/pr36728-2.c -O3 -g line 18 *x == (char) 25
FAIL: gcc.dg/guality/pr36728-2.c -O3 -g line 18 arg1 == 1
FAIL: gcc.dg/guality/pr36728-2.c -O3 -g line 18 arg2 == 2
FAIL: gcc.dg/guality/pr36728-2.c -O3 -g line 18 arg3 == 3
FAIL: gcc.dg/guality/pr36728-2.c -O3 -g line 18 arg4 == 4
FAIL: gcc.dg/guality/pr36728-2.c -O3 -g line 18 arg5 == 5
FAIL: gcc.dg/guality/pr36728-2.c -O3 -g line 18 arg6 == 6
FAIL: gcc.dg/guality/pr36728-2.c -O3 -g line 18 arg7 == 30
FAIL: gcc.dg/guality/pr36728-2.c -O3 -g line 18 y == 2
FAIL: gcc.dg/guality/pr36728-2.c -Os line 18 y == 2
XPASS: gcc.dg/guality/pr41353-1.c -O0 line 28 j == 28 + 37
FAIL: gcc.dg/guality/pr41353-1.c -O1 line 28 i == 37
FAIL: gcc.dg/guality/pr41353-1.c -O1 line 28 i1 == 2 * 37
FAIL: gcc.dg/guality/pr41353-1.c -O1 line 28 i2 == 3 * 37
XPASS: gcc.dg/guality/pr41353-1.c -O1 line 28 j == 28 + 37
FAIL: gcc.dg/guality/pr41353-1.c -O2 line 28 i == 37
FAIL: gcc.dg/guality/pr41353-1.c -O2 line 28 i1 == 2 * 37
FAIL: gcc.dg/guality/pr41353-1.c -O2 line 28 i2 == 3 * 37
XPASS: gcc.dg/guality/pr41353-1.c -O2 line 28 j == 28 + 37
FAIL: gcc.dg/guality/pr41353-1.c -O2 -flto -fno-use-linker-plugin -flto-partition=none line 28 i == 37
FAIL: gcc.dg/guality/pr41353-1.c -O2 -flto -fno-use-linker-plugin -flto-partition=none line 28 i1 == 2 * 37
FAIL: gcc.dg/guality/pr41353-1.c -O2 -flto -fno-use-linker-plugin -flto-partition=none line 28 i2 == 3 * 37
XPASS: gcc.dg/guality/pr41353-1.c -O2 -flto -fno-use-linker-plugin -flto-partition=none line 28 j == 28 + 37
FAIL: gcc.dg/guality/pr41353-1.c -O2 -flto -fuse-linker-plugin -fno-fat-lto-objects line 28 i == 37
FAIL: gcc.dg/guality/pr41353-1.c -O2 -flto -fuse-linker-plugin -fno-fat-lto-objects line 28 i1 == 2 * 37
FAIL: gcc.dg/guality/pr41353-1.c -O2 -flto -fuse-linker-plugin -fno-fat-lto-objects line 28 i2 == 3 * 37
XPASS: gcc.dg/guality/pr41353-1.c -O2 -flto -fuse-linker-plugin -fno-fat-lto-objects line 28 j == 28 + 37
FAIL: gcc.dg/guality/pr41353-1.c -O3 -g line 28 i == 37
FAIL: gcc.dg/guality/pr41353-1.c -O3 -g line 28 i1 == 2 * 37
FAIL: gcc.dg/guality/pr41353-1.c -O3 -g line 28 i2 == 3 * 37
XPASS: gcc.dg/guality/pr41353-1.c -O3 -g line 28 j == 28 + 37
FAIL: gcc.dg/guality/pr41353-1.c -Os line 28 i == 37
FAIL: gcc.dg/guality/pr41353-1.c -Os line 28 i1 == 2 * 37
FAIL: gcc.dg/guality/pr41353-1.c -Os line 28 i2 == 3 * 37
XPASS: gcc.dg/guality/pr41353-1.c -Os line 28 j == 28 + 37
FAIL: gcc.dg/guality/pr41616-1.c -O2 -flto -fuse-linker-plugin -fno-fat-lto-objects execution test
FAIL: gcc.dg/guality/pr43051-1.c -O1 line 40 v == 1
FAIL: gcc.dg/guality/pr43051-1.c -O2 line 35 v == 1
FAIL: gcc.dg/guality/pr43051-1.c -O2 line 40 v == 1
FAIL: gcc.dg/guality/pr43051-1.c -O2 -flto -fno-use-linker-plugin -flto-partition=none line 35 v == 1
FAIL: gcc.dg/guality/pr43051-1.c -O2 -flto -fno-use-linker-plugin -flto-partition=none line 40 v == 1
FAIL: gcc.dg/guality/pr43051-1.c -O2 -flto -fuse-linker-plugin -fno-fat-lto-objects line 35 v == 1
FAIL: gcc.dg/guality/pr43051-1.c -O2 -flto -fuse-linker-plugin -fno-fat-lto-objects line 40 v == 1
FAIL: gcc.dg/guality/pr43051-1.c -O3 -fomit-frame-pointer -funroll-loops -fpeel-loops -ftracer -finline-functions line 35 v == 1
FAIL: gcc.dg/guality/pr43051-1.c -O3 -fomit-frame-pointer -funroll-loops -fpeel-loops -ftracer -finline-functions line 40 v == 1
FAIL: gcc.dg/guality/pr43051-1.c -O3 -g line 35 v == 1
FAIL: gcc.dg/guality/pr43051-1.c -O3 -g line 40 v == 1
FAIL: gcc.dg/guality/pr43051-1.c -Os line 40 v == 1
FAIL: gcc.dg/guality/pr45882.c -O2 -flto -fuse-linker-plugin -fno-fat-lto-objects line 16 d == 112
FAIL: gcc.dg/guality/pr45882.c -O2 -flto -fuse-linker-plugin -fno-fat-lto-objects line 16 e == 142
FAIL: gcc.dg/guality/pr54200.c -O1 line 20 z == 3
FAIL: gcc.dg/guality/pr54200.c -O2 line 20 z == 3
FAIL: gcc.dg/guality/pr54200.c -O2 -flto -fno-use-linker-plugin -flto-partition=none line 20 z == 3
FAIL: gcc.dg/guality/pr54200.c -O2 -flto -fuse-linker-plugin -fno-fat-lto-objects line 20 z == 3
FAIL: gcc.dg/guality/pr54200.c -O3 -g line 20 z == 3
FAIL: gcc.dg/guality/pr54200.c -Os line 20 z == 3
FAIL: gcc.dg/guality/pr54519-1.c -O1 line 20 x == 36
FAIL: gcc.dg/guality/pr54519-1.c -O1 line 20 y == 25
FAIL: gcc.dg/guality/pr54519-1.c -O1 line 23 x == 98
FAIL: gcc.dg/guality/pr54519-1.c -O1 line 23 y == 117
FAIL: gcc.dg/guality/pr54519-1.c -O2 line 20 x == 36
FAIL: gcc.dg/guality/pr54519-1.c -O2 line 23 x == 98
FAIL: gcc.dg/guality/pr54519-1.c -O2 -flto -fno-use-linker-plugin -flto-partition=none line 20 x == 36
FAIL: gcc.dg/guality/pr54519-1.c -O2 -flto -fno-use-linker-plugin -flto-partition=none line 20 y == 25
FAIL: gcc.dg/guality/pr54519-1.c -O2 -flto -fno-use-linker-plugin -flto-partition=none line 20 z == 6
FAIL: gcc.dg/guality/pr54519-1.c -O2 -flto -fno-use-linker-plugin -flto-partition=none line 23 x == 98
FAIL: gcc.dg/guality/pr54519-1.c -O2 -flto -fno-use-linker-plugin -flto-partition=none line 23 y == 117
FAIL: gcc.dg/guality/pr54519-1.c -O2 -flto -fno-use-linker-plugin -flto-partition=none line 23 z == 8
FAIL: gcc.dg/guality/pr54519-1.c -Os line 20 x == 36
FAIL: gcc.dg/guality/pr54519-1.c -Os line 23 x == 98
FAIL: gcc.dg/guality/pr54519-2.c -O1 line 17 x == 6
FAIL: gcc.dg/guality/pr54519-2.c -O2 -flto -fno-use-linker-plugin -flto-partition=none line 17 y == 25
FAIL: gcc.dg/guality/pr54519-2.c -O2 -flto -fuse-linker-plugin -fno-fat-lto-objects line 17 y == 25
FAIL: gcc.dg/guality/pr54519-3.c -O1 line 20 x == 36
FAIL: gcc.dg/guality/pr54519-3.c -O1 line 20 y == 25
FAIL: gcc.dg/guality/pr54519-3.c -O1 line 20 z == 6
FAIL: gcc.dg/guality/pr54519-3.c -O1 line 23 x == 98
FAIL: gcc.dg/guality/pr54519-3.c -O1 line 23 y == 117
FAIL: gcc.dg/guality/pr54519-3.c -O1 line 23 z == 8
FAIL: gcc.dg/guality/pr54519-3.c -O2 line 20 z == 6
FAIL: gcc.dg/guality/pr54519-3.c -O2 line 23 z == 8
FAIL: gcc.dg/guality/pr54519-3.c -O2 -flto -fno-use-linker-plugin -flto-partition=none line 20 y == 25
FAIL: gcc.dg/guality/pr54519-3.c -O2 -flto -fno-use-linker-plugin -flto-partition=none line 20 z == 6
FAIL: gcc.dg/guality/pr54519-3.c -O2 -flto -fno-use-linker-plugin -flto-partition=none line 23 y == 117
FAIL: gcc.dg/guality/pr54519-3.c -O2 -flto -fno-use-linker-plugin -flto-partition=none line 23 z == 8
FAIL: gcc.dg/guality/pr54519-3.c -O2 -flto -fuse-linker-plugin -fno-fat-lto-objects line 20 y == 25
FAIL: gcc.dg/guality/pr54519-3.c -O2 -flto -fuse-linker-plugin -fno-fat-lto-objects line 20 z == 6
FAIL: gcc.dg/guality/pr54519-3.c -O2 -flto -fuse-linker-plugin -fno-fat-lto-objects line 23 y == 117
FAIL: gcc.dg/guality/pr54519-3.c -O2 -flto -fuse-linker-plugin -fno-fat-lto-objects line 23 z == 8
FAIL: gcc.dg/guality/pr54519-3.c -O3 -g line 20 z == 6
FAIL: gcc.dg/guality/pr54519-3.c -O3 -g line 23 z == 8
FAIL: gcc.dg/guality/pr54519-3.c -Os line 20 z == 6
FAIL: gcc.dg/guality/pr54519-3.c -Os line 23 z == 8
FAIL: gcc.dg/guality/pr54519-4.c -O1 line 17 x == 6
FAIL: gcc.dg/guality/pr54519-4.c -O1 line 17 y == 25
FAIL: gcc.dg/guality/pr54519-4.c -O2 line 17 y == 25
FAIL: gcc.dg/guality/pr54519-4.c -O2 -flto -fno-use-linker-plugin -flto-partition=none line 17 y == 25
FAIL: gcc.dg/guality/pr54519-4.c -O2 -flto -fuse-linker-plugin -fno-fat-lto-objects line 17 y == 25
FAIL: gcc.dg/guality/pr54519-4.c -O3 -g line 17 y == 25
FAIL: gcc.dg/guality/pr54519-4.c -Os line 17 y == 25
FAIL: gcc.dg/guality/pr54519-5.c -O1 line 17 x == 6
FAIL: gcc.dg/guality/pr54519-5.c -O1 line 17 y == 25
FAIL: gcc.dg/guality/pr54519-5.c -O2 line 17 y == 25
FAIL: gcc.dg/guality/pr54519-5.c -O2 -flto -fno-use-linker-plugin -flto-partition=none line 17 y == 25
FAIL: gcc.dg/guality/pr54519-5.c -O2 -flto -fuse-linker-plugin -fno-fat-lto-objects line 17 y == 25
FAIL: gcc.dg/guality/pr54519-5.c -O3 -g line 17 y == 25
FAIL: gcc.dg/guality/pr54519-5.c -Os line 17 y == 25
FAIL: gcc.dg/guality/pr54551.c -O1 line 18 a == 4
FAIL: gcc.dg/guality/pr54551.c -O2 line 18 a == 4
FAIL: gcc.dg/guality/pr54551.c -O2 -flto -fno-use-linker-plugin -flto-partition=none line 18 a == 4
FAIL: gcc.dg/guality/pr54551.c -O3 -g line 18 a == 4
FAIL: gcc.dg/guality/pr54551.c -Os line 18 a == 4
FAIL: gcc.dg/guality/pr54693-2.c -O1 line 21 x == 10 - i
FAIL: gcc.dg/guality/pr54693-2.c -O2 line 21 x == 10 - i
FAIL: gcc.dg/guality/pr54693-2.c -O2 -flto -fno-use-linker-plugin -flto-partition=none line 21 x == 10 - i
FAIL: gcc.dg/guality/pr54693-2.c -O2 -flto -fuse-linker-plugin -fno-fat-lto-objects line 21 x == 10 - i
FAIL: gcc.dg/guality/pr54693-2.c -O3 -fomit-frame-pointer -funroll-loops -fpeel-loops -ftracer -finline-functions line 21 x == 10 - i
FAIL: gcc.dg/guality/pr54693-2.c -O3 -g line 21 x == 10 - i
FAIL: gcc.dg/guality/pr54693-2.c -Os line 21 y == 20 - 2 * i
FAIL: gcc.dg/guality/pr54693-2.c -Os line 21 z == 30 - 3 * i
FAIL: gcc.dg/guality/pr54693.c -O1 line 22 i == c - 48
FAIL: gcc.dg/guality/pr54693.c -O2 line 22 i == c - 48
FAIL: gcc.dg/guality/pr54693.c -O2 -flto -fno-use-linker-plugin -flto-partition=none line 22 i == c - 48
FAIL: gcc.dg/guality/pr54693.c -O2 -flto -fuse-linker-plugin -fno-fat-lto-objects line 22 i == c - 48
FAIL: gcc.dg/guality/pr54693.c -O3 -fomit-frame-pointer -funroll-loops -fpeel-loops -ftracer -finline-functions line 22 i == c - 48
FAIL: gcc.dg/guality/pr54693.c -O3 -g line 22 i == c - 48
FAIL: gcc.dg/guality/pr54693.c -Os line 22 i == c - 48
FAIL: gcc.dg/guality/pr68860-1.c -O2 -flto -fno-use-linker-plugin -flto-partition=none line 14 arg1 == 1
FAIL: gcc.dg/guality/pr68860-1.c -O2 -flto -fno-use-linker-plugin -flto-partition=none line 14 arg2 == 2
FAIL: gcc.dg/guality/pr68860-1.c -O2 -flto -fno-use-linker-plugin -flto-partition=none line 14 arg3 == 3
FAIL: gcc.dg/guality/pr68860-1.c -O2 -flto -fno-use-linker-plugin -flto-partition=none line 14 arg4 == 4
FAIL: gcc.dg/guality/pr68860-1.c -O2 -flto -fno-use-linker-plugin -flto-partition=none line 14 arg5 == 5
FAIL: gcc.dg/guality/pr68860-1.c -O2 -flto -fno-use-linker-plugin -flto-partition=none line 14 arg6 == 6
FAIL: gcc.dg/guality/pr68860-1.c -O2 -flto -fno-use-linker-plugin -flto-partition=none line 16 arg1 == 1
FAIL: gcc.dg/guality/pr68860-1.c -O2 -flto -fno-use-linker-plugin -flto-partition=none line 16 arg2 == 2
FAIL: gcc.dg/guality/pr68860-1.c -O2 -flto -fno-use-linker-plugin -flto-partition=none line 16 arg3 == 3
FAIL: gcc.dg/guality/pr68860-1.c -O2 -flto -fno-use-linker-plugin -flto-partition=none line 16 arg4 == 4
FAIL: gcc.dg/guality/pr68860-1.c -O2 -flto -fno-use-linker-plugin -flto-partition=none line 16 arg5 == 5
FAIL: gcc.dg/guality/pr68860-1.c -O2 -flto -fno-use-linker-plugin -flto-partition=none line 16 arg6 == 6
FAIL: gcc.dg/guality/pr68860-1.c -O2 -flto -fuse-linker-plugin -fno-fat-lto-objects line 14 arg1 == 1
FAIL: gcc.dg/guality/pr68860-1.c -O2 -flto -fuse-linker-plugin -fno-fat-lto-objects line 14 arg2 == 2
FAIL: gcc.dg/guality/pr68860-1.c -O2 -flto -fuse-linker-plugin -fno-fat-lto-objects line 14 arg3 == 3
FAIL: gcc.dg/guality/pr68860-1.c -O2 -flto -fuse-linker-plugin -fno-fat-lto-objects line 14 arg4 == 4
FAIL: gcc.dg/guality/pr68860-1.c -O2 -flto -fuse-linker-plugin -fno-fat-lto-objects line 14 arg5 == 5
FAIL: gcc.dg/guality/pr68860-1.c -O2 -flto -fuse-linker-plugin -fno-fat-lto-objects line 14 arg6 == 6
FAIL: gcc.dg/guality/pr68860-1.c -O2 -flto -fuse-linker-plugin -fno-fat-lto-objects line 16 arg1 == 1
FAIL: gcc.dg/guality/pr68860-1.c -O2 -flto -fuse-linker-plugin -fno-fat-lto-objects line 16 arg2 == 2
FAIL: gcc.dg/guality/pr68860-1.c -O2 -flto -fuse-linker-plugin -fno-fat-lto-objects line 16 arg3 == 3
FAIL: gcc.dg/guality/pr68860-1.c -O2 -flto -fuse-linker-plugin -fno-fat-lto-objects line 16 arg4 == 4
FAIL: gcc.dg/guality/pr68860-1.c -O2 -flto -fuse-linker-plugin -fno-fat-lto-objects line 16 arg5 == 5
FAIL: gcc.dg/guality/pr68860-1.c -O2 -flto -fuse-linker-plugin -fno-fat-lto-objects line 16 arg6 == 6
FAIL: gcc.dg/guality/sra-1.c -O1 line 43 a.j == 14
FAIL: gcc.dg/guality/sra-1.c -O2 line 43 a.j == 14
FAIL: gcc.dg/guality/sra-1.c -O2 -flto -fno-use-linker-plugin -flto-partition=none line 43 a.j == 14
FAIL: gcc.dg/guality/sra-1.c -O2 -flto -fuse-linker-plugin -fno-fat-lto-objects line 43 a.j == 14
FAIL: gcc.dg/guality/sra-1.c -O3 -g line 43 a.j == 14
FAIL: gcc.dg/guality/sra-1.c -Os line 43 a.j == 14
FAIL: gcc.dg/guality/vla-1.c -O0 line 17 sizeof (a) == 6
FAIL: gcc.dg/guality/vla-1.c -O0 line 24 sizeof (a) == 17 * sizeof (short)
FAIL: gcc.dg/guality/vla-1.c -O1 line 17 sizeof (a) == 6
FAIL: gcc.dg/guality/vla-1.c -O1 line 24 sizeof (a) == 17 * sizeof (short)
FAIL: gcc.dg/guality/vla-1.c -O2 line 17 sizeof (a) == 6
FAIL: gcc.dg/guality/vla-1.c -O2 line 24 sizeof (a) == 17 * sizeof (short)
FAIL: gcc.dg/guality/vla-1.c -O2 -flto -fno-use-linker-plugin -flto-partition=none line 17 sizeof (a) == 6
FAIL: gcc.dg/guality/vla-1.c -O2 -flto -fno-use-linker-plugin -flto-partition=none line 24 sizeof (a) == 17 * sizeof (short)
FAIL: gcc.dg/guality/vla-1.c -O2 -flto -fuse-linker-plugin -fno-fat-lto-objects line 17 sizeof (a) == 6
FAIL: gcc.dg/guality/vla-1.c -O2 -flto -fuse-linker-plugin -fno-fat-lto-objects line 24 sizeof (a) == 17 * sizeof (short)
FAIL: gcc.dg/guality/vla-1.c -O3 -g line 17 sizeof (a) == 6
FAIL: gcc.dg/guality/vla-1.c -O3 -g line 24 sizeof (a) == 17 * sizeof (short)
FAIL: gcc.dg/guality/vla-1.c -Os line 17 sizeof (a) == 6
FAIL: gcc.dg/guality/vla-1.c -Os line 24 sizeof (a) == 17 * sizeof (short)
FAIL: gcc.dg/guality/vla-2.c -O0 line 16 sizeof (a) == 5 * sizeof (int)
FAIL: gcc.dg/guality/vla-2.c -O0 line 25 sizeof (a) == 6 * sizeof (int)
FAIL: gcc.dg/guality/vla-2.c -O1 line 16 sizeof (a) == 5 * sizeof (int)
FAIL: gcc.dg/guality/vla-2.c -O1 line 25 sizeof (a) == 6 * sizeof (int)
FAIL: gcc.dg/guality/vla-2.c -O2 line 16 sizeof (a) == 5 * sizeof (int)
FAIL: gcc.dg/guality/vla-2.c -O2 line 25 sizeof (a) == 6 * sizeof (int)
FAIL: gcc.dg/guality/vla-2.c -O2 -flto -fno-use-linker-plugin -flto-partition=none line 16 sizeof (a) == 5 * sizeof (int)
FAIL: gcc.dg/guality/vla-2.c -O2 -flto -fno-use-linker-plugin -flto-partition=none line 25 sizeof (a) == 6 * sizeof (int)
FAIL: gcc.dg/guality/vla-2.c -O2 -flto -fuse-linker-plugin -fno-fat-lto-objects line 16 sizeof (a) == 5 * sizeof (int)
FAIL: gcc.dg/guality/vla-2.c -O2 -flto -fuse-linker-plugin -fno-fat-lto-objects line 25 sizeof (a) == 6 * sizeof (int)
FAIL: gcc.dg/guality/vla-2.c -O3 -g line 16 sizeof (a) == 5 * sizeof (int)
FAIL: gcc.dg/guality/vla-2.c -O3 -g line 25 sizeof (a) == 6 * sizeof (int)
FAIL: gcc.dg/guality/vla-2.c -Os line 16 sizeof (a) == 5 * sizeof (int)
FAIL: gcc.dg/guality/vla-2.c -Os line 25 sizeof (a) == 6 * sizeof (int)
FAIL: gcc.dg/ipa/iinline-attr.c scan-ipa-dump inline "hooray[^\\\\n]*inline copy in test"
FAIL: gcc.dg/simulate-thread/atomic-other-short.c -O0 -g thread simulation test
FAIL: gcc.dg/simulate-thread/atomic-other-short.c -O2 -g thread simulation test
FAIL: gcc.dg/simulate-thread/atomic-other-short.c -O3 -g thread simulation test
FAIL: gcc.dg/tree-ssa/ivopts-lt-2.c scan-tree-dump-times ivopts "PHI <p_" 1
FAIL: gcc.dg/tree-ssa/ivopts-lt-2.c scan-tree-dump-times ivopts "PHI" 1
FAIL: gcc.dg/tree-ssa/ivopts-lt-2.c scan-tree-dump-times ivopts "p_[0-9]* <" 1
FAIL: gcc.dg/tree-ssa/pr15826.c scan-tree-dump-times optimized " & | goto " 0
XPASS: gcc.dg/tree-ssa/ssa-dom-cse-2.c scan-tree-dump optimized "return 28;"
FAIL: gcc.dg/vect/costmodel/ppc/costmodel-vect-33.c scan-tree-dump-times vect "vectorization not profitable" 1
=== gcc Summary ===
# of expected passes 101663
# of unexpected failures 240
# of unexpected successes 21
# of expected failures 323
# of unsupported tests 2020
/home/gccbuild/build/nightly/build-gcc-trunk/gcc/xgcc version 7.0.0 20160425 (experimental) [trunk revision 235406] (GCC)
=== gfortran tests ===
Running target unix
FAIL: gfortran.dg/ieee/large_2.f90 -O0 execution test
FAIL: gfortran.dg/ieee/large_2.f90 -O1 execution test
FAIL: gfortran.dg/ieee/large_2.f90 -O2 execution test
FAIL: gfortran.dg/ieee/large_2.f90 -O3 -fomit-frame-pointer -funroll-loops -fpeel-loops -ftracer -finline-functions execution test
FAIL: gfortran.dg/ieee/large_2.f90 -O3 -g execution test
FAIL: gfortran.dg/ieee/large_2.f90 -Os execution test
=== gfortran Summary ===
# of expected passes 41994
# of unexpected failures 6
# of expected failures 80
# of unsupported tests 82
/home/gccbuild/build/nightly/build-gcc-trunk/gcc/testsuite/gfortran/../../gfortran version 7.0.0 20160425 (experimental) [trunk revision 235406] (GCC)
=== go tests ===
Running target unix
FAIL: go.test/test/ken/cplx2.go execution, -O2 -g
=== go Summary ===
# of expected passes 7250
# of unexpected failures 1
# of expected failures 1
# of untested testcases 7
# of unsupported tests 3
/home/gccbuild/build/nightly/build-gcc-trunk/gcc/testsuite/go/../../gccgo version 7.0.0 20160425 (experimental) [trunk revision 235406] (GCC)
=== obj-c++ tests ===
Running target unix
=== obj-c++ Summary ===
# of expected passes 1446
# of expected failures 10
# of unsupported tests 77
/home/gccbuild/build/nightly/build-gcc-trunk/gcc/testsuite/obj-c++/../../xg++ version 7.0.0 20160425 (experimental) [trunk revision 235406] (GCC)
=== objc tests ===
Running target unix
=== objc Summary ===
# of expected passes 2789
# of unsupported tests 68
/home/gccbuild/build/nightly/build-gcc-trunk/gcc/xgcc version 7.0.0 20160425 (experimental) [trunk revision 235406] (GCC)
=== boehm-gc tests ===
Running target unix
FAIL: boehm-gc.c/gctest.c -O2 execution test
=== boehm-gc Summary ===
# of expected passes 11
# of unexpected failures 1
# of unsupported tests 1
=== libatomic tests ===
Running target unix
=== libatomic Summary ===
# of expected passes 54
=== libffi tests ===
Running target unix
=== libffi Summary ===
# of expected passes 1914
# of unsupported tests 30
=== libgo tests ===
Running target unix
=== libgo Summary ===
# of expected passes 134
/home/gccbuild/build/nightly/build-gcc-trunk/./gcc/gccgo version 7.0.0 20160425 (experimental) [trunk revision 235406] (GCC)
=== libgomp tests ===
Running target unix
=== libgomp Summary ===
# of expected passes 4912
# of unsupported tests 320
=== libitm tests ===
Running target unix
=== libitm Summary ===
# of expected passes 42
# of expected failures 3
# of unsupported tests 1
=== libjava tests ===
Running target unix
=== libjava Summary ===
# of expected passes 2582
# of expected failures 4
=== libstdc++ tests ===
Running target unix
=== libstdc++ Summary ===
# of expected passes 10876
# of expected failures 67
# of unsupported tests 380
Compiler version: 7.0.0 20160425 (experimental) [trunk revision 235406] (GCC)
Platform: powerpc64le-unknown-linux-gnu
configure flags: --prefix=/opt/gcc-nightly/trunk --with-as=/usr/bin/as --with-ld=/usr/bin/ld --enable-languages=c,c++,fortran,objc,obj-c++,java,go --with-cpu=power8 --enable-lto --enable-decimal-float --with-long-double-128
fail XPASS: gcc.test-framework/dg-bogus-exp-XF.c (test for excess errors)
fail FAIL: gcc.test-framework/dg-do-assemble-exp-P.c (test for excess errors) (PRMS 42)
fail FAIL: gcc.test-framework/dg-do-compile-exp-P.c (test for excess errors) (PRMS 42)
fail FAIL: gcc.test-framework/dg-do-link-exp-P.c (test for excess errors) (PRMS 42)
fail FAIL: gcc.test-framework/dg-do-run-exp-P.c (test for excess errors) (PRMS 42)
fail FAIL: gcc.test-framework/dg-dot-run-exp-P.c (test for excess errors) (PRMS 42)
fail FAIL: gcc.test-framework/dg-dox-run-exp-XF.c (test for excess errors) (PRMS 42)
fail FAIL: gcc.test-framework/dg-output-exp-P.c (test for excess errors) (PRMS 42)
fail FAIL: gcc.test-framework/dg-output-exp-XF.c (test for excess errors) (PRMS 42)
fail FAIL: gcc.test-framework/dg-warning-exp-P.c warning test (test for warnings, line 9) (PRMS 42)
=== Test Framework Summary ===
# of expected passes 2524
# of unexpected failures 10
| https://gcc.gnu.org/legacy-ml/gcc-testresults/2016-04/msg02386.html |
IJERPH | Free Full-Text | Insights into Asparaginase from Endophytic Fungus Lasiodiplodia theobromae: Purification, Characterization and Antileukemic Activity
Endobiotic fungi are considered as a reservoir of numerous active metabolites. Asparaginase is used as an antileukemic drug specially to treat acute lymphoblastic leukaemia. The presented study aims to optimize the media conditions, purify, characterize, and test the antileukemic activity of the asparaginase induced from Lasiodiplodia theobromae. The culture medium was optimized using an experiment designed by The Taguchi model with an activity ranging from 10 to 175 IU/mL. Asparaginase was induced with an activity of 315 IU/mL. Asparaginase was purified with a specific activity of 468.03 U/mg and total activity of 84.4 IU/mL. The purified asparaginase showed an approximate size of 70 kDa. The purified asparaginase showed an optimum temperature of 37 °C and an optimum pH of 6. SDS reduced the activity of asparaginase to 0.65 U/mL while the used ionic surfactants enhanced the enzyme activity up to 151.92 IU/mL. The purified asparaginase showed a Km of 9.37 µM and Vmax of 127.00 µM/mL/min. The purified asparaginase showed an IC50 of 35.2 ± 0.7 IU/mL with leukemic M-NFS-60 cell lines and CC50 of 79.4 ± 1.9 IU/mL with the normal WI-38 cell line. The presented study suggests the use of endophytic fungi as a sustainable source for metabolites such as asparaginase, provides an opportunity to develop a facile, eco-friendly, cost-effective, and rapid synthesis of antileukemic drugs, which have the potential to be used as alternative and reliable sources for potent anticancer agents.
Background:
Insights into Asparaginase from Endophytic Fungus Lasiodiplodia theobromae : Purification, Characterization and Antileukemic Activity
by
Hani A. Moubasher 1 ,
Bassem A. Balbool 2,* ,
Yosra A. Helmy 3 ,
Amnah Mohammed Alsuhaibani 4 ,
Ahmed A. Atta 5 ,
Donia H. Sheir 6 and
Ahmed M. Abdel-Azeem 7,*
Botany and Microbiology Department, Faculty of Science, Cairo University, Giza 12613, Egypt
Biotechnology Department, Faculty of Biotechnology, October University for Modern Sciences and Arts, 6th October 12451, Egypt
Department of Animal Hygiene, Zoonoses and Animal Ethology, Faculty of Veterinary Medicine, Suez Canal University, Ismailia 41522, Egypt
Department of Physics, College of Science, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia
6
Chemistry of Natural and Microbial Products Department, National Research Center, Giza 12622, Egypt
7
Botany and Microbiology Department, Faculty of Science, Suez Canal University, Ismailia 41522, Egypt
*
Authors to whom correspondence should be addressed.
Int. J. Environ. Res. Public Health 2022 , 19 (2), 680; https://doi.org/10.3390/ijerph19020680
Received: 10 November 2021 / Revised: 19 December 2021 / Accepted: 24 December 2021 / Published: 7 January 2022
(This article belongs to the Special Issue New Advances in Environmental Microbiology )
Versions Notes
Abstract
:
Endobiotic fungi are considered as a reservoir of numerous active metabolites. Asparaginase is used as an antileukemic drug specially to treat acute lymphoblastic leukaemia. The presented study aims to optimize the media conditions, purify, characterize, and test the antileukemic activity of the asparaginase induced from
Lasiodiplodia theobromae
. The culture medium was optimized using an experiment designed by The Taguchi model with an activity ranging from 10 to 175 IU/mL. Asparaginase was induced with an activity of 315 IU/mL. Asparaginase was purified with a specific activity of 468.03 U/mg and total activity of 84.4 IU/mL. The purified asparaginase showed an approximate size of 70 kDa. The purified asparaginase showed an optimum temperature of 37 °C and an optimum pH of 6. SDS reduced the activity of asparaginase to 0.65 U/mL while the used ionic surfactants enhanced the enzyme activity up to 151.92 IU/mL. The purified asparaginase showed a K
m
of 9.37 µM and V
max
of 127.00 µM/mL/min. The purified asparaginase showed an IC
50
of 35.2 ± 0.7 IU/mL with leukemic M-NFS-60 cell lines and CC
50
of 79.4 ± 1.9 IU/mL with the normal WI-38 cell line. The presented study suggests the use of endophytic fungi as a sustainable source for metabolites such as asparaginase, provides an opportunity to develop a facile, eco-friendly, cost-effective, and rapid synthesis of antileukemic drugs, which have the potential to be used as alternative and reliable sources for potent anticancer agents.
Keywords:
metabolites 1
;
endophytic fungi
;
asparaginase
;
induction
;
purification
;
antileukemia
1. Introduction
Endobiotic (endophytic) fungi are microfungi that live inside the host plant tissue intercellularly and/or intracellularly without any apparent pathological symptoms [ 1 ]. To be able to sustain steady symbiosis, endophytes secrete chemical substances to help the plants to acclimatize better to the harsh environment [ 2 ]. As a treasure mine of bioactive metabolites, endophytic fungi are a sustainable source of various natural products viz: quinones, saponins, alkaloids, steroids, phenolic acids, terpenoids, and tannins that exhibit antimicrobial and anticancer properties [ 3 ].
Asparaginase (EC 3.5.1.1) is classified among amidohydrolases, it hydrolyzes the asparagine into aspartic acid (aspartate) and ammonium (NH 4 + ) [ 4 ]. Clementi [ 5 ] reported asparaginase for the first time in the serum of guinea pig. Furthermore, Mashburn [ 6 ] extracted asparaginase from E.coli and reported its antileukemic properties for the first time.
Clinical data published over the last two decades suggests that asparaginase is a vital element in the treatment of acute lymphoblastic leukaemia (ALL) [
6
,
7
]. Both normal and leukemic cells require the amino acid asparagine for the proliferation process. Normal cells can synthesize asparagine for their growth with the help of asparagine synthetase (AS, EC 6.3.5.4). While, neoplastic cells lack asparagine synthetase [
8
], thus they are dependent on the serum asparagine to grow and proliferate. The administration of asparaginase to ALL patients depletes the serum asparagine due to its hydrolytic activity, which will lead to inhibition of neoplastic cells proliferation process and in return it will die off and arrest in G-1 phase [
9
].
The extracellular production of asparaginases is mainly dependent on the optimization of cultural conditions, to produce it in a bulk amount with a cheap method. The production is mainly based on optimizing the carbon and nitrogen sources, other parameters as; pH, temperature and inoculum size [ 10 ].
Different methods were reported to produce asparaginase from microorganisms including solid state fermentation and submerged fermentation—induction and purification methods vary between microorganisms [ 7 , 8 , 9 , 10 ]. Several trials were designed by scientists to purify asparaginase with a high purity and yield in order to use asparaginase as a drug [ 11 , 12 , 13 , 14 ]. The trials included the precipitation of total protein using ammonium sulphate followed by ion exchange column chromatography [ 15 ].Other reports used ammonium sulphate followed by size exclusion gel filtration chromatography [ 16 , 17 ]. Other researchers used the affinity columns for direct purification of asparaginase [ 18 ].
Purified asparaginase from E. coli and Erwinia chrysanthemi was used clinically to treat the acute lymphoblastic leukemia, but it showed allergic side effects which led to death [ 19 , 20 , 21 ]. The harsh side effects associated with the bacterial asparaginase was related to the prokaryotic origin of the purified enzyme [ 19 ]. Hence, researchers started to target fungi as a safe alternative eukaryotic source to produce asparaginase to decrease the associated allergic reactions [ 22 ]. Asparaginases were recorded from several fungal species such as Mucor hiemalis , Aspergillus niger , A. flavus , A. nidulans , A. terreus [ 23 , 24 ].
Due to the ability of endophytes to produce several enzymes and other natural products with high activity, researchers targeted endophytic fungi as a source of asparaginase. Balbool et al. screened the ability of 25 endophytic fungal isolates to produce asparaginase, 7 isolates showed positive asparaginase results. Lasiodiplodia theobromae recorded the highest asparaginase activity out of the tested isolates [ 24 ].
The present study is focusing on the production of asparaginase with maximum activity by optimizing the medium condition and induction of asparaginase from
Lasidiplodia theobromae
, followed by the purification of asparaginase and the characterization of the purified asparaginase. Furthermore, the antileukemic activity of the purified asparaginase was tested against the mouse myelogenous leukemia carcinoma cells (M-NFS-60).
2. Materials and Methods
2.1. Microorganism
Lasiodiplodia theobromae was obtained from the Suez Canal University Fungarium, Ismailia, Egypt (SCUF-TP2016). It was selected based on a continuing work from previous studies carried out by Balbool [ 24 ].
2.2. Optimization of Media Conditions and Asparaginase Induction
To optimize the culture conditions to produce asparaginase with maximum activity, a Taguchi statistical model was used [
25
]. The experimental design created several conditions as orthogonal arrays to ensure an efficient and reproducible experiment with minimal errors. During the presented experimental design three variables were studied under temperature of 28 °C; asparagine (nitrogen source), glucose (carbon source), and pH. Each of the three variables is represented by three variation levels. The experiment size was nine trials (layout L9) with a degree of freedom 8 [
26
], (for more details please check
supplementary materials
).
To produce asparaginase with maximum activity; 5 mm disks of
L. theobromae
were inoculated in 10 flasks containing 100 mL Malt Extract Agar media (MEA) and incubated for 7 days at 28 °C. One liter of 1% asparagine (substrate) was prepared in bi distilled water and distributed into 10 flasks (100 mL), and then autoclaved at 121 °C for 15 min. Grown fungal mats (average 0.2 g for each flask) were transferred into each flask and incubated at 28 °C for 48 h.
Enzyme activity was estimated with directed Nesslerization according to Wriston [ 27 ] using asparagine as substrate. The enzyme activity was expressed as international unit (IU); IU is defined as the amount of enzyme needed to liberate one micromole of ammonium per minute at pH = 7.00 and 37 °C. The activity was estimated and compared to the results out of Taguchi design.
2.3. Purification of Asparaginase
2.3.1. Total Protein Precipitation
The extracellular protein precipitation was carried out by cold acetone precipitation method [ 28 ]. Acetone was kept at −80 °C prior to precipitation, 2× cold acetone was added to the culture filtrate and incubated at −20 °C for 2 h. The samples were centrifuged at 13,000 rpm for 15 min at 4 °C. The supernatant was discarded, and the pellet obtained were dissolved in a suitable volume of 50 mM Tris buffer (pH 7) and stored at −80 °C till further use.
2.3.2. Ion Exchange Chromatography
The collected precipitate of asparaginase was further fractionated by prepacked ion exchange column (Hi-trap-Q-FF, 5 mL, GE). The column was equilibrated by 5× of column volume of Tris buffer (till reaching UV baseline stability) (50 mM, pH 7). The enzyme was eluted by gradient concentrations of NaCl (0–1 M) with a rate of 1.5 mL/min. The activity was estimated. The fractions that showed high enzymatic activity was collected together, concentrated using chilled acetone and the enzyme activity and total protein were estimated. The collected fractions were further purified using gel filtration chromatography using Sephadex G-100.
2.3.3. Size Exclusion Gel-Filtration Chromatography
The collected precipitate of asparaginase from the ion exchange column was further fractionated by gel- filtration Sephadex G-100 column. After 2 days swelling of Sephadex G100 particles, the resin was poured to the column (2 × 40 cm), and the column was equilibrated by Tris buffer (50 mM, pH 7), with a flow rate of 12 mL/h. The enzyme was loaded to the top of the column, eluted by the same buffer, and the activity, protein contents, and molecular homogeneity of the eluted fractions were assessed. The most active fractions collected together to be checked on SDS–PAGE.
2.4. Estimation of Total Protein
Total protein concentration was estimated by measuring the absorbance at 280 nm. First, the standard curve of Bovine serum albumin (BSA) was created. Different dilutions of BSA ranging from 50 to 450 µg/mL were prepared by adding the adequate volume of BSA stock solution (1 mg/mL) and double distilled water in test tubes. The absorbance versus concentration graph was used to estimate the protein content of the unknown protein sample ( Supplementary Materials ).
Estimation of Enzyme Molecular Weight Using SDS PAGE
The homogeneity of the bands and the molecular weight of the purified asparaginase were estimated using SDS-PAGE according to the instructions of Laemmli [ 29 ], using 12% separating gel (6.8) and 5% stacking gel (pH 8.8). The molecular weight of the appeared protein bands was calculated from the inference of authentic protein marker (BLUEstain™ 2 Protein ladder, 5-245 kDa). The marker consists of approximately 0.1–0.4 mg/mL of each protein in the buffer (20 mM Tris- phosphate, pH 7.5 at 25 °C), 2% SDS, 0.2 mM Dithiothreitol, 3.6 M Urea, and 15% ( v / v ) Glycerol). The protein bands were stained with Coomassie brilliant blue R-250.
2.5. Enzyme Characterization
2.5.1. Determination of the Optimum Reaction Temperature and Stability
To study the effect of temperature on the purified asparaginase, 0.25 mL of the purified enzyme was pre-incubated with 0.75 mL of 50 mM Tris buffer (pH 7) at temperature range from 20 °C to 70 °C. Followed with assaying the asparaginase activity under the standard reaction conditions [ 30 , 31 ]. The temperature stability was studied by mixing 1.5 mL of purified enzyme and 4.5 mL buffer (pH 7) together and incubated at 37 °C. Removed each time at different time intervals (0 min, 30 min, 1 h, 2 h, 4 h, 5 h and 24 h) was 1 mL of the mixture, and the enzyme activity was estimated according to Mashburn and Wriston [ 6 ].
2.5.2. Effect of pH on Asparaginase Activity
The effect of pH on asparaginase activity was studied over a pH range of 3 to 10 using different buffers; acetate buffer (pH 3, 4 and 5), Phosphate buffer (pH 6–6.5), and Tris base buffer (pH 7–10) [ 11 ]. The assay was performed by pre-incubating 0.25 mL of purified enzyme with 0.75 mL of each of the buffers at 37 °C for 30 min. The enzyme activity was estimated according to Mashburn and Wriston [ 6 ].
2.5.3. Effect of Inhibitors, Activators on Asparaginase Activity
The influence of inhibitors and activators (2 mM) was analyzed using ethylenediaminetetraacetate (EDTA), N-ethylemaleimide (NEM), phenylmethylsulphonylfluoride (PMSF), Triton-X 100, Tween-80, sodium dodecyl sulphate (SDS), and β-mercaptoethanol (β-ME) [ 32 ]. A pre-incubation was conducted for 30 min after mixing 0.25 mL of the enzyme with 0.75 mL of the concerned inhibitor/activator. The activity was determined as previously mentioned.
2.5.4. Enzyme Kinetics
The kinetic parameters (K m and V max ) of the purified asparaginase were determined by linear regression from Lineweaver-Burk and Michaelis-Menten plots with different concentrations of asparagine (substrate) (0 mM–20 mM) [ 11 ].
2.6. Testing the Antileukemic Activity
Cytotoxicity Evaluation Using the Viability Assay
Cell line propagation
WI-38 cells (human lung fibroblast normal cells) were propagated in Dulbecco’s modified Eagle’s medium (DMEM) supplemented with 10% heat-inactivated fetal bovine serum, 50 µg/mL gentamycin, 1% L-glutamine and 4-(2-hydroxyethyl)-1-piperazinethanesulfonic acid (HEPES) buffer. All cells were maintained at 37 °C in humidified atmosphere with 5% CO 2 and were sub-cultured two times a week [ 33 ].
M-NFS-60 (mouse myelogenous leukemia carcinoma cells) were propagated in RPMI-1640, supplemented with 10% heat-inactivated fetal bovine serum, 1% L-glutamine, HEPES buffer, and 50 µg/mL gentamycin. All cells were maintained at 37 °C in a humidified atmosphere with 5% CO 2 and were sub-cultured two times a week [ 34 ].
Cytotoxicity evaluation
Cytotoxicity of the purified asparaginase was tested on mouse leukemia cell line: M-NFS-60 (mouse myelogenous leukemia carcinoma cells) to determine the Median Minimal Inhibitory Concentration (MIC
50
) and the mammalian cell line: WI-38 cells (human lung fibroblast normal cells) to verify the Median Minimal Cytotoxic Concentration (MCC
50
), according to methods described by [
35
]. Cells were seeded in 96-well plate at a cell concentration of 1 × 10
4
cells per well in 100 µL of growth medium. Fresh medium containing serial two-fold dilutions of the purified asparaginase were prepared. After 24 h of seeding, the media containing serial asparaginase were added to confluent monolayer cells dispended into 96-well, flat bottomed micro-titer plates (Falcon, NJ, USA) using multichannel pipette. Three wells were used for each concentration of the test sample (experiments were carried in triplicates), control cells were incubated without test sample. The micro-titer plates were incubated at 37 °C in humidified incubator with 5% CO
2
for a period of 24 h. After the end of incubation period, media were aspirated, and 1% crystal violet solution was added to each well for 30 min. The stain was removed, and the plates were rinsed using tap water until all excess stain is removed. Glacial acetic acid (30%) was then added to all wells and mixed thoroughly, and then the absorbance of the plates were measured after gently shaken using microplate reader (Tecan Trading AG, Switzerland.) at a wavelength of 490 nm. All the results were corrected for background absorbance detected in wells without adding stain. Treated samples were compared with the cell control in the absence of the purified asparaginase.
Cell cytotoxicity effect of the purified asparaginase was calculated to determine the number of viable cells and the percentage of viability was calculated as.
Viability
percentage
ODc
×
100
where ODt is the mean optical density of the three wells treated with each concentration of asparaginase, ODc is the mean optical density of untreated cells.
The relation between the surviving cells and the asparaginase used concentrations was plotted to get the survival curve of each tumor cell line after treatment with the purified asparaginase. The cytotoxic concentration (MCC
50
), the concentration required to cause toxic effect in 50% of intact cells, was estimated from graphic plots of the dose response curve for each concentration, using prism software (San Diego, CA, USA).
2.7. Statistics
The data were presented in tables using the Microsoft excel 365, figures were created using the Prism ver. 8. All experiments were carried out in triplicates, all data were reported with mean ± SEM.
3. Results
3.1. Optimization of Media Conditions
Among the nine different experiments that were performed according to Taguchi model, two of them; experiment 9 and 8 showed a high asparaginase activity with activities of 175 IU/mL, 135 IU/mL respectively, other experiments showed activities ranging from 75–10 IU/mL ( Figure 1 ). However, on inducing asparaginase the enzyme activity was estimated to be 315 IU/mL.
3.2. Purification of Asparaginase
The purification of asparaginase from
L. theobromae
was carried out with a combination of some steps, starting with total protein precipitation using chilled acetone, ion-exchange chromatography on Q-FF column, and gel filtration Sephadex G-100. After precipitation of the induced enzyme with chilled acetone, asparaginase showed a specific activity of 36.71 IU/mg with a total activity of 250 IU/mL in a 6.81 mg/mL total protein (
Table 1
). Concentrated enzyme was loaded into pre-equilibrated Q-FF ion exchange column and eluted using gradient concentrations of NaCl (0–1 M). All fractions eluted only with 0.3 M NaCl showed asparaginase activity (
Figure 2
). All fractions showed high asparaginase activity were collected together and concentrated, the asparaginase activity was estimated to be 138.91 IU/mL and the specific activity was 105.88 U/mg. For further purification, concentrated fractions were loaded into a pre-equilibrated Sephadex G-100 column. All positive fractions were collected together and concentrated. Collected fraction showed a total activity of 84.4 IU/mL, a specific activity of 468.03 U/mg compared to the induced enzyme specific activity (
Table 1
) (for more details please check
supplementary materials
).
Estimation of Enzyme Molecular Weight
The purified asparaginase showed a band around 70 kDa compared to the reference protein ladder ( Figure 2 ).
3.3. Enzyme Characterization
3.3.1. Effect of pH on Asparaginase Activity
According to the results presented in Figure 3 a, the optimum pH for the purified asparaginase was 6, while at pH 10 the enzyme lost its activity, starting from pH 3 the enzyme retained 51.22% of its activity, while at pH 4, 5 retained 72.22%, 77.43% respectively of its activity, the enzyme activity started to decrease simultaneously with increasing the pH value.
3.3.2. Effect of Temperature on Asparaginase Activity
The purified asparaginase showed an activity over a wide range of temperatures (20–60 °C). The optimum temperature was 37 °C with an activity of 84.41 IU/mL, followed by 40 °C with 82.52 IU/mL ( Figure 3 b).
The purified asparaginase showed complete stability at 37 °C for 1, 2 and 4 h, while the activity decreased to 43.2 IU/mL after 5 h. The enzyme lost its activity totally after 24 h ( Figure 3 c).
3.3.3. Effect of Inhibitors and Activators on Asparaginase Activity
The effect of different inhibitors and activators was studied on the purified asparaginase, where SDS showed a reduction in the enzyme activity to 0.65 IU/mL (10.35% relative activity), while EDTA, NEM, and PMSF showed no effect on asparaginase activity, in contrast β-mercaptoethanol, Tween 80, and Triton-x 100 enhanced the enzyme specific activity to 130%, 143.48% and 151.92% respectively regarding the control ( Figure 3 d).
3.3.4. Determination of Enzyme Kinetics
According to results in Figure 3 e 1, 2, Michaelis constant K m and maximum velocity V max of the purified asparaginase from L. theobromae were 9.370 µM and 127.00 IU min −1 respectively.
3.4. Estimation of Asparaginase Antileukemic Activity
3.4.1. Evaluation of Cytotoxicity against M-NFS-60 Cell Line
Different concentrations of the purified asparaginase starting with 84.00 IU/mL to 2.62 IU/mL were tested against mouse myelogenous leukemia carcinoma cells to estimate the MIC 50 value, results revealed that the MIC 50 was 35.2 ± 0.7 IU/mL ( Figure 4 ).
3.4.2. Evaluation of Cytotoxicity against WI-38 Cell Line
Different concentrations of the purified asparaginase starting with 84.00 IU/mL to 2.62 IU/mL were tested against WI-38 cells (human lung fibroblast normal cells) to estimate MCC 50 value, results revealed that the MCC 50 was 79.4 ± 1.9 IU/mL ( Figure 5 ).
4. Discussion
Zhao et al. [ 36 ] and Jia et al. [ 37 ] reported that the activity of the bioactive metabolites produced by endophytes is considered similar or higher than those produced by host plants. Schulz et al. [ 38 ] reported that plant defense mechanisms and fungal virulence factors develop a balance mechanism by secreting different novel bioactive metabolites.
Lasiodiplodia theobromae was reported to produce several bioactive compounds used as anticancer, antifungal, antioxidant, anti-inflammatory such as: Lasiodiplodin [ 39 ], amylase [ 40 ], Paclitaxel [ 41 ], Felix [ 42 ] reported L. theobromae strain with the ability to produce: (3 S ,4 S )-4-acetyl-3-methyl-2-dihydrofuranone, (2 R /2 S ,3 S ,4 S )-3-epibotryodiplodin, and jasmonic acid.
Our results showed that L. theobromae produces asparaginase extracellularly with a high enzymatic activity, while, Narayana et al. [ 43 ] reported that most of the asparaginase with microbial sources is intracellular. Extracellular asparaginase interacts minimally with the cellular constituents and is easier to extract; hence, the induction of extracellular asparaginases with high activity would be more advantageous.
To produce asparaginase with maximum activity, nine experiments were designed using Taguchi model. Taguchi model results showed a variation of asparaginase activity from 175 to 10 IU/mL, the variation of the results obtained were compatible with Ali et al. [ 34 ] who designed a model of 19 experiments for the optimization of asparaginase from A. sydowii and F. oxysporum with asparaginase activity ranging from 37-146 IU/mL and 33 to 143 IU/mL respectively. Ashok et al. [ 41 ] used Taguchi design to simulate nine experiments with asparaginase activities ranging from 3.94 to 20.57 IU/mL from Trichosporon asahii.
Another experiment designed for the induction of asparaginase with a maximum activity by incubating a five-days-old culture mat of
L. theobromae
with asparagine for two days and the asparaginase activity was estimated as 315 IU/mL. The incubation of the grown
L. theobromae
mat with asparagine solely as a substrate for asparaginase enhanced the selective release of asparaginase with a maximum activity with other extracellular enzymes, Nossal et al. [
44
] designed a similar experiment for the selective release of some degrading enzymes viz: alkaline phosphatase, cyclic phosphodiesterase, 5’-nucleotidase, acid phosphatase from E.coli by osmotic shock using different salts concentrations.
Asparaginase from
L. theobromae
was purified with a total activity of 84.40 IU/mL, specific activity of 468.03 IU/mg, and 13.68 purification folds. The estimated activity is considered low compared to Thakur et al. [
11
] who reported an activity of 222.18 IU/mL and a specific activity of 69.43 IU/mg, Mohamed et al. [
45
] reported an activity of 127 IU/mL and a specific activity of 846.IU/mg, and it was higher than the activity reported by Abbas [
46
] who reported an activity of 13.1 IU/mL and 0.4 IU/mg specific activity. The variation of activities would be related to the growth condition of each organism, the variation of extraction protocols.
To estimate the molecular weight of the purified asparaginase using SDS-PAGE, it was compared against known protein marker. SDS-PAGE showed a band of asparaginase by around 70 kDa. The presented result is similar to Huang [ 47 ] who reported a weight of 72 kDa and Hong [ 48 ] who reported an asparaginase of 71 kDa. Asparaginases showed a variation on the molecular weights where, Cedar and Schwartz [ 49 ] and Shifrin et al. [ 50 ] reported asparaginase from E. coli with 141 kDa, Scheetz et al. [ 51 ] reported asparaginase from Fusarium tricinctum with 161–170 kDa, Manna et al. [ 52 ] reported asparaginase from Pseudomonas stutzeri with 34 kDa and El-Bessouny [ 13 ] who recorded asparaginase from Pseudomonas aeruginosa at 160 kDa.
The purified asparaginase was characterized, where it showed a working pH range of 3–9, with an optimum pH of 6; Abbas [ 46 ] reported a working pH of 3–12 and an optimum pH of 10, on the other hand, Thakur [ 11 ] reported a working pH range of 3–10 and optimum pH of 7.
On testing the working temperature range, purified asparaginase showed activity over a temperature range of 20–60 °C with an optimum temperature of 37 °C which is in agreement with [ 11 , 45 , 53 ]. On the other hand, Gaffar and Shethna [ 54 ] reported an asparaginase isolated from Azotobacter vinelandii with optimum temperature of 48 °C and Mesas [ 55 ] reported an optimum temperature of 40 °C for asparaginase isolated from Corynebacterium glutamicum .
During the presented study some inhibitors and activators were studied against the purified asparaginase. SDS was the only reagent that showed reduction in the enzyme activity and retained 0.65% of the relative activity which was reported earlier by Thakur [ 11 ]. Which would be related to the SDS mode of action. Where it disturbs the structure of the protein which brings the folded protein structure into a linear model and coats the protein with uniform negative charges; leading to masking of the protein charges.
EDTA showed no effect on the purified enzyme which elucidated the fact that asparaginase is not an metalloenzyme, which is similar to data on
Candida utilits
by Sakamoto [
56
]. Regardless the fact of the non-metalloenzyme nature of the purified asparaginase some reports suggested that asparaginase is a metal activated enzyme where, El-Naggar et al. [
8
] reported that asparaginase from
Sterptomyces brollosae
showed an increase on activity in the presence of Mg
2+
, Mn
2+
and Co
2+
ions. Sonaimuthu [
57
] showed a metal activating characters with Mn
2+
with asparaginase purified from
Fusarium culmorum
.
Tween 80 and Triton X-100 enhanced the activity with a relative activity of 170% and 180%, β-mercaptoethanol enhanced the enzyme activity with a relative activity of 130% our result was in agreement with Raha et al. [
58
]. The native protein structure mainly stabilized by the formation of disulfide bond [
59
], β-mercaptoethanol is a strong reducing agent that inhibit the formation of disulfide bonds in cysteine residues [
60
]. L-asparaginase was activated by the addition of β-mercaptoethanol. Hamza and Engel [
61
] reported the presence of free sulphydryl groups in the enzymes, such as cysteine residues will make it unstable and will aggregate the enzymes and the addition of β-mercaptoethanol and other ionic surfactants
viz;
Tween 80 and Triton X-100 will enhance the enzymatic activity.
NEM and PMSF showed an insignificant effect on the enzyme activity; which may be due to the absence of cysteine or serine on the active site of the purified asparaginase, our results are compatible with Thakur [ 11 ].
The activity of the purified asparaginase was assayed against different concentrations of asparagine (0–20 mM) to determine the kinetic properties, the purified enzyme showed a very low K m of 9.37 µM and V max of 127.00 U min −1 . The recorded K m value considered lower than the recorded K m of Mucor hiemalis ; 4 mM [ 11 ], Penicillium ; 4 mM [ 62 ], such low K m value reflects the high affinity of the purified asparaginase towards asparagine as substrate.
The anti-leukemic effect of the purified asparaginase was studied against mouse myelogenous leukemia carcinoma cells to estimate the median minimal inhibitory concentration (MIC 50 ). Results revealed that the MIC 50 was 35.2 ± 0.7 U/mL which is lower than the MIC 50 of A. sydowii (50 U/mL) and F. oxysporum (62.5 U/mL) [ 31 ]. It is also considered higher than the MIC 50 of Phaseolus vulgaris (0.75 U/mg) [ 45 ]. The lower the MIC value, the lower the doses needed and the better the efficacy of the anticancer drug [ 63 ].
Tanfous et al. [ 64 ] related the antileukemic activity of asparaginase to its capability to hydrolyze asparagine in the serum, thus depleting serum asparagine; which is essential for the proliferation of leukemic cells. Several trials were carried out by scientists to discover asparaginase and test its role in the inhibition of leukemic cells [ 5 , 65 , 66 , 67 ]. Asparagine is produced by asparagine synthetase (ASNS), which is encoded by ASNS gene [ 68 ]. Gervasini and Vgace [ 69 ] hypothesized that ASNS genes in the malignant lymphoblasts cells have low expression or cannot regulate the expression of ASNS when exposed to asparaginase. Thus, we can hypothesize that the leukemic cells are more dependent on the extracellular sources of asparagine, thus the administration of asparaginase will selectively depletes serum asparagine leading to suppression of the growth of leukemic cells.
The presented results showed that the MIC
50
(35.2 ± 0.7 IU/mL) of the purified asparaginase was around double the MCC
50
(79.4 ± 1.9 IU/mL) where MCC
50
value represents half the cytotoxic concentration of the tested asparaginase on normal cells. Such ratio indicates that the tested asparaginase is considered safe where it requires double of the asparaginase concentration to reach the MCC
50
. With treating the leukemic cell line with the purified asparaginase, our results revealed that the carcinoma cell line reached cell death up to 83.05% with the highest concentration of the purified enzyme (84 IU/mL) which is equal to about double the MIC
50
; respectively, leukemic cells require a high concentration of asparagine to keep viable [
64
].
5. Conclusions
In conclusion, the presented results proved that endophytic mycobiota especially isolated from extreme environment is considered as a source of safe novel bioactive compounds. This study sheds the light on a new application of endophytic native taxa and it recommends the production of the extracellular induced endophytic asparaginase on a high scale to be used as a safe antileukemic drug and in food industries. Future studies must focus on the screening for bioactive compounds secreted by Egyptian endophytic mycobiota to find a safe alternative for the traditional pharmaceutical compounds or discovering a novel compound to be used in industrial, agricultural, and medical applications.
Supplementary Materials
The following are available online at https://www.mdpi.com/article/10.3390/ijerph19020680/s1 , Figure S1. Standard curve of different concentrations of BSA, Figure S2. Elution profile of asparaginase from L. theobromae from the Q-FF ion exchange column. The column was pre-equilibred with 50 mM Tris buffer (pH 7) and fractions were eluted with a gradient solution of NaCl (0-1M) prepared in same buffer, and Figure S3. Elution profile of asparaginase from L. theobromae from the gel-filtration column (Sephadex G-100). Fractions were eluted with 50 mM Tris buffer (pH 7). Table S1. The nine models generated by Taguchi design.
Author Contributions
Conceptualization, H.A.M., B.A.B. and A.M.A.-A.; methodology, H.A.M., D.H.S. and B.A.B.; software, B.A.B., Y.A.H., A.M.A., D.H.S. and A.A.A.; validation, H.A.M., B.A.B., Y.A.H., A.M.A., A.A.A., D.H.S. and A.M.A.-A.; formal analysis, H.A.M., B.A.B., Y.A.H., A.M.A., D.H.S. and A.M.A.-A.; investigation, H.A.M., B.A.B., D.H.S. and A.M.A.-A.; resources, A.A.A.; writing—original draft preparation, H.A.M., B.A.B. and A.M.A.-A.; writing—review and editing, H.A.M., B.A.B., Y.A.H., A.M.A., D.H.S., A.A.A. and A.M.A.-A.; funding acquisition, A.A.A. All authors have read and agreed to the published version of the manuscript.
Funding
This research received no external funding.
Institutional Review Board Statement
Not Applicable.
Informed Consent Statement
Not Applicable.
Data Availability Statement
Not Applicable
Acknowledgments
We appreciate and thank Taif University for the financial support for Taif University Re-searchers Supporting Project (TURSP-2020/22), Taif University, Taif, Saudi Arabia. We would like to present their deep appreciation to Abdel Ghaffar Abu El Saoud, Botany and Microbiology Department, Faculty of Science, Suez Canal University for his support and help during the data analysis of the results. Also, to the members of Saint Katherine Protectorate for their support during the samples collection in the early stages of the research work progress.
Conflicts of Interest
The authors have no conflicts of interest to declare. All co-authors have seen and agreed with the contents of the manuscript.
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Figure 1. Asparaginase activities of Taguchi design experiments.
Figure 2. Purified asparaginase from L. theobromae on SDS-PAGE. ( a ) protein ladder, ( b ) purified asparaginase.
Figure 2. Purified asparaginase from L. theobromae on SDS-PAGE. ( a ) protein ladder, ( b ) purified asparaginase.
Figure 3. ( a ) The effect of pH on the purified asparaginase from L. theobromae . ( b ) The effect of temperature on the purified asparaginase from L. theobromae . ( c ) Thermal stability of purified asparaginase from L. theobromae at 37 °C. ( d ) Effect of inhibitors and activators on purified asparaginase from L. theobromae . ( e ) Purified asparaginase kinetics. 1. Michaelis Menten plot for the purified asparaginase enzyme from L. theobromae . 2. The different activities value of purified asparaginase from L. theobromae with increasing the substrate concentrations.
Figure 3. ( a ) The effect of pH on the purified asparaginase from L. theobromae . ( b ) The effect of temperature on the purified asparaginase from L. theobromae . ( c ) Thermal stability of purified asparaginase from L. theobromae at 37 °C. ( d ) Effect of inhibitors and activators on purified asparaginase from L. theobromae . ( e ) Purified asparaginase kinetics. 1. Michaelis Menten plot for the purified asparaginase enzyme from L. theobromae . 2. The different activities value of purified asparaginase from L. theobromae with increasing the substrate concentrations.
Figure 4. Viability response of M-NFS-60 cell line against serial two-fold dilutions of purified asparaginase from L. theobromae .
Figure 4. Viability response of M-NFS-60 cell line against serial two-fold dilutions of purified asparaginase from L. theobromae .
Figure 5. Viability response of WI-38 cell line against serial two-fold dilutions of purified asparaginase from L. theobromae .
Figure 5. Viability response of WI-38 cell line against serial two-fold dilutions of purified asparaginase from L. theobromae .
Table 1. Summary of the steps involved in the purification of asparaginase from L. theobromae .
Table 1. Summary of the steps involved in the purification of asparaginase from L. theobromae .
Step Total Protein (mg) Activity * (IU/mL) Specific Activity (IUmg −1 ) Purification Fold Yield % Induced enzyme 9.21 315.00 34.20 1.00 100.00 Acetone 6.81 250.00 36.71 1.07 79.37 Q-FF (0.3M NaCl) 1.31 138.91 105.88 3.10 44.10 Sephadex G-100 0.18 84.40 468.03 13.68 26.79
* One unit of asparaginase (IU) is defined as the amount of enzyme that liberates 1 μmol of ammonia min −1 AT 37 °C.
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(PDF) Microstructure Representation and Reconstruction of Heterogeneous Materials Via Deep Belief Network for Computational Material Design
PDF | Integrated Computational Materials Engineering (ICME) aims to accelerate optimal design of complex material systems by integrating material... | Find, read and cite all the research you need on ResearchGate
December 2016 Journal of Mechanical Design
139(7)
DOI: 10.1115/1.4036649
Authors:
Ruijin Cang
Arizona State University
Yaopengxiao Xu
Shaohua Chen
Shaohua Chen
This person is not on ResearchGate, or hasn't claimed this research yet.
Yongming Liu
Arizona State University
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Abstract and Figures
Integrated Computational Materials Engineering (ICME) aims to accelerate optimal design of complex material systems by integrating material science and design automation. For tractable ICME, it is required that (1) a structural feature space be identified to allow reconstruction of new designs, and (2) the reconstruction process be property-preserving. The majority of existing structural presentation schemes rely on the designer's understanding of specific material systems to identify geometric and statistical features, which could be biased and insufficient for reconstructing physically meaningful microstructures of complex material systems. In this paper, we develop a feature learning mechanism based on convolutional deep belief network to automate a two-way conversion between microstructures and their lower-dimensional feature representations, and to achieves a 1000-fold dimension reduction from the microstructure space. The proposed model is applied to a wide spectrum of heterogeneous material systems with distinct microstructural features including Ti-6Al-4V alloy, Pb63-Sn37 alloy, Fontainebleau sandstone, and Spherical colloids, to produce material reconstructions that are close to the original samples with respect to 2-point correlation functions and mean critical fracture strength. This capability is not achieved by existing synthesis methods that rely on the Markovian assumption of material microstructures.
(a) Samples and random synthesis results of material systems that are assumed to be Markovian [48]. (b-c) Random synthesis of the Ti-6Al-4V alloy microstructure following the synthesis algorithm from [48]. The synthesis is based on (b) a single sample and (c) 100 samples from Fig. 14. Image courtesy of Dr. Ramin Bostanabad.
…
(a) Three layers of human face features extracted at increasing length scales [55]. (b) A schematic comparison between an RBM and an autoencoder. a i (b j ) and v i (h j ) are the bias and state values of visible (hidden) layer, respectively. W i j indicates the weights between the visible and hidden layers.
…
Visualizations of filters for the 5 layers: The 1st layer has two filters, each with 12 orientations (see Sec. 3.1). Due to limited space, Only the first 144 and 25 filters from the 3rd and 4th layers, respectively, are shown.
…
From left to right, reconstructions when only the 1 st , only the 2 nd , and both nodes from the 5th layer are activated, respectively
…
+8
Comparison between random reconstructions from (a) the 4th and (b) the 5th layers, sampled from the corresponding design spaces ({0, 1} 1000 in (a) and {0, 1} 30 in (b)).
…
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Microstructure Representation and
Reconstruction of Heterog
eneous Materials via
Deep Belief Netw
ork f
or Computational Material
Design ∗
Ruijin Cang 1
, Y
aopengxiao Xu 2
, Shaohua Chen 2
, Y
ongming Liu 1
, Y
ang
Jiao 2 and Max Yi Ren 1
1 Department of Mechanical Engineering, Arizona State University ,
T
empe
1 Department of Materials Science and Engineer ing, Arizona State
Univ
ersity
, T
empe
March 8, 2017
Abstract
Integrated Computational Materials Engineering (ICME) aims to accelerate op-
timal design of complex material systems b
y integrating material science and design
automation.
For tractable ICME, it is required that (1) a structural feature space
be identified to allow reconstruction of new designs, and (2) the reconstruction
process be property-preserving.
The majority of existing structural presentation
schemes rely on the designer’
s understanding of specific material systems to identify
geometric and statistical features, which could be biased and insufficient f
or recon-
structing physically meaningful micros
tructures of complex material systems.
In
this paper, we de
velop a feature learning mechanism based on con
volutional deep
belief network to automate a two-w
ay conv
ersion between microstructures and
their lower
-dimensional feature representations,and to achie
ve a 1000-f
old dimen-
sion reduction from the microstructure space.
The proposed model is applied to
a wide spectrum of heterogeneous material systems with distinct microstructural
features including Ti-6Al-4V allo
y, Pb63-Sn37 allo
y, F
ontainebleau sandstone, and
Spherical colloids, to produce material reconstructions that are close to the original
samples with respect to 2-point correlation functions and mean critical fracture
strength.
This capability is not achieved b
y existing synthesis methods that rel
y on
the Markovian assumption of material microstructures.
∗ The paper is to be appeared on JMD
1
arXiv:1612.07401v2 [cond-mat.mtrl-sci] 6 Mar 2017
1 Introduction
Integrated Computational Materials Engineering (ICME) has been promoted by the
Material Genome Initiative to fundamentally chang
e the strategies for de
veloping and
manufacturing advanced material systems to meet the urging demands in ener
gy, health
and national security. Pioneer
ing ICME works hav
e demonstrated successes in design-
ing a variety of material systems, including functional polymers [1, 2, 3], alloy
s and
ceramics [4, 5, 6], and polymer-matrix composites [7, 8], to name a f
ew
.
Nonetheless,
existing ICME methods lack scalability and ha
ve limited applications to multiscale
and high-resolution microstructures.
T
o this end, this paper proposes a computational
tool for extraction and recons
truction of microstructure features on multiple length
scales.
The developed methodology from this paper could lead to better definition of
the design space and enable computational design of complex material systems. In the
remainder of this section, we introduce the mathematical formulation of the material
microstructure design problem and review contemporary feature e
xtraction techniques.
Specifications of the proposed model and demonstrations of its performance can be
found in Section 3.
The advantages and limitations of the proposed algorithm will be
discussed in Section 4, follow
ed by conclusions in Section 5.
1.1
Material design as an optimization problem
We s
tart by providing an o
verview of ICME to justify the necessity of design at the
structure level.
Computational mater
ial design can be mathematically formulated as
follow
s:
A material microstructure is represented as a 2D or 3D image z ∈ Z , where
Z is the image space. Each element of z defines the composition or phase at its
location.
The image is called feasible
when some processing setting θ ∈ Θ e xists,
such that z = p ( θ ) , with p ( · ) being the process-structure mapping, e.g., a physics-
based simulation, and Θ the set of all available processing settings. Consider a material
property of interest, e.g., critical fracture force of alloy, derived from a s
tructure-property
mapping f ( · ) : y = f ( z ) . Finding the optimal material property y ∗ through an all-in-one
approach, i.e., θ ∗ = arg min θ ∈ Θ y = f ( p ( θ )) , may not be fav orable for the f ollowing
reasons:
(1) Finding the optimal θ ∗
can be computationally intractable if the problem is
combinatorial, e.g., a combination of multiple processing techniques is needed.
(2) The
mapping p ( θ ) is often stochastic, i.e., a certain processing setting can lead to a set of
microstructure images.
One solution is to perform a nested optimization by first finding
a target microstructure z ∗ that optimizes y
, then searching f
or a processing setting θ ∗
to
match z ∗ . This approach can be mathematically f ormulated as the following structure
design problem constrained by processing f
easibility:
min
feasible z y = f ( z ) . (1)
1.2
Scientific challenges in optimal material structure design
For complex material systems, sol
ving Eq.
(1) will encounter the following issues: The
high sensitivity of material properties on microstructure details requires high-resolution
2
microstructure images leading to high-dimensional Z
; and the nonlinear processing-
structure mapping makes the feasible domain within Z costl y to be characterized.
These issues can be alleviated if the dimensionality of the design space can be reduced.
Dimension reduction is possible due to the existence of common structural patterns
in the given material system, indicating that there exis
ts a feature representation that
concisely encodes the raw material images.
Further, since the structural patterns are
often related to processing feasibility and material properties, the encoding may lead to
easier-to-construct predictive models f
or the processing-structure-property mappings.
Advantag
es of feature representations were confirmed b
y recent studies for homog
e-
neous nanoparticle composite design tasks [7, 8].
However
, current practices rely on the
designer’s unders
tanding of specific material systems to identify geometric (e.g., parti-
cle size and orientation) and statistical descriptors (e.g., correlation functions) that are
likely to e
xplain variances in material properties.
Generating such quantitativ
e features
for complex
material systems could be difficult for human designers, or
, the manually
defined feature set would be insufficient f
or reconstruction of phy
sically meaningful
microstructures.
Feature e
xtraction methods through the use of deep conv
olutional
networks could potentially address this issue.
Informally, this line of approaches use
sampled microstructures to learn a mapping x = Φ( z ) and its inverse z = Φ − 1 ( x ) (the
unsupervised learning step), where x is a learned feature representation of z from a
feature space X , before mapping x to the perf ormance y (the supervised learning step).
A unique challenge in dev
eloping a feature e
xtraction mechanism f
or (material)
design is the demanding quality of decoding (or called reconstruction), i.e., the recon-
struction Φ(Φ − 1 ( z )) shall “match” z , so that any design searc hed in X can be correctly
validated through a phy
sics-based simulation or an experiment.
In Sec. 3.5,
we ex-
amine both the visual appearances, the 2-point correlation functions,
and the mean
property values of Φ(Φ − 1 ( z )) and z . Visually meaningful decoding is yet challenging
for exis
ting deep networks, which tends to neglect local details while preserving key
features during the reconstruction [9, 10, 11].
To illustrate, photos can be encoded as
text labels with a state-of-the-art deep network (e.g., [12, 13]) but image res
toration
from text labels is hard to be precise [11, 14].
Existing studies have achie
ved limited
success at this challenge by imposing s
tructures onto the image space, e.g., constraining
the smoothness of the reconstructed image [9, 10, 14].
This study first inv
estigates a
deep network model and postprocessing steps to enable random recons
truction of the
complex microstructure of Ti-6Al-4V allo
y samples.
We then sho
w that the proposed
model can be applied to other material systems, including Pb-Sn (lead-tin) alloy
, Pore
structure of Fontainebleau sandstone, and 2D suspension of spherical colloids.
1.3
Contributions and limitations
T
o the authors know
ledge, this is the first study that de
velops a deep network model f
or
both feature extraction and recons
truction of complex material systems.
In addition,
we show that our method preserv
es material properties statistically through reconstruc-
tion.
These properties include the 2-point correlation function and the critical fracture
strength.
T
wo major limitations still exist:
First, while computationally inexpensive,
the current reconstruction process is by nature non-scalable.
A hybrid approach that
combines the proposed feature extraction netw
ork and a stochastic material synthesis
3
model will be discussed.
Second, the mechanical properties of individual samples
are not preserved, demanding higher reconstruction quality and better preservation of
property-related microstructure features through the network model.
2
Related W
ork
Design at the microstructure level b
y changing the composition, phases and morpholo-
gies could lead to the discovery of unprecedented material sys
tems with advanced
performance [15].
The challenges, howe
ver
, exist in the modeling of interactions
among multiple material constituents to predict the properties, and the automation of
material design at microstructure level.
In the following, w
e review e
xisting studies that
concern the latter challenge, and then introduce background know
ledge f
or the proposed
approach based on Conv
olutional Deep Belief Network (CDBN).
2.1
Microstructure parametrization and reconstruction
Conventional material design relies on choosing different material compositions from
material databases [16].
For example, carbon-fibre reinforced epoxy are applied to
replace the wooden oars for better perf
ormance [17].
This composition-based approach
is often limited and cannot be applied in the design of complex materials systems due to
the existence of f
eatures other than constituents that gov
ern material properties.
Such
features include morphology of microstructure, i.e., the spatial arrangement of local
microstructural features [18], the heterogeneity in microstructure [7] and others.
A
quantitative representation of material systems is thus needed.
A review from [7] summarizes three categories of microstructure representations:
(1) physical descriptors (e.g., composition descriptors such as volume fraction, dis-
persion descriptors [19, 20, 21, 22, 23, 24] such as averag
e distance between fillers,
and geometry descriptors [19, 23, 25, 26, 27, 28, 29, 30] such as the size of fillers),
(2) 2-point or N
-point correlation functions [31, 20, 25, 26, 27], and (3) random
fields [25, 32, 33, 34].
Accordingly
, a variety of material reconstruction schemes
have been de
vised for different microstructure representations.
Examples include the
Gaussian random field method[35], stochastic optimization method [36, 37, 38, 39],
gradient-based method [40], phase-retrieval method[41], iterative methods based on
multi-point statistics[42, 43], Bay
esian Network Method[44] and cross-correlation func-
tions [45, 46], and image synthesis method [26, 47].
Recently, a new reconstruction
method is proved to be efficient at synthesizing Mar kovian microstructures [48] where
the probability distribution of the material composition at each pixel (or vo
xel) is deter
-
mined by its local surroundings and the conditional probability model can be applied
homogeneously across a microstructure sample, see Fig. 1a f or examples. However , the
Markovian assumption ma
y not hold for comple
x material systems.
In fact, the algo-
rithm from [48] produces less plausible synthesis results when trained on Ti-6Al-4V
alloy samples, see Fig. 1b and c, especially when high v
ariances in grain directions and
sizes exist.
4
Figure 1:
(a) Samples and random synthesis results of material systems that are assumed
to be Markovian [48].
(b-c) Random synthesis of the Ti-6Al-4V alloy microstructure
following the synthesis algorithm from [48].
The synthesis is based on (b) a single
sample and (c) 100 samples from Fig.
14.
Image courtesy of Dr
.
Ramin Bostanabad.
2.2
Conv
olutional deep networ
k
Convolutional netw
orks hav
e long been used for f
eature extraction, with applications to
object and voice recognition [49] and detection [50], reinforcement learning [51, 52, 53],
analogy making [54] and many others.
By stacking multiple lay
ers, a convolutional
deep network can learn from input training data multi-scale features that contribute to
the explanation of the corresponding outputs, without necessarily being guided by the
outputs.
For example, using a large set of human face imag
es, a network can e
xtract
various face elements, including basic edges from the 1
st la
yer
, eyes and noses from the
2 nd, and partial faces from the
3 rd, see Fig. 2a. A forward pass of an image through
the trained network essentially c
hecks the existence of these f
eatures in the image, and
thus using the output of the network for prediction (e.g., face recognition) is more
effective than using raw imag
e pixel values [55].
While a deep network may invol
ve
a large number of model parameters, the training is made tractable by using s
tochastic
gradient descent [56] along with back
-propagation (for deterministic models) [57] and
contrastive div
ergence (f
or probabilistic models such as Res
tricted Boltzmann Machines
(RBM)) [58].
The proposed Convolutional Deep Belief N
etwork is one type of deep network that
consists of stacked RBM la
yers.
By the nature of RBM, the network is generative,
meaning that it can perform both dimension reduction to map an input microstructure
to a low-dimensional f
eature space, and reconstruction of the microstructure for a giv
en
sample in the feature space.
It should be noted that other models could also be developed
for reconstruction purpose, including Autoencoder [59] (see Fig. 2b f
or an illustration
and
[60] for an example), V
ar
iational Autoencoder (V
AE) [61, 14], and the Generative
Adversarial Netw
ork (GAN) [62].
5
Figure 2:
(a) Three lay
ers of human face features e
xtracted at increasing length
scales [55].
(b) A schematic comparison between an RBM and an autoencoder. a i
( b j ) and v i
( h j ) are the bias and state values of visible (hidden) lay er, respectiv ely . W ij
indicates the weights between the visible and hidden la
yers.
2.3
Restricted Boltzmann Machine
A fully-connected RBM la
yer consists of visible (input) and hidden (output) nodes,
see Fig. 2b.
With weighted edges connecting these tw
o sets of nodes, it is a complete
bipartite graph.
The set of edges connecting from all visible nodes to one hidden node
acts as a convolution filter applied to the in
put image.
The output of the convolution is
transformed by a sigmoid function, and treated as the activation of the corresponding
hidden nodes.
The state
of each hidden node is a binary number drawn from a Bernoulli
distribution parameterized by the activation.
A Convolutional RBM (or CRBM) is a
special type of RBM where all image batches in the input la
yer (of the size of the filters)
share K filters, so that the hidden layer f orms a binary image with K channels, each
produced by conv
olving the input imag
e with a filter. Thus, a CRBM only has a subset
of the visible nodes connecting to each of the hidden nodes (see Fig. 3a).
In the rest of
the paper, the term “filter” and “feature
” are used interchangeabl
y
.
Learning an RBM (and CRBM) model through an set of input images takes the
following procedure.
Notations follow Fig. 2.
Consider a model with n
visible and
m hidden nodes, and let v i and h j be the states of the i th visible and the j th hidden
nodes, respectively
.
When visible units are binary-valued, the total energy of the lay
er
is defined as:
E ( v , h ; θ ) = −
n
X
i =1
a i v i −
m
X
j =1
b j h j −
n
X
i =1
m
X
j =1
v i W ij h j . (2)
In the above eq
uation, θ := { W , a , b }
is a set of model parameters to be estimated,
within which W
is a matrix of network weights, and a and b
are the biases in the visible
and hidden nodes, respectively
.
The joint probability of visible and hidden states is
6
defined based on this energy function as:
Pr ( v , h | θ ) = exp( − E ( v , h | θ ))
Z ( θ ) , (3)
where Z ( θ ) = P
v , h
exp( − E
( v , h | θ )) is a partition function to make Pr
( v , h | θ ) a valid
probability mass function.
The marginal probability of the visible state is:
Pr ( v | θ ) = 1
Z ( θ ) X e − E ( v , h | θ ) . (4)
Thus, the log-likelihood of the model parameters θ
, given training data at the vis-
ible layer
, can be written as φ ( θ ; v ) = log( Pr ( v | θ )) = φ + − φ − , where φ + =
log P h exp( − E ( v , h )) and φ − = log Z = log P v , h exp( − E ( v , h )) are called the
positive and negativ
e parts.
Finding the maximum likelihood estimator of θ requires
applying stochastic gradient descend to φ ( θ ; v )
.
The gradient of the positive part
can be simply calculated as ∂φ +
∂W ij = v i Pr ( h j = 1 | v ) , while the negative gradient
∂φ −
∂W ij = Pr ( v i = 1 , h j = 1) is usually computationally expensiv e due to the calculation
of the partition function.
This issue, however
, can be resolved b
y using contrastive
divergence [58] to
provide an asymptotic approximation of ∂φ −
∂W ij by iteratively sam-
pling from the conditional probabilities Pr ( v i = 1 | h ) = sigmoid P j W ij h j + a i
and Pr ( h j = 1 | v ) = sigmoid ( P i W ij v i + b j ) .
2.4
Probabilistic max-pooling
In a deep network, a max-pooling layer is often inserted after a conv
olution lay
er
to reduce the number of hidden nodes.
This allows f
ew
er network weights to be
computed in the follow
-up lay
ers and also allow f
eatures of larger length scales to be
extracted.
Specific to CDBN, a probabilistic max-pooling layer segments the output
image of a hidden RBM lay
er into blocks ( 2 × 2
in this study) and assigns the associated
pooling node a binary value α
by drawing from a Bernoulli distribution defined by
the activations of the hidden nodes.
The activations for the four hidden nodes are
denoted by I i for i = 1 , 2 , 3 , 4
.
The probability for the pooling node to be activated is
Pr ( α = 1) = 1 − (1 + P 4
i =1 I i ) − 1 . For backward pooling during the reconstruction,
we assign ones to all four nodes in the bloc
k if α = 1
or other
wise zeros.
Fig. 3b
summarizes the pooling procedure.
3
Proposed CDBN for f
eature extraction and material
reconstruction
The proposed network has three CRBM lay
ers and two full
y-connected RBM lay
ers.
Each of the first two CRBM la
yers is f
ollow
ed by a 2 × 2
probabilistic max-pooling
layer
.
The conv
olutional filters for the first three la
yers are set respectiv
ely as follo
ws:
6 × 6 ,
9 × 9 , and
9 × 9 in filter size, 1 , 24 and 40 in the number of channels, and 24 , 40
7
Figure 3:
(a) CRBM and pooling lay
ers (b) Forward and backw
ard probabilistic max-
pooling procedures with 2 × 2 blocks
8
and 288 in the number of filters. The size of the five hidden layers are correspondingly
200 × 200 × 1 , 97 × 97 × 24 , 44 × 44 × 40 , 36 × 36 × 288 and 30 × 1 . Notice that
the image size shrinks along the depth of the network due to the conv
olution operation.
For example, conv
olving an imag
e of 200 × 200
with the filter of 6 × 6
will lead to
an output of (200 − 6 + 1) × (200 − 6 + 1) . This size will fur ther be divided by 4
after the max-pooling process, which makes the dimension 97 × 97
.
In addition, the
number of filters corresponds to the number of channels of the hidden layer
.
Table 1
summarizes the model and training parameters.
One typical measure to prevent the
learning of trivial filters is to set a target sparsity for the hidden nodes, so that on av
erage
a filter can only activate a limited number of hidden nodes and thus represents a specific
image pattern.
For the first four lay
ers, a target sparsity of 0 . 1
is imposed on the hidden
layer activ
ations.
The p λ
values specify the weights on the gradient of the sparsity
penalty during the training.
Both target sparsity and p λ
values are manuall
y tuned so
that the training of the network can achiev
e low recons
truction error.
During network
training, we set the learning rate to 0 . 005
, initial momentum to 0 . 1
, final momentum
to 0 . 9 , and use one iteration of contrastive div ergence f or gradient approximation. The
network weights are initialized b
y drawing from independent normal distributions with
a standard deviation of 0 . 02 . In addition, with 2 , 000
epochs training for the first f
our
training layer and 20 , 000
f
or the last lay
er is applied in our cases.
On a workstation
withIntel Xeon E5-1620 v3 @3.5GHz CPU, GeF
orce GTX Titan 1080 GPU and 64
GB
Memory, the training takes 14134 seconds with 100
in
put images of size 200 × 200 for
each and 1363130
network parameters.
Table 1: Network and algorithmic parameters
Layer
#filter
filter size
sparsity p λ
rotation
1 st 2 6 × 6 0.1 10 12
2 nd 40 9 × 9 0.1 10 N/A
3 rd 288 9 × 9 0.1 10 N/A
4 th 1000 36 × 36 0.1 10 N/A
5 th 30 1000 × 1 0 0 N/A
3.1
Orientation-invariant filters
One common trait of microstructure images is the existence of lo
w-lev
el features that are
similar under linear transformations.
For example, grain boundaries of alloy samples in
Fig. 1b are only different by orientations (of elongated grains).
Therefore filters of the
first CRBM lay
ers can be parametrized by linear transformations, so that training of a
small set of filters will be sufficient to capture all features, thus significantly accelerate
the training process.
Such as the material system of Ti64 Fig 4, which is composed
by lines with different orientation visually
, so the basic features for these kinds of
material system should be edges with various orientations.
In our proposed model,
K = 2 rotation-invariant filters are incorporated, and S = 12 mannually pre-defined
orientations with an interval of 15 degrees are given.
This setting will result in 24 filters
by training only 2(each one with 12 different orientations).
Let the rotation matrices
be { T s } S
s =1 , thus the parameter ized filter for the s th orientation and the j th filter be
9
T T
s W j , where W j is the j th column of W . Following [63], the energy function can
be updated as:
E ( v , h ; θ ) = −
K
X
j =1
S
X
s =1
( T s v
) T W j h j,s −
K
X
j =1
S
X
s =1
b j,s h j,s − c T v . (5)
Note that among all S
hidden nodes for the j
th filter
, at most one can be activated, i.e.,
P S
s =1 h j,s ≤ 1 , for h j,s ∈ { 0 , 1 } , j = 1 , ..., K . This is achieved b y considering h j,s
an outcome of a multi-class classifier, with
Pr ( h j,s = 1 | v ) = exp ( T s v ) T W j + b j,s
1 + P S
s 0 =1 exp(( T s 0 v ) T W j + b j,s 0 ) . (6)
The conditional probability of the visible nodes will be kept the same as before.
With
these updates, training of the rotation-invariant filters follo
ws the discussion in Sec. 2.3.
3.2
Explanation of the network model
The choice of the network configuration requires some e
xplanation.
The first four lay
ers
are used to extract features at increasing length scales. The 5th layer is added to further
reduce the dimensionality of the data by learning the correlations among the 4th layer
activations, i.e., the co-existence of global f
eatures in the samples.
The number of nodes
at layer 4 and 5 are manuall
y configured to achiev
e a balance between high dimension
reduction and low reconstruction error.
Howe
ver
, we did not test all possibilities to
confirm that our network design yields the best result.
Fig. 4 visualizes filters of the five la
yers, learned from 100 Ti-6Al-4V alloy samples
that are produced from the same laser sintering process.
The visualization of each filter
is done by iterativel
y conv
olving the filter (the network w
eights) with filters from the
previous lay
ers 1
.
It is worth noting that the visualizations from the 5th lay
er include
images of almost all black pix
els.
This is because the output images from these filters
have almos
t uniform pixel v
alues, appearing to be zeros after nor
malization.
Also
note that these filters are non-trivial, as the effect of activating multiple nodes at the
output layer has nonlinear effect in the in
put space, i.e., the reconstructed image is not
a simple addition of filter visualizations, because of the sigmoid operations throughout
the network.
T
o demonstrate, we sho
w in Fig. 5(a)-(c) the reconstructions when the 1st,
the 2nd, and both filters are activated.
T
o further justify the network architecture, we observ
ed through experiments that
the random microstructure reconstructions obtained using the 5-layer netw
ork hav
e
larger variance than those from without the 5th la
yer, as illustrated in Fig. 6.
This
result indicates that the 5th layer is effectiv
e for a
voiding the creation of repetitiv
e
microstructure samples.
10
Figure 4:
Visualizations of filters for the 5 layers:
The 1
st lay
er has two filters, each
with 12 orientations (see Sec. 3.1).
Due to limited space, Only the first 144 and 25
filters from the 3
rd and 4
th layers, respectiv
ely
, are shown.
11
Figure 5:
From left to r
ight, reconstructions when only the 1 st , only the 2 nd
, and both
nodes from the 5th layer are activ
ated, respectively
Figure 6:
Comparison between random reconstructions from (a) the 4th and (b) the 5th
layers, sampled from the corresponding design spaces ( { 0 , 1 } 1000 in (a) and { 0 , 1 } 30 in
(b)).
12
Figure 7:
Postprocessing steps:
Column (a) shows the original reconstruction and its
3rd layer activ
ations (288 channels) with enlarged sample c
hannels; Column (b) shows
the reconstruction after thresholding the 3rd layer activ
ations at 0.5; Column (c) shows
the further improved reconstruction after skeletonization.
13
3.3
Reconstruction and postprocessing
T
o reconstruct random microstructures, one starts by randomly assigning binary values
to the last lay
er of the trained CDBN, and inv
ersely sample the previous la
yers through
deconvolution.
T
o speed up the process, we directly treat activations (real values
between 0 and 1) as the states of hidden nodes, to avoid dra
wing from Bernoulli
distributions and eliminate randomness during the reconstruction.
W
e discuss below
the necessity of post-processing steps to av
oid undesirable reconstructions.
First, we observe that with the proposed recons
truction method, the 3rd hidden layer
(a 36 × 36 × 288 image) is ov erly saturated, see Fig. 7a. It happens because the forward
path of the proposed network has a Bernoulli sampling process, making the activation
hidden layer binaries.
But during the reconstruction, the sampling process is avoided
in order to eliminate randomness.
This causes the issue that the slightly activated
nodes in the 3rd layer across its 288 c
hannels, which should have a high
chance to be
sampled as zeros, to accumulatively affect the input la
yer
, by creating o
verlapped grain
boundaries (as black pixels) and undesirably rendering such regions as v
oids.
Through
experiments, we found that thresholding the activ
ations of the 3rd layer at τ = 0 . 5
achieves the lo
wes
t averag
e reconstruction error from the original Ti64 samples, see
Fig. 7b.
Some random reconstructions using this threshold are shown in Fig. 8a.
It
is worth noting that this fixed threshold value ma
y result in invalid recons
tructions for
some binary combinations at the output layer
, see Fig. 8a, two row
s of the reconstruction
microstructures are processed with the same threshold value 0 . 5
, but the performance
is very different.
The four imag
es in the second row hav
e more unexpected v
oids than
the images in the first row
.
One potential solution is to fine-tune the threshold for each
individual reconstruction based on a heuristic criterion, e.g.,
one can remove in
valid
voids in Ti64 reconstructions b
y thesholding the hidden layer so that the v
olume fraction
of the resultant microstructure falls into a range calculated by v
alid reconstructions of
the original samples, see Fig. 8b for an example.
Nonetheless, we are yet to identify
thresholding criteria that are universal across all material systems.
Secondly
, we notice that the resultant grain boundaries are wider than those from
the original samples.
This is due to the convolution and the max-pooling operations
in the first three lay
ers of the proposed CDBN. Applying an e
xisting skeletonization
method [64] to the reconstruction results in the final outcome in Fig. 7c.
Lastly
,
the
convolution operation tends to smear the recons
tructed image towards its boundary
.
The reported reconstruction results in this paper are the cropped areas ( 143 × 143
)
without the blurred margins, which are resultant from the convolution.
3.4
Random reconstruction results
Here we demonstrate the reconstruction performance of the proposed CDBN on f
our
material systems:
Ti-6Al-4V (100 images in Fig. 14), Pb-Sn(lead-tin) (60 images in
Fig. 15), Pore structure of Fontainebleau sandstone (60 imag
es in Fig. 16) and 2D sus-
pension of spherical colloids (80 images in Fig. 17).
Methods used to generate images
of these four material systems are as f
ollow
s:
Ti64 are generated from physics-based
1 This procedure is different from microstructure reconstruction (see Sec. 3.3) in that the sigmoid function
is not applied to the convolution results.
14
Figure 8:
(a) A threshold of 0.5 does not always guarantee valid recons
tructions, see
the second row (b) Threshold can be fine-tuned based on a heuristic criterion:
Here we
test a set of threshold values and pick the one that yields a v
olume fraction closest to
the averag
e volume fraction of reconstructions of the original samples ( ρ = 0 . 51
).
15
kinetic Monte Carlo simulations [65] for beta to alpha phase transition starting from
beta phase field; Pb-Sn optical images are generated from polished Pb-Sn solder ball
surface [66]; sandstone images are virtual 2D slices from 3D tomography reconstruc-
tion [67]; and random sphere packing are generated using Monte Carlo simulations [68].
The CDBN specifications follow Sec. 3: Its input and output are a 200-by-200 image
and a 30-dimensional binary vector, respectiv
ely
.
To generate microstructures, we can
assign binary values to the 30 output neurons, and perform convolution backw
ards
using the learned features.
Fig. 9 provides a visual comparison between samples and
the corresponding random reconstructions.
The first three material systems follo
w
almost the same network setting, with the e
xception f
or Ti-6Al-4V alloy where the firs
t
layer is orientation-inv
ariant.
The network for spherical colloids is slightly different
than the other three, since its universal local feature, a sphere, can be directl
y extracted
from a single CRBM layer
.
Thus the rest four lay
ers in this case are all fully
-connected
RBMs.
From the results, it is evident that the proposed network has some general
applicability across material systems.
Figure 9:
A comparison between random reconstructions (bottom) and the original
samples (top) for f
our different material systems.
3.5
Deeper understanding of the proposed model
T
o further understand the performance and limitations of the proposed CDBN, we
conduct two additional studies:
The first concerns the restoration of or
iginal samples,
and the second validates the reconstruction of the material property of interest, i.e.,
the critical fracture force computed using a recently dev
eloped volume-compensated
16
lattice-particle (VCLP) method [69].
For the first study
, samples of the original Ti-6Al-4V alloy micros
tructure images
and their corresponding reconstructions are shown in Fig. 11.
A close examination
reveals discrepancies betw
een the reconstructed and the original images.
We believ
e
that such discrepancies are caused by the nature of the netw
ork:
Similar local patter
ns
are learned as a single filter, and are replaced by this filter during reconstruction.
Increasing the number of filters to learn may alleviate this issue, yet will also increase
the computational cost for learning the network. Therefore a compromise is necessary.
For example, f
or Ti64, Pb-Sn and Sandstone, we use 2 filters with 12 orientations in
the first CRBM lay
er, and may f
ail to capture features (e.g., line segments) that do not
belong to these pre-set orientations.
The use of probabilistic max-pooling may also
contribute to the discrepancies as forward and backward pooling do not preserv
e the
activations.
Note that preservation of local microstructure patterns can be achiev
ed
relatively easil
y for simple sys
tems such as spherical colloids.
T
o quantitativel
y access the accuracy of the reconstructions, we computed the two-
point correlation function S 2 ( r ) , which gives the probability of two randoml y selected
points separated by distance r falling
into the same phase of interes
t, for both the samples
and the associated reconstructions.
Fig. 10 shows the comparison.
It can be seen that
S 2 for the reconstructed microstructures statisticall y match the corresponding target
structures well, ex
cept for the Ti64 sy
stem.
W
e note that for the Ti64 sy
stem, both S 2
for the targ
et and reconstruction exhibit clear oscillations for small r v alues, indicating
significant short range correlations due to the mutual exclusion v
olume between the
grains.
The wavelengths associated with the oscillations indicate the av
erage grain
width, and are the same in both functions.
The oscillation in the reconstructed S 2
is
apparently stronger
, which is due to more uniform grain size and shape distribution in
the reconstructed microstructure, and the missing of local details from the samples.
Figure 10:
The 2-point correlation functions for the four different materials.
In addition, we inves
tigate the performance-wise discrepancies introduced by the
reconstructions.
Specifically
, we calculate the critical fracture force of three sets of
samples:
the original samples, their reconstructions, and 100 random reconstructions,
using VCLP
. The simulation results from four material systems are summarized in
Fig. 12, with two findings:
(1) the average fracture forces of the three groups are
statistically similar within each material sys
tem; and (2) discrepancies in the fracture
17
Figure 11:
Comparison between the samples (top) and their reconstructions (bottom).
Details of the two fail to match.
force are visible between the original samples and their reconstructions, due to the
aforementioned reconstruction error.
We ar
gue that finding (1) is a desirable result,
Figure 12:
a) Comparison on critical fracture strength among the four material systems
between the original samples (black), their corresponding reconstructions(gray) and
random reconstructions (white) (b) Comparison on critical fracture strength among
individual original images and the related reconstruction images (color online)
while individual-wise property matching may not be necessary.
This is because each
processing setting may produce various structures with small variance in their property
values.
Thus, during the structural design, it is required that the set of reconstructions
of all samples derived from the same processing parameters (as is the case in this study)
have s
tatistically the same property as the original samples.
18
4 Discussion
Here we provide more discussions on the limitations and future directions of the pre-
sented work.
4.1 Limitations
First, we note that the netw
ork is designed to only reconstruct images of a fixed size,
which is not desirable when scalable synthesis of material systems is needed.
One
potential solution is to apply a conditional probability model (e.g., [48]) to the outputs
of a hidden layer of the CDBN that represent the activ
ations of key micros
tructure
patterns.
The intuition is that while the Markovian assumption may not directl
y hold
at the image lev
el (i.e., image pixels cannot be homogeneousl
y inferred from their
surroundings), the activations of local patterns may still be captured by this assumption.
Such a hybrid model could be used to produce new microstructure patches giv
en its
surrounding patches, thus achieving synthesis of complex material samples.
Secondly
, identification of proper network specifications (e.g., the number of lay
ers,
the number of filters, and filter sizes) is non-trivial.
In fact, an arbitrary choice of these
parameters could lead to abysmal f
eature extraction and reconstruction performance.
Due to the unknown sensitivity of the performance with respect to the modeling param-
eters, the authors cannot claim that the presented model is universally applicable to all
material systems, despite the fact that the model w
orked well on the f
our demonstrated
systems.
Thirdly
, the size of training samples can significantly affect the reconstruction
performance.
T
o show this, we learned three network models based on 10 and 50
training samples randomly drawn from the 100 Ti64 imag
es.
We then reconstruct 100
random images using each of the trained models and image-wise v
ariances for each
model are calculated as 0.2644, 0.2863, and 0.4205 respectively.
As expected, the
result shows that a larg
er training data leads to more distinct filters, which leads to the
reconstructions with high variance Fig. 13.
Figure 13:
(a-c) Sample reconstructions (without skeletonization) based on models
trained from 10, 50, and 100 samples,
respectively.
The variances among random
reconstructions for these three cases are 0.2644, 0.2863, and 0.4205, respectivel
y
.
The
variance is calculated from 100 reconstructions in each case.
19
Lastly
, it is also worth noting that the proposed network essentiall
y learns a lower
-
dimensional manifold from the image space using limited samples.
Howev
er, it does
not provide a feasible region within this manif
old.
As a result, random reconstructions
are not guaranteed to be physicall
y meaningful, and a validation through processing-
structure mapping is needed.
It is therefore desirable that certain known physics-based
rules (i.e., constraints on features) can be incorporated into the feature extraction process
to eliminate or reduce the chance of creating infeasible reconstructions.
4.2
From material reconstruction to material design
As mentioned in the introduction, the feature learning method proposed in this paper has
two potential contributions to computationally efficient material design:
The reduced
design space will enable more tractable search for comple
x microsturcture designs, and
allows statis
tical models with better prediction performance to be built for process-
structure-property mappings.
Achieving the latter, how
ever
, requires the learned fea-
tures to be able to explain variance in material properties (in the structure-property
mapping), and in processing settings (in the process-structure mapping).
While this
study does not directly demonstrate the connection betw
een features and properties or
processing parameters, successful reconstructions through the developed model show
ed
its potential at learning microstructure patterns, which could be fine-tuned through a
supervised model to statistically explain properties or processing parameters.
5 Conclusions
This paper presented a novel methodology f
or feature e
xtraction and reconstruction
of complex microstructures through a conv
olutional deep belief network.
Using four
different material systems, we show
ed that the proposed 5-lay
er CDBN model, along
with postprocessing techniques, can achiev
e significant dimension reduction,visually
and statistically plausible random reconstruction, and statisticall
y preserve the critical
fracture strength values after reconstruction.
Key limitations include (1) the lack
of scalability in reconstruction, (2) the individual discrepancies in fracture strength
between original and reconstructed images, and (3) the lack of guarantee of the validity
of the reconstructions, i.e.,
the threshold for the reconstruction is only empirically
chosen.
Nonetheless, the demonstrated advantages o
ver e
xisting material reconstruction
approaches show
ed that our method could lead to more efficient representations of
complex microstructures, which is critical to accelerating ICME.
Ac
know
ledgement
This work is partially supported by NSF CMMI under grant No.
1651147 (Program
Manager:
Mary Tone
y) and by DOD D
ARPA under grant No.
N66001-14-1-4036
(Program Manager:
Fariba Fahroo, DARP
A Mentor:
Michael Maher).
R. C. and Y.
R. thank the startup funding from the Arizona State University
.
The authors thank
Dr.
Honglak Lee, Dr.
Kihyuk Sohn and Y
e Liu for their support on the CDBN
20
implementation, and Dr.
Wei Chen, Dr
.
Hongyi Xu, Dr.
Ramin Bostanabad for
valuable discussion.
All source codes and datasets are available at https://github.
com/DesignInformaticsLab/Material-Design .
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Appendix:
Sample Microstructure Imag
es
Figure 14:
Ti-6Al-4V alloy
26
Figure 15:
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Figure 16:
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27
Figure 17:
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Materials-by-design has been historically challenging due to complex process-microstructure-property relations. Conventional analytical or simulation-based approaches suffer from low accuracy or long computational time and poor transferability, further limiting their applications in solving the inverse material design problem. Here, we establish a deep learning- and genetic algorithm-based framework that combines forward prediction and inverse exploration. Our framework provides an end-to-end solution for microstructure optimization to achieve application-specific mechanical properties of materials. In this study, we select the widely used Ti-6Al-4V to demonstrate the effectiveness of this framework by tailoring its microstructure to achieve various yield strength and elastic modulus across a large design space, while minimizing the stress concentration factor. Compared with conventional methods, our framework is efficient, versatile, and readily transferrable to other materials and properties. Paired with additive manufacturing's potential in controlling local microstructural features, our method has far-reaching potential for accelerating the development of application-specific, high-performing materials.
View Show abstract
... For instance, in the context of microstructural generation, incorporating statistical information, such as geometry descriptors [96]
, as a constraint, can help ensure the generated structures adhere to certain physical properties. ...
Recent Advances and Applications of Machine Learning in Experimental Solid Mechanics: A Review Preprint Full-text available
Mar 2023
Hanxun Jin Enrui Zhang Horacio Dante Espinosa
For many decades, experimental solid mechanics has played a crucial role in characterizing and understanding the mechanical properties of natural and novel materials. Recent advances in machine learning (ML) provide new opportunities for the field, including experimental design, data analysis, uncertainty quantification, and inverse problems. As the number of papers published in recent years in this emerging field is exploding, it is timely to conduct a comprehensive and up-to-date review of recent ML applications in experimental solid mechanics. Here, we first provide an overview of common ML algorithms and terminologies that are pertinent to this review, with emphasis placed on physics-informed and physics-based ML methods. Then, we provide thorough coverage of recent ML applications in traditional and emerging areas of experimental mechanics, including fracture mechanics, biomechanics, nano-and micro-mechanics, architected materials, and 2D material. Finally, we highlight some current challenges of applying ML to multi-modality and multi-fidelity experimental datasets and propose several future research directions. This review aims to provide valuable insights into the use of ML methods as well as a variety of examples for researchers in solid mechanics to integrate into their experiments. * Corresponding authors.
View Show abstract
... CNNs can then assimilate microstructural morphology directly f rom image data through f eature maps, or the patterns of neural activations in convolution layers. The idea is that, since these f eature maps encode geometric patterns of pixels, they can be used as shape descriptors [44,[57][58] [59]
[60][61][62][63]. The benef it of the CNN-based approaches is that the human designer does not need to predef ine a set of f eatures to describe shapes. ...
Artificial Intelligence Approaches for Energetic Materials by Design: State of the Art, Challenges, and Future Directions Article Full-text available
Feb 2023
Joseph Choi Phong Cong Hong Nguyen Oishik Sen Stephen Baek
Artificial intelligence (AI) is rapidly emerging as a enabling tool for solving complex materials design problems. This paper aims to review recent advances in AI‐driven materials‐by‐design and their applications to energetic materials (EM). Trained with data from numerical simulations and/or physical experiments, AI models can assimilate trends and patterns within the design parameter space, identify optimal material designs (micro‐morphologies, combinations of materials in composites, etc.), and point to designs with superior/targeted property and performance metrics. We review approaches focusing on such capabilities with respect to the three main stages of materials‐by‐design, namely representation learning of microstructure morphology (i.e., shape descriptors), structure‐property‐performance (S‐P‐P) linkage estimation, and optimization/design exploration. We leave out “process” as much work remains to be done to establish the connectivity between process and structure. We provide a perspective view of these methods in terms of their potential, practicality, and efficacy towards the realization of materials‐by‐design. Specifically, methods in the literature are evaluated in terms of their capacity to learn from a small/limited number of data, computational complexity, generalizability/scalability to other material species and operating conditions, interpretability of the model predictions, and the burden of supervision/data annotation. Finally, we suggest a few promising future research directions for EM materials‐by‐design, such as meta‐learning, active learning, Bayesian learning, and semi‐/weakly‐supervised learning, to bridge the gap between machine learning research and EM research.
View Show abstract
In situ electron microscopy: modalities of dynamic measurements to capture fundamental physical or chemical processes down to the atomic scale Chapter
Jan 2023
Mitsuhiro Murayama Josh Stuckner
View
Characterization of porous membranes using artificial neural networks
Article
Apr 2023 ACTA MATER
Yinghan Zhao Patrick Altschuh Jay Santoki Britta Nestler
View
Constructing Microstructural Evolution System for Cement Hydration From Observed Data Using Deep Learning Article
Jul 2023
Jifeng Guo C. L. Philip Chen Lin Wang
Liangliang Zhang
Cement has been widely used in civil engineering directly and plays a critical role in cement-based materials, e.g., concrete. As the microstructural evolution of cement hydration predominates the final physical properties, an accurate simulation of hydration is highly required to enable scientists to evaluate the performance and help design new cementitious materials. However, despite significant effort and progress, a satisfactory model to realistically and accurately simulate the evolution of three-dimensional (3-D) microstructure has not yet to be constructed, mainly because cement hydration is one of the most complex phenomena in material science. In this work, a novel near-realistic microstructural model is proposed to simulate the cement hydration system using deep learning and cellular automata. It is designed to break through the bottleneck of fidelity to real microstructural evolution. The dynamical system is constructed based on a 3-D cellular automaton, in which behavior is controlled by deep neural networks distilled from microstructural images. In addition, a dynamic stratified sampling method with variable capacity is proposed to ensure the representativeness of samples for reducing the computation cost of training. Experiments manifest that the simulated hydration is in accordance with the actual development in different aspects, such as near-realistic microstructure and approximate process. Furthermore, the constructed system also demonstrates promising generalization capability even under various conditions.
View Show abstract
GrainNN: A neighbor-aware long short-term memory network for predicting microstructure evolution during polycrystalline grain formation Article
Feb 2023 COMP MATER SCI
Yigong Qin Stephen DeWitt
Balasubramaniam Radhakrishnan George Biros
High fidelity simulations of grain formation in alloys are an indispensable tool for process-to-mechanical-properties characterization. Such simulations, however, can be computationally expensive as they require fine spatial and temporal discretizations. Their cost becomes an obstacle to parametric studies and ensemble runs and ultimately makes downstream tasks like optimal control and uncertainty quantification challenging. To enable such downstream tasks, we introduce GrainNN, an efficient and accurate reduced-order model for epitaxial grain growth in additive manufacturing conditions. GrainNN is a sequence-to-sequence long-short-term-memory (LSTM) deep neural network that evolves the dynamics of manually crafted features. Its innovations are (1) an attention mechanism with grain-microstructure-specific transformer architecture; and (2) an overlapping combination of several clones of the network to generalize to grain configurations that are different from those used for training. This design enables GrainNN to predict grain formation for unseen physical parameters, grain number, domain size and geometry. Furthermore, GrainNN not only reconstructs the quantities of interest but also can be pointwise accurate. In our numerical experiments, we use a polycrystalline phase field method to both generate the training data and assess GrainNN. For multiparametric, ensemble simulations with many grains, GrainNN can be orders of magnitude faster than phase field simulations, while delivering 5%–15% pointwise error. This speedup includes the cost of the phase field simulations for generating training data.
View Show abstract
Variational Autoencoder-Based Topological Optimization of an Anechoic Coating: An Efficient- and Neural Network-Based Design Article
Jan 2022
Yiping Sun Zhaoyu Li Jiadui Chen Meng Tao
View
Show more
Deep neural networks are easily fooled: High confidence predictions for unrecognizable images Conference Paper Full-text available Jun 2015 Anh Nguyen Jason Yosinski Jeff Clune View Generative Adversarial Nets Article Jun 2014 Ian Goodfellow Jean Pouget-Abadie Mehdi Mirza Y. Bengio We propose a new framework for estimating generative models via an adversarial process, in which we simultaneously train two models: a generative model G that captures the data distribution, and a discriminative model D that estimates the probability that a sample came from the training data rather than G. The training procedure for G is to maximize the probability of D making a mistake. This framework corresponds to a minimax two-player game. In the space of arbitrary functions G and D, a unique solution exists, with G recovering the training data distribution and D equal to 1/2 everywhere. In the case where G and D are defined by multilayer perceptrons, the entire system can be trained with backpropagation. There is no need for any Markov chains or unrolled approximate inference networks during either training or generation of samples. Experiments demonstrate the potential of the framework through qualitative and quantitative evaluation of the generated samples. View Show abstract Very Deep Convolutional Networks for Large-Scale Image Recognition Technical Report Sep 2014 Karen Simonyan Andrew Zisserman In this work we investigate the effect of the convolutional network depth on its accuracy in the large-scale image recognition setting. Our main contribution is a thorough evaluation of networks of increasing depth, which shows that a significant improvement on the prior-art configurations can be achieved by pushing the depth to 16-19 weight layers. These findings were the basis of our ImageNet Challenge 2014 submission, where our team secured the first and the second places in the localisation and classification tracks respectively. View Show abstract Auto-Encoding Variational Bayes Conference Paper Dec 2014 Diederik P. Kingma Max Welling How can we perform efficient inference and learning in directed probabilistic models, in the presence of continuous latent variables with intractable posterior distributions, and large datasets? We introduce a stochastic variational inference and learning algorithm that scales to large datasets and, under some mild differentiability conditions, even works in the intractable case. Our contributions is two-fold. First, we show that a reparameterization of the variational lower bound yields a lower bound estimator that can be straightforwardly optimized using standard stochastic gradient methods. Second, we show that for i.i.d. datasets with continuous latent variables per datapoint, posterior inference can be made especially efficient by fitting an approximate inference model (also called a recognition model) to the intractable posterior using the proposed lower bound estimator. Theoretical advantages are reflected in experimental results. View Show abstract Imagenet classification with deep convolutional neural networks Conference Paper Jan 2012 Alex Krizhevsky Ilya Sutskever Geoffrey E. Hinton We trained a large, deep convolutional neural network to classify the 1.2 million high-resolution images in the ImageNet LSVRC-2010 contest into the 1000 dif- ferent classes. On the test data, we achieved top-1 and top-5 error rates of 37.5% and 17.0% which is considerably better than the previous state-of-the-art. The neural network, which has 60 million parameters and 650,000 neurons, consists of five convolutional layers, some of which are followed by max-pooling layers, and three fully-connected layers with a final 1000-way softmax. To make training faster, we used non-saturating neurons and a very efficient GPU implemen- tation of the convolution operation. To reduce overfitting in the fully-connected layers we employed a recently-developed regularization method called dropout that proved to be very effective. We also entered a variant of this model in the ILSVRC-2012 competition and achieved a winning top-5 test error rate of 15.3%, compared to 26.2% achieved by the second-best entry View Show abstract The tradeoffs of large scale learning Article Jan 2007 Adv Neural Inform Process Syst Léon Bottou Olivier Bousquet View Attribute2Image: Conditional Image Generation from Visual Attributes Conference Paper Oct 2016 Xinchen Yan Jimei Yang Kihyuk Sohn Honglak Lee This paper investigates a novel problem of generating images from visual attributes. We model the image as a composite of foreground and background and develop a layered generative model with disentangled latent variables that can be learned end-to-end using a variational auto-encoder. We experiment with natural images of faces and birds and demonstrate that the proposed models are capable of generating realistic and diverse samples with disentangled latent representations. We use a general energy minimization algorithm for posterior inference of latent variables given novel images. Therefore, the learned generative models show excellent quantitative and visual results in the tasks of attribute-conditioned image reconstruction and completion. View Show abstract Understanding deep image representations by inverting them Conference Paper Jun 2015 Aravindh Mahendran Andrea Vedaldi View Accurate stochastic reconstruction of heterogeneous microstructures by limited x-ray tomographic projections Article Jul 2016 J MICROSC-OXFORD Hechao Li C. Shashank Kaira J.C.E. Mertens Yang Jiao An accurate knowledge of the complex microstructure of a heterogeneous material is crucial for its performance prediction, prognosis and optimization. X-ray tomography has provided a nondestructive means for microstructure characterization in 3D and 4D (i.e. structural evolution over time), in which a material is typically reconstructed from a large number of tomographic projections using filtered-back-projection (FBP) method or algebraic reconstruction techniques (ART). Here, we present in detail a stochastic optimization procedure that enables one to accurately reconstruct material microstructure from a small number of absorption contrast x-ray tomographic projections. This discrete tomography reconstruction procedure is in contrast to the commonly used FBP and ART, which usually requires thousands of projections for accurate microstructure rendition. The utility of our stochastic procedure is first demonstrated by reconstructing a wide class of two-phase heterogeneous materials including sandstone and hard-particle packing from simulated limited-angle projections in both cone-beam and parallel beam projection geometry. It is then applied to reconstruct tailored Sn-sphere-clay-matrix systems from limited-angle cone-beam data obtained via a lab-scale tomography facility at Arizona State University and parallel-beam synchrotron data obtained at Advanced Photon Source, Argonne National Laboratory. In addition, we examine the information content of tomography data by successively incorporating larger number of projections and quantifying the accuracy of the reconstructions. We show that only a small number of projections (e.g. 20-40, depending on the complexity of the microstructure of interest and desired resolution) are necessary for accurate material reconstructions via our stochastic procedure, which indicates its high efficiency in using limited structural information. The ramifications of the stochastic reconstruction procedure in 4D materials science are also discussed. View Show abstract Training products of experts by minimizing contrastive divergence Article Jan 2000 G. Hinton View Show more
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Network Working Group E. Lear, Ed.
Internet-Draft Cisco Systems GmbH
Intended status: Informational March 01, 2014
Expires: September 02, 2014
Internet Technology Adoption and Transition
draft-lear-iab-itat-report-00
Abstract
The Internet Technology Adoption and Transition (ITAT) Workshop took
place on December 4th and 5th of 2013. The focus of the workshop was
on models to facilitate adoption of Internet protocols, with
particular emphasis at the waist of the hourglass. This report
summarizes contributions and discussions. As the topics were wide
ranging, there is no single set of recommendations for IETF
participants to pursue at this time. Instead, in the classic sense
of early research, we note areas that deserve further exploration.
Status of This Memo
This Internet-Draft is submitted in full conformance with the
provisions of BCP 78 and BCP 79.
Internet-Drafts are working documents of the Internet Engineering
Task Force (IETF). Note that other groups may also distribute
working documents as Internet-Drafts. The list of current Internet-
Drafts is at http://datatracker.ietf.org/drafts/current/.
Internet-Drafts are draft documents valid for a maximum of six months
and may be updated, replaced, or obsoleted by other documents at any
time. It is inappropriate to use Internet-Drafts as reference
material or to cite them other than as "work in progress."
This Internet-Draft will expire on September 02, 2014.
Copyright Notice
Copyright (c) 2014 IETF Trust and the persons identified as the
document authors. All rights reserved.
This document is subject to BCP 78 and the IETF Trust's Legal
Provisions Relating to IETF Documents
(http://trustee.ietf.org/license-info) in effect on the date of
publication of this document. Please review these documents
carefully, as they describe your rights and restrictions with respect
to this document. Code Components extracted from this document must
Lear Expires September 02, 2014 [Page 1]
Internet-Draft ITAT Report March 2014
include Simplified BSD License text as described in Section 4.e of
the Trust Legal Provisions and are provided without warranty as
described in the Simplified BSD License.
Table of Contents
1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . 3
1.1. Organization of This Report . . . . . . . . . . . . . . . 3
2. Motivations and Review of Existing Work . . . . . . . . . . . 4
3. Economics of Protocol Adoption . . . . . . . . . . . . . . . 5
3.1. When can bundling help adoption of network
technologies or services? . . . . . . . . . . . . . . . . 5
3.2. Internet Protocol Adoption: Learning from Bitcoin . . . . 5
3.3. Long term strategy for a successful deployment of
DNSSEC - on all levels . . . . . . . . . . . . . . . . . 6
3.4. Framework for analyzing feasibility of Internet
protocols . . . . . . . . . . . . . . . . . . . . . . . . 6
3.5. Best Effort Service as a Deployment Success Factor . . . 7
4. Innovative / Out There Models . . . . . . . . . . . . . . . . 7
4.1. On the Complexity of Designed Systems (and its effect
on protocol deployment) . . . . . . . . . . . . . . . . . 7
4.2. Managing Diversity to Manage Technological
Transition . . . . . . . . . . . . . . . . . . . . . . . 8
4.3. On Economic Models of Network Technology Adoption,
Design, and Viability . . . . . . . . . . . . . . . . . . 8
5. Making Standards Better . . . . . . . . . . . . . . . . . . . 8
5.1. Standards: A love/hate relationship with patents . . . . 8
5.2. Bridge Networking Research and Internet
Standardization: Case Study on Mobile Traffic
Offloading and IPv6 Transition Technologies . . . . . . . 9
5.3. An Internet Architecture for the Challenged . . . . . . . 9
6. Other Challenges and Approaches . . . . . . . . . . . . . . . 9
6.1. Resilience of the commons: routing security . . . . . . . 10
6.2. Getting to the next version of TLS . . . . . . . . . . . 10
7. Outcomes . . . . . . . . . . . . . . . . . . . . . . . . . . 10
7.1. Work for the IAB and the IETF . . . . . . . . . . . . . . 11
7.2. Potential for the Internet Research Task Force . . . . . 11
7.3. Opportunities For others . . . . . . . . . . . . . . . . 11
8. Security Considerations . . . . . . . . . . . . . . . . . . . 12
9. Acknowledgments . . . . . . . . . . . . . . . . . . . . . . . 12
10. Attendees . . . . . . . . . . . . . . . . . . . . . . . . . . 12
11. References . . . . . . . . . . . . . . . . . . . . . . . . . 12
11.1. Normative References . . . . . . . . . . . . . . . . . . 12
11.2. Informative References . . . . . . . . . . . . . . . . . 13
Appendix A. Changes . . . . . . . . . . . . . . . . . . . . . . 14
Author's Address . . . . . . . . . . . . . . . . . . . . . . . . 14
Lear Expires September 02, 2014 [Page 2]
Internet-Draft ITAT Report March 2014
1. Introduction
[Ed: this is adapted from our call for papers.]
The Internet is a complex ecosystem that encompasses all aspects of
society. At its heart is a protocol stack with an hourglass shape,
and IP at its center. Recent research points to possible
explanations for the success of such a design and for the significant
challenges that arise when trying to evolve or change its middle
section, e.g., as partially evident in the difficulties encountered
by IPv6. We have a number of other key examples to consider,
including the next generation of HTTP and WebRTC. The eventual
success of many if not all of these protocols will largely depend on
our understanding of not only what features and design principles
contribute lasting value, but also on how (initial) deployment
strategies can succeed in unlocking that value to foster protocol
adoption. The latter is particularly important in that most if not
all Internet protocols exhibit significant externalities that create
strong barriers to adoption, especially in the presence of a well-
established incumbent. Taking into account RFC 5218 on what makes a
protocol successful, this workshop sought to explore how the complex
interactions of protocols design and deployment affect their success.
One of the workshop's goals was, therefore, to encourage discussions
to develop an understanding of what makes protocol designs successful
not only in meeting initial design goals but more importantly in
their ability to evolve as these goals and the available technology
change. Another equally important goal was to develop protocol
deployment strategies that ensure that new features can rapidly gain
enough of a foothold to ultimately realize broad adoption. Such
strategies must be informed by both operational considerations and
economic factors.
Participants this workshop consisted of operators, researchers from
the fields of computer science and economics, as well as engineers.
Contributions were wide ranging. As such, this report makes few if
any recommendations for the IETF to consider, although there are
some.
1.1. Organization of This Report
This report records our discussions. At the end of the workshop we
reviewed potential follow-up items. These will be highlighted at
each point during the report, and a summary is given at the end.
Lear Expires September 02, 2014 [Page 3]
Internet-Draft ITAT Report March 2014
Section 2 discusses the economics of protocol adoption. Section 3
delves into an examination of recent operational challenges and some
success stories. Section 4 examines different views of success
factors. Finally section 5 summarizes views of the participants, and
identifies a few key insights.
2. Motivations and Review of Existing Work
Our workshop began with an introduct that asks the question: is the
neck of the Internet hourglass closed for business? We have numerous
instances where progress has been slow, the three biggest that come
to mind being IPv6 [RFC2480], SCTP [RFC4960], and DNSSEC [RFC4034].
The impact of DNSSEC is of particular interest, because it is relied
upon for the delivery of other services, such as DANE [RFC6698] as
well as application discovery mechanisms[refneeded]. Thus slowdown
at the neck of the glass can have an impact closer to the lip.
Even when we consider the classic neck of the hourglass to be IP and
transport layers, it was suggested that the hourglass might extend as
high as the application layer.
______________________
\ /
\ Applications /
\ /
\ /
\ /
\__________/
| HTTP(s)| Has the neck moved?
|________|
/ \
/ TCP/IP \
/______________\
/ MPLS/ \
/ Framing \
/____________________\
/ Physical \
/________________________\
This idea was rebutted by the argument that protocols do continue to
evolve, that protocols like SMTP and IMAP in the applications space
have continued to evolve, as has the transport layer.
Lear Expires September 02, 2014 [Page 4]
Internet-Draft ITAT Report March 2014
We moved on to a review of [RFC5218] which discusses protocol success
factors. This work was presented in an IETF plenary some time ago,
and was the basis for this ongoing work. There were two clear
outcomes from the discussion. The first was that successive Internet
Architecture Boards should review and consider that document in the
context of evaluating birds of a feather (BoF) session proposals at
the IETF, so that any working group proposal is carefully crafted to
address a specific design space and provide positive net value.
Another aspect was to continue work on tracking the value specific
works in terms of success, wild success, or failure. On that last
point, failure remains difficult to judge, particularly at the neck
of the hourglass.
3. Economics of Protocol Adoption
Several papers were submitted that looked at economic aspects of
protocol adoption.
3.1. When can bundling help adoption of network technologies or
services?
Economics of bundling is a long studied field, but not as applied to
protocols. It is relevant to the IETF and inherent to two key
notions: layering and "mandatory to implement". Two current examples
include DANE atop DNSSEC and WebRTC atop SCTP. The workshop reviewed
a model [Weber13] that examines the concept that bundling of
technologies can lead to several possible outcomes, which includes
more or less adoption of both. This will depend on a number of
factors, including the costs, benefits, and externalities associated
with adopting each. The work we considered involved two independent
technologies. One question was what happens where one technology
depends on the other. That is directly tied to "mandatory to
implement" discussions within the IETF. That is a matter for follow-
on work. IETF participants can provide researchers anecdotal
experience to help improve models in this area.
3.2. Internet Protocol Adoption: Learning from Bitcoin
We considered an examination of protocol success factors in the
context of Bitcoin[Bohme13]. Here, there were any number of barriers
to success, including adverse press, legal uncertainties, glitches
and breaches, previous failed attempts, and speculative attacks,
amongst others. Bitcoin has thusfar overcome these barriers thanks
to several key factors:
o First, there is a built-in reward system for early adopters.
Participants are monetarily rewarded at an exponentially declining
rate.
Lear Expires September 02, 2014 [Page 5]
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o There exist exchanges or conversion mechanisms to directly convert
bitcoin to other currencies.
o Finally, there is some store fo value in the currency itself.
The first two of these factors may be transferrable to other
approaches. That is- one key protocol success factor is direct
benefit to the participant. Another key protocol success factor is
ability to interface with other systems for mutual benefit.
A key message from this presentation is that if a protocol imposes
externalities or costs on other systems, find a means to establish
incentives for those other players for implementation. As it
happened we had a limited example of how to do this that is directly
relevant to the IETF.
3.3. Long term strategy for a successful deployment of DNSSEC - on all
levels
We reviewed the approach Sweden's .SE registry has taken to improving
deployment of DNSSEC[Lowinder13]. .SE has roughly 1.5 million
domains. IIS manages the ccTLD. They made the decision to encourage
deployment of DNSSEC within .SE. They began by understanding who
their stakeholders were, and examined financial, legal, and technical
aspects to deployment. As they began their rollout, they charged
extra for DNSSEC. As they put it, this didn't work very well.
They went on to fund development of OpenDNSSEC to remove technical
barriers to deployment at end sites, noting that tooling was lacking
in this area. Even with this development, more tooling is necessary,
as they point out a need for APIs between the signing zone and the
registrar.
To further encourage deployment, the government of Sweden provided
financial incentives to communities to see that their domains were
signed. .SE further provided an incentive to registrars to see that
their domains were signed. In summary, .SE examined all the players
and provided incentives for each to participate.
The workshop discussed whether or not this model could be applied to
other domains. .SE was in a position to effectively subsidize DNS
deployment because of their ability to set prices. This may be
appropriate for certain other top level domains, but it was pointed
out that the margins of other domains do not allow for a cost
reduction to be passed on at this point in time.
3.4. Framework for analyzing feasibility of Internet protocols
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One of the goals of the workshop was to provide ways to determine
when work in the IETF was likely to lead to adoption. We considered
an interative approach that combines value net analysis, deployment
environment analysis, and technical architecture analysis that leads
to feasibility and solution analysis[Leva13]. This work provided an
alternative to RFC 5218 that had many points in common. The case
study examined was that of MPTCP. Various deployment challenges were
observed. First and foremost, increasing bandwidth within the
network seems to decrease attractiveness of MPTCP. Second, the
benefit/cost tradeoff by vendors was not considered attractive.
Third, not all parties may agree on the benefits.
Solutions analysis suggested five separate approaches to improve
deployment, including open source, lobbying of various implementors,
proxy deployment, and implementation by parties where they own both
ends of a connection.
3.5. Best Effort Service as a Deployment Success Factor
When given the choice between vanilla and chocolate, why not choose
both? We considered an approach that became a recurring theme
throughout the workshop, which was to examine when it was necessary
to make a choice between technologies, but rather to implement
multiple mechanisms to achieve adoption[Welzl13]. The workshop
discussed the case of Skype, where it will use the best available
transport mechanism to improve communication between clients, rather
than to tie fate to any specific transport. The argument goes that
such an approach provides a means to introduce new transports such as
SCTP. This would be an adaptation of "Happy Eyeballs" [RFC6555].
4. Innovative / Out There Models
There were several approaches presented that examined how we look at
protocol adoption.
4.1. On the Complexity of Designed Systems (and its effect on protocol
deployment)
We reviewed a comparison between the hourglass model and what systems
biologists might call the bowtie model[Meyer13]. The crux of this
comparison is that both rely on certain building blocks to accomplish
a certain end. In the case of our hourglass model, IP sits notably
in the center, whereas in the case of systems biology, as adenosine
triphosphate (ATP) is the means by which all organisms convert
nutrients to usable energy.
We also examined the notion of "robust yet fragile", which examines
the balance between the cost of implementing robust systems versus
Lear Expires September 02, 2014 [Page 7]
Internet-Draft ITAT Report March 2014
their value. That is, highly efficient systems can might prove
fragile in the face of failure or hard to evolve.
The key question asked during this presentation was how we could
apply what has been learned in systems biology or what do the
findings reduce to for engineers? The answer was that more work is
needed. The discussion highlighted the complexity of the Internet in
terms of predicting network behavior. As such, one promising area to
examine may be that of network management.
4.2. Managing Diversity to Manage Technological Transition
We considered the difference between planned versus unplanned
technology transitions[Kohno13]. They examined several transitions
at the link, IP, and application layers in Japan. One key claim in
the study is that there is a phase difference in the diversity trend
between each layer. The statistics presented show that indeed HTTP
is the predominant substrate for other applications. Another point
made was that "natural selection" is a strong means to determine
technology.
Along these lines there were two papers submitted that examined the
formation and changes to the hourglass in the context of evolutionary
economics. Unfortunately the presentor was unable to attend due to
illness. The work was discussed at the workshop, and there were
different points of views as to the approach.
4.3. On Economic Models of Network Technology Adoption, Design, and
Viability
We considered how network protocol capabilities enable certain sorts
of services that are beneficial to consumers and service providers.
This model looks at smart data pricing (SDP) in which some behavior
is desired and rewarded through a pricing model.[Sen13] The example
given was use of time-dependent pricing (TDP) and demonstrated how a
service provider was able to load shift traffic to off-peek periods.
Explict Congestion Notification (ECN) and RADIUS were used by the
project alongside a simple GUI. This sort of work may prove useful
to service providers as caching models evolve over time. The
question within the room is how will protocol developers consider
these sorts of requirements.
5. Making Standards Better
There were several papers that focused on how standards are produced.
5.1. Standards: A love/hate relationship with patents
Lear Expires September 02, 2014 [Page 8]
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One of the biggest barriers to deployment is that of the unseen
patent by the non-practicing entity (NPE).[Lear13] While this problem
is relatively well understood by the industry, the discussion looked
at patents as a means to improve interoperability. Those who hold
patents have the ability to license them in such a way that a single
approach is the result.
5.2. Bridge Networking Research and Internet Standardization: Case
Study on Mobile Traffic Offloading and IPv6 Transition
Technologies
Not for the first time there was a presentation and discussion about
the gap between the research community and standards organizations.
Two cases were examined: mobile offloading and IPv6 transition
technologies.[Ding13] In the case of mobile offloading, a mechanism
was examined that required understanding of both 3GPP and IETF
standards. Resistance in both organizations was encountered. In the
3GPP, the problem was that the organization already had an offloading
model in play. In the IETF, the problem was a lack of understanding
of the interdisciplinary space. The researchers noted that in the
case of the IETF, they may have taken the wrong tact by having jumped
into the solution without having fully explained the problem they
were trying to solve. In the case of IPv6 transition technologies
researchers encountered a crowded field and not much appetite for new
transition technologies.
The workshop discussed whether the standards arena is the best venue
or measurement of success for researchers. The IRTF is meant to
bridge academic research and the IETF. As we will discuss below,
several avenues for continued dialog are contemplated.
5.3. An Internet Architecture for the Challenged
We held a very provocative discussion about whether the existing
Internet architecture serves the broadest set of needs. Three
specific aspects were examined: geographic, technical, and socio-
economic. Researchers presented an alternative hourglass or protocol
architecture known as Lowest Common Denominator Networking (LCDNet)
that re-examines some of the base assumptions of the existing
architecture, including its "always on" nature.[Sathiaseelan13]
The workshop questioned many of the baseline assumptions of the
researchers. In part this may have been due to constrained
discussion time on the topic, where a fuller explanation was
warranted.
6. Other Challenges and Approaches
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Internet-Draft ITAT Report March 2014
We held a number of other discussions about different approaches to
technology adoption. We should highlight that a number of papers
were transmitted to the workshop on routing security, two of which
were not possible to present.
6.1. Resilience of the commons: routing security
We discussed a presentation on the tragedy of the commons in the
context of global inter-domain routing[Robachevsky13]. The "Internet
Commons" is a collection of networks that we depend on but do not
control. The main threat to the commons in the context of BGP is
routing pollution, or unwanted or unnecessary routing entries. The
Internet Society has been working with service providers to improve
resiliency by driving a common understanding of both problem and
solution space, and developing a shared view with regard to risk and
benefits, with the idea being that there would be those who would
engage in reciprocal cooperation with the hopes that others would do
similarly in order to break the tragedy.
What was notable in discussion was that there was no magic bullet to
addressing the resiliency issue, and that this was a matter of
clearly identifying the key players and convincing them that their
incentives were aligned. It also involved developing approaches to
measure resiliency.
6.2. Getting to the next version of TLS
Originally the workshop had planned to look at the question of
whether we could mandate stronger security. This evolved into a
discussion about getting to the next version of Transport Layer
Security (TLS), and what challenges lie ahead. It was pointed out
that there were still many old versions of TLS in existence today,
due to many old implementations. In particular, it was pointed out
that a substantial amount of traffic is still encrypted using triple
DES.
One concern about the next generation is that perfect could become
the enemy of good. Another point that was made was that perhaps a
testing platform might help interoperability. Finally, there was
some discussion about how new versions of TLS get promoted.
7. Outcomes
This wide ranging workshop discussed many aspects that go to the
success or failure of the work of the IETF. While there is no single
silver bullet that we can point to for making a protocol successful,
the workshop did discuss a number of outcomes and potential next
steps.
Lear Expires September 02, 2014 [Page 10]
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7.1. Work for the IAB and the IETF
The IAB's role in working group formation consists of providing
guidance to the IESG on which birds of a feather sessions should be
held, review of proposed working group charters, and shepherding some
work so that it can reach a suitable stage for standardization. In
each of these stages the IAB has an opportunity to apply the lessons
of RFC 5218, as well as other work such as the notion of bundling
choices, when members give advice.
In addition to working group creation, the IAB has an opportunity to
track and present protocol success stories, either through wikis or
through discussion at plenary sessions. For instance, there is much
interest at the moment of this report in Bitcoin, its success, and
what parallels and lessons can be drawn. Specifically it would be
useful to track examples of first mover advantages.
Finally, one area that the IETF may wish to consider, relating
specifically to DNSSEC, as raised by our speakers was standardization
of the provisioning interface of DNSSEC (DS keys) between parent and
child zone. Contributions in this area would be welcome.
7.2. Potential for the Internet Research Task Force
There are at least two possible activities that the IRTF might wish
to consider. The first would be a research group that considers
protocol alternatives and recommendations that might be useful in
areas where environments are constrained, due to bandwidth or other
resources. Such a group has already been proposed, in fact.
The second possibility is a more general group that focuses on
economic considerations relating to Internet protocol design. In
particular there were a number of areas that were presented to the
working group that deserve further investigation, and could use
collaboration between researchers, engineers, and operators. Two
examples include work on bundling as well as systems biology.
7.3. Opportunities For others
Incentive models often involve many different players. As we
considered work in the workshop, our partners such as ICANN, and the
RIRs can continue to play a role in encouraging deployment of
protocols through their policies. Their members can also participate
in any activity of the IRTF that is related to this work.
Specifically, RIRs have a specific role to play in encouraging
security fo the routing system, and ICANN has a specific role to play
in securing the domain name service.
Lear Expires September 02, 2014 [Page 11]
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The suggestion was made that the IETF working groups could leverage
graduate students in many Universities around the world in helping
review documents (drafts, RFCs etc). This would serve as a source of
education in real world processes to students, and would engage the
research community in IETF processes more thoroughly, as well as
providing a scale-out resource for handling the IETF review workload.
Several attendees who have such students were prepared to try this
out.
8. Security Considerations
This document does not discuss a protocol. Security for the workshop
itself was excellent.
9. Acknowledgments
The IAB would like to thank the program committee, who consisted of
Roch Guerin, Constantine Dovrolis, Hannes Tschofenig, Joel Halpern,
Eliot Lear, and Richard Clayton.
A special debt of gratitude is owed to our hosts, Ross Anderson and
Richard Clayton for arranging an excellent venue for our discussions.
10. Attendees
The following people attended the ITAT workshop:
Aaron Yi Ding, Adrian Farrel, Andrei Robachevzsky, Arjuna
Sathiaseelan, Bjoern Zeeb, Dave Meyer, Dave Thaler, Dongting Yu,
Eliot Lear, Elwyn Davies, Erik Nordmark?, Hannes Tschofenig, Joel
Halpern, Jon Crowcroft, Lars Eggert, Martin Stiemerling?, Michael
Welzl, Michiel Leenaars, Miyo Kohno, Rainer Bohme, Richard Clayton,
Roch Guerin, Ross Anderson, Russ Housley, Sam Smith, Sean Turner,
Soumya Sen, Spencer Dawkins, Steven Weber, Tapio Levae, Toby
Moncaster, Tony Finch
11. References
11.1. Normative References
[RFC5218] Thaler, D. and B. Aboba, "What Makes For a Successful
Protocol?", RFC 5218, July 2008.
Lear Expires September 02, 2014 [Page 12]
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11.2. Informative References
[Bohme13] Bohme, R., "Internet Protocol Adoption: Learning from
Bitcoin", December 2013.
[Ding13] Yi Ding, A., Korhonen, J., Savolainen, T., Kojo, M.,
Tarkoma, S., and J. Crowcroft, "Bridge Networking Research
and Internet Standardization: Case Study on Mobile Traffic
Offloading and IPv6 Transition Technologies", December
2013.
[Kohno13] Kohno, M., Asaba, T., and F. Baker, "Managing Diversity to
Manage Technological Transition", December 2013.
[Lear13] Lear, E. and D. Mohlenhoff, "Standards: a love/hate
relationship with patents", December 2013.
[Leva13] Leva, T. and H. Soumi, "Framework for analyzing
feasibility of Internet protocols", December 2013.
[Lowinder13]
Eklund Lowinder, A.M. and P. Wallstrom, "Long term
strategy for a successful deployment of DNSSEC - on all
levels", December 2013.
[Meyer13] Meyer, D. M., "On the Complexity of Engineered Systems
(and its effect on protocol deployment)", December 2013.
[RFC2480] Freed, N., "Gateways and MIME Security Multiparts", RFC
2480, January 1999.
[RFC4034] Arends, R., Austein, R., Larson, M., Massey, D., and S.
Rose, "Resource Records for the DNS Security Extensions",
RFC 4034, March 2005.
[RFC4960] Stewart, R., "Stream Control Transmission Protocol", RFC
4960, September 2007.
[RFC6555] Wing, D. and A. Yourtchenko, "Happy Eyeballs: Success with
Dual-Stack Hosts", RFC 6555, April 2012.
[RFC6698] Hoffman, P. and J. Schlyter, "The DNS-Based Authentication
of Named Entities (DANE) Transport Layer Security (TLS)
Protocol: TLSA", RFC 6698, August 2012.
[Robachevsky13]
Robachevsky, A., "Resilience of the commons: routing
security", December 2013.
Lear Expires September 02, 2014 [Page 13]
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[Sathiaseelan13]
Sathiaseelan, A., Trossen, D., Komnios, I., Ott, J., and
J. Crowcroft, "An Internet Architecture for the
Challenged", December 2013.
[Sen13] Sen, S., "On Economic Models of Network Technology
Adoption, Design, and Viability", December 2013.
[Weber13] Weber, S., Guerin, R., and J. C. Oliveira, "When can
bundling help adoption of network technologies or
services?", December 2013.
[Welzl13] Welzl, M., "The "best effort" service as a deployment
success factor", December 2013.
Appendix A. Changes
This section to be removed prior to publication.
o 00 Initial Revision.
Author's Address
Eliot Lear (editor)
Cisco Systems GmbH
Richtistrasse 7
Wallisellen, ZH CH-8304
Switzerland
Phone: +41 44 878 9200
Email: [email protected]
Lear Expires September 02, 2014 [Page 14] | https://www.potaroo.net/ietf/all-ids/draft-lear-iab-itat-report-00.txt |
Browsing Computing Conference Papers by Title
Browsing Computing Conference Papers by Title
Now showing items 49-68 of 153
An efficient programming framework for socially assistive robots based on separation of robot behavior description from execution
Jayawardena, Chandimal ; Kuo, I-Han ; MacDonald, B.A. ( IEEE Computer Society , 2013 )
One of the main challenges in socially assistive robotics is providing flexible and easy-to-use programming tools for users. Unlike other robots, designing socially assistive robots includes the subject-matter-experts ...
Engaging children in diabetes education through mobile games
Baghaei, Nilufar ; Casey, John ; Nandigam, David ; Sarrafzadeh, Hossein ; Maddison, R. ( International Association for the Development of the Information Society (IADIS) , 2017-04 )
Traditional methods for diabetic education rely heavily on written materials and there is only a limited amount of resources targeted at educating diabetic children.
Mobile games can be effective, evidence-based, and ...
Enhancing customers’ knowledge and decision making using augmented reality
Boonrat, W. ; Vaidya, V. ; Baghaei, Nilufar ; Sharifzadeh, Hamid ; Ahmed, A. ; Casey, John ( Asia-Pacific Society for Computers in Education (APSCE) , 2020-11 )
Augmented reality has seen massive success in recent years as it provides an opportunity for a seamless and rich user interaction with the real world. Recent studies have shown augmented and virtual reality can play a ...
Enhancing engagement and collaborative learning skills in multi-touch software for UML diagramming
Basheri, Mohammed ; Burd, Liz ; Munro, Malcolm ; Baghaei, Nilufar ( The International Society of the Learning Sciences , 2013 )
The use of Multi-touch interfaces for collaborative learning has received significant attention. Their ability to synchronously accommodate multiple users is an advantage in co-located collaborative design tasks. This paper ...
Ensemble learning methods for decision making : status and future prospects
Ali, Shahid ; Tirumala, Sreenivas Sremath ; Sarrafzadeh, Hossein ( Institute of Electrical and Electronics Engineers (IEEE) , 2015-07 )
In real world situations every model has some weaknesses and will make errors on training data. Given the fact that each model has certain limitations, the aim of ensemble learning is to supervise their strengths and ...
Ensemble Statistical and Heuristic Models for Unsupervised Word Alignment
Mohaghegh, Mahsa ; Sarrafzadeh, Hossein ; Mohammadi, Mehdi ( IEEE (Institute of Electrical and Electronics Engineers) , 2014 )
Statistical word alignment models need large amounts of training data while they are weak in small-sized corpora. This paper proposes a new approach of an unsupervised hybrid word alignment technique using an ensemble ...
Estimating the risk of fraud against e-services
Yesuf, AS. ; Probst, Christian ( Springer International Publishing , 2018-11 )
Industry is continuously developing, deploying, and maintaining e-services to transform traditional offerings. While protection of traditional services is well understood, their digital transformation often is vulnerable ...
ETL tools for data warehousing : an empirical study of open source Talend Studio versus Microsoft SSIS
Katragadda, Ranjith ; Tirumala, Sreenivas Sremath ; Nandigam, David ( Institute of Electrical and Electronics Engineers (IEEE) , 2015-01 )
Relational databases are bound to follow various database integrity rules and constraints that makes the reporting a time consuming process. Data Warehousing has evolved out of the desperate need for easy access to structured ...
Evaluating VANET Routing Protocols for Auckland Area
Barmada, Bashar ; Alobaidi, Naji ; Ardekani, Iman ; Erfanian.Sabaee, M. ; Ramirez-Prado, Guillermo ( 2018-10 )
This paper provides a performance evaluation for several popular Vehicular Ad-Hoc Network (VANET) protocols, namely AODV, DSR, OLSR, DSDV, GPSR, CBRP, and ZRP with Nakagami fading propagation model for Auckland area. The ...
Evaluation of IPv6 with IPSec in IEEE 802.11n Wireless LAN using Fedora 15 Operating System
Kolahi, Samad ; Cao, Yuqing (Rico) ; Chen, Hong ( Institute of Electrical and Electronics Engineers (IEEE) , 2013-07-07 )
IPSec (IP Security) is a robust technique for securing communications over the Internet. Due to security algorithms used, transferring data using IPSec is known to be significantly slow. In this paper using a test bed ...
Evaluation of statistical text normalisation techniques for Twitter
Sosamphan, P. ; Liesaputra, Veronica ; Yongchareon, Dr. Sira ; Mohaghegh, Dr Mahsa ( IC3K , 2016-11 )
One of the major challenges in the era of big data use is how to ‘clean’ the vast amount of data, particularly from micro-blog websites like Twitter. Twitter messages, called tweets, are commonly written in ill-forms, ...
Eve : an affect-sensitive pedagogical agent
Fourie, Leon ; Overmyer, Scott ; Shanbehzadeh, Jamshid ; Sarrafzadeh, Hossein ; Alexander, Samuel T.V. ( Global Business and Technology Association , 2014-07 )
Easy with Eve is an affect-sensitive tutoring system that features Eve, an animated pedagogical agent that adapts to student emotion based on the results of an observational study of human tutors. This paper presents the ...
A framework for evaluating anti spammer systems for Twitter
Ho, K. ; Liesaputra, Veronica ; Yongchareon, Dr. Sira ; Mohaghegh, Dr Mahsa ( Springer Verlag , 2017-10-20 )
Despite several benefits to modern communities and businesses, Twitter has attracted many spammers overwhelming legitimate users with unwanted and disruptive advertising and fake information. Detecting spammers is always ...
Free and open source intrusion detection systems : a study
Tirumala, Sreenivas Sremath ; Sathu, Hira ; Sarrafzadeh, Hossein ( IEEE , 2015-07 )
Importance of cyber security cannot be denied in the current cyber environment. With continuous growth of internet, cyber security has become a necessity for both big and reputed organizations as well as small businesses ...
From modelling domain knowledge to metacognitive skills : extending a constraint-based tutoring System to support collaboration
Baghaei, Nilufar ; Mitrovic, Branko ( 2007 )
Constraint-based tutors have been shown to increase individual learning in real classroom studies, but would become even more effective if they provided support for collaboration. COLLECT-UML is a constraint-based intelligent ...
From source coding to MIMO : a Multi-Level Unequal Error Protection
Barmada, Bashar ; Rehman, Saeed ( Institute of Electrical and Electronics Engineers (IEEE) , 2016-11 )
In this paper, unequal error protection (UEP) on different levels of the transmission system is proposed. Starting from the source coding level, two priority layers are produced, high priority (HP) and low priority (LP). ...
Fuzzy C-means based on automated variable feature weighting
Nazari, Mousa ; Shanbehzadeh, Jamshid ; Sarrafzadeh, Hossein ( Newswood Ltd. , 2013 )
Fuzzy C-means (FCM) is a powerful clustering algorithm and has been introduced to overcome the crisp definition of similarity and clusters. FCM ignores the importance of features in the clustering process. This affects its ...
The global cyber security workforce : an ongoing human capital crisis
Fourie, Leon ; Pang, Shaoning ; Kingston, Tamsin ; Hettema, Hinne ; Watters, Paul ; Sarrafzadeh, Hossein ( Global Business and Technology Association , 2014-07 )
Cyber threats pose substantial risk to government, businesses and individuals. There is an alarming shortage of trained professionals and academic programs to train and produce these professionals. Many countries including ...
Global solar radiation prediction using artificial neural network models for New Zealand
Ahmad, Aziz ; Anderson, T.N. ( Solar 2014 Conference & Expo , 2014-05 )
In this study, nonlinear autoregressive recurrent neural networks with exogenous input (NARX) were used to predict global solar radiation across New Zealand. Data for nine hourly weather variables recorded across New Zealand ...
Greening and optimizing energy consumption of sensor nodes in the Internet of Things through energy harvesting : challenges and approaches
Airehrour, David ; Gutiérrez, J. ; Ray, S. K. ( 2016-05 )
This paper presents a survey of current energy efficient technologies that could drive the IoT revolution while examining critical areas for energy improvements in IoT sensor nodes. The paper reviews improvements in emerging ...
| https://www.researchbank.ac.nz/handle/10652/1591/browse?etal=-1&offset=48&order=ASC&rpp=20&sort_by=1&type=title |
Discourses on social inequality in the NGO annual reports of Bangladesh: an analysis from the impression management perspective | Request PDF
Request PDF | Discourses on social inequality in the NGO annual reports of Bangladesh: an analysis from the impression management perspective | Purpose The main objective of this article is to explore the discourses on social inequality in the annual reports of Bangladeshi... | Find, read and cite all the research you need on ResearchGate
Discourses on social inequality in the NGO annual reports of Bangladesh: an analysis from the impression management perspective
DOI: 10.1108/ARA-09-2022-0208
Purpose
The main objective of this article is to explore the discourses on social inequality in the annual reports of Bangladeshi NGOs.
Design/methodology/approach
To fulfil this objective, a discourse analysis was conducted on the latest annual reports of ten renowned NGOs in Bangladesh. The findings were interpreted from the impression management perspective.
Findings
It was found that the NGOs of Bangladesh are highlighting several social inequality issues such as poverty, gender inequality, inequality related to getting healthcare, legal and education facilities, etc. in their annual reports. Several impression management tactics were applied in the narratives of the annual reports. The NGOs portrayed themselves as “problem solvers” who are the saviors of distressed people.
Practical implications
This study will facilitate improving the understanding of NGO communication. Policymakers will be able to understand the disclosures of NGOs and consider the necessity to provide guidance that may lead to better information dissemination through reports.
Originality/value
This study will contribute to the limited literature on NGO disclosures from the context of developing economies. In the context of NGO, this research is methodologically novel as it applies discourse analysis and interprets the findings through the lens of impression management.
This paper attempts to evaluate the governance capabilities of Lifebuoy Friendship Hospital (LFH), a corporate social responsibility project in Bangladesh, in terms of significant long-term social impact, operationally defined as sustainability for the present study. Drawing on the SCALERS model proposed by Bloom and Chatterji (2009), under their proposed seven “capabilities” which determine the extent to which a project is able to scale “wide” and “deep,” the paper assesses the prospect of “scaling up” the project to create significant long-term social impact. The study used focus group discussions and interviews to collect data in four villages of remote chars (island bars in the river beds) located in the Jamuna River at Gaibandha district in the northern part of Bangladesh. In total, four FGDs were conducted. Managers from the corporation (Unilever Bangladesh Limited) and the non-governmental organization (Friendship)—who were directly assigned to the project—were interviewed. Some of the key findings of the paper include the following: (i) LFH’s governance capabilities are limited; (ii) although the initiative provides vital healthcare services to some of the most vulnerable and desperately poor communities, management of the project in terms of stakeholder participation—has been marginal; and (iii) the extent to which the project is able to scale—“wide” and “deep” was found to be low. To the question—“What does the project ultimately result in?”—the result found was that—the project did not bring about any significant participation of the community, except being mere recipients of health care service; no significant effort toward income generation for long-term sustainability of LFH; commitment of Unilever Bangladesh Limited (UBL), in this case, was limited mainly to financial resources; entire dependence on a single source of fund (UBL in this case) was identified as another cause of vulnerability for this project. Some of the major lessons arising out of the study may have relevance for other studies. The study suggests issues that need to be considered for significant long-term social impact of other similar initiatives.
NGOs, trust, and the accountability agenda
Non-governmental organizations (NGOs) are undergoing an alleged crisis of trustworthiness.
The past decades have seen an increase in both academic and practitioner scepticism, particularly
given the transformations many NGOs have undergone in size, professionalism, and political
importance. The accountability agenda, which stresses transparency and external oversight, has
gained a significant amount of traction as a means to solve this crisis. But the causal link between
the implementation of these recommendations and increased trustworthiness among donors has
never been considered. This article bridges this gap by drawing on theoretical innovations in trust
research to put forward three arguments. First, the proponents of the accountability agenda are
implicitly working with a rational model of trust. Second, this model does not reflect important
social characteristics of trust between donors and NGOs. Third, this mismatch means that the
accountability agenda might do more to harm trust in NGOs than to help it.
An Evaluation of Corporate Social Responsibility Communication on the Websites of Telecommunication Companies Operating in Ghana: Impression Management Perspectives
Purpose
Corporate social responsibility (CSR) communication on corporate websites have become an emerging trend by firms. Similarly, corporate websites have been used to manage stakeholders’ impressions about the organization. Meanwhile, CSR by firms have been criticized for been a manipulative tactics used by firms. The purpose of this paper therefore is to ascertain how telecommunication companies operating in Ghana communicate CSR on their corporate websites.
Design/methodology/approach
This study used a qualitative content analysis technique. It also used Bolino et al.’s (2008) impression management framework as the conceptual framework. Data were extracted from the websites of four telecommunication companies operating in Ghana. Data were analyzed using thematic analysis techniques.
Findings
The results show that the companies use impression management in communicating CSR on their corporate websites. Account, assertive impression management; blaring, boasting, defensive impression management; demonstrative impression management; exemplification, favor-rendering, illustrative impression management; ingratiation, other-enhancement, other-focused impression management; self-enhancement, self-focused impression management; and self-promotion tactics are tactics prevalent in the CSR communication of the companies. Actor-to-actor link impression management and other emotional appeal also emerged as some of the impression management tactics used by the companies.
Originality/value
This provides insights into how organizations use impression management in their CSR communication on their corporate websites. Studies of this nature are limited. Again, studies specifically adapting Bolino et al.’s impression management to study CSR communication on corporate websites are rare.
Impression Management Tactics in Sustainability Reporting
Purpose
– The study aims to analyzes how companies present their actions to give the impression that they are sustainable actors. It identifies the organizational impression management tactics that companies use in sustainability reporting.
Design/methodology/approach
– A qualitative template analysis of two sustainability reports was conducted to inductively identify the organizational impression management tactics that companies use in sustainability reporting.
Findings
– The study identified eight organizational impression management tactics used in sustainability reporting, four of which relate to how companies present their actions while the remaining four are characteristic of the writing styles that companies use.
Research limitations/implications
– The study is exploratory in nature and does not claim to identify all existing impression management tactics. Therefore, future research is needed to confirm the results and identify possible additional tactics.
Practical implications
– Companies can use impression management tactics that more strongly aim to shape the impressions that stakeholders hold or tactics that more neutrally inform stakeholders of their actions. Companies need to make a choice between the two, considering that stakeholders’ expectations of sustainability reporting would be useful.
Originality/value
– The study shows the different ways that companies use impression management in sustainability reporting, thus lending insight into a perspective on sustainability reporting that has rarely been explored in previous research.
Corporate environmental responsibility and accountability: What chance in vulnerable Bangladesh?
Crit Perspect Account
Bangladesh has recently been enjoying significant economic growth mainly arising from an export led development strategy. However, in that process its natural environment has been degraded and become more vulnerable in geophysical terms (e.g. environmental pollution). Much of the Bangladeshi populations are also vulnerable in socio-economic terms due primarily to widespread poverty. In this context we ask, albeit sceptically, whether there is any chance of holding corporations to account for their environmental responsibilities. Using the notions of vulnerability and ecological rifts we answer this question by providing evidence from published sources and a series of 32 semi-structured interviews with Bangladeshi stakeholder groups. Key findings include, inter alia, corporate reluctance to take responsibility for the environmental impact of their activities. Our interviewees discuss the possibility of a role for mandatory corporate reporting in enhancing corporate accountability and we argue that this is essential if the contradictions and irrationalities of the globalized capitalist system are to be made visible. Achieving such accountability, however, will not be easy due to a lack of political will and the prohibitive costs involved. Incurring such costs could raise the dangerous prospect of Bangladesh losing business to other, less regulated, economies.
An empirical study on the determinants of information disclosure of Malaysian non-profit organizations
Asian Rev Account
Yap Bee Wah
Purpose
– The purpose of this paper is to examine the determinants of the extent of disclosure by non-profit organizations (NPOs) in Malaysia due to the growing interest in the disclosure practice studies of NPOs and given the importance of disclosure to ensure accountability and transparency.
Design/methodology/approach
– This study involves three phases. First, the paper identifies information items NPOs need to disclose. Second, the paper conducts an online survey to determine the ratings of importance for the disclosure items. Third, the paper measures the extent of disclosure from the annual returns of 101 Malaysian NPOs for the year 2009. The paper uses hierarchical regression analysis to determine the significant determinants of information disclosure.
Findings
– The key determinants are establishment of an external audit, financial performance and government support in terms of grants. The results show that the presence of external auditors promotes better reporting practice. Malaysian NPOs that receive funding and those with better financial standing disclose more information.
Research limitations/implications
– The sample only covers NPOs with tax-exempt status in the state of Selangor and Wilayah Persekutuan in Malaysia. The sample size of 101 registered NPOs limits the generalization of the results. Inclusion and analyses of additional NPOs may offer generalizable results.
Practical implications
– This study provides empirical evidence concerning the establishment of external audit for better information disclosure. It also provides 88 items that are important and required by stakeholders.
Originality/value
– The study is based on 88 items of information according to the needs of stakeholders for information. The NPOs reporting index can assist the preparers of charity reporting in fulfilling the stakeholders’ requirements. The reporting index can also be used to assess the information disclosure of NPOs in Malaysia.
Ethos, Logos, Pathos: Strategies of Persuasion in Social/Environmental Reports
Article
Full-text available
Sep 2012
Account Forum
Colin Higgins
Robyn Walker
We demonstrate how persuasive strategies activate the ‘middle ground’ discourses of responsible and sustainable business constructed in three social/environmental reports. Drawing on insights from impression management and communication studies, and Kenneth Burke's understanding that rhetoric is all pervasive, we focus on Aristotle's rhetorical ‘proofs’: ethos (credibility), logos (reason), and pathos (emotion). We study the social/environmental reports produced by three New Zealand companies during a wider discursive struggle over the ‘proper’ role of business in society. We argue that persuasive strategies facilitate the social effects of ‘middle ground’ discourse by making business-centred understandings of social responsibility and sustainability appear reasonable and business organisations appear trustworthy in their pursuit of sustainable development. This study complements discourse analyses of social/environmental reporting by providing a finer-grained picture of how language use influences how social actors think, feel and act.
Perceptions of Company Performance: A study of impression management
Article
Full-text available
Debbie Wills
A MultiLevel Review of Impression Management Motives and Behaviors
Article
Full-text available
Dec 2008
Mark C. Bolino
K. Michele Kacmar
William H Turnley
J. Bruce Gilstrap
This article selectively reviews studies of impression management (IM) published since 1988 and identifies strengths, limitations, and future research directions in three key areas: research investigating the use of IM at the individual level of analysis (e.g., performance appraisal); research that applies IM theory, concepts, and thinking to better understand organizational phenomena (e.g., feedback seeking); and research investigating organizational-level IM (e.g., how firms create legitimacy). Following their review, the authors offer some overarching recommendations for future examinations of IM in organizations, giving particular attention to the need for clear definitions and categories of IM behaviors and the value of multi-level investigations.
Discretionary Disclosure Strategies in Corporate Narratives: Incremental Information or Impression Management?
Article
Full-text available
Dec 2007
Doris M. Merkl-Davies
Niamh M. Brennan
Prior research assumes that discretionary disclosures either (a) contribute to useful decision making by overcoming information asymmetries between managers and firm outsiders (informational perspective); or (b) constitute opportunistic behavior whereby managers exploit information asymmetries between them and firm outsiders through engaging in biased reporting, i.e. impression management (opportunistic perspective). We consider possible theoretical underpinnings of the two competing positions. We discuss different theories explaining managers' motives to engage in impression management or to provide incremental information. We identify various theories, in particular from behavioral finance and from psychology that explain why investors might be susceptible to managerial impression management. We examine the discretionary disclosure strategies applied by managers in corporate narratives, classifying them into seven categories. This enables a better understanding of the wide range of techniques applied by managers to manage impressions/enhance disclosure quality. We bring together both capital markets and behavioral research on whether discretionary narrative disclosure strategies influence decision making and whether, therefore, they are effective. Finally, we suggest future research opportunities. We propose alternative theories from the accounting, management, and social psychology literature to suggest additional impression management motivations and strategies not previously considered in a financial reporting context. We take different theories and prior research in behavioral finance and psychology to put forward new avenues for studying the effect of discretionary narrative disclosures on users, and to explain why users might be influenced by managerial impression management.
Impression Management: Developing and Illustrating a Scheme of Analysis for Narrative Disclosures - A Methodological Note
Article
Full-text available
Jun 2009
Account Audit Account J
Niamh M. Brennan
Encarna Guillamón-Saorín
Aileen Pierce
Purpose – This paper aims to develop a holistic measure for analysing impression management and for detecting bias introduced into corporate narratives as a result of impression management. Design/methodology/approach – Prior research on the seven impression management methods in the literature is summarised. Four of the less-researched methods are described in detail, and are illustrated with examples from UK annual results' press releases (ARPRs). A method of computing a holistic composite impression management score based on these four impression management methods is developed, based on both quantitative and qualitative data in corporate narrative disclosures. An impression management bias score is devised to capture the extent to which impression management introduces bias into corporate narratives. An example of the application of the composite impression management score and impression management bias score methodology is provided. Findings – While not amounting to systematic evidence, the 21 illustrative examples suggest that impression management is pervasive in corporate financial communications using multiple impression management methods, such that positive information is exaggerated, while negative information is either ignored or is underplayed. Originality/value – Four impression management methods are described in detail, illustrated by 21 examples. These four methods are examined together. New impression management methods are studied in this paper for the first time. This paper extends prior impression management measures in two ways. First, a composite impression management score based on four impression management techniques is articulated. Second, the composite impression management score methodology is extended to capture a measure for bias, in the form of an impression management bias score. This is the first time outside the USA that narrative disclosures in press releases have been studied.
Accounting and Navigating Legitimacy in Tanzanian NGOs
Article
Full-text available
May 2006
Account Audit Account J
Andrew Goddard
Mussa Juma Assad
Purpose
– The purpose of this paper is to investigate the phenomenon of accounting in non‐governmental organisations (NGOs). It seeks to understand accounting processes and reporting practices in NGOs and the conditions that sustain those processes and practices. NGOs have become important institutions in world affairs but accounting research has not developed significant interest in their operations.
Design/methodology/approach
– The research executes a grounded theory strategy as the principal methodology for the inquiry. Fieldwork was undertaken in three Tanzanian NGOs.
Findings
– The research established the importance of accounting in the process of navigating organisational legitimacy. This was achieved due to its important role in symbolising organisational competence. Two principal strategies were employed by organisations in navigating legitimacy – building credibility and bargaining for change.
Originality/value
– The paper makes a contribution to the limited empirical research into accounting in NGOs in developing countries and to grounded theory, accounting research. The principal finding, that in the NGOs studied the primary purpose of accounting was its symbolic use in navigating legitimacy and that it has a minimal role to play in internal decision making, is an important finding for practice as well as for understanding and knowledge. Finally, the paper sheds light on accountability in NGOs by narrating how the phenomenon is constructed and perceived by organisations and stakeholders. Future research should extend our understanding of these phenomena across a broader range of NGOs to incorporate differences in geographical location, religious affiliation and also include Northern donor organisations.
On James Bond and the Importance of NGO Accountability
Article
Full-text available
May 2006
Account Audit Account J
Jeffrey Unerman
Brendan O'Dwyer
Purpose
The purpose of this paper is to set out key issues in the academic study of non‐governmental organisation (NGO) accountability, and to introduce papers appearing in this special issue on NGO accountability.
Design/methodology/approach
This is a discussion paper exploring key issues theoretically.
Findings
The paper finds that there are many aspects of NGO accountability which should be explored in greater depth in future studies. Several other issues have been examined in the papers in this special issue of Accounting, Auditing & Accountability Journal .
Research limitations/implications
There is a possibility that the issues explored in this paper, and the other papers in this special issue, will lead to a considerable growth in academic studies in this area.
Practical implications
The paper is a contribution to the growing debate on NGO accountability.
Originality/value
The paper sets an agenda for research into NGO accountability.
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Discourse analysis: making complex methodology simple.
Conference Paper
Full-text available
Jul 2004
Tanya Bondarouk
H.J.M. Ruël
Discursive-based analysis of organizations is not new in the field of interpretive social studies. Since not long ago have information systems (IS) studies also shown a keen interest in discourse (Wynn et al, 2002). The IS field has grown significantly in its multiplicity that is echoed in the discourse, which policy makers and end-users use when they talk or write about IS. Understanding their discourse might shed light on understanding their behavior with information technologies. However, so far discourse-based IS studies lag both a conceptual grounding and the ‘route descriptions’ of the method. The paper illustrates the multidisciplinary genesis of what actually constitutes “discourse” and elaborates on the main principles of doing discourse analysis in IS studies. By examining the theoretical foundations of discourse analysis, we show that its goal is to interpret the hidden meaning about information technologies, covered by a text. A researcher achieves that by a constant interplay between texts (project documents, interviews with the end-users or managers, manuals of IS), discourse (sets of the texts), and context (historical an, social background). We shall analyze the practical applications of the method and demonstrate an eight-steps mode for conducting discourse analysis for interpretive IS studies. By elaborating on “doing discourse analysis” we shall give an example based on the interviews conducted with the end-users regarding implementation of a personnel management system in a larger Dutch university.
NGOs, Civil Society and Accountability: Making the People Accountable to Capital
Article
Full-text available
May 2006
Account Audit Account J
David Collison
Jan Bebbington
Rob Gray
Purpose
The purpose of this research is to seek to understand and explain the non‐governmental organisation (NGO) and its location in civil society in order to provide a basis for future research work. The paper aims to explore and develop understandings of accountability specifically in the context of the NGO and then extend these insights to the accountability of all organisations.
Design/methodology/approach
The paper is framed within a theoretical conception of accountability and is primarily literature‐based. In addition secondary data relating to the issues of concern are collated and synthesised.
Findings
The research finds that the essence of accountability lies in the relationships between the organisation and the society and/or stakeholder groups of interest. The nature of this relationship allows us to infer much about the necessary formality and the channels of accountability. In turn, this casts a light upon taken‐for‐granted assumptions in the corporate accountability and reminds us that the essence and basis of success of the corporate world lies in its withdrawal from any form of human relationship and the consequential colonisation and oppression of civil society.
Research limitations/implications
The principal implications relate to: our need to improve the analytical incisiveness of our applications of accountability theory; and the possibility of the accounting literature offering more developed insights to the NGO literature. The primary limitations lie in the paper in being: exploratory of a more developed understanding of accountability; and a novel excursion into the world of the NGO and civil society – neither of which feature greatly in the accounting literature.
Practical implications
These lie in the current political struggles between civil society and capital over appropriate forms of accountability. Corporations continue to avoid allowing themselves to be held accountable whilst civil society organisations are often accountable in many different and informal ways. Ill‐considered calls from capital for more oppressive NGO accountability are typically, therefore, hypocritical and inappropriate.
Originality/value
NGOs are introduced in a detailed and accessible way to the accounting literature. The concept of accountability is further developed by examination of relationships and channels in the context of the NGO and, through Rawls' notion of “closeness”, is further enriched.
Impression management tactics in Covid-19 related disclosures: a study on the annual reports of Bangladeshi listed insurance companies
Article
Oct 2022
Dewan Mahboob Hossain
Md. Saiful Alam
Mohammed Mazumder
Purpose
The purpose of this article is to explore the impression management practices in Covid-19 related discourses in the annual reports of the insurance companies in Bangladesh.
Design/methodology/approach
To fulfil this objective, the authors have conducted a discourse analysis of the Covid-19 related corporate narratives in the latest annual reports of listed insurance companies. The findings are then interpreted through the lens of impression management theory, following the impression management strategies identified by Caliskan et al. (2021).
Findings
It is found that companies tried to manage the impression of the stakeholders through the strategic use of language. There is evidence that the companies used assertive and performance-oriented tactics to impress their stakeholders. In few cases, defensive strategies were applied.
Practical implications
This study will facilitate improving the understanding of corporate communication during the Covid-19 crisis. Policymakers will be able to understand the current status of Covid-19 related disclosures and consider the necessity to provide guidance that may lead to better accountability during the crisis.
Originality/value
This study will contribute to the limited literature on Covid-19 related disclosure from the context of developing economies. This research is methodologically novel as it applies discourse analysis and interprets the findings through the lens of impression management.
Impression management tactics in the CEO statements of Turkish sustainability reports
Jul 2021
Arzu Ozsozgun Caliskan
Emel Esen
Ralf Barkemeyer
In this study, we construct a classificatory scheme of impression management tactics and apply it to a sample of sustainability report and annual report CEO statements issued by large Turkish companies. We find a wide range of impression management tactics applied in both types of CEO statements. However, impression management in sustainability report CEO statements emerges as more limited and uniform, revealing clearer prioritizations of impression management tactics when compared to annual report CEO statements. Sustainability report CEO statements emphasize tactics that allow the company to highlight carefully selected, isolated aspects of their sustainability engagement. At the same time, they rarely employ tactics that are geared towards more systematic (quantitative) performance evaluation. We attribute these differences to the way in which corporate sustainability performance is commonly conceptualized and evaluated, emphasising qualitative performance dimensions rather than the reporting of quantitative performance metrics. This results in the application of a different impression management tactics mix and limits the usefulness of sustainability reports as an accountability mechanism when compared to corporate annual reports. In addition, we provide tentative evidence for the context‐specific nature of impression management, with the choice of impression management tactics reflecting the institutional environment a company is based in.
Social and environmental accounting in developing countries: contextual challenges and insights
Mar 2021
Account Audit Account J
Wei Qian
Carol Tilt
Ataur R. Belal
Purpose
The purpose of this paper is to review most recent developments of social and environmental accounting (SEA) in the context of developing countries and to offer insights for the latest research in this field. It also provides an introduction to the AAAJ special issue.
Design/methodology/approach
The authors have undertaken a conceptual overview of the field developed in the past two decades (2001–2020) with a view to identify major themes, trends and future research directions.
Findings
The overview reveals that only 43 SEA papers addressing contextual challenges of developing countries have been published in leading accounting journals in the last 20 years. The coverage of these publications is concentrated in a small number of countries and regions. Interdisciplinary accounting journals, especially AAAJ, are the main publishing outlets in this field. The topic areas are dominated by social accounting challenges, with much less focus on environmental accounting, although developing countries are particularly exposed to the threats of climate change, water pollution and biodiversity loss. The literature reviewed uses elaborating, problematising and theorising contexts as three main contextualisation approaches to analyse contextual themes framed around regulatory, political, cultural and religious, and social-economic systems. Although various conceptual lenses have been adopted in the developing country SEA literature, the use of institutional theory and its various extensions to address political and cultural complexities seems to become more prominent, as shown in most of the contributions included in this special issue.
Research limitations/implications
This review is limited to leading accounting journals. SEA research increasingly published in other disciplines such as in management, social and environmental areas might provide a more comprehensive view in this research field.
Originality/value
In this paper, inter alia , the authors review and synthesise the previous literature in a conceptual framework, illustrating and highlighting the importance of contextual framing of SEA in developing countries. Based on this review, the authors propose some ideas for a future research agenda aiming to advance the field. The authors expect this paper and the special issue to act as a reference point for emerging SEA researchers from developing countries to raise more scholarly impactful enquiries in this area.
NGO Accountability: A Conceptual Review across the Engaged Disciplines
Mar 2021
Marcel Kaba
Non-governmental organizations (NGOs) are pivotal actors in international affairs. They manage billions of dollars in funding, work all around the world, and shape global policies and standards. It thus comes as no surprise that the subject of accountability has drawn the interest of an increasing number of scholars across disciplines. Though there seems to be agreement about its desirability, accountability is also described as chameleon-like and ambiguous. And despite calls for more cross-disciplinary learning and conceptual clarity, there does not exist a comprehensive review of accountability conceptualizations across and within disciplines, or how the different meanings relate to each other. Based on the conceptual review of 217 research articles published within the last twenty years, this study identifies and analyzes conceptualizations of accountability in the major journals of five engaged disciplines: accounting, development studies, international relations and political science, organization studies and management, and public administration. Integrating this broad scholarship reveals that: (1) there exist 113 different conceptualizations of accountability, 90 of which are rarely used and appear in less than 5 percent of all analyzed articles, (2) scholars have used forty-three different conceptualizations in 2019 compared to seventeen conceptualizations in 2009, (3) many conceptualizations refer to same phenomena by different name (duplication), and different phenomena by the same name (conflict), and that (4) conceptual ambiguity contributes to ambiguity among the forty different terms used to measure and operationalize accountability. These findings illustrate a lack of cross-disciplinary learning and accumulation of knowledge, and suggest that new conceptualizations be introduced only if one or more of the 113 existing ones don't already capture an idea sufficiently. The purpose of this article is to serve as a concept map for scholars when debating and charting new directions for the study of accountability.
Gender-related Discourses in Corporate Annual Reports: An Exploratory Study on The Bangladeshi Companies
Dec 2020
J Account Organ Change
Md. Saiful Alam
Mohammed Mazumder
Al Amin
Dewan Mahboob Hossain
Objective: The main objective of this study is to explore the gender related discourses in the annual reports of the listed companies in Bangladesh.
Methodology: In order to fulfill this objective, a Sociological Discourse Analysis (SDA) of the gender related texts in the annual reports of Bangladeshi companies [listed in the Dhaka Stock Exchange (DSE)] was conducted. Sandberg and Holmlund’s (2015) Organizational Impression Management (OIM) tactics (description, praise, admission, defense and writing styles) was applied as the analytical framework of SDA. The findings of the study were interpreted from a triangulation of two different theories: legitimacy theory and impression management theory.
Findings: The study suggests that the companies in Bangladesh are disclosing gender related information to a limited extent. They provide some information in relation to equal opportunities, business activities targeted to women and corporate contribution to women welfare. Most of these gender related discourses are rhetorical in nature. The companies used various impression management tactics such as description, praise, positive writing style, vague writing style and emotional writing style.
Originality: This is one of the very few studies that illustrates the corporate gender reporting of a developing economy - Bangladesh. To make a unique contribution on the corporate gender disclosure, the study has drawn its analysis from a triangulation of the impression management and the legitimacy perspectives. Also, the use of SDA for annual report analysis has informed the readers about ‘how’ the corporate narratives are presented in the annual reports rather than ‘what’ issues are disclosed as commonly done in a content analysis.
Limitation: This study is exploratory in nature and focuses on cross-sectional data. Thus, it does not identify the trend of corporate gender reporting over the years.
Why Do Corporate Actors Engage in Pro-Social Behavior? A Bourdieusian Perspective on Corporate Social Responsibility
Article
May 2013
ORGANIZATION
Dominik van Aaken
Violetta Splitter
David Seidl
Drawing on Pierre Bourdieu’s theory of social practice this paper develops a novel approach to the study of CSR. According to this approach, pro-social activities are conceptualized as social practices that are employed by individual managers in their personal struggles for social power. Whether such practices are enacted or not depends on the (1) particular features of the social field in which the managers are embedded, (2) the individual managers’ socially shaped dispositions and (3) their respective stock of different forms of capital. By combing these three concepts the Bourdieusian approach provides a particularly fruitful theoretical lens on CSR phenomena, not least as this allows reconciling seemingly competing conceptualizations in the existing CSR literature such as economic vs. non-economic motivation as drivers of CSR activity, micro- vs. macro-level explanations and voluntaristic vs. deterministic views of managers’ behaviors.
NGO accountability: retrospective and prospective academic contributions
Jul 2019
Account Audit Account J
Gloria Agyemang
Brendan O'Dwyer
Jeffrey Unerman
Purpose
The purpose of this paper is to offer a retrospective and prospective analysis of the themes explored in the 2006 Accounting, Auditing and Accountability Journal special issue on non-governmental organisation (NGO) accountability.
Design/methodology/approach
The paper is a reflective review essay.
Findings
The paper outlines how a number of themes in the 2006 special issue addressing downward accountability, hierarchical accountability and management control have been subsequently developed in a selection of papers from the accounting literature. The development of these themes leads to several suggestions for future research in NGO accountability.
Originality/value
The paper offers a systematic, original perspective on recent developments in certain areas of the field of NGO accountability.
Social Inequality: Forms, Causes, and Consequences
Book
Jul 2019
Charles E. Hurst
Heather M. Fitz Gibbon
Anne M. Nurse
Persuasive language of responsible organisation? A critical discourse analysis of Corporate Social Responsibility (CSR) reports of Nigerian oil companies
Jun 2019
Account Audit Account J
Dr Uzoechi Nwagbara
Ataur R. Belal
Purpose
The purpose of this paper is to investigate how language (choice) in CSR reports of leading oil companies in Nigeria is used to portray an image of “responsible organisation”.
Design/methodology/approach
This paper draws insights from communication studies (persuasion theory) and critical discourse analysis (CDA) studies to discursively unpack all those subtle and visible, yet equally invisible, linguistic strategies (micro-level elements): wording (single words), phrases and chains of words (clauses/sentences). These linguistic strategies (micro-level elements) proxy organisational discourses (meso-level elements), which are reflective of wider social practices (macro-level elements). The authors base the investigation on CSR reports of six leading oil companies in Nigeria from 2009 to 2012.
Findings
The findings of this study reveal that (leading) Nigerian oil companies linguistically use CSR reports to persuasively construct and portray the image of “responsible organisation” in the eyes of wider stakeholders (the communities) despite serious criticism of their corporate (ir) responsibility.
Originality/value
As opposed to the previous content analysis based studies, this paper contributes to the emerging stream of CDA studies on CSR reporting by providing a finer-grained linguistic analytical schema couched in Fairclough’s (2003) approach to CDA (and persuasion theory). This helps to unravel how persuasive language/discourse of responsible organisation is enacted and reproduced. The authors thus respond to the calls for theoretical plurality in CSR reporting research by introducing persuasion theory from communication studies literature which has hitherto been rarely applied.
Sustainability reporting practices and their social impact to NGO funding in Italy
Apr 2019
Patrizia Gazzola
Stefano Amelio
Fragkoulis Papagiannis
Zenon Michaelides
This study analyses the growing social trends of sustainability reporting practices in non-governmental organisations (NGOs). Taking a preliminary step toward NGO funding, we consider the current lack of information disclosure in existing reporting practices, which are diverse and unsustainable. We investigate key organisational information in order to discover any potential links between funding sources and disclosure practices. In Italy, today there is an on-going effort to encourage public engagement in civil society. A percentage-tax law allows taxpayers to dedicate ‘cinque per mille’ (one-half percent)of their income to NGOs, which is then deducted from their tax obligation (Hereafter, ‘5 per thousand’). Our primary research objective is to understand if there is a link between the ‘5 per thousand’ donations that NGOs receive for providing social impact, and their reporting practices. Therefore, we critically analyse if and how sustainable reporting practices are achieved within the top 100 most funded NGOs that receive the ‘5 per thousand’ donation. We examine public data from official government records published by the Italian Revenue Agency. The findings suggest that sustainability reporting offers a number of financial and social advantages, including social impact that builds trust towards the idea of civil society and its funders.
NGO accounting and accountability: past, present and future
Article
Carolyn Cordery
I. Thomson
Ataur R. Belal
The main aim of this paper is to introduce key themes of NGO accounting and accountability and provide an overview of the papers included in this special issue. These papers deal with formal reporting issues related to the regulatory requirements as well as various alternative forms of informal accountability mechanisms which are more related with the core social purpose of the organisation. This special issue contributes not only to the scholarly debates on NGO accounting and accountability but also to the various issues facing policy makers and NGO practitioners. We have provided a robust research agenda for future researchers.
HIGHLIGHTS
• We define the term ‘NGO’ for the purposes of this issue, concluding that NGOs’ social purposes and the constraint on distribution of surpluses are the two common characteristics.
• This definition encourages researchers to cast their net wider when considering contexts in which to undertake their NGO study.
• NGO accountability discharge is broadening to a wider range of stakeholders.
• There are many NGO accounting and accountability issues that warrant further research.
Empathy, closeness, and distance in non-profit accountability
Jul 2018
Account Audit Account J
Ericka Costa
Caterina Pesci
Michele Andreaus
Emanuele Taufer
Purpose
Drawing on the phenomenological concepts of “empathy” and “communal emotions” developed by Edith Stein (1917, 1922), the purpose of this paper is to discuss the co-existence both of the legitimacy and accountability perspectives in voluntarily delivered social and environmental reporting (SER), based on different “levels of empathy” towards different stakeholders.
Design/methodology/approach
The paper adopts an interpretive research design, drawn from Stein’s concept of empathy by using a mixed-method approach. A manual content analysis was performed on 393 cooperative banks’ (CB) social and environmental reports from 2005 to 2013 in Italy, and 14 semi-structured interviews.
Findings
The results show that CBs voluntarily disclose information in different ways to different stakeholders. According to Stein, the phenomenological concept of empathy, and its understanding within institutions, allows us to interpret these multiple perspectives within a single social and environmental report. Therefore, when the process of acquiring knowledge in the CB–stakeholder relationship is complete and mentalised (level 3, re-enactive empathy), the SER holds high informative power, consistent with the accountability perspective; on the contrary, when this process is peripheral and perceptional (level 1, basic empathy), the SER tends to provide more self-assessment information, attempting to portray the bank in a positive light, which is consistent with the legitimacy perspective.
Originality/value
The concept of empathy introduced in this paper can assist in interpreting the interactions between an organisation and different stakeholders within the same social and environmental report. Moreover, the approach adopted in this paper considers different stakeholders simultaneously, thus responding to previous concerns regarding the lack of focus on multiple stakeholders.
Constituting the governable NGO: The correlation between conduct and counter-conduct in the evolution of funder-NGO accountability relations
ACCOUNT ORG SOC
Roel Boomsma
Brendan O'Dwyer
This paper mobilises a governmentality framing drawing on Miller and Rose (1990) and Rose and Miller (1992) to examine how fluctuating rationalities and programmes of government shaped the construction of accountability over several decades in the relationship between Dutch development NGOs and their governmental funder. It unveils a dynamic, mutually constitutive interrelationship between an assortment of NGO accountability technologies and the shifting rationalities and programmes that underpinned their emergence and adoption. We show how a rationale idealising improved NGO accountability through quality improvement underwent constant modification in a context where programmes seeking to facilitate this ideal were congenitally failing and continually altered. Within these efforts to shape the conduct of NGOs we call attention to the constitutive role of NGO ‘counter-conduct’ – conduct by NGOs motivated by a desire to be governed differently (Foucault, 2007). We uncover what Foucault (2007) refers to as the “correlation between conduct and counter-conduct” (p. 196) in the process through which accountability technologies were mutually moulded in the interactions between NGOs and their governmental funder; a correlation frequently overlooked in analyses of governmentality. We unearth five interrelated forms of NGO counter-conduct - associating self-governance with good governance; concentrating engagement at the programmatic level; pre-emption; ‘working around’ core programmatic aims; and aligning the ‘rules of competition’ with existing expertise. We illustrate how this counter-conduct was initially, albeit not ultimately, constitutive of governmentality as it stimulated shifts towards programmatic aims of cost consciousness, increased professionalisation, and enhanced NGO cooperation. Within this process, the creation of competition for funding among NGOs emerged as an objective of accountability thereby offering a counterpoint to prior research which frequently perceives competition for funding as an explanation for increased attention to NGO accountability.
Rhetoric as a form of persuasion in disclosing poverty-related CSR activities in corporate disclosures: The case of Bangladesh
Jan 2017
Nik Nazli Nik Ahmad
Siti Alawiah Siraj
Dewan Mahboob Hossain
Manuscript type: Research paper. Research aim: This study aims to identify the persuasive strategies applied by Bangladeshi companies in disclosing poverty related corporate social responsibility (CSR) activities in their annual reports. Design/ Methodology/ Approach: This study applies the discourse analysis as an approach in exploring the narratives of Bangladeshi companies’ annual reports. It specifically focuses on the three classifications of Aristotle’s rhetoric while explanations are also drawn from the impression management theory. Research findings: This study concludes that the disclosures of the Bangladeshi companies’ CSR activities are rhetorical in nature. The analysis suggests that these companies try to portray themselves as pro-social and helpful towards the poor. Theoretical contribution/ Originality: Rather than focusing on ‘what’ was disclosed (which is the objective of most prior studies on CSR reporting in Bangladesh), this study highlights ‘how’ the disclosure was done. This study also focuses on a particular aspect which is poverty related and a linguistic analysis is used to perform the analysis which is unlike previous studies. Practitioner/ Policy implication: This study calls for the participation of regulators and stakeholders in introducing appropriate regulations that can ensure a ‘balanced’ disclosure of the companies’ CSR activities so that stakeholders are not misled. Research limitation: The main limitation of this research is that it focuses on only one kind of impression management strategies, namely rhetorical appeals.
Social movement NGOs and the comprehensiveness of conflict mineral disclosures: evidence from global companies
ACCOUNT ORG SOC
Muhammad Azizul Islam
Chris J Van Staden
Conflict minerals refer to raw materials associated with conflicts and human rights violations in conflict zones around the world. Concern about the lack of transparency in the mineral supply chains of global corporations has led to increased stakeholder concern and pressure through protest action. In particular since 2009, numerous public-private collaborations, including collaborations with NGOs and industry-led initiatives, have sought greater transparency in companies' sourcing from conflict mineral zones. This has led to the enactment of the 'Dodd-Frank Act' in the US to regulate the disclosure of involvement in conflict minerals. This requirement suggests that corporate obligations now go beyond their own operations and that companies are held accountable for the actions of their suppliers with regards to their supply chains.While the act requires minimum disclosure by companies, we hypothesise that companies' collaboration with social movement NGOs and activist protests against companies will influence the comprehensiveness of their conflict mineral disclosures. Our hypothesis is grounded in social movement theory and the theory of collaboration. We test our hypothesis by focusing on a sample of global electronic reliant companies from 20 countries. Consistent with our expectations, we find that collaboration with NGOs (as social movement organizations) and activist protest lead to more comprehensive, and therefore more transparent, disclosures. Our findings suggest that in the presence of activist protest, NGO collaboration with corporations has a higher impact on the comprehensiveness of conflict mineral disclosures. Furthermore, the marginal effects on disclosure are more strongly driven by NGO collaboration than activist protest. Our findings have practical and policy implications in that improved corporate transparency is the result of social movement actions via NGOs, i.e., regulation on its own may not result in comprehensive disclosures.
Introduction: Discourse Studies — Important Concepts and Terms
Chapter
Jan 2008
Ruth Wodak
Exploring the implications of integrated reporting on organisational reporting practice: Evidence from highly regarded integrated reporters
Article
Oct 2016
Abdifatah Ahmed Haji
Dewan Mahboob Hossain
Purpose
The purpose of this paper is to examine “how” the adoption of integrated reporting (IR), and the embedded multiple capitals framework, has influenced organisational reporting practice. In particular, the paper examines how companies report and integrate multiple capitals in various organisational reporting channels following the introduction of an “apply or explain” IR requirement in South Africa.
Design/methodology/approach
Using a qualitative case study approach based on discourse analysis, this paper examines various organisational reports including integrated reports, standalone sustainability reports, websites and other online materials of highly regarded, award-winning, integrated reporters in South Africa over a four-year period (2011-2014), following the introduction of IR requirement. The authors draw five impression management techniques, namely, rhetorical manipulation, thematic manipulation, selectivity, emphasis in visual presentation and performance comparisons to explain disclosure and integration of multiple capitals.
Findings
The authors find that companies are increasingly conforming to reporting language espoused in existing IR guidelines and multiple capital frameworks over time. For instance, it is found that the research cases have increasingly used specific grammars in existing IR guidelines such as “capitals” and “material” issues, with companies acknowledging the “interdependencies” and “trade-offs” between multiple capitals. Companies have also started to recognise that the capitals are subject to “increases, decreases, and transformations” over time. However, the disclosures are generic, rather than company-specific, and lack substance, often framed in synthetic charming aimed to showcase adoption of IR practice. In addition, the current discourse on multiple capital disclosures is one of the defending, even promoting, organisational reputation, rather than recognising how organisational actions, or inactions, impact multiple capitals. The paper concludes that the emerging IR practice, and the embedded multiple capital framework, has not really improved the substance of organisational reports.
Practical implications
The results of this study have a number of implications for regulatory authorities, public and private sector organisations as well as academic researchers. For regulatory authorities, the results inform relevant regulatory authorities how IR practice is taking shape over time, particularly within the context of a regulatory setting. Second, the empirical analyses, which focused on highly regarded, award-wining, integrated reporters, draw the attention of regulatory bodies as well as users of corporate reports to concerns related to a growing number of rating agencies of organisational reports. Finally, for academic researchers, the theoretical implications of this study is that, given the pervasive use of multiple impression management techniques in various organisational reports, the authors support the notion that corporate disclosure practices should be examined through the lens of multiple theoretical perspectives to enhance our understanding of the nature of organisational reporting practice.
Originality/value
This study provides a more focused preliminary empirical account of the implications of IR practice, and the embedded multiple capital frameworks, on the quality of organisational reporting practice following the adoption of mandatory IR requirement in South Africa.
Discourse and Social Psychology
Book
Jan 1994
Jonathan Potter
Margaret Wetherell
Grassroots accountability promises in rights-based approaches to development: The role of transformative monitoring and evaluation in NGOs
Article
Jul 2016
ACCOUNT ORG SOC
Susan O'Leary
The aim of this study is to investigate the rights-based approach to development and how its embedded promise of self-determination is enacted in the accountability relationships between NGOs and their beneficiaries. In doing so, the study seeks to highlight accountability as a process that enacts a specified promise. This occurs not simply in terms of promising to provide an account of conduct or behaviour; instead the promise can stem from moral responsibilities, ones which have transformational and societal implications, and initiate strategic choices (for example, appropriate accounting practices) regarding the enactment of this promise (Brown & Moore, 2001; Dubnick, 2005). This conceptualisation of accountability is proposed as particularly relevant in the context of rights-based NGOs as this development approach has important moral, societal and strategic implications for the manner in which NGOs are accountable to their beneficiaries. The study uses insights from transformative learning theory (Mezirow, 1978) to understand how the promise of self-determination is enacted in these accountability relationships. It presents two case studies of NGOs – RuralLife and Unison - who sought to transform their target communities into active, engaged and self-determined citizens with the support of grassroots accountability practices of monitoring and evaluation.
Legitimacy, accountability and impression management in NGOs: the Indian Ocean tsunami
Sep 2015
Account Audit Account J
Susan Lee Conway
Patricia O'Keefe
Sue Hrasky
Purpose
– Prior research has investigated legitimation strategies in corporate annual reports in the for-profit sector. The purpose of this paper is to investigate this phenomenon in an NGO environment. It investigates Australian overseas aid agencies’ responses to criticism of the relief effort following the Indian Ocean tsunami in 2004. It aims to determine whether voluntary annual report disclosures were reflective of impression management and/or of the discharge of functional accountability.
Design/methodology/approach
– The paper applies content analysis to compare the structure and content of the annual reports of 19 Australian overseas aid agencies before and after the Indian Ocean tsunami.
Findings
– Results suggest voluntary disclosure in annual reports significantly increased post-tsunami and was more consistent with impression management activity rather than functional accountability suggesting a response to the legitimacy challenge. The use of impression management tactics differed with agency size, with larger agencies using ingratiation in order to appear more attractive while smaller ones promoted their particular achievements.
Originality/value
– This paper makes a contribution by extending prior impression management and legitimacy literature to an NGO environment. It has implications for the development of these theories as it looks at organisations where the stakeholders are different from the for-profit sector and profits are not the main concern. It raises issues about the concept of accountability in the NGO sector, and how the nature of organisation reporting is changing to address the challenges of a sector where access to funds is highly competitive.
Impression Management: The Self-Concept, Social Identity, and Interpersonal Relations.
Jul 1981
CONTEMP SOCIOL
Marvin B. Scott
Barry R. Schlenker
The co-construction of NGO accountability
Article
Jan 2015
Account Audit Account J
Roel Boomsma
Brendan O'Dwyer
Purpose
– The purpose of this paper is to deepen and advance the understanding of the construction of accountability within the relationship between government funders and development non-governmental organisations (NGOs).
Design/methodology/approach
– The paper presents a case study examining the process through which an influential Dutch development NGO, Oxfam Novib, constructed its own accountability while simultaneously seeking to influence shifts in government funder accountability requirements. It enrols a combination of comprehensive archival data on the Dutch government’s financing scheme for NGOs from 1965 to 2012 and in-depth interviews with Oxfam Novib managers and Dutch government officials. The co-evolution in accountability within Oxfam Novib and the government funding scheme is conceptualised using the notions of imposed, felt and adaptive accountability
Findings
– The case unveils the dynamics through which accountability within a major government funding scheme for NGOs was co-constructed by Oxfam Novib and the Dutch government’s development aid department. In particular, it reveals how this process was influenced by an internal evolution in Oxfam Novib’s organisational approach to accountability and an institutional context characterised by consensus-based economic and social policy making. The case also unveils the process through which Oxfam Novib’s influence declined as more demanding, narrowly focused government accountability requirements emerged in a setting that was increasingly critical of NGOs.
Originality/value
– The paper presents a rare example of a context where development NGOs have proactively sought and secured influence over the accountability demands of a key donor. It is unique in combining consideration of the internal evolution of accountability within an individual NGO (conceptualised as an evolution from felt to adaptive accountability) with a progression in the form of accountability required by governmental funders. The paper unveils the conditions under which NGO-preferred conceptions of accountability may gain (and lose) influence among key funders.
The advertising of corporate social responsibility in a Brazilian bank
Jan 2013
Int J Bank Market
Edson Roberto Scharf
Josiane Fernandes
Purpose
– Organizations achieve brand awareness through marketing efforts. Studies show that advertising plays a central role in garnering results. The purpose of this paper is to analyze the corporate social responsibility (CSR) advertised by a retail bank in Brazil.
Design/methodology/approach
– Critical discourse analysis (CDA) was adopted, with the three steps proposed by Fairclough: textual analysis, processing analysis, and social analysis. This approach allows in‐depth analysis of the CSR discourse present in communications of organizations with their target.
Findings
– Literature indicates that consumers prefer to obtain personal advantages rather than benefits to the environment in which they live. This could influence organizations’ preference towards communication campaigns that demonstrate CSR actions, and that additionally communicate benefits which individuals receive. However, one of the largest banks using advertising limited to CSR‐specific aspects achieves impressive brand awareness results.
Originality/value
– This study presents evidence that CSR advertising can stimulate brand awareness without using commercial aspects in its content.
Social and Environmental NGOs’ Perceptions of Corporate Social Disclosures: The Case of Bangladesh
Jun 2013
Account Forum
Mahmood Momin
This paper explores the perceptions of Corporate Social Disclosure (CSD) in non-government organisations within the context of a developing country: Bangladesh. Many prior studies have looked at CSD practice from the managerial perspective, while providing less of an insight into non-managerial stakeholder perspectives. Several researchers have argued that the social and environmental accounting literature needs to incorporate the voice of non-managerial stakeholders in CSD development. This paper contributes to the stakeholder-perception-based CSD literature. Semi-structured interviews were carried out in selected social and environmental NGOs of both overseas and Bangladeshi origin. The results suggest that NGO executives are sceptical of current CSD practice. To them, current CSD is ad hoc and no more than a public relations exercise, lacking credibility. Most importantly, owing to structural constraints NGO executives assign lesser significance to CSD than to direct corporate involvement in social development. They described structural constraints as: high levels of poverty, weak governmental structures, dependence on foreign aid and a small group of local business people, lack of awareness of CSD, and an underdeveloped stakeholder relationship. All of these constraints are embedded within the socio-cultural and political history of Bangladesh. NGO executives believe strongly in action rather than words. They suggest that corporations need to engage in social development and to improve their social performance in order to meet their social and environmental responsibilities to the Bangladeshi people.
An Exploration of the Relationship between Language Choice in CEO Letters to Shareholders and Corporate Reputation
Sep 2012
Account Forum
Russell Craig
Niamh M. Brennan
This paper proposes a taxonomy to assist in more clearly locating research on aspects of the association between corporate reputation and corporate accountability reporting. We illustrate how our proposed taxonomy can be applied by using it to frame our exploration of the relationship between measures of reputation and characteristics of the language choices made in CEO letters to shareholders. Using DICTION 5.0 software we analyse the content of the CEO letters of 23 high reputation US firms and 23 low reputation US firms. Our results suggest that company size and visibility each have a positive influence on the extent to which corporate reputation is associated with the language choices made in CEO letters. These results, which are anomalous when compared with those of Geppert and Lawrence (2008), highlight the need for caution when assessing claims about the effects on corporate reputation arising from the language choice in narratives in corporate annual reports.
Impression Management: A Literature Review and Two-Component Model
Jan 1990
Mark Leary
Robin Kowalski
Impression management, the process by which people control the impressions others form of them, plays an important role in interpersonal behavior. This article presents a 2-component model within which the literature regarding impression management is reviewed. This model conceptualizes impression management as being composed of 2 discrete processes. The 1st involves impression motivation—the degree to which people are motivated to control how others see them. Impression motivation is conceptualized as a function of 3 factors: the goal-relevance of the impressions one creates, the value of desired outcomes, and the discrepancy between current and desired images. The 2nd component involves impression construction. Five factors appear to determine the kinds of impressions people try to construct: the self-concept, desired and undesired identity images, role constraints, target's values, and current social image. The 2-component model provides coherence to the literature in the area, addresses controversial issues, and supplies a framework for future research regarding impression management.
The future of the field: Discourse analysis in the 1990s
Jan 1990
TEUN A. DIJK
CEO letters as legitimacy builders: coupling text to numbers
Nov 2010
Kristina Jonäll
Purpose
The purpose of this paper is to describe and interpret the CEO letter in the annual reports of three multinational Swedish companies. This study focuses on the CEOs' comments on accounting principles and rules, on company decisions and actions, and on external events. Examination of CEO letters reveals how CEOs make themselves accountable to readers and establish their own and their companies' legitimacy.
Design/methodology/approach
A strategic design was used to select the three companies;.the three criteria used in making the selection were company nationality, age, and stock market listing. A fourth criterion was that the company had been a nominee in the Stockholm Stock Exchange “Best Annual Report” contest. Based on a social constructivist approach, with inspiration from the field of discourse psychology, a discursive action model (DAM) is applied in this research.
Findings
The analysis shows that the CEO letters at two of the three companies do not emphasize numbers and text. In the third company's CEO letters, the numbers are an important component and are balanced with text. It was found that one explanation of the CEO letter format is the CEO's wish to persuade readers of the company's legitimacy, excellence, and future survival. The CEO letter is intended to strengthen readers' confidence in the company.
Originality/value
This paper provides insight into how CEOs use CEO letters in annual reports to craft a corporate image for readers.
Accountability of NGOs in Bangladesh A critical overview
Jun 2003
NGOs in Bangladesh have been recognized as effective change agents in the socio-economic arena throughout the world. Their contributions in micro credit, non-formal education and primary health care are widely known. NGOs play a significant role in society. NGO accountability, as a result, has become a critical issue. NGO accountability in Bangladesh has been examined here in relation to patrons, clients and themselves. Of the three relationships only accountability to patrons is in a near satisfactory state. Accountability to clients is handicapped by lack of opportunities of beneficiaries to participate meaningfully in NGO policy making. Accountability to themselves is adversely affected due to the adherence to a strictly hierarchical system and the influence of founding and charismatic NGO leaders.
The Shifting Meaning of Governance: Public Accountability of Third Sector Organizations in an Emergent Global Regime
Apr 2002
Int J Publ Admin
Enamul Choudhury
In the context of the global transmission of organizational forms and public values, the traditional boundaries of governance that have relied on legal and organizational measures of answerability are no longer adequate for the meaning of public accountability. With the growing involvement of third sector organizations in governance (through contracting, mobilizing, advocacy, and developmental activities), the traditional meaning of accountability is shifting towards an emergent accountability regime. To identify the global scope of the regime, the paper utilizes a framework of multiple accountability – recently articulated for the nonprofit organizations of the North, and extends its scope to include the accountabili ty expectations and experiences of the non-governmental organizations in the South.
Corporate environmental reporting through the lens of semiotics
Sep 2009
Asian Rev Account
Haslinda Yusoff
Purpose
The purpose of this paper is to understand the motives behind corporate environmental reporting in Malaysia and Australia from an alternative perspective, i.e. through semiotics.
Design/methodology/approach
Reviews are made on the annual reports of the top 50 public companies in both countries, and the uses of business languages in those reports are investigated. The research concentrates on the significations of environmental messages made through paradigmatic and syntagmatic tests.
Findings
Corporate environmental disclosures made by the public companies in Malaysia and Australia signify similar form of motives. The tones, orientations, and patterns of environmental disclosures indicate that environmental information is a strategic mechanism used towards enhancing good corporate reputation.
Research limitations/implications
Environmental reporting plays a significant role in promoting corporate “green” image in conjunction with the aims for better social integration.
Practical implications
Semiotics offers a useful basis that enables a greater understanding of why companies prepare and disclose environmental information. Such an understanding holds the potential to provide ideas and guide policy‐makers, and other stakeholders (and users) of corporate environmental information.
Originality/value
This paper is the first to comparatively investigate the corporate motives and intention of environmental reporting practices via the application of semiotics on a two‐country data, specifically Malaysia and Australia.
From functional to social accountability: Transforming the accountability relationship between funders and non-governmental development organisations
Jun 2007
Account Audit Account J
Purpose
The purpose of this paper is to analyse the evolving nature of the accountability relationship between a group of Irish non‐governmental development organisations (NGDOs) and their primary governmental funder.
Design/methodology/approach
The examination is undertaken in the context of a unique funder‐led initiative to instil a broad social accountability focus among NGDOs while re‐orienting the NGDO‐funder accountability dynamic towards a partnership‐based approach – whereby the accountability entity would effectively be a supra‐organisation comprising the funder and the NGDOs. The empirical content of the paper is derived from a series of in‐depth interviews with senior individuals working within the Irish NGDO sector, along with a comprehensive analysis of documentary sources.
Findings
The partnership rhetoric central to promoting the enhanced focus on social accountability across the “virtual” accountability supra‐organisation has not been transformed into reality, and the NGDO‐funder accountability relationship within the supra‐organisation remains centred on control and justification. A lack of resources, organisational commitment, guidance, and expertise from the governmental funder has contributed to an attitude of scepticism among many NGDOs towards both the partnership rhetoric and the accompanying adoption of the central tenets of social accountability, particularly downward accountability to beneficiaries.
Research limitations/implications
The research is based on a detailed analysis in a specific context which may limit its wider applicability. Nevertheless, it adds insights to the developing academic literature on NGO accountability, with particular reference to their broader social accountabilities.
Practical implications
Although highly context‐specific, the findings of the study will be useful to researchers and policy makers interested in understanding how NGDO‐funder accountability relationships can move towards mutual accountability and genuine partnerships focused on promoting social accountability.
Originality/value
Very few in‐depth academic examinations of the evolving nature of NGDO‐funder accountability relationships in specific NGO contexts have emerged in the accountability literature. Many of the insights in this paper are derived from individuals inside organisations in the NGDO sector who are regularly addressing issues of accountability, both social and otherwise. This provides in‐depth, highly‐informed insider perspectives on the evolving nature of these relationships, especially in the context of attempts to promote more partnership‐based approaches to the delivery of development aid.
Corporate Communication and Impression Management – New Perspectives Why Companies Engage in Corporate Social Reporting
This paper addresses the theoretical framework on corporate social reporting. Although that corporate social reporting has been analysed from different perspectives, legitmacy theory currently is the dominating perspective. Authors employing this framework suggest that social and environmental disclosures are responses to both public pressure and increased media attention resulting from major social incidents such as the Exxon Valdez oil spill and the chemical leak in Bhopal (India). More specifically, those authors argue that the increase in social disclosures represent a strategy to alter the public''s perception about the legitimacy of the organisation. Therefore, we suggest using corporate communication as an overarching framework to study corporate social reporting in which corporate image and corporate identity are central.
| https://www.researchgate.net/publication/369009421_Discourses_on_social_inequality_in_the_NGO_annual_reports_of_Bangladesh_an_analysis_from_the_impression_management_perspective |
Structure and Property Correlations in FeS | Request PDF
Request PDF | Structure and Property Correlations in FeS | For iron-sulfide (FeS), we investigate the correlation between the structural details, including its dimensionality and composition, with its... | Find, read and cite all the research you need on ResearchGate
Structure and Property Correlations in FeS
December 2016
Physica C Superconductivity534
DOI: 10.1016/j.physc.2016.12.006
Authors:
<here is a image f2f62089ad6ff61c-d19572ff1996375a>
S.J. Kuhn
S.J. Kuhn
<here is a image 1937ee36a50dd27a-fa33d150fae83bfe>
Michelle K Kidder
Oak Ridge National Laboratory
<here is a image 2cbfe8ba49c278d9-b83164f219f1864c>
D. S. Parker
Oak Ridge National Laboratory
<here is a image 1937ee36a50dd27a-fa33d150fae83bfe>
Chloe Dela Cruz
Manila Central University
Abstract
For iron-sulfide (FeS), we investigate the correlation between the structural details, including its dimensionality and composition, with its magnetic and superconducting properties. We compare, theoretically and experimentally, the two-dimensional (2D) layered tetragonal ("t-FeS") phase with the 3D hexagonal ("h-FeS") phase. X-ray diffraction reveals iron-deficient chemical compositions of t-Fe0.93(1)S and h-Fe0.84(1)S that show no low-temperature structural transitions. First-principles calculations reveal a high sensitivity of the 2D structure to the electronic and magnetic properties, predicting marginal antiferromagnetic instability for our compound (sulfur height of zS = 0.252) with an ordering energy of about 11 meV/Fe, while the 3D phase is magnetically stable. Experimentally, h-Fe0.84S orders magnetically well above room temperature, while t-Fe0.93S shows coexistence of antiferromagnetism at TN = 116 and filamentary superconductivity below Tc = 4 K. Low temperature neutron diffraction data reveals antiferromagnetic commensurate ordering with wave vector km= (0.25,0.25,0) and 0.46(2) μB/Fe. Additionally, neutron scattering measurements were used to find the particle size and iron vacancy arrangement of t-FeS and h-FeS. The structure of iron sulfide has a delicate relationship with the superconducting transition; while our sample with a =3.6772(7) Å is a filamentary superconductor coexisting with an antiferromagnetic phase, previously reported samples with a > 3.68 Å are bulk superconductors with no magnetism, and those with a ≈ 3.674 Å show magnetic properties.
<here is a image 175d1bd4b7439d95-754927124da715c1>
... Although FeS appears far away from the T -O structural transition and electronic nematic order as demonstrated by extensive experimental results, the possibility of magnetic instabilities in the vicinity of FeS has not been fully explored. Neutron scattering experiments on FeS have revealed magnetic excitations similar to those in other iron-based materials, as well as features reminiscent of magnetic Bragg peaks
[25,
26], while μSR measurements suggest the existence of weak disordered magnetism [27]. ...
... In addition, there is a very broad feature that corresponds to a continuous spread of c-axis spacings as shown in Fig. 3(d). The prominent peak corresponds to a portion of the sample with c = 5.09 ± 0.02 Å, consistent with previous reports of SC FeS [22,
25,
28,33]. We notice that the smaller peak at c = 4.11 ± 0.03 Å corresponds to Q = 1.53 ± 0.01 Å −1 , which is the same as that of the right shoulder at 21.73 • observed in the single-crystal XRD pattern in Fig. 2(b). ...
... In Fig. 4, we show field-dependent splittings of the magnetic susceptibilities between the field-cooling (FC) and zerofield-cooling (ZFC) measurements
[25]
. A weak diamagnetic response presents below 4 K for the ZFC measurements with H ab plane, H = 500 and 1000 Oe. ...
Observation of a C -type short-range antiferromagnetic order in layer spacing expanded FeS
Article
Mar 2020
<here is a image cacfa9bae18d5ecb-a3d69a70730b6614> Meng Wang
<here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Ming Yi
<here is a image ff84860be038c7cf-c5fb1b544aa5ab98> Benjamin Frandsen
R. J. Birgeneau
We report neutron diffraction studies of FeS single crystals obtained from Rb
x
Fe2-y S2 single crystals via a hydrothermal method. While no
5
×
5
iron vacancy order or block antiferromagnetic order typical of Rb
x
Fe2-y S2 is found in our samples, we observe C-type short-range antiferromagnetic order with moments pointed along the c axis hosted by a different phase of FeS with an expanded interlayer spacing. The Néel temperature for this magnetic order is determined to be 170 ± 4 K. Our finding of a variant FeS structure hosting this C-type antiferromagnetic order demonstrates that the known FeS phase synthesized in this method is in the vicinity of a magnetically ordered ground state, providing insights into understanding a variety of phenomena observed in FeS and the related FeSe1-x S
x
iron chalcogenide system.
... The recent discoveries of superconductivity in tetragonal FeS (mackinawite) and the structural, compositional, and electronic property similarities of mackinawite to other iron chalcogenide superconductors have created much excitement. 3,
4
In previously published work, it is evident that there has been a considerable disagreement on the conductivity of FeS with reported semiconducting and metallic properties. 6,7 Many authors have recently, however, reported the metallic behavior of mackinawite at room temperature. ...
... 6,7 Many authors have recently, however, reported the metallic behavior of mackinawite at room temperature. 8−12 There are only a few reports of superconductivity, particularly when hydrothermal synthesis was employed,
4,
8,10,11,13 due to both challenges in synthesizing a phase-pure stoichiometric material and its very low superconducting transition temperature (T c = 3.5−5 K), which decreases with increasing pressure in contrast to the FeSe system. 1 Efforts have been made to increase the T c of FeS from 5 to 8 K by metal hydroxide intercalation. 14 Finding a physical approach to increase the T c , however, is still a challenge. ...
Morphology Control in the Hydrothermal Synthesis of FeS Nanoplatelets
Article
Jul 2020
CRYST GROWTH DES
<here is a image c689c5df3c5f5906-59c41d537ac6335a> Melonie Thomas
<here is a image fedf38cc786d5450-1ec02b65740c4719> Ahamed Ullah
<here is a image ded2f08f72627e81-c5935052411e3d52> Rose Pham
<here is a image c0764d310e5f8c81-406b3c6fe4f492ff> John P. Selegue
FeS nanoplatelets were synthesized using a surfactant-assisted hydrothermal synthesis. The product is highly crystalline and has a preferred growth direction with a [001] plate normal. The platelet diagonal, thickness, and shape can be controlled by varying the iron starting material or the surfactant employed in the synthesis. The diagonal and thickness of the nanoplatelets were found to reduce by factors of up to 22 and 8×, respectively, when an Fe(II)-containing iron source—rather than Fe(III)—was employed in the synthesis. Specific combinations of the surfactant and the iron source were seen to determine the platelet shape, resulting in rectangular, polygonal, and shard-like shapes.
... [12][13][14][15][16][17] In fact, since more than a century, pyrrhotite has been an important test material for understanding of magnetism in matter. [18][19][20]
[21]
Characteristic properties of monoclinic 4C pyrrhotite are its peculiar magnetic anisotropy with an extremely strong hard axis along the c-direction 18,19,22,23 and a phase transition at around 30 K, which is indicated among others by the decrease of the spontaneous magnetization and resistivity. 24,25 The transition is important in rock and paleomagnetism because it serves as a key to detect monoclinic pyrrhotite in geological and extraterrestrial bodies. ...
... 6,8,10 The underlying mechanism of the transition is controversial in matters of a crystallographic or a magnetic origin.
21,
[25][26][27] Several neutron diffraction and M€ ossbauer spectroscopic studies provided an insight into the low-temperature properties of 4C pyrrhotite but could not yield a concluding answer to this question. 14,26,28,29 In two recent studies on single crystals, magnetic rotational symmetry data were used as a strong argument that the anisotropy breaking associated with the low-temperature transition stems from a crystallographic change in the 4C pyrrhotite similar to that known for the classical Verwey transition in magnetite. ...
Ordered defects in Fe 1− x S generate additional magnetic anisotropy symmetries
Article
Full-text available
Jan 2018
<here is a image 9cc1d4fb55d23a32-3f885c0e12eb1c6b> Dimitrios Koulialias
<here is a image 1937ee36a50dd27a-fa33d150fae83bfe> M. Charilaou
<here is a image 65116b3b6a9a9e9c-d14839c19ea081dd> Robin Schäublin
<here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Andreas U. Gehring
Non-stoichiometric monoclinic 4C pyrrhotite (Fe7S8), a ferrimagnetic monosulfide that has been intensively used as a remanence carrier to infer the magnetization of the Earth's crust and extraterrestrial materials, exhibits a characteristic low-temperature transition accompanied by complex modifications in anisotropy and magnetization. We demonstrate that the magnetic rotational symmetry of the 4C pyrrhotite is critically affected by the order of the defective Fe-sites, and this in turn is a key to decipher the physics behind the low-temperature transition. Our torque experiments and numerical simulations show an emergent four-fold rotational symmetry in the c-plane of the 4C pyrrhotite at T < 30 K. This symmetry breaking associated with the transition is caused by the competitive interaction of two inherently hexagonal systems generated by two groups of Fe-sites with different local anisotropy fields that stem from the vacancy arrangement in the 4C stacking sequence, and it is triggered by changes in the spin orbit coupling due to the overlap of Fe-Fe electron orbitals at low-temperature. This mechanism provides a new explanation for the magnetic transition in 4C pyrrhotite at low temperature and could also cast light on non-trivial magnetic phenomena in defective systems.
... All the three samples showed a semiconductor-like behaviour, that is, R xx increases with decreasing temperature. However, when the temperature is further reduced to around 70 K, a gradual crossover to a metallic conducting behaviour is found due to a structural phase transition accompanied by a magnetic transition [31][32][33][34]
[35]
. Interestingly, we find that T s decreases from 80 K for 1T-FeS, 63 K for 1T-FeSe and 49 K for 1T-FeTe. ...
Composition and phase engineering of metal chalcogenides and phosphorous chalcogenides
Article
Full-text available
Jun 2022
NAT MATER
<here is a image 91ca2354c3d8c971-ca346bd88075c435> Jiadong Zhou
<here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Chao Zhu
<here is a image d65efca7bf3f554a-d1bae70be695b94c> Yao Zhou
<here is a image 70201d9743f7db39-6897b60d3c5295ae> Zheng Liu
Two-dimensional (2D) materials with multiphase, multielement crystals such as transition metal chalcogenides (TMCs) (based on V, Cr, Mn, Fe, Cd, Pt and Pd) and transition metal phosphorous chalcogenides (TMPCs) offer a unique platform to explore novel physical phenomena. However, the synthesis of a single-phase/single-composition crystal of these 2D materials via chemical vapour deposition is still challenging. Here we unravel a competitive-chemical-reaction-based growth mechanism to manipulate the nucleation and growth rate. Based on the growth mechanism, 67 types of TMCs and TMPCs with a defined phase, controllable structure and tunable component can be realized. The ferromagnetism and superconductivity in FeXy can be tuned by the y value, such as superconductivity observed in FeX and ferromagnetism in FeS2 monolayers, demonstrating the high quality of as-grown 2D materials. This work paves the way for the multidisciplinary exploration of 2D TMPCs and TMCs with unique properties. A competitive-chemical-reaction-based growth mechanism by controlling the kinetic parameters can easily realize the growth of transition metal chalcogenides and transition metal phosphorous chalcogenides with different compositions and phases.
... In contrast to FeSe, the x-ray diffraction experiment indicated no structural transition down to 10 K in FeS [4,
5]
. The T c of FeS continuously decreases for hydrostatic pressures up to 2.2 GPa [6], while a second superconducting dome for higher pressures from 5 to 22.3 GPa has been observed with an enhanced T c [7]. ...
Thermoelectricity and electronic correlation enhancement in FeS by light Se doping
Article
Jan 2022
<here is a image be066ea2a64ea194-7234e4b44d69406c> Yu Liu
<here is a image 818474d46b9ba389-a2f3481367212d48> Aifeng Wang
Valentin N. Ivanovski
<here is a image fef274c10af9db33-5eeb2afcbf72d15c> C. Petrovic
We report thermoelectric studies of FeS1−xSex (x=0,0.06) superconducting single crystals that feature high irreversibility fields and critical current density Jc comparable to materials with much higher superconducting critical temperatures (Tc's). The ratio of Tc to the Fermi temperature TF is very small, indicating weak electronic correlations. With a slight selenium substitution on sulfur site in FeS both Tc/TF and the effective mass m* rise considerably, implying increase in electronic correlation of the bulk conducting states. The first-principle calculations show rise of the density of states at the Fermi level in FeS0.94Se0.06 when compared to FeS, which is related not only to Fe but also to chalcogen-derived electronic states.
... Among the most known compounds are mackinawite (FeS 1-x ), troilite (FeS), pyrrhotite (Fe 1-x S), greigite (Fe 3 S 4 ), pyrite (FeS 2 ), and marcasite (FeS 2 ). These compounds may exhibit antiferromagnetic, p-type metallic conductivity or superconductivity [25][26]
[27]
. Among other uses, iron sulfides such as pyrite, pyrrhotite, and mackinawite have been studied for wastewater treatment to remove toxic metals, radionuclides, and organic contaminants [28]. ...
Hybrid Materials Based on Pyrrhotite, Troilite, and Few-Layered Graphitic Nanostructures: Synthesis, Characterization, and Cyclic Voltammetry Studies
Article
Jun 2021
APPL SURF SCI
<here is a image cd1b56dbc80a0f39-0b8ee378607d79ac> Cristina L. Rodríguez-Corvera
Ana Laura Elías
<here is a image 5673268f628adcd6-5fa2dc8ac6aaeab7> Aarón Morelos-Gómez
<here is a image 30b108bf1da61830-914e0ef2a2e52259> Florentino López-Urías
Hybrid nanomaterials are complex systems containing two or more types of nanostructures that can be joined covalently or via Van der Waals forces to form a hybrid nanomaterial. In this work, we produced hybrid carbon nanomaterials with embedded FeS-based nanoparticles through a facile one-step AACVD method at 850 °C in a two-furnace approach. A nebulized solution containing n-hexane and ferrocene was employed as a carbon and iron source. As nitrogen and sulfur source, thiourea powder was evaporated in the first furnace taking into account its main endothermic process that occurs at ∼180 °C and ∼220 °C. Therefore, we use three temperatures, close to these values (190°C and 230°C), and another temperature above (290°C). The results show a strong dependence between the evaporation temperature of thiourea and the synthesized structure. At the lower temperature we obtain flower-like carbon fibers with embedded troilite nanoparticles. At the intermediate thinner fibers covered by troilite and pyrrhotite rod nanoparticles were formed, which in turn, are enclosed by few graphitic layers (8GL). At a higher temperature of ∼ 290 ° C, large FeS nanostructures with hexagonal platelet morphology and few graphite layers prevailed. XRD characterizations revealed graphitic carbon, FeS troilite, and Fe7S8 pyrrhotite phases. Through cyclic voltammetry measurements, the electrochemical processes involved in the synthesized carbon nanohybrids were qualitatively studied. By X-ray photoelectron spectroscopy analysis (XPS) the nitrogen and sulfur co-doping were observed for all samples, as well as the presence of oxygen, nitrogen and sulfur functional groups which vary in their atomic content for each case.
... Superconductivity in FeS has been observed below T c ¼ 5 K [6] with some variation due to sample dependence
[14]
. Scanning tunneling spectroscopy points to strong-coupling superconductivity [15], and Hall conductivities can be fitted with a two-band model [16]. ...
Two-Dome Superconductivity in FeS Induced by a Lifshitz Transition
Article
Full-text available
Sep 2018
<here is a image 081d087f1cf6df16-45bcaae57d79330d> Makoto Shimizu
<here is a image d5876cfaea86eac8-081964c8d71dff65> Nayuta Takemori
Daniel Guterding
Harald O. Jeschke
Among iron chalcogenide superconductors, FeS can be viewed as a simple, highly compressed relative of FeSe without a nematic phase and with weaker electronic correlations. Under pressure, however, the superconductivity of stoichiometric FeS disappears and reappears, forming two domes. We perform electronic structure and spin fluctuation theory calculations for tetragonal FeS in order to analyze the nature of the superconducting order parameter. In the random phase approximation, we find a gap function with d-wave symmetry at ambient pressure, in agreement with several reports of a nodal superconducting order parameter in FeS. Our calculations show that, as a function of pressure, the superconducting pairing strength decreases until a Lifshitz transition takes place at 4.6 GPa. As a hole pocket with a large density of states appears at the Lifshitz transition, the gap symmetry is altered to sign-changing s wave. At the same time, the pairing strength is severely enhanced and increases up to a new maximum at 5.5 GPa. Therefore, our calculations naturally explain the occurrence of two superconducting domes in FeS.
... Very recently commensurate magnetic order with a wave vector of q = (0.25,0.25,0) was found in FeS below T N = 116 K using neutron powder diffraction.
39
In the Raman spectra no anomalies can be seen around 120 K even if the range is studied with fine temperature increments of 10 K as shown in Appendix B. However, a small change in the temperature dependence of the c-axis parameter is observed around 100 K by XRD 18 which could be related to this type of magnetic order. Since the influence on the volume is small there is no detectable impact on the phonons. ...
Phonon anomalies in FeS
Article
Full-text available
Dec 2017
A. Baum
A. Milosavljević
<here is a image 38e2f865219aa885-1ac4c031a7b61b05> Nenad Lazarević
<here is a image c2de40cb810aaca3-8b23ceb0668524d7> R. Hackl
We present results from light scattering experiments on tetragonal FeS with the focus placed on lattice dynamics. We identify the Raman active A1g and B1g phonon modes, a second order scattering process involving two acoustic phonons, and contributions from potentially defect-induced scattering. The temperature dependence between 300 and 20K of all observed phonon energies is governed by the lattice contraction. Below 20K the phonon energies increase by 0.5-1 cm$^{-1}$ thus indicating putative short range magnetic order. Along with the experiments we performed lattice-dynamical simulations and a symmetry analysis for the phonons and potential overtones and find good agreement with the experiments. In particular, we argue that the two-phonon excitation observed in a gap between the optical branches becomes observable due to significant electron-phonon interaction.
... The real partition coefficient can be thoroughly understood and taken into account by considering the different charged microspecies that can interact with the biological substrate. 19,
20
Ofloxacin affinity versus membranes, under various environmental conditions, is very important in determining drug passage. Phospholipid vesicles were used as biomembrane models. ...
Combining molecular Modeling with experimental methodologies: Mechanism of membrane permeation and accumulation of ofloxacin
Article
Jan 2003
BIOORGAN MED CHEM
<here is a image 1cc4753d4d47ef91-98751ee531d627e7> Massimo Fresta
Salvatore Guccione
<here is a image 62ee1645aa2f22ab-f048f54734f3a3a4> Andrea Rosario Beccari
<here is a image a458eddcd3c5810d-27aa86524913bb85> Giovanni Puglisi
The interaction between ofloxacin, as a model drug of the fluoroquinolone class, and biomembranes was examined as the possible initial step in a transmembrane diffusion process. Dipalmitoylphosphatidylcholine was used for the preparation of biomembrane models. The influence of environmental conditions and protonation on molecular physicochemical behavior, and hence on the membrane interaction, was investigated by differential scanning calorimetry (DSC). This technique has been shown to be very effective in the interpretation of interactions of drug microspeciations with biomembranes. These findings suggest that the interaction occurred owing to ionic and hydrophobic forces showing how the passage through the membrane is mainly favored in the pH interval 6-7.4. It was demonstrated that a pH gradient through model membranes may be responsible for a poorly homogeneous distribution of ofloxacin (or other related fluoroquinolones), which justifies the in vivo accumulation properties of this drug. DSC experiments, which are in agreement with computational data, also showed that the complexing capability of ofloxacin with regard to Mg(++) or Ca(++) may govern the drug entrance into bacterial cells before the DNA Girase inhibition and could ensure the formation of hydrophobic and more fluid phospholipid domains on the surface of the model membrane. These regions are more permeable with regard to various solutes, as well as ofloxacin, allowing a so-called 'self-promoted entrance pathway'. The combination of experimental methodologies with computational data allowed a further rationalization of the results and opened new perspectives into the mechanism of action of ofloxacin, namely its interaction with lipid bilayers and drug-divalent cation complex formation, which might be extended to the entire fluoroquinolone class. Ofloxacin accumulation within Escherichia coli ATCC 25922 was measured as a function of time. Also in this example, the environmental conditions influenced ofloxacin penetration and accumulation. The in vitro experiments, reported here, show that a suitable balance of hydrophilic and hydrophobic fluoroquinolone properties needs to occur for there to be increased drug permeation.
Vacancy-plane-mediated exfoliation of sub-monolayer 2D pyrrhotite
Article
Full-text available
Jan 2023
Jian-Jhang Lee
Yi-Hung Chiu
Zhi-Long Yen
<here is a image ed213db8f697adc6-90be4a2b70fadf5b> Ya-Ping Hsieh
Conventional exfoliation exploits the anisotropy in bonding or compositional character to delaminate 2D materials with large lateral size and atomic thickness. This approach, however, limits the choice to layered host...
Low thermal expansion for self-compounded Fe1Co S over a wide temperature range
Article
Feb 2023
CERAM INT
Tingjiao Xiong
Xuelian Wang
Peng Tong
<here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Y. P. Sun
Latent heat thermal storage of solid-state phase transition in thermally stabilized hexagonal FeS
Article
Mar 2023
SCRIPTA MATER
Xuelian Wang
<here is a image dd416794fb5e1de1-f34171d6edb47f31> Xuekai Zhang
Peng Tong
<here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Y. P. Sun
Large amounts of heat are required in areas such as food processing and textile industries to maintain equipment in the medium-temperature zone 393–573 K. However, thermal storage materials that work at this temperature are rare. Hexagonal iron sulfide FeS exhibits a solid-state phase transition at 420 K, accompanied by a high entropy change. The quenched FeS is unstable when subjected to a thermal cycling test, and the related entropy change declines. A secondary hexagonal phase with Fe deficiency was confirmed by neutron powder diffractions. Annealing FeS at temperatures slightly higher than Tt can accelerate the formation of the secondary phase. Once the sample is stabilized, the entropy change is no longer changeable. The thermally stabilized FeS sample exhibits a relatively high thermal storage density up to 136 J/cm³. This work suggests a new solid candidate for the application of solid-state phase transition latent heat energy storage in the medium-temperature region.
Latent Heat Thermal Storage of Solid-State Phase Transition in Thermally Stabilized Hexagonal FeS
Article
Jan 2022
Xuelian Wang
<here is a image dd416794fb5e1de1-f34171d6edb47f31> Xuekai Zhang
Peng Tong
<here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Y. P. Sun
Latent Heat Thermal Storage of Solid-State Phase Transition in Thermally Stabilized Hexagonal FeS
Article
Jan 2022
Xuelian Wang
<here is a image dd416794fb5e1de1-f34171d6edb47f31> Xuekai Zhang
Peng Tong
<here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Y. P. Sun
FeS–Ga2S3–In2S3 System
Article
Oct 2021
<here is a image a019e2462c3e530d-eaf6a5b1de836ebf> Faik M. Mammadov
<here is a image 13a1cdfb56fea4b1-ddd3a618448d6873> Dunya Mahammad Babanly
<here is a image 846683b1713c8158-cf3bb63eda67ac8e> Imamaddin Amiraslanov
<here is a image f393570ad3a5aedf-c33d5b3eb445d499> Mahammad Baba Babanly
The superconductivity and transport properties in FeTe with S addition
Article
Oct 2021
VACUUM
<here is a image 58560bdc9108bc40-6e5b2cbda18b9108> Qingshuang Ma
<here is a image 8124f504757f8e97-f72370d53172e3d6> Qiuzhi Gao
Wenze Shan
<here is a image b634c844eb057322-bf805893bd643ed7> Zongqing Ma
In the past few years, iron chalcogenide compounds have attracted considerable attentions due to its unique superconductivity and simplest structure. Till now, many studies have been devoted to explore the superconductivity in iron chalcogenides, including FeSe, FeTe, FeS and their derivatives produced by intermediate doping. However, compared with FeSe, although the superconductivity in S doped FeTe has been widely studied, very few attempts have been reported on the transport properties for this material. Herein the evolution of the superconductivity and the Hall effect up to high S addition levels in FeTe1-xSx (0 ≤ x ≤ 0.5) were studied. It suggests that S substitution for Te sites can effectively suppress the antiferromagnetic ordering and introduce bulk superconductivity in FeTe. The highest Tc ∼9.0 K is achieved in FeTe0.8S0.2 with nominal S content. Hall effect suggests that S addition in FeTe undergoes a reconstruction of hole-type Fermi surface, indicating doping or enhancement of scattering of hole carriers. This work systemically studied the superconductivity of FeTe with S addition and proposes complementary understanding for the intrinsic transport mechanism of iron-based superconductivity.
Chemical Pressure Boost Record‐High Superconductivity in van der Waals Materials FeSe 1− x S x
Article
Full-text available
Jul 2021
ADV FUNCT MATER
<here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Ruijin Sun
<here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Shifeng Jin
<here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Jun Deng
<here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Xiaolong Chen
High pressure has become a powerful platform for creating and controlling novel states of matter, including high temperature (Tc) superconductivity. However, the emergent phenomena generally disappear as high pressure is removed and cloud prospects for future applications. Here, from a distinguishing perspective, FeSe1−xSx is reported as 2D van der Waals materials with extraordinary high‐Tc at ambient pressure, where the superconductivity is boosted by extreme “chemical pressure” inside the materials. Superior to external high pressure, isovalent S substitution in FeSe leads to a much greater compression rate within the superconducting iron‐chalcogenide layer, which guarantees an unabridged superconducting dome that peaked at 37.5 K. Density functional theory calculations reveal that the decreased lattice and structural parameters contribute together for the shift of Fe 3dx2−y2 orbital, which creates a new hole‐pocket at the Fermi level that intimately correlated with the enhanced superconductivity. This study demonstrates the design of materials with optimized superconductivity by introducing chemical pressure. Physical pressure can drastically increase the transition temperature (Tc) of many superconductors. This study shows in tetragonal FeSe, a simple 2D van der Waals material, that isovalent atomic substitution can mimic the effect of high‐pressure and boost record‐high superconductivity under ambient conditions.
Electrical properties and AC susceptibility of FeS added YBa2Cu3O7−δ superconductor
Article
Full-text available
Apr 2021
APPL PHYS A-MATER
M. I. H. Nur-Suraya
<here is a image 17fa7c1633064370-1729af4dd0b86b82> J. Nur-Akasyah
<here is a image 9a2c80eb279097ad-8d6263eafe7a8448> R. Abd-Shukor
The opposing properties of superconductivity and magnetism are an interesting phenomenon. In this work, the effects of antiferromagnetic iron sulfide (FeS) addition on YBa2Cu3O7−δ superconductor were studied. Samples with nominal starting compositions YBa2Cu3O7−δ (FeS)x for x = 0–1.0 wt.% were prepared using the solid-state reaction method. X-ray diffraction patterns showed that the YBa2Cu3O7−δ phase and orthorhombicity were preserved with FeS addition. Scanning electron micrographs showed that addition of FeS decreased the average grain size while maintaining the grain morphology of granular structure. FeS does not suppress the onset transition temperature, Tc onset and AC susceptibility transition temperature, Tcχ, which were found to be in the range of 89–92 K and 92–93 K for all samples, respectively. However, the peak temperature, Tp of the imaginary part of the susceptibility and zero-resistance temperature, Tc zero were severely suppressed with FeS addition. The critical current density at the peak temperature of the imaginary part of the susceptibility, Jc(Tp) for all samples were calculated to be in the range of 16–19 A/cm2. This work showed that FeS affected the connectivity between the grains which weakened the intergranular coupling and decreased the flux pinning energy.
Predictability as a probe of manifest and latent physics: The case of atomic scale structural, chemical, and polarization behaviors in multiferroic Sm-doped BiFeO 3
Article
Mar 2021
Maxim Ziatdinov
<here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Nicole Creange
Xiaohang Zhang
<here is a image 01cfe64b3e98c9a4-7a2d765a08f3e643> Sergei V. Kalinin
The predictability of a certain effect or phenomenon is often equated with the knowledge of relevant physical laws, typically understood as a functional or numerically derived relationship between the observations and known states of the system. Correspondingly, observations inconsistent with prior knowledge can be used to derive new knowledge on the nature of the system or indicate the presence of yet unknown mechanisms. Here, we explore the applicability of Gaussian processes (GP) to establish predictability and uncertainty of local behaviors from multimodal observations, providing an alternative to this classical paradigm. Using atomic resolution scanning transmission electron microscopy (STEM) of multiferroic Sm-doped BiFeO3 across a broad composition range, we directly visualize the atomic structure and structural, physical, and chemical order parameter fields for the material. GP regression is used to establish the predictability of the local polarization field from different groups of parameters, including the adjacent polarization values and several combinations of physical and chemical descriptors, including lattice parameters, column intensities, etc. We observe that certain elements of microstructure, including charged and uncharged domain walls and interfaces with the substrate, are best predicted with specific combinations of descriptors, and this predictability and associated uncertainties are consistent across the composition series. The associated generative physical mechanisms are discussed. It is also found that certain parameter combinations tend to predict the orthorhombic phase in the cases where rhombohedral phase is observed, suggesting a potential role of clamping and confinement phenomena in phase equilibrium in Sm-BiFeO3 system close to morphotropic phase boundary. We argue that predictability and uncertainty in observational data offer a new pathway to probe the physics of condensed matter systems from multimodal local observations.
Large negative thermal expansion promoted by microstructure in hexagonal Fe1-xCoxS
Article
J ALLOY COMPD
X. L. Wang
<here is a image b6ad0385d18bf465-00ac407149ad4b49> Peng Tong
<here is a image a7285ab6aee0de0e-35ebee779739680f> Jianchao Lin
<here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Y. P. Sun
Materials showing negative thermal expansion (NTE) can be used as thermal expansion compensators. Here, we report the NTE behavior in hexagonal Fe1-xCoxS (0 ≤ x ≤ 0.15) alloys. NTE appears near room temperature when x is increased to 0.09, shifts to lower temperature as x increases, and finally disappears for x ≥ 0.15. For x = 0.10, the inherent volumetric coefficient of thermal expansion (αV) measured by diffraction method is about -29.8 ppm/K. However, the value obtained by dilatometric method is increased to -97.2 ppm/K. The pores among the grains in polycrystalline sample are suggested to account for the extra NTE performance. The present study suggests that the NTE of the alloys with anisotropic lattice thermal expansion can be adjusted effectively by controlling the microstructure.
Two-Dimensional Magnetic Materials: Structures, Properties and External Controls
Article
Full-text available
Dec 2020
<here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Shuqing Zhang
<here is a image 3daa531864344f9b-55a500cd89e7c3e7> Runzhang Xu
<here is a image cf95ab64e90312e6-a23b2bf1452ecd70> Nannan Luo
<here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Xiaolong Zou
Since the discovery of intrinsic ferromagnetism in atomically thin Cr2Gr2Te6 and CrI3 in 2017, research on two-dimensional (2D) magnetic materials has become a frontier area. Based on 2D magnetic materials and their heterostructures, exotic physical phenomena in the atomically thin limit have been discovered, such as quantum anomalous Hall effect, magneto-electric multiferroics, and magnon valleytronics. Furthermore, magnetism in these ultrathin magnets can be effectively controlled by external perturbations, such as electric field, strain, doping, chemical functionalization, and stacking engineering. These attributes make 2D magnets ideal platforms for fundamental research and promising candidates for various spintronic applications. This review aims at providing an overview on the structures, properties, and external controls of 2D magnets, as well as the challenges and potential opportunities in this field.
Iron sulfide effects on AC susceptibility and electrical properties of Bi1.6Pb0.4Sr2CaCu2O8 superconductor
Article
Full-text available
M. J. Masnita
<here is a image 9a2c80eb279097ad-8d6263eafe7a8448> R. Abd-Shukor
Magnetism and superconductivity are mutually exclusive phenomena and their interactions are interesting to study. In this work we studied the effects of antiferromagnetic FeS additions on the superconducting properties of Bi1.6Pb0.4Sr2CaCu2O8 (Bi-2212). Samples with starting composition Bi1.6Pb0.4Sr2CaCu2O8(FeS)x for x = 0 to 5.0 wt. % were prepared using the solid state reaction method. The powder X-ray diffraction (XRD) patterns showed that the Bi-2212 phase was dominant in samples with x ≤ 0.2 wt. % (≥ 92 % volume fraction). Field emission scanning electron micrographs showed plate-like structure which increased in flakiness with FeS addition. The non-added samples showed the highest zero resistance temperature, Tc-zero and onset temperature, Tc-onset at 72 K and 83 K, respectively. The peak temperature, Tp of the imaginary part of the AC susceptibility increased for x ≤ 0.2 wt. % samples indicating an increase in the flux pinning force. The x = 5.0 wt. % samples showed the Bi-2212 (63 %) and Bi-2201 (37 %) phase and semiconducting-like behavior without any superconducting transition. This work showed that nano-sized FeS can be used to increase the flakiness and flux pinning force of Bi1.6Pb0.4Sr2CaCu2O8 for x ≤ 0.2 wt. %.
Superconductivity with Tc= 7 K under pressure for Cu-, and Au-doped BaFe2As2
Article
<here is a image 3b5826685217a829-1f13e49155a4e382> Zheng Gai
Li Li
<here is a image 2cbfe8ba49c278d9-b83164f219f1864c> D. S. Parker
A. S. Sefat
It is noteworthy that chemical substitution of BaFe2As2 (122) with the noble elements Cu and Au gives superconductivity with a maximum Tc = 3 K, while Ag substitution (Ag-122) stays antiferromagnetic. For Ba(Fe1-xTMx)2As2, TM= Cu, Au, or Ag, and by doping an amount of x=0.04, a-lattice parameter slightly increases (0.4%) for all TM dopants, while c-lattice decreases (-0.2%) for TM=Cu, barely moves (0.05%) for Au, and increases (0.2%) for Ag. Despite the naive expectation that the noble elements of group 11 should affect the quantum properties of 122 similarly, they produce significant differences extending to the character of the ground state. For the Ag-122 crystal, evidence of only a filamentary superconductivity is noted with pressure. However, for Au and Cu doping (x0.03) we find a substantial improvement in the superconductivity, with Tc increasing to 7 K and 7.5 K, respectively, under 20 kbar of pressure. As with the ambient pressure results, the identity of the dopant therefore has a substantial impact on the ground state properties. Density functional theory calculations corroborate these results and find evidence of strong electronic scattering for Au and Ag dopants, while Cu is comparatively less disruptive to the 122 electronic structure.
Atomic Layer Deposition of Two-Dimensional Layered Materials: Processes, Growth Mechanisms, and Characteristics
Article
<here is a image be1ed57d02251c93-f07eef984a5d109b> Jiyu Cai
Xiaoxiao Han
<here is a image e2e2012a08156c66-34758184db18ab8a> Xin Wang
<here is a image e84a12e16fa5af35-172b3f38b002b739> Xiangbo (Henry) Meng
Since the discovery of graphene, there has been an ever-increasing interest in two-dimensional (2D) layered materials with exceptional properties. To this end, a variety of synthesis methods have been developed. However, it is still challenging to produce large-scale high-quality single-crystalline 2D materials. In this regard, atomic layer deposition (ALD) has recently shown great promise and has stimulated more and more research efforts, ascribed to its unique growth mechanism and distinguished capabilities to achieve nanoscale films with excellent uniformity, unrivaled conformality, and atomic-scale controllability. This review comprehensively summarizes recent progress on ALD for 2D atomic sheets, including 25 different materials and more than 80 ALD processes. This work highlights different technical routes to ALD, their precise controllability, and their underlying principles for 2D materials. It is expected that this work will help boost more research efforts for controllable growth of high-quality 2D materials via ALD.
Unravelling Lewis Acidic and Reductive Characters of Normal and Inverse Nickel-Cobalt Thiospinels in Directing Catalytic H2O2 Cleavage
Article
J HAZARD MATER
Minsung Kim
<here is a image a02a6806fa34ff39-e5580bc4ca360c00> Jung-Hyun Lee
<here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Kim Sangjin
Jongsik Kim
(Inverse) spinel-typed bimetallic sulfides are fascinating H2O2 scissors because of the inclusion of S2-, which can regenerate metals (Mδ+, δ ≤ 2) used to produce •OH via H2O2 dissection. These sulfides, however, were under-explored regarding compositional, structural, and electronic tunabilities based on the proper selection of metal constituents. Motivated by S-modified Niδ+/Coδ+ promising to H2O2 cleavage, Ni2CoS4, NiCo2S4, NiS/CoS were synthesized and contrasted with regards to their catalytic traits. Ni2CoS4 provided the greatest activity in dissecting H2O2 among the catalysts. Nonetheless, Ni2CoS4 catalyzed H2O2 scission primarily via homogeneous catalysis mediated by leached Niδ+/Coδ+. Conversely, NiCo2S4, NiS, and CoS catalyzed H2O2 cleavage mainly via unleached Niδ+/Coδ+-enabled heterogeneous catalysis. Of significance, NiCo2S4 provided Lewis acidic strength favorable to adsorb H2O2 and desorb •OH compared to NiS and CoS, respectively. Of additional significance, NiCo2S4 provided S2- with lesser energy required to reduce M(δ+1)+ via e- transfer than NiS/CoS. Hence, NiCo2S4 prompted H2O2 scission cycle per unit time better than NiS/CoS, as evidenced by kinetic assessments. NiCo2S4 was also superior to Ni2CoS4 because of the elongated lifespan anticipated as •OH producer, resulting from heterogeneous catalysis with moderate Niδ+/Coδ+ leaching. Furthermore, NiCo2S4 revealed the greatest recyclability and mineralization efficiency in decomposing recalcitrants via •OH-mediated oxidation.
Stannites – A New Promising Class of Durable Electrocatalysts for Efficient Water Oxidation
Article
Full-text available
Matthias Driess
<here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Jan Niklas Hausmann
Eva M. Heppke
<here is a image 2b6203065a7802c9-50c843a573d68eb2> Prashanth Menezes
The oxygen evolution reaction (OER) through water oxidation is a key process for multiple energy storage technologies required for a sustainable energy economy such as the formation of the fuel hydrogen from water and electricity or metal‐air batteries. Herein, we investigate the suitability of Cu2FeSnS4 for the OER and demonstrate its superiority over iron sulfide, iron (oxy)hydroxides and benchmark noble‐metal catalysts in alkaline media. Electrodeposited Cu2FeSnS4 yields the current densities of 10 and 1000 mA/cm2 at overpotentials of merely 228 and 330 mV, respectively. State‐of‐the‐art analytical methods are applied before and after electrocatalysis to uncover the fate of the Cu2FeSnS4 precatalyst during OER conditions and to deduce structure‐activity relationships. Cu2FeSnS4 is the first compound reported for OER among the broad class of stannite structure type materials containing multiple members with highly active earth‐abundant transition‐metals for OER.
Core-shell electrospun and doped LiFePO4/FeS/C composite fibers for Li-ion batteries
Article
J ALLOY COMPD
Rattiya Hongtong
<here is a image 38f21d47f73cb8bf-d44a523d7393b6af> Panya Thanwisai
Rattakarn Yensano
<here is a image 493c7d4d81e17949-419e38233659a869> Nonglak Meethong
Core-shell olivine-type electrospun and doped LiFePO4/FeS/C composite fibers were synthesized via a single-step process employing an electrospinning method using LiOH·H2O, metal sul phates, H3PO4, citric acid, and polyvinylpyrrolidone (PVP) as the starting materials. Electron microscopy studies showed that the mean diameter of the core-shell composite fibers was about 280 ± 20 nm with a LiFePO4 phase forming a core with a diameter of about 100 ± 20 nm and a carbon shell with a thickness of 80 ± 20 nm. An FeS phase was formed by a direct reduction of iron (II) sulfate (FeSO4) that was evenly distributed within the core region of the composite fibers and further improved the electronic conductivity of the fibers. Na¹⁺, Mg²⁺, and Al³⁺ doping ions affected fiber morphology and electrochemical performance. All composite fibers showed excellent electrochemical performance. However, Al³⁺ ions improved the electrochemical performance of the composite fibers to a significantly greater degree than Na¹⁺ and Mg²⁺ doping ions, increasing the electronic and ionic conductivities of the material while maintaining their core-shell composite fiber characteristics.
Grasping Periodic Trend and Rate-Determining Step for S-Modified Metals of Metal Sulfides Deployable to Produce OH via H2O2 Cleavage
<here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Kim Sangjin
<here is a image 39d3f0717d8ee518-6bc52c8c7e75d9eb> Satadeep Bhattacharjee
Iron sulfides are fascinating catalytic phases because these include S-modified Fe δ+ (δ ≤ 2) species functioning as H 2 O 2 activators to form [rad] OH used for oxidatively degrading aqueous contaminants (e.g., phenol). As an initial step for locating S-modified metal species (M δ+ ) that outperform Fe δ+ in catalytic H 2 O 2 cleavage, hexagonal metal sulfides (MS) were synthesized using Mn, Fe, Co, Ni, and Cu to understand electric potential-assisted H 2 O 2 scission kinetics on M δ+ species. Ni δ+ species were found to show the greatest [rad] OH productivity among all M δ+ species studied, mainly resulting from the Lewis acidic nature of Ni δ+ species adequate to expedite the liberation of [rad] OH species. This was partially evidenced by H 2 O 2 activation/phenol degradation runs on M δ+ species, wherein initial H 2 O 2 activation rate (-r H2O2,0 ) or initial phenol degradation rate (-r PHENOL,0 ) of Ni δ+ species was 3–9 times those of the other M δ+ species. Ni δ+ species, therefore, were located in the middle of the volcano-shaped curve plotting -r H2O2,0 (or -r PHENOL,0 ) versus the type of M δ+ . Kinetic assessment of M δ+ species under fine-tuned reaction environments also showed that regardless of varying H 2 O 2 concentrations, M δ+ species were found to retain their -r H2O2,0 values in the absence of electric potentials. Conversely, M δ+ species could enhance -r PHENOL,0 values at larger electric potentials, where greater energies were likely exerted on M δ+ species. This indeed corroborated that [rad] OH desorption from M δ+ species was the rate-determining step to direct catalytic H 2 O 2 scission. In addition to heterogeneous catalytic nature of Ni δ+ species in fragmenting H 2 O 2 , outstanding H 2 O 2 scission ability provided by Ni δ+ species could also compensate for their moderate catalytic stability at pH-neutral condition.
Accurate determination of the Fermi surface of tetragonal FeS via quantum oscillation measurements and quasiparticle self-consistent GW calculations
We perform de Haas–van Alphen measurements and quasiparticle self-consistent GW (QSGW) calculations on FeS. The calculated Fermi surface (FS) consists of two hole and two electron cylinders. We observe all the eight predicted FS cross sections experimentally. With momentum-independent band-energy adjustments of less than 0.1 eV, the maximum deviation between the calculated and observed cross sections is less than 0.2% of the Brillouin zone area for B∥c. The carrier density is ∼0.5 carriers/Fe. The mass enhancements are nearly uniform across the FS cylinders and moderate, ∼2. The absence of a third hole cylinder with dxy character is favorable for the formation of a nodal superconducting gap.
Quantum magnetism in minerals
<here is a image 1937ee36a50dd27a-fa33d150fae83bfe> D. S. Inosov
The discovery of magnetism by the ancient Greeks was enabled by the natural occurrence of lodestone – a magnetized version of the mineral magnetite. Nowadays, natural minerals continue to inspire the search for novel magnetic materials with quantum-critical behaviour or exotic ground states such as spin liquids. The recent surge of interest in magnetic frustration and quantum magnetism was largely encouraged by crystalline structures of natural minerals realizing pyrochlore, kagome, or triangular arrangements of magnetic ions. As a result, names like azurite, jarosite, volborthite, and others, which were barely known beyond the mineralogical community a few decades ago, found their way into cutting-edge research in solid-state physics. In some cases, the structures of natural minerals are too complex to be synthesized artificially in a chemistry lab, especially in single-crystalline form, and there is a growing number of examples demonstrating the potential of natural specimens for experimental investigations in the field of quantum magnetism. On many other occasions, minerals may guide chemists in the synthesis of novel compounds with unusual magnetic properties. The present review attempts to embrace this quickly emerging interdisciplinary field that bridges mineralogy with low-temperature condensed-matter physics and quantum chemistry.
Heat Transfer Characteristics of Aluminum Sputtered Fabrics
Al was sputtered onto four substrates: nylon, polyester, cotton/polyester, and shape memory polyurethane nanoweb, and the heat-transfer characteristics of the resultant materials were investigated by surface temperature measurements. The thickness of the Al layer increased linearly with sputtering time. The heat-transfer mechanisms of the multilayer systems in terms of conduction, convection, and radiation were investigated under steady-state conditions using a hot plate as a heat source in contact with Al-sputtered fabrics. The Al-sputtered fabric was placed on the hot plate, which was maintained at 35 °C, and exposed to open air, which was maintained at 15 °C. The temperatures of the air-facing surfaces of hot plate-Al-fabric-air (i.e., Al-phase-down) and hot plate-fabric-Al-air (i.e., Al-phase-up) systems were used to investigate the heat-transfer mechanism. It was found that heat dissipation to ambient air was much higher for the Al-phase-up system than for the Al-phase-down system. Heat-transfer coefficients of the Al surfaces were calculated and found to increase with the thickness of the Al layer. Furthermore, different conductive thermal resistances were observed for different fabrics prepared with the same Al-sputtering time. Consequently, differences in their thicknesses, pore sizes, and thermal conductivities were suggested to have significant effects on their heat-transfer properties.
Nanocrystalline Iron Monosulfides Near Stoichiometry
<here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Dennice Roberts
<here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Alyssa Landin
<here is a image 1613534122031691-69e361a8012ed05d> Tim Ritter
<here is a image 4bac20eae3ad16dc-583a489ac1025799> Conrad Stoldt
Solids composed of iron and sulfur are earth abundant and nontoxic, and can exhibit interesting and technologically important optical, electronic, and magnetic phenomena. However, the iron-sulfur (Fe-S) phase diagram is congested in regions of slight non-stoichiometric iron vacancies, and even when the iron atomic composition changes by even a few percent at standard temperature and pressure, there are myriad stable crystal phases that form with qualitatively different electronic properties. Here, we synthesized and characterized nanocrystals of the pyrrhotite-4M structure (Fe7S8) in an anhydrous oleylamine solvent. Upon heating from 140 °C to 180 °C, the solid sequentially transformed into two kinetically trapped FeS intermediate phases before reaching the pyrrhotite-4M final product. Finally, we assessed the effects of iron vacancies using the stoichiometric end-member, troilite, as a reference system. Density functional theory calculations show that iron vacancies in troilite shift the structure from hexagonal FeS to a monoclinic structure, similar to crystal structures of pyrrhotites, and suggest that this iron deficient troilite may be a stable intermediate between the two crystal structures. The calculations predict that defects also close the band gap in iron deficient troilite.
A visible light FeS/Fe 2 S 3 /zeolite photocatalyst towards photodegradation of ciprofloxacin
<here is a image f3bedbbe40bbd7f9-cd19b8d07b508e3e> Alireza Nezamzadeh-Ejhieh
FeS and Fe2S3 semiconductors were coupled and supported onto clinoptilolite nanoparticles (CN) via sulfidizing of Fe(II) and Fe(III) exchanged CN. The composite was characterized by X-ray diffraction (XRD), scanning electron microscope-energy dispersive x-ray (SEM-EDX), transmission electron microscopy (TEM) and diffuse reflectance spectroscopy (DRS) techniques. To study of the synergistic effects of supporting and coupling, the photocatalytic activities of FeS-CN, Fe2S3-CN and FeS-Fe2S3-CN catalysts were evaluated in the photodegradation of ciprofloxacin (CIP) aqueous solution. The ratio of FeS/Fe2S3 played an important role in the photocatalytic activity of the coupled systems, so the catalyst FF1 which ion exchanged in a solution containing 0.1 mol L⁻¹ Fe(II) and 0.15 mol L⁻¹ Fe(III) showed the best activity in the degradation of CIP. To study the interactions of the experimental variables on the photocatalytic activity of the FeS-Fe2S3-CN catalyst, experiments were designed using response surface methodology (RSM) approach. The best results were obtained in the run with the following conditions: pH 3.7, catalyst dose of 2.8 g L⁻¹, 3.8 mg L⁻¹ of CIP during 102 min irradiation of the suspension. The satisfactory correlation coefficient (R² = 0.9480) for the second order polynomial model, confirmed that the predicted data by RSM well agree with the experimental results.
Structural Analysis of Germanium (Ge)-Containing Ferrous Calcium Silicate Magnesia Slag for Applications of Black Copper Smelting
<here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Mohammad Al Hossaini Shuva
<here is a image aaa07ce63cbb8256-dbc9ca3cb90f2183> M Akbar Rhamdhani
<here is a image 1aaf7ff615369553-3b0a0bd636c7460e> Geoffrey Brooks
<here is a image 224f684c6e3fc27f-51baa64d9e44730d> Markus A Reuter
Ferrous-calcium-silicate (FCS) based slag has been used in the copper industry over the last two decades. The FCS slag has also been used in a secondary copper processing such as in black copper smelting which has different operation conditions compared to that of typical primary copper processing. In the process, a variety of copper bearing scraps from sources such as industrial waste, consumer waste and electronic waste (e-waste) are used. The valuable metals in these secondary resources are distributed in different phases during the process. Understanding the behaviour of the valuable elements at the relevant conditions is vital for optimizing the process and to maximize the recovery of the elements. In this study, we investigated the structure of Ge-containing FCS-based slag at different conditions (oxygen partial pressure and temperature) using Fourier-Transform Infrared (FTIR) spectroscopy to explore the effect of the polymerization on the behaviour of the valuable element Ge in the slag. It was found that experimental parameters significantly influence the slag structure, and therefore, the partitioning of Ge in the slag. A correlation between the distribution ratio of Ge and the slag structure has developed in the current study.
Comparison of band structure and superconductivity in FeSe 0.5 Te 0.5 and FeS
CHINESE PHYS B
<here is a image 44a298f2b9122035-28acb69913c5fc19> Yang Yang
<here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Feng Shi-Quan
<here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Yuan-Yuan Xiang
<here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Wan-Sheng Wang
The isovalent iron chalcogenides, FeSe0.5Te0.5 and FeS, share similar lattice structures but behave very differently in superconducting properties. We study the underlying mechanism theoretically. By first principle calculations and tightbinding fitting, we find the spectral weight of the dX2-Y2 orbital changes remarkably in these compounds. While there are both electron and hole pockets in FeSe0.5Te0.5 and FeS, a small hole pocket with a mainly dX2-Y2 character is absent in FeS. We find the spectral weights of dX2-Y2 orbital change remarkably, which contribute to electron and hole pockets in FeSe0.5Te0.5 but only to electron pockets in FeS. We then perform random-phase-Approximation and unbiased singular-mode functional renormalization group calculations to investigate possible superconducting instabilities that may be triggered by electron-electron interactions on top of such bare band structures. For FeSe0.5Te0.5, we find a fully gapped s-wave pairing that can be associated with spin fluctuations connecting electron and hole pockets. For FeS, however, a nodal dxy (or dx2-y2in an unfolded Broullin zone) is favorable and can be related to spin fluctuations connecting the electron pockets around the corner of the Brillouin zone. Apart from the difference in chacogenide elements, we propose the main source of the difference is from the dX2-Y2 orbital, which tunes the Fermi surface nesting vector and then influences the dominant pairing symmetry.
Topological crystalline antiferromagnetic state in tetragonal FeS
Full-text available
<here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Ning Hao
<here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Fawei Zheng
Ping Zhang
Shun-Qing Shen
Stable magnetic order in materials usually breaks some spatial symmetries such that the electronic structures are strongly reconstructed and present some new features such as Dirac-cone structure. Here, we find that tetragonal FeS is a topological insulator with the pair checker-board antiferromagnetic (PCB-AFM)order, named "topological crystalline antiferromagnetic state", in which, the (010) surface of tetragonal FeS supports non- trivial surface states protected by the product of fractional translation symmetry, mirror symmetry, and time- reversal (TR) symmetry, while other surfaces are topologically trivial due to the glide-plane mirror symmetry breaking. Our finding indicates that the non-trivial topological states could emerge accompanying with some magnetic orders, and the corresponding symmetry breaking provides possible ways to modulate charge and spin transport of surface electrons in these classes of materials.
Multi-layered Chalcogenides with potential for magnetism and superconductivity
PHYSICA C
Li Li
<here is a image 2cbfe8ba49c278d9-b83164f219f1864c> D. S. Parker
Clarina R. dela Cruz
A. S. Sefat
Layered thallium copper chalcogenides can form single, double, or triple layers of Cu-Ch separated by Tl sheets. Here we report on the preparation and properties of Tl-based materials of TlCu2Se2, TlCu4S3, TlCu4Se3 and TlCu6S4, and compare to reports on layered ACu2nChn+1 materials with A = Ba, K, Rb, and Cs, and Ch = S, Se. Having no long-range magnetism for these materials is quite surprising considering the possibilities of inter- and intra-layer exchange interactions through Cu 3d, and we measure by magnetic susceptibility and confirm by neutron diffraction. First principles density-functional theory calculations for both the single-layer TlCu2Se2 (isostructural to the 122 iron-based superconductors) and the double-layer TlCu4Se3 suggest a lack of Fermi-level spectral weight that is needed to drive a magnetic or superconducting instability. The electronic structure calculations show a much greater likelihood of magnetism for multiple structural layers with Fe.
The Prediction of Skin Permeability by Using Physicochemical Data
Article
May 1997
ATLA-ALTERN LAB ANIM
Lisa A. Kirchner
Richard P. Moody
Edward Doyle
Ih Chu
A database on physicochemical properties and skin permeation compiled by Health Canada was analysed by using linear regression analysis. The correlation between permeability coefficient (Kp) and the octanol-water partition coefficient ( Kow) has been improved by grouping the compounds according to their respective molar volumes. Linear regression analysis of the individual groups has demonstrated a positive correlation for the majority of the groups, with the compounds in the lowest molar volume range (≤ 75.Å3) having the best correlation (r2 = 0.86), and the compounds in the highest molar volume range (≥ 301Å3) being the least well-correlated (r2 = 0.55). Due to the diversity of the chemicals used in this analysis, and the statistically significant correlations obtained, this model could permit the prediction of skin permeation of a wide variety of chemical compounds. Although of a Simplistic nature, and not yet experimentally validated, this quantitative structure-activity relationship may be useful for predicting human skin permeability coefficients for compounds that fall within the constraints of this data set.
Understanding the comparative molecular field analysis (CoMFA) in terms of molecular quantum similarity and DFT-based reactivity descriptors
Article
Jun 2015
J MOL MODEL
<here is a image e4129ddd82291d71-8fc315174e6e347f> Alejandro Morales-Bayuelo
Ricardo A. Matute
<here is a image 78ebc205a9d313a9-b8d9d76e9435092f> Julio Caballero
The three-dimensional quantitative structure-activity relationship (3D QSAR) models have many applications, although the inherent complexity to understand the results coming from 3D-QSAR arises the necessity of new insights in the interpretation of them. Hence, the quantum similarity field as well as reactivity descriptors based on the density functional theory were used in this work as a consistent approach to better understand the 3D-QSAR studies in drug design. For this purpose, the quantification of steric and electrostatic effects on a series of bicycle [4.1.0] heptane derivatives as melanin-concentrating hormone receptor 1 antagonists were performed on the basis of molecular quantum similarity measures. The maximum similarity superposition and the topo-geometrical superposition algorithms were used as molecular alignment methods to deal with the problem of relative molecular orientation in quantum similarity. In addition, a chemical reactivity analysis using global and local descriptors such as chemical hardness, softness, electrophilicity, and Fukui functions, was developed. Overall, our results suggest that the application of this methodology in drug design can be useful when the receptor is known or even unknown.
Study of piezoelectric, magnetic and magnetoelectric measurements on SrBi 3Nb 2FeO 12 ceramic
Article
Dec 2004
CERAM INT
<here is a image bd8685ede3d1c81c-fe4377ce84ff06e7> Adiraj Srinivas
Freddy Yin Chiang Boey
<here is a image 8df2369ee5b34cf2-58b9d865caaff42c> Thirumany Sritharan
S. V. Suryanarayana
SrBi3Nb2FeO12 (SBNF) is a three-layered perovksite in the system SrBi2Nb2O9 (SBN) + (n). BiFeO3 (BF) system with n=1. In order to achieve the magnetic and magnetoelectric (ME) nature, the material should consist of ferroelectric and magnetic ordering. In the present system, the addition of BiFeO3 to SBN makes the material both ferroelectric and magnetic, to realise magnetoelectric output. The piezoelectric nature of the material is investigated by using the resonance and anti resonance measurement. The magnetisation measurements carried out at room temperature showed a slim hysteresis loop indicating the material consists of antiferromagnetic ordering. The dynamic magnetoelectric measurements performed at room temperature and at 77K, showed that magnetoelectric output is high at 77K.
ChemInform Abstract: The Characterization of Chemical Structures Using Molecular Properties. A Survey
Article
Jun 2010
J Chem Inform Comput Sci
<here is a image cb2c8bdccdef58b4-263a12a966a822e4> David J Livingstone
Generating hypotheses about molecular Structure-Activity relationships (SARs) by solving an optimization problem
Article
Sep 2009
Stat Anal Data Min
<here is a image afb9afa8bc56e8e4-317af42c2a3b767b> Junshui Ma
<here is a image e78a984bcbe97eee-a185e71b2cc21a0d> Christopher Tong
<here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Andy Liaw
<here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Vladimir Svetnik
This paper proposes a new automatic hypothesis-generation algorithm for structure–activity relationship (SAR) rules, which is capable of investigating chemical compound activities in the context of multiple substructure interactions. The algorithm is formulated as an optimization problem based on a carefully selected criterion, APostDiff(s), and the globally optimal solution to the optimization problem can be obtained with a fast search algorithm developed using the data-mining concept known as frequent set. Three public datasets are used to demonstrate the proposed method. Copyright © 2009 Wiley Periodicals, Inc. Analysis and Data Mining 1: 161-174, 2009
Strong anisotropy in nearly ideal-tetrahedral superconducting FeS single crystals
Article
Full-text available
Dec 2015
Christopher K. H. Borg
<here is a image a2ea94330e834a6f-9b56e0806eb141d4> Xiuquan Zhou
Christopher Eckberg
Efrain E. Rodriguez
We report the novel preparation of single crystals of tetragonal iron
sulfide, FeS, which exhibits a nearly ideal tetrahedral geometry with bond
angle of 110.2(2) $^\circ$. Grown via hydrothermal de-intercalation of
K${_x}$Fe${_{2-y}}$S${_2}$ crystals, the silver, plate-like crystals of FeS
remain stable up to 200 $^\circ$C under air and 250 $^\circ$C under inert
conditions, even though the mineral material "mackinawite" (FeS) is known to be
metastable. FeS single crystals exhibit a superconducting state below $T_c$=4~K
as determined by electrical resistivity, magnetic susceptibility, and heat
capacity measurements, confirming the presence of a bulk superconducting state.
Normal state measurements yield an electronic specific heat of 5~mJ/mol-K$^2$,
and paramagnetic, metallic behavior with a low residual resistivity of $\sim
250~\mu\Omega$cm. Magnetoresistance measurements performed as a function of
magnetic field angle tilted toward both transverse and longitudinal
orientations with respect to the applied current reveal a remarkable
two-dimensional behavior. This is paralleled in the superconducting state,
which exhibits the largest known upper critical field $H_{c2}$ anisotropy of
all iron-based superconductors, with $H_{c2}^{||ab}(0) /
H_{c2}^{||c}(0)=$(2.75~T)/(0.275~T)=10. Comparisons to theoretical models for
2D and anisotropic-3D superconductors, however, suggest that FeS is a 3D
superconductor with a large effective mass anisotropy, raising interesting
questions about the comparison to the high-$T_c$ iron-based relatives of this
compound.
Multi-band superconductivity and large anisotropy in FeS crystals
Article
Nov 2015
<here is a image 3ebdb57de0d90f40-873fa7b4a89076d2> Hai Lin
Yufeng Li
Jie Xing
Hai-Hu Wen
By using a hydrothermal method, we have successfully grown crystals of the
newly discovered superconductor FeS, which has an isostructure of the iron
based superconductor FeSe. The superconductivity appears at about 4.5K, as
revealed by both resistive and magnetization measurements. It is found that the
upper critical field is relatively low, with however an rather large anisotropy
$\gamma=[(dH_{c2}^{ab}/dT)/(dH_{c2}^{c}/dT)]_{T_c}\approx6$. A huge
magnetoresistivity (180% at 9T and 5K, H//c-axis) together with a non-linear
behavior of Hall resistivity vs. external field H are observed. The strong
temperature dependent Hall coefficient, non-linear Hall effect and huge
magnetoresistivity indicate a multi-band superconductivity in the new
superconductor FeS.
Structural transition and superconductivity in hydrothermally synthesized FeX (X = S, Se)
Article
Sep 2015
Ursula Pachmayr
<here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Natalie Fehn
<here is a image eeb499f59af30725-48e549c4f90affce> Dirk Johrendt
Tetragonal beta-FeSe obtained by hydrothermal reaction is not superconducting
and transforms to a triclinic structure at 60 K unlike superconducting FeSe
from solid state synthesis, which becomes orthorhombic at 90 K. In contrast,
tetragonal iron sulphide FeS from hydrothermal synthesis is superconducting at
4.8 K but undergoes no structural transition. Our results suggest that the
absence of superconductivity in hydrothermally synthesized FeSe may be
associated to the low-temperature structure with zigzag chains of iron atoms,
which is different from the known orthorhombic Cmme structure of
superconducting FeSe.
Transformation of mackinawite to greigite: An in situ X-ray powder diffraction and transmission electron microscope study
Article
Full-text available
Mar 1997
AM MINERAL
Pamela E. Champness
Alistair R. Lennie
<here is a image cba3c1d3430e6202-53587915050010bd> Simon Redfern
David J. Vaughan
Synthetic mackinawite (tetragonal FeS) has been found to transform rapidly to greigite (Fe3S4) above ∼373 K during heating experiments, as observed by in situ X-ray diffraction. Using monochromatic synchrotron radiation (λ = 0.60233 Å), we measured the unit-cell parameters of both synthetic mackinawite between 293 and 453 K and of greigite formed from this mackinawite between 293 and 593 K. The coefficients of thermal expansion for mackinawite are α1 = α2 = (1.36 ± 0.11) × 10-5, α3 = (2.98 ± 0.12) × 10-5, and αvol = (5.67 ± 0.19) × 10-5 between 293 and 453 K. The coefficients of thermal expansion for greigite are α1 = α2 = α3 = (1.63 ± 0.15) × 10-5, and αvol = (4.86 ± 0.25) × 10-5 between 293 and 593 K. On further heating in situ, we observed the reaction greigite → pyrrhotite + magnetite. Partial transformation of mackinawite to greigite was also observed using transmission electron microscopy (TEM) following in situ heating. Electron diffraction patterns show that (001) of mackinawite is parallel to (001) of greigite, and [110] of mackinawite is parallel to [100] of greigite. This orientation relationship confirms that the cubic close-packed S array in mackinawite is retained in greigite and implies that oxidation of some Fe2+ in mackinawite drives rearrangement of Fe to form the new phase. Small regions of the crystallites show Moiré fringes resulting from the lattice mismatch between mackinawite and greigite. Electron diffraction patterns of mackinawite subjected to prolonged exposure to the atmosphere also show faint spots corresponding to greigite. We propose that in these experiments surplus Fe is accommodated by reaction with either adsorbed O2 or H2O to form amorphous nanophase Fe-O(H). Because greigite is so easily formed by oxidation from mackinawite, greigite should be an important precursor for pyrite nucleation, although any orientation relationship between greigite and pyrite remains to be determined.
Synthesis and Rietveld crystal structure refinement of mackinawite, tetragonal FeS
Article
Dec 1995
A R Lenn1e
<here is a image cba3c1d3430e6202-53587915050010bd> Simon Redfern
<here is a image d40529bb767aa452-ec59b6b219e8deea> Paul F. Schofield
David J. Vaughan
Mackinawite, tetragonal FeS, has been synthesised by reacting iron with Na2S solutions. A Rietveld structure refinement of X-ray powder diffraction data, recorded using X-rays monochromated from synchrotron radiation with a wavelength of 0.6023 A, has been performed. The structure has been refined in the tetragonal s~ace group, P4/nmm, and has the following cell parameters: a = 3.6735(4), c = 5.0328(7) A, V = 67.914(24) A 3. Our refinement shows that the FeS4 tetrahedron in mackinawite is almost perfectly regular, with a much smaller distortion than has been previously reported. An improved X-ray diffraction data set is provided. I~Ywo~s: mackinawite, Rietveld structure refinement, synthesis.
The 40m General Purpose Small-Angle Neutron Scattering Instrument at Oak Ridge National Laboratory
Article
Full-text available
Oct 2012
G. D. Wignall
Katherine M Bailey
Michelle V. Buchanan
<here is a image 36a6dae7d5e226b0-cb5978b677206604> Volker Urban
A high-flux, 40m long small-angle neutron scattering (SANS) instrument has been constructed at Oak Ridge National Laboratory (ORNL). The facility utilizes a mechanical velocity selector, pinhole collimation and a high count-rate (> 105 Hz), large-area (1m2) two-dimensional position-sensitive detector. The incident wavelength ( ), resolution ( / ), incident collimation and sample-detector distance are independently variable under computer control. The detector can translate 45cm off axis to increase the overall Q-range (< 0.001 < Q = 4 -1sin < 1 -1), where 2 is the angle of scatter. The design and characteristics of this instrument are described along with examples of scattering data to illustrate the performance.
Crystal, magnetic, and electronic structures, and properties of new BaMnPnF (Pn = As, Sb, Bi)
Article
Dec 2013
<here is a image 06663e3f9269101d-d9f1c2224d65fdaf> Bayram Saparov
V. O. Garlea
A. S. Sefat
David J. Singh
New BaMnPnF (Pn = As, Sb, Bi) are synthesized by stoichiometric reaction of elements with BaF2. They crystallize in the P4/nmm space group, with the ZrCuSiAs-type structure, as indicated by X-ray crystallography. Electrical resistivity results indicate that Pn = As, Sb, and Bi are semiconductors with band gaps of 0.73 eV, 0.48 eV and 0.003 eV (extrinsic value), respectively. Powder neutron diffraction reveals a G-type antiferromagnetic order below TN = 338(1) K for Pn = As, and below TN = 272(1) K for Pn = Sb. Magnetic susceptibility increases with temperature above 100 K for all the materials. Density functional calculations find semiconducting antiferromagnetic compounds with strong in-plane and weaker out-of-plane exchange coupling that may result in non-Curie Weiss behavior above TN. The ordered magnetic moments are 3.65(5) μB/Mn for Pn = As, and 3.66(3) μB/Mn for Pn = Sb at 4 K, as refined from neutron diffraction experiments.
Tetragonal-to-Orthorhombic Structural Phase Transition at 90K in the Superconductor Fe1.01Se
Article
Full-text available
Jul 2009
Peter W. Stephens
R. J. Cava
Tyrel M. McQueen
A. J. Williams
In this Letter we show that superconducting Fe1.01Se undergoes a structural transition at 90 K from a tetragonal to an orthorhombic phase but that nonsuperconducting Fe1.03Se does not. High resolution electron microscopy at low temperatures further reveals an unexpected additional modulation of the crystal structure of the superconducting phase that involves displacements of the Fe atoms, and that the nonsuperconducting composition shows a different, complex nanometer-scale structural modulation. Finally, we show that magnetism is not the driving force for the phase transition in the superconducting phase.
Density functional study of FeS, FeSe, and FeTe: Electronic structure, magnetism, phonons, and superconductivity
Article
Aug 2008
Alaska Subedi
<here is a image 35c4d376a7ef03d2-349384a44ef07eb8> Lijun Zhang
David J. Singh
<here is a image 2e24b6402a598a6a-3e3559d47816d3c7> Mao-Hua Du
We report density functional calculations of the electronic structure, Fermi surface, phonon spectrum, magnetism, and electron-phonon coupling for the superconducting phase FeSe, as well as the related compounds FeS and FeTe. We find that the Fermi-surface structure of these compounds is very similar to that of the Fe-As based superconductors, with cylindrical electron sections at the zone corner, cylindrical hole surface sections, and depending on the compound, other small hole sections at the zone center. As in the Fe-As based materials, these surfaces are separated by a two-dimensional nesting vector at (π,π). The density of states, nesting, and Fermi-surface size increase, going from FeSe to FeTe. Both FeSe and FeTe show spin-density wave (SDW) ground states, while FeS is close to instability. In a scenario where superconductivity is mediated by spin fluctuations at the SDW nesting vector, the strongest superconductor in this series would be doped FeTe.
Coexistence of superconductivity and a spin density wave in pnictides: Gap symmetry and nodal lines
Article
Full-text available
Jul 2009
Phys Rev B
<here is a image 2cbfe8ba49c278d9-b83164f219f1864c> D. S. Parker
<here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Maxim G Vavilov
Andrey V. Chubukov
<here is a image 1937ee36a50dd27a-fa33d150fae83bfe> I. I. Mazin
We investigate the effect of a spin-density wave (SDW) on s± superconductivity in Fe-based superconductors. We show that, contrary to the common wisdom, no nodes open at the new, reconnected Fermi surfaces when the hole and electron pockets fold down in the SDW state, despite the fact that the s± gap changes sign between the two pockets. Instead, the order parameter preserves its sign along the newly formed Fermi surfaces. The familiar experimental signatures of an s± symmetry are still preserved, although they appear in a mathematically different way. For a regular s case (s++) the nodes do appear in the SDW state. This distinction suggests a specific way to experimentally separate an s± state from a regular s in the pnictides. We argue that recently published thermal-conductivity data in the coexisting state are consistent with the s±, but not the s++ state.
Antiferromagnetism and metal‐semiconductor transition in iron sulfides FeSx, 1≤x≪1.25
Article
Jun 1986
<here is a image 70c35fedd8ef8540-b4ae2fcadbdd4a6c> Sotirios Sakkopoulos
An explanation of the semiconductor‐to‐metal transition in iron sulfides FeS x 1≤x≪1.25 at the β transformation temperature T β is given, based on the splitting of a half‐filled impurity band by the antiparallel arrangement of the magnetic moments on the iron atoms on successive cation layers in these compounds. This impurity band originates from the energy levels associated with dislocations and lattice defects, mainly Fe vacancies. For T≪T β , the splitting produces two impurity subbands separated by a narrow energy gap, which gives semiconducting properties to the compounds. For T≫T β , the antiparallel arrangement of the atomic magnetic moments ceases to exist and the impurity band as a whole bridges completely the energy gap between the valence and conduction bands, giving metallic properties to the sulfides.
Magnetic ordering in tetragonal FeS: Evidence for strong itinerant spin fluctuations
Article
Feb 2011
Phys Rev B
<here is a image dc80e1710ff6a26f-b1f545c2e24e4e17> Kideok D Kwon
Keith Refson
Sharon E. Bone
Garrison Sposito
Mackinawite is a naturally-occurring layer type FeS mineral well-known to be
important in biogeochemical cycles and, more recently, to the development of
microbial fuel cells. Conflicting results have been published as to the
magnetic properties of this mineral, with M\"ossbauer spectroscopy indicating
no magnetic ordering and density functional theory predicting an
antiferromagnetic ground state, similar to the Fe-based high-temperature
superconductors with which it is isostructural and for which it is known that
magnetism is suppressed by strong itinerant spin fluctuations. We investigated
this latter possibility for mackinawite using photoemission spectroscopy (PES),
near-edge X-ray absorption fine structure spectroscopy (XAS), and density
functional theory (DFT) computations. Our Fe 3s core-level PES spectrum of
mackinawite showed a clear exchange-energy splitting (2.9 eV) consistent with a
1 {\mu}B magnetic moment on the Fe ions, while the Fe L-edge XAS spectrum
indicated rather delocalized Fe 3d electrons in mackinawite similar to those in
Fe metal. DFT computations demonstrated that the ground state of mackinawite is
single-stripe antiferromagnetic, with an Fe magnetic moment (2.7 {\mu}B) that
is significantly larger than the experimental estimate and has a strong
dependence on the S height and lattice parameters. All of these trends signal
the existence of strong itinerant spin fluctuations.If strong spin fluctuations
prove to be the mediators of electron pairing in these Fe-based
superconductors, we conjecture that mackinawite may be one of the simplest
Fe-based superconductors.
Extreme sensitivity of superconductivity to stoichiometry in Fe1+δSe
Article
Jan 2009
Phys Rev B
Tyrel M. McQueen
<here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Qing Huang
<here is a image 98c2f627688a00a9-f5a72fa697cf9a56> Vadim Ksenofontov
Robert J. Cava
The recently discovered iron arsenide superconductors appear to display a universal set of characteristic features, including proximity to a magnetically ordered state and robustness of the superconductivity in the presence of disorder. Here we show that superconductivity in Fe1+δSe, which can be considered the parent compound of the superconducting arsenide family, is destroyed by very small changes in stoichiometry. Further, we show that nonsuperconducting Fe1+δSe is not magnetically ordered down to 5 K. These results suggest that robust superconductivity and immediate instability against an ordered magnetic state should not be considered as intrinsic characteristics of iron-based superconducting systems.
Superconductivity in the PbO-Type Structure ??-FeSe
Article
Oct 2008
P NATL ACAD SCI USA
Fong-Chi Hsu
Jiu-Yong Luo
<here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Kuo-Wei Yeh
<here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Maw-Kuen Wu
The recent discovery of superconductivity with relatively high transition temperature (Tc) in the layered iron-based quaternary oxypnictides La[O(1-x)F(x)] FeAs by Kamihara et al. [Kamihara Y, Watanabe T, Hirano M, Hosono H (2008) Iron-based layered superconductor La[O1-xFx] FeAs (x = 0.05-0.12) with Tc = 26 K. J Am Chem Soc 130:3296-3297.] was a real surprise and has generated tremendous interest. Although superconductivity exists in alloy that contains the element Fe, LaOMPn (with M = Fe, Ni; and Pn = P and As) is the first system where Fe plays the key role to the occurrence of superconductivity. LaOMPn has a layered crystal structure with an Fe-based plane. It is quite natural to search whether there exists other Fe based planar compounds that exhibit superconductivity. Here, we report the observation of superconductivity with zero-resistance transition temperature at 8 K in the PbO-type alpha-FeSe compound. A key observation is that the clean superconducting phase exists only in those samples prepared with intentional Se deficiency. FeSe, compared with LaOFeAs, is less toxic and much easier to handle. What is truly striking is that this compound has the same, perhaps simpler, planar crystal sublattice as the layered oxypnictides. Therefore, this result provides an opportunity to better understand the underlying mechanism of superconductivity in this class of unconventional superconductors.
Fe-Te (iron-tellurium)
Jan 1990
H. Okamoto
L.E. Tanner
Coexistence of low-moment magnetism and superconductivity in tetragonal FeS and suppression of T c under pressure
Article
Apr 2016
S. Holenstein
<here is a image 7c581b60fc2f262f-ab8b65d3b10d2cbc> Z. Guguchia
H. Luetkens
Ursula Pachmayr
We report local probe ($\mu$SR) measurements on the recently discovered tetragonal FeS superconductor which has been predicted to be electronically very similar to superconducting FeSe. Most remarkably, we find that low moment ($10^{-2}-10^{-3}\mu_\mathrm{B})$ disordered magnetism with a transition temperature of $T_\mathrm{N}\approx 20$ K microscopically coexists with bulk superconductivity below $T_\mathrm{c}=4.3(1)$ K. From transverse field $\mu$SR we obtain an in-plane penetration depth $\lambda_\mathrm{ab}(0)=223(2)$ nm for FeS. The temperature dependence of the corresponding superfluid density $\lambda_\mathrm{ab}^{-2}(T)$ indicates a fully gapped superconducting state and is consistent with a two gap s-wave model. Additionally, we find that the superconducting $T_\mathrm{c}$ of FeS continuously decreases for hydrostatic pressures up to 2.2 GPa.
Nodal superconducting gap in tetragonal FeS
Article
Mar 2016
Jie Xing
<here is a image 3ebdb57de0d90f40-873fa7b4a89076d2> Hai Lin
Yufeng Li
Hai-Hu Wen
Low-temperature specific heat has been measured in FeS superconductor with the transition temperature of 4.55 K. It is found that the low-temperature electronic specific heat Ce/T can be fitted to a linear relation in the low-temperature region, but fails to be described by an exponential relation as expected by an s-wave gap. We try fittings to the data with different gap structures and find that a model with one or two nodal gaps can fit the data. Under a magnetic field, the field induced specific heat coefficient Δγe=[Ce(H)−Ce(0)]/T shows the Volovik relation Δγe(H)∝H, suggesting the presence of nodal gap(s) in this material.
Magneto-electronic coupling in modulated defect-structures of natural Fe1−xS
Article
Aug 2015
<here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Michalis Charilaou
<here is a image 97da88edfddb6b6d-3c134360226b95ea> Jessica Kind
<here is a image 9cc1d4fb55d23a32-3f885c0e12eb1c6b> Dimitrios Koulialias
<here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Andreas U. Gehring
We provide compelling experimental evidence that the low-temperature transition in natural non-stoichiometric Fe7S8, a major magnetic remanence carrier in the Earth's crust and in extraterrestrial materials, is a phenomenon caused by magnetic coupling between epitaxially intergrown superstructures. The two superstructures differ in their defect distribution, and consequently in their magnetic anisotropy. At T < 30 K, the magnetic moments of the superstructures become strongly coupled, resulting in a 12-fold anisotropy symmetry, which is reflected in the anisotropic magneto-resistance.
Observation of Superconductivity in Tetragonal FeS
Article
Aug 2015
J AM CHEM SOC
Xiaofang Lai
<here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Hui Zhang
<here is a image f54489f9f840cba8-0be50c0ccc601415> Yingqi Wang
<here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Fuqiang Huang
The possibility of superconductivity in tetragonal FeS has attracted considerable interest because of its similarities to the FeSe superconductor. However, all efforts made to pursue superconductivity in tetragonal FeS have failed so far, and it remains controversial whether tetragonal FeS is metallic or semiconducting. Here we report the observation of superconductivity at 5 K in tetragonal FeS that is synthesized by the hydrothermal reaction of iron powder with sulfide solution. The obtained samples are highly crystalline and less air-sensitive, in contrast to those reported in the literature, which are meta-stable and air-sensitive. Magnetic and electrical properties measurements show that the samples behave as a paramagnetic metal in the normal state and exhibit superconductivity below 5 K. The high crystallinity and the stoichiometry of the samples play important roles in the observation of superconductivity. The present results demonstrate that tetragonal FeS is a promising new platform to realize high-temperature superconductors.
Evidence for non-metallic behaviour in tetragonal FeS (mackinawite)
Article
Sep 2014
MATER CHEM PHYS
<here is a image e6a926caf0f57ccd-ddc8705b192e42cc> SJ Denholme
Satoshi Demura
Hiroyuki Okazaki
<here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Yoshihiko Takano
We report conductivity measurements for mackinawite at atmospheric pressure and up to values of 1.64 GPa. As far as the authors are aware, this is the first low temperature transport measurements to be conducted on mackinawite. The sample shows semiconducting-like behaviour up to the maximum pressures applied but with a gradual flattening of the resistivity curve it is tentatively suggested that the system will undergo a semiconductor–metallic transition with a further application of pressure. Interestingly, this contradicts band structure and more recent density functional theory (DFT) calculations which predict a metallic system. However, the experimental data agrees with the original prediction of semiconducting behaviour made by Bertaut 1965. This research also shows that, at least in its parent form, mackinawite does not exhibit a superconductive state unlike its iso-structural counterpart tetragonal FeSe. This is also briefly discussed.
Synthesis and Rietveld Crystal Structure Refinement of Mackinawite, Tetragonal FeS
Article
Dec 1995
Alistair R. Lennie
P. F. SCHOAELD
D. J. V AUGHAN
Mackinawite, tetragonal FeS, has been synthesised by reacting iron with Na2S solutions. A Rietveld structure refinementof X-ray powder diffractipn data, recorded using X-rays monochromated from synchrotron radiationwith a wavelength of 0.6023 A, has been performed. The structure has been refined in the tetragonal sJ'.!lce group, P4/nmm, and has the following cell parameters: a = 3.6735(4), c = 5.0328(7) A, V = 67.914(24) A3.Our refinement shows that the FeS4 tetrahedron in mackinawite is almost perfectly regular, with a much smallerdistortion than has been previously reported. An improved X-ray diffraction data set is provided.
| https://www.researchgate.net/publication/311853801_Structure_and_Property_Correlations_in_FeS |
Journal of Moral Education
Journal of Moral Education | Citations: 417 | The Journal of Moral Education provides a unique interdisciplinary forum for consideration of all aspects of moral education and development across the lifespan. It contains philosophical analyses, reports of empirical research and evaluation of educational strategies which... | Read 319 articles with impact on ResearchGate, the professional network for scientists.
Journal of Moral Education
Published by Taylor & Francis (Routledge)
Online ISSN: 1465-3877
Print ISSN: 0305-7240
Publications
A Sex Police for Adults with "Mental Retardation"? Comment on Spiecker and Steutel
Article
Stephen Greenspan
This article is a rebuttal of the claim by Spiecker and Steutel that sex between people with mild and moderate "mental retardation" is morally permissable only with the substitutive consent of caregivers. After a review of historical, empirical and practical considerations, an ethical analysis is undertaken which concludes that Spiecker and Steutel's arguments are deeply flawed and their proposed policy morally objectionable.
Rights not Restrictions for Learning Disabled Adults: A response to Spiecker and Steutel
Article
Mal Leicester
Pam Cooke
What follows is a response to an article by Spiecker and Steutel in which they pose the question of whether sex between people with "mental retardation" (sic) is morally permissible and in which they argue that since many such people cannot give "valid consent", the additional consent of caretakers may be required. However, we argue that the term "mental retard" is offensive and that either the UK terminology ("the learning disabled") or the internationally accepted term ("intellectually disabled") are more acceptable. Moreover, we point out that Spiecker and Steutel are mistaken. Many "learning disabled" people can and do give "valid consent". In any case, their question is itself dubious. Why should two learning disabled people who want to have sex together need anyone else's consent? In addition, we briefly address the rights of the learning disabled to the same sexual freedom as others, on the one hand, and to freedom from sexual exploitation on the other hand. Finally, we consider the implications of these issues for moral education. We suggest that carers need to develop empathy and, where necessary, advocacy skills. We point to the existence of training programmes on sexuality and protection issues.
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High School Teaching of Bioethics in New Zealand, Australia and Japan
Article
Yukiko Asada
Miho Tsuzuki
Shiro Akiyama
[...]
Darryl Macer
An International Bioethics Education Survey was conducted in Australia (A), Japan (J) and New Zealand (NZ) in mid‐1993. National random samples of high schools were selected, and mail response questionnaires were sent to a biology (b) and a social studies (s) teacher at each school through the principals. The number of respondents and response rate were: NZb 206 (55%), NZs 96 (26%), Ab 251 (48%), As 114 (22%), Jb 560 (40%) and Js 383 (27%). This paper compares knowledge and teaching of 15 selected topics related to bioethics and biotechnology, with particular focus on the teaching of social, ethical and environmental issues of in vitro fertilisation, prenatal diagnosis, biotechnology, nuclear power, pesticides and genetic engineering. The survey found that these issues were, generally, covered more in biology classes than in social science classes; and that there were differences in coverage among the three countries, with most coverage in Australia and least in Japan. Open questions looked at images of bioethics, and the reasons why about 90% of teachers thought bioethics was needed in education. Open questions on teaching materials, current and desired are also discussed. The data suggest a need for the development of more and higher quality materials, for the moral education that is conducted, especially in biology and social studies classes.
Selected Bioethical Issues in Japanese and German Textbooks of Biology for Lower Secondary Schools
Article
Malte Peters
Yumiko Ono
Koji Shimizu
Manfred Hesse
Some aspects of the coverage of bioethical issues in Japanese (11) and German (10 series) biology textbooks for lower secondary school have been investigated, concentrating on the treatment of environmental issues. It was found that German textbooks devote more space to these problems than the Japanese ones and that the style of presentation in German books is aimed at appealing to the emotions of the pupils, whereas that of the Japanese ones is a more traditional scientific one. The inclusion of ethical view points in biology teaching is discussed in this context.
Professional and Moral Development for Care Work: some observations on the process
Article
Tom Kitwood
Several aspects of the professional education of those who work in caring roles are discussed, with particular reference to dementia. Three experiential learning exercises are described, together with the opportunities they provide for moral development. Suggestions are made about the moral demands of care work, and general inferences are drawn for the practice of moral education.
Ethics in Islam: Key concepts and contemporary challenges
Article
Ataullah Siddiqui
This paper seeks to contribute to an understanding of the development of ethics in the contemporary Muslim world. The paper begins with a brief introduction of the terms “ethics” and “morals”, and explains the basic terms used by Islamic scholars to elucidate them. The concept of change in new circumstances is explained briefly and finally the paper focuses on some recent attempts by Muslim scholars to address contemporary issues faced by Muslims in Europe and other parts of the world, such as medical ethics, citizenship and nationalities and copyright issues, vis‐à‐vis earlier concepts formulated by Muslim scholars.
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Development of children's moral evaluations of modesty and self-promotion in diverse cultural settings
Article
Full-text available
Ann Cameron
Cindy Lau
Genyue Fu
Kang Lee
This cross-cultural study of the moral judgements of Mainland Han-Chinese, Chinese-Canadian, and Euro-Canadian children aged seven to 11 examined the evaluations of narrative protagonists' modest lies and self-promoting truthful statements in situations where they had done a good deed. The story characters had thus either lied or told the truth about a prosocial act that they had committed. Chinese children judged modest lies more positively and boastful truths less positively than Euro-Canadian children. Chinese and Chinese-Canadian children rated immodest statements more negatively than did Euro-Canadian children. The cultural differences were greatest with the oldest children. Chinese children rated modest lies significantly more positively than either Canadian group who did not differ from each other but an interaction between age and culture revealed the three groups to be significantly different at age 11 with Chinese children most positive, followed by Chinese-Canadian children, and with Euro- Canadian children evaluating modest lies least positively. Cultural strictures and acculturation factors respecting modesty and self-enhancement are reflected in these differences.
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The Defining Issues Test and the Four Component Model: Contributions to professional education
Article
Muriel J Bebeau
This article reviews studies examining the effect of professional education on ethical development. Most studies limit assessment to the measurement of moral judgement, observing that moral judgement plateaus during professional school unless an ethics intervention is present. Whereas interventions influence the shift to postconventional reasoning (the DIT P score), a more illuminating picture of change may emerge if researchers examined DIT profiles. More importantly, limiting assessment to measures of moral judgement ignores important aspects of moral functioning suggested by the Four Components Model. Assessment methods have been validated for sensitivity, role concept and ethical implementation that could be adapted to provide individuals in a particular profession with a more complete picture of abilities needed for real-life professional practice.
Consistencies and Inconsistencies in Nurses’ Ethical Reasoning
Article
Jeanette Lawrence
Ann Helm
Inconsistencies in individual nurses’ decisions about ethical situations and their justifications are examined in the light of changes due to contemporary feminism and professionalization of the nursing role. Empirical identification of ambiguities identified by practitioners is suggested as a component of professional education.
Moral Sensitivity and Its Contribution to the Resolution of Socio-Scientific Issues
Article
Troy D. Sadler
This study explores models of how people perceive moral aspects of socio-scientific issues. Thirty college students participated in interviews during which they discussed their reactions to and resolutions of two genetic engineering issues. The interview data were analyzed qualitatively to produce an emergent taxonomy of moral concerns recognized by the participant. The participants expressed sensitivity to moral aspects including concern and empathy for the well-being of others, an aversion to altering the natural order and slippery slope implications. In arriving at their final resolutions, many participants integrated their moral concerns with non-moral factors. The patterns revealed suggest that moral and non-moral concerns act in concern as they influence socio-scientific decision-making.
Reasonable Paternalism and the Limits of Sexual Freedom: A response to Greenspan and Leicester and Cooke
Article
Jan Steutel
Ben Spiecker
This response argues that Greenspan's comment is basically incoherent, and that the position taken by Leicester and Cooke has unacceptable practical consequences. Greenspan admits that many people with 'mental retardation' lack adult decision-making capacities, but at the same time assumes that they have these very capacities in assigning them freedom rights. Leicester and Cooke consistently argue that people with 'mental retardation' do have adult reasoning powers and therefore should be given freedom rights. But this point has the rather disquieting implication that both the practice of treating 'mental retardation' as an exempting condition and the practice of giving them important special welfare rights seem to loose their justification.
Designing an Outcome‐based Ethics Curriculum for Professional Education: strategies and evidence of effectiveness
Article
Muriel J Bebeau
Goodlad and colleagues argue that teacher education curricula do not include rigorous discourse about the moral dimensions of teaching. This paper offers guidance for developing such curricula drawn from the author's experience devising and implementing a professional ethics curriculum for dentistry. Grounded in Rest's Four Component Model of Morality, the curriculum includes methods and measures for assessing (1) ethical sensitivity; (2) moral reasoning and judgement; (3) moral motivation and commitment; and (4) moral implementation outcomes as well as instructional strategies to facilitate their development. Evidence drawn from the extensive literature on the psychology of morality, and from outcome studies of the effectiveness of the dental ethics curriculum, illustrate that a curriculum of rather modest duration can influence ethical development in measurable ways.
Sex Between People with "Mental Retardation": An Ethical Evaluation
Article
Ben Spiecker
Jan Steutel
Is sex between people with "mental retardation" [1] morally permissible and, if at all, under what conditions? This paper tries to answer this question, but only with regard to sex between biologically mature individuals with mild or moderate mental retardation. First, the concepts of "sexual activity" and mental retardation" are analysed briefly, which is challenging given the widely divergent and sometimes rather awkward definitions of these concepts. On the basis of this analysis, it is argued that the liberal principle of mutual consent, if taken as a necessary condition of permissible sex, has unacceptable consequences for people with mental retardation. Many forms of sex between them would be morally impermissible, given the fact that their limited powers of practical reasoning will often make valid consent well-nigh impossible. As an alternative to the liberal principle of permissible sex, conditions are specified that include the additional consent of caretakers. If people with mental retardation do not have the capacities of practical deliberation required for valid consent, care providers with mature reasoning powers should act as their substitutes. Finally, some important implications for the moral education of future care professionals are spelled out.
Parenting by lying
Article
Full-text available
Gail Heyman
Diem H Luu
Kang Lee
The present set of studies identifies the phenomenon of `parenting by lying', in which parents lie to their children as a means of influencing their emotional states and behaviour. In Study 1, undergraduates (n = 127) reported that their parents had lied to them while maintaining a concurrent emphasis on the importance of honesty. In Study 2 (n = 127), parents reported lying to their children and considered doing so to be acceptable under some circumstances, even though they also reported teaching their children that lying is unacceptable. As compared to European American parents, Asian American parents tended to hold a more favourable view of lying to children for the purpose of promoting behavioural compliance.
The "ethics of belief" and education in science and morals.
M.A.B. Degenhardt
Educational worries about indoctrination are linked to matters of rationality and of the ethics of belief. It is suggested that these are both threatened by too-open approaches to moral education and by too-closed approaches to science education. The moral importance of what is involved points to the need to inform the teaching of all disciplines by reflection on their rational foundations. (PsycINFO Database Record (c) 2012 APA, all rights reserved)
The Value of a Developmental Approach to Evaluating Character Development Programmes: An outcome study of Facing History and Ourselves
Article
Full-text available
Lynn Hickey Schultz
Dennis J. Barr
Robert L. Selman
An outcome study of the Facing History and Ourselves (FHAO) programme is used to illustrate a developmental evaluation methodology developed by the Group for the Study of Interpersonal Development (GSID). The GSID approach to programme evaluation of character development programmes embeds the evaluation into a theoretical framework consonant with the theoretical underpinnings of the programme, using measures sharing the same theoretical assumptions as the practice. The subjects in this study were students in eighth-grade social studies and language arts classes in public schools located in suburban and urban communities in the United States. The sample included 346 subjects in 14 FHAO classes (212 FHAO students) and eight comparison classes (134 comparison students). A 10-week Facing History and Ourselves curriculum was taught in the FHAO classrooms either in late winter or spring. The study demonstrated that eighth-grade students in Facing History classrooms showed increases across the school year in relationship maturity and decreases in racist attitudes and self-reported fighting behaviour relative to comparison students, although these findings were complicated by interaction effects with gender. The gains Facing History students made in moral reasoning and in civic attitudes and participation were not significantly greater than the comparison students, although there was a significant difference between the groups on the civic measure at post-test. The study highlights the benefits of using a developmental measure of social competence to evaluate character development programmes that are based on similar assumptions. (PsycINFO Database Record (c) 2012 APA, all rights reserved)
Verbal Processing of the Defining Issues Test by Principled and Non-Principled Moral Reasoners
Jeanette Lawrence
Administered 6 principled and 6 nonprincipled items from the Defining Issues Test (DIT) by J. R. Rest (1979) to 3 groups of Ss selected on the basis of age, education, and high and low pretest DIT scores. Ss were 13 male and 10 female philosophy graduate students; 16 male graduate students from a conservative fundamentalist seminary (mean age 27.4 yrs); and 11 male and 12 female 9th graders (mean age 15.3 yrs). Items were rated under a thinking-aloud condition and then were sorted for understandability and endorsement. Philosophy students used more principled prescriptives overall, understood and endorsed principled items, and understood and rejected unprincipled items. Seminarians rejected both principled and unprincipled items and infused their ratings with religious meanings. Seminarians used nonprincipled items more frequently than did philosophy students and less than did high school students. High school students preferred principled items that they could not fully understand. (PsycINFO Database Record (c) 2012 APA, all rights reserved)
The Hidden Messages of Schoolbooks
Robin Richardson
Contends that bias in schoolbooks cannot be considered independently of the wider question of bias in teaching generally and suggests ways in which teachers can handle controversial issues. Schoolbooks currently being published in Britain are surveyed and their messages measured against a draft checklist. The customary procedure for producing schoolbooks is discussed, and methods by which publishers may be pressured to change their current practices are considered. (PsycINFO Database Record (c) 2012 APA, all rights reserved)
Should educators accommodate intolerance? Homosexuality and the Islamic case
Full-text available
Michael S. Merry
The ideological interface between Muslims and liberal educators undoubtedly is strained in the realm of sex education, and perhaps on no topic more so than homosexuality. Mark Halstead argues that schools should not try to ‘undermine the faith' of Muslims, who object to teaching homosexuality as an ‘acceptable alternative lifestyle'. In this article, I will argue against his monolithic presentation of Islam. Furthermore, I will argue that because Halstead presents a narrow view of Islam he is neglectful of gay and lesbian Muslims who are particularly vulnerable to the unrepentant hostilities of their own communities, and he limits the options available to sex educators in such a way as to discourage genuine encounters between homosexuals and Muslims.
Books and becoming good: Demonstrating Aristotle's theory of moral development in the act of reading
Article
Amanda Cain
In the Nicomachean ethics , Aristotle sets down a scattered and fractional account of the development of moral virtue within young people. Philosopher Martha Nussbaum defends Aristotle's neglect of a systematic account of moral development and argues that more complex expressions of character-building, such as learning to expose oneself to proper desires, feelings, pleasures and pains, are better illustrated through drama or literature than through philosophy. In this vein, the author draws upon literary thinkers J.B. Kerfoot, Sven Birkerts and Wayne C. Booth, as well as the imaginative Harry Potter series by J. K. Rowling, to illustrate more concretely Aristotle's process of moral development. The author concludes with a proviso about the vulnerability of the connected process of reading and moral development in the current consumer culture.
Bridging the Divide: The role of perceived control in mediating reasoning and activism
Philip G. Laird
One-hundred-and-two students, either actively or not actively involved in the pro-choice or pro-life movements, completed the Defining Issues Test (DIT) and Spheres of Control (SOC) measure. Participants also rated their degree of involvement in on-campus activities. Abortion activists more frequently endorsed principled and anti-establishment moral issues, and scored higher on sociopolitical control than did non-activists. SOC and DIT scores served to discriminate abortion activists from non-activists--more so for women than for men. Self-reported ratings of activism moderated self-reported assessments of control for abortion activists, such that more involved students rated themselves as feeling greater sociopolitical and interpersonal control than less involved students. Results are discussed in terms of the possible relationship between reasoning, control and behaviour.
Institutionalization versus self-regulation: A contextual analysis of responsibility among adolescent sportsmen
Thierry Long
Nathalie Pantaleon
Gerard Bruant
The present study, which sought to analyse adolescent sportsmen's representations of responsibility, was mainly guided by the philosophical literature on this topic. A body of literature suggests that the contextual factors of sport practice, particularly regarding the rules that regulate play, may have a key role in the building of such representations. Semi-structured interviews were conducted with two groups of 18 teenagers: one group of institutionalised athletes (who played soccer or basketball in a structured and official context) and one group of self-organised athletes (who played the same sports in a self-regulated context). The qualitative analysis showed that the institutionalised players described responsibility in functional terms; this result was explained by the rigid characteristics of their context of practice, which was based on task division and performance. In contrast, the self-organised players described responsibility in moral terms; this result was explained by an open context of practice based on interaction. The overall results of our study raise questions about the educational capacity of institutionalised sport and the objective conditions that promote the social and moral development of young people.
Sexual freedom rights for adolescents? A rejoinder to Agnes Tellings
Jan Steutel
Agnes Tellings rightly observes that adolescents, if compared with pre-pubescent children, are much more capable of making their own choices and therefore should be granted much more freedom to arrange their own lives. However, the capacity of adolescents to make prudent choices still seems to be below the threshold of competence. Therefore, interpreting their growing freedom in terms of freedom rights (or rights of self-determination) seems to be mistaken. If the freedoms granted to adolescents can be explained in terms of rights at all, they could better be understood as rights to experiment. And even if some of the freedoms adolescents might have are not experimental, parents still retain the authority to veto their choices, albeit only for pressing reasons.
Justice in the home: Children's and adolescents' perceptions of the fair distribution of household chores
Nicole Thomson
The present study examined the fairness judgements and reasoning offered by children and adolescents in the context of the division of household labour among siblings. The data were examined for grade level differences in the endorsement of three distributive justice principles (equality, equity and need). Male and female third grade, sixth grade and ninth grade participants were read a total of six stories, each describing four siblings engaged in household chores. Two stories each represented the principles of equality, equity and need. Participants indicated how fair they thought the division of chores was using a 5-point Likert scale, and then provided a rationale for each fairness rating. Findings indicated endorsement of the equality principle by the majority of participants, regardless of grade level. Analyses also revealed that the sixth graders were the least likely to view as fair a division of labour based on need. Overall, the study's findings support the notion that the endorsement of the principles of justice depends on the circumstances of the situation.
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Experiences of African American Empowerment: A Jamesian perspective on agency
Phyllis Curtis-tweed
This essay draws from the work of William James and three African American pragmatists, W.E.B. Du Bois, Ralph Ellison and Cornel West, to explore the moral relevance of the self as an empowered agent among African American youth. The focus is on Jamesian agency as a function of the individual's awareness of options in context, the self-empowerment that allows one to access those options, and the resulting behaviour that actualises perceived potentials. Case examples clarify how the awareness of self as an active and choice-making agent normally has moral primacy for African Americans. These examples draw on both justice and care perspectives to clarify the possibilities of human development and social change through highly developed human agency.
Islamic Education teachers' perceptions of the teaching of akhlāq in Malaysian secondary schools
Ab Halim Tamuri
The teaching of akhlāq (moral values) in Islamic Education lessons is one of the important aspects in the Integrated Curriculum for Secondary Schools in Malaysia. Its purpose is to develop the potential of the individual in a holistic, balanced and integrated manner, encompassing the intellectual, spiritual, emotional and physical aspects in order to create a balanced and harmonious human being with high moral standards. The aim of this article is to examine teachers' perceptions of the teaching of akhlāq at secondary school level. Data were collected from 22 respondents about the process of teaching and learning akhlāq, the school environment and the internal and external factors that might influence the students' akhlāq. The study found that most of the Islamic Education teachers interviewed were satisfied with the process of teaching and learning akhlāq in their schools. Despite a few weaknesses in terms of implementation, they believed that school activities, religious activities and school regulations at their schools gave positive and significant contributions to the development of students' akhlāq. It was also found that peers, negative attitudes among some teachers, parents and local communities, the mass media, entertainment centres and the demands of jobs had negative influences on the students' akhlāq.
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Moral maturity and autonomy: Appreciating the significance of Lawrence Kolhberg's Just Community
Graham P. McDonough
Lawrence Kohlberg's Just Community program of moral education has conceptual significance to his theoretical work in the field of moral development. This argument contends that a perspective recognizing the Just Community as conceptually significant provides a more comprehensive picture of Kohlberg's work than do critical perspectives that limit their scope to his Structural Stage Model of moral development. Apprehending the Just Community's conceptual significance provides the opportunity to respond to critics, like Carol Gilligan and Helen Haste, who have suggested that Kohlberg's work is inattentive to notions of attachment in morality, but who either neglect or dismiss consideration of the Just Community in making these conclusions. The argument concludes by stating that a more philosophically comprehensive and mature understanding of morality was developing in Kohlberg's Just Community, a project undertaken well in advance of these major criticisms.
The social mediation of a moral dilemma: Appropriating the moral tools of others
Val D. Turner
Elisha A. Chambers
Much effort, on a philosophical and a research basis, has been applied to the subject of moral development framed within a constructivist, Piagetian stage‐type format. These efforts have focused on the process of the individual's construction of a moral base and the individual's corresponding level of moral development. At this point in time, little research has been directed at analysing the sociocultural influences on morality construction, moral decision‐making and moral development within the framework of a specific developmental theory. This research examined the processes involved in the resolution of a moral dilemma within a group setting, and evaluated the usefulness of a Vygotskian theoretical base in analysing these observations. This study provides initial evidence supporting the utility of a Vygotskian conceptual model. Additional research exploring the importance of the social aspects of moral processing, reasoning and development is needed.
Moral Voices of Women and Men in the Christian Liberal Arts College: Links between views of self and views of God
Kaye Cook
Daniel C. Larson
Monique D. Boivin
Views of self (using Gilligan's paradigm) and of the Christian God (using a similar, newly-developed paradigm) were explored in 44 first-year and senior Christian college students. Men aligned with a self-ethic of justice; women, more often with justice than predicted. Moral voice thus appears contextually dependent, contrary to Gilligan's earlier predictions. Senior students integrated both views of self, but not both views of God, more often than first-year students. This suggests that the Christian liberal arts context nurtures integrated and complex views of the self, but authoritative views of God. All but one student described God as authoritative; most did not see God as relational. This preference for authoritative views of God perhaps shaped the heavy justice self-ethic. Consistent with earlier findings, justice views of the self were generally elicited by impersonal dilemmas; authoritative views of God, in contrast, were equally associated with both impersonal and personal dilemmas.
Children's attitudes toward superheroes as a potential indicator of their moral understanding
Full-text available
Justin Martin
McCrary's work in the late 1990s suggested that superheroes influence children's development of moral values. Similarly, Bauer and Dettore advocated adults' and educators' monitoring of children's superhero play to help children foster cooperation and conflict resolution skills. The purpose of this study was to explore the relationship between children's attitudes toward themselves and their attitudes towards superheroes. Forty-two fourth-grade children (aged 9-11) from a school in Massachusetts completed a questionnaire. Results indicated that participants generally rated themselves and their superhero as being high on prosocial behaviour. Findings suggest that there may be a relationship between how children feel about themselves and how they feel about superheroes.
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Did the Moral Education Establishment Kill Character? An autopsy of the Death of Character
Full-text available
Perry L. Glanzer
This essay examines James Davison Hunter's claim that the moral education establishment is responsible for the death of character. I contend that although Hunter's rhetoric about the "death of character" is distracting and his claims against the moral education establishment are overstated, moral educators must grapple with his finding that effective moral education requires a coherent moral culture with a clear conception of public and private good. I attempt to draw out the implications of Hunter's finding by comparing past Soviet and current American forms of moral education. Finally, I conclude that the effectiveness of moral education is threatened not only when character is separated from its nourishing social, historical and cultural moorings, but also when moral autonomy and respect for diversity is undermined. Thus, in the last part of the essay, I discuss three possibilities for how public education can both allow comprehensive approaches to moral education and adhere to liberalism's appreciation for moral autonomy and diversity.
On the duty of educating respect: A response to Robin Barrow
Graham Haydon
This article is a response to Robin Barrow's John Wilson Memorial Lecture `On the duty of not taking offence'. The present article takes issue with some of Barrow's claims and explores further the implications for moral education of some current views on the giving and taking of offence. Accounts are offered both of `inherent offensiveness' (an important theme in Barrow's lecture) and of offence to persons. The questions `are people too ready to take offence?' and `are we too concerned about offending others?' are discussed, and attention is given to offensive language and the moral educational stance we should take towards it. Finally, it is argued that the chief value that should underpin the judgements we need to make about the giving and taking of offence is respect, and that we have a general duty to educate respect.
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Note on a cross‐cultural test of Gilligan's ethic of care1
Arne Vikan
Cleonice Camino
Angela Biaggio
One hundred and twenty students from both Brazil and Norway were tested with Skoe's Ethic of Care Interview (ECI), which is a test of Gilligan's hypothesized gender-related ethic of care. Subjects were also tested with Bem's Sex Role Inventory and Triandis's Test of Cultural Orientations. The ECI was shown to be related neither to gender nor to sex-role concepts, and lower ECI scores from the Brazilian sample could be related to their higher collectivism scores on Triandis's test. The results suggest that Gilligan's ethic of care, as tested by the ECI, is not gender-related and may be culture specific.
Moral Democratic Education and Homosexuality: Censoring morality
John E Petrovic
With the increasingly heard voices of gays, lesbians and bisexuals in American society and their demands for recognition have come the responses of religious conservatives. In this article I consider whether the extreme moral positions that religious conservatives take are defensible. More specifically, I want to consider whether teachers who embrace such conservative positions should be permitted to act on them in their classrooms. My arguments lead me to distinguish between moral democratic and moralistic positions. The former I examine using the virtue of recognition and the principle of non-oppression. I conclude that democracy requires the positive portrayal of homosexuality in schools and precludes teachers expressing their beliefs against it.
27 Citations
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The Development of Justice Conceptions and the Unavoidability of the Normative
KRISTJA´NSSON K
This article spells out the way in which normative concerns unavoidably enter into the design and interpretation of empirical research on children's development of justice conceptions, with special emphasis on Damon's well-known stage theory of such development. Normative considerations provide assumptions not only about what counts as a conception of justice in the first place but also what counts as a better or a worse conception. Damon, for one, relies on the questionable normative premise that all distributive choices are choices about justice. An alternative research programme is suggested, based on piecemeal mutual adjustments between the normative and the empirical, a programme which would focus on children's desert-based emotions.
Coping with guilt and shame: A narrative approach
Mia Silfver
Autobiographical narratives (N = 97) of guilt and shame experiences were analysed to determine how the nature of emotion and context relate to ways of coping in such situations. The coding categories were created by content analysis, and the connections between categories were analysed with optimal scaling and log-linear analysis. Two theoretical perspectives were tested: the view that shame generally is a more maladaptive emotion than guilt, and the view that in situations where responsibility is ambiguous, both guilt and shame feelings are likely to be maladaptive. In line with the latter, chronic rumination was more likely to occur in situations where responsibility was ambiguous compared to situations where the respondent's responsibility was clear, regardless of emotion. In addition, reparative behaviour was less frequently reported in shame situations than in situations where the respondent felt guilty or both guilty and ashamed. The findings supported the view that the nature of emotional reaction and the nature of the situation both affect the ways of coping.
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Defining features of moral sensitivity and moral motivation: Pathways to moral reasoning in medical students
Kelly R Morton
Joanna S. Worthley
John K. Testerman
Marita L Mahoney
Kohlberg's theory of moral development explores the roles of cognition and emotion but focuses primarily on cognition. Contemporary post‐formal theories lead to the conclusion that skills resulting from cognitive‐affective integration facilitate consistency between moral judgement and moral behaviour. Rest's four‐component model of moral development delineates these skills specifically. The components, moral motivation, moral sensitivity, moral reasoning and moral character, operate as multidimensional processes that facilitate moral development and subsequently promote moral behaviour. The relationships between these components have been relatively unexplored, thereby missing the opportunity to unpack the processes underlying moral growth and development. In this study, moral motivation (spirituality), moral sensitivity (post‐formal skills) and moral reasoning are operationalized to examine the mediational effects of moral sensitivity of medical students. In the complex moral environment of medical students opportunities arise to question values and develop cognitive‐affective skills, among them spirituality and post‐formal thinking which are linked to increases in post‐conventional moral reasoning. The models tested indicate that moral sensitivity mediates the relationship between moral motivation and moral reasoning.
Rejoinder to Nucci's "Morality, Religion and Public Education in Pluralist Democracies"
Rob Kunzman
Three rebuttals are offered here: my argument applies not only to monotheistic religious students; the relationship between God and the good is far more complex and contested than Nucci claims; and I do not contend that religious students rely entirely on religious dictates in their ethical thinking, but rather that the influences are likely to be a mixture of religion and personal judgement. Nucci's concern about hegemonic imposition of ethical perspectives is certainly valid, but civic respect in a pluralist democracy requires thoughtful engagement with a diversity of ethical thought, however complicated and challenging this may be.
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Pragmatic, ethical and moral: Towards a refinement of the discourse approach
Article
Johan Luttenberg
Christiaan Hermans
T.C.M. Theo Bergen
In this article we will address the issue of obtaining insight into the way in which teachers deal with the normative side of their profession. We outline the problem that forms the context of our question (the difference in the meaning of good teaching in the process-product model and in ethical models) and we discuss Oser's discourse approach as a solution for that problem. His discourse approach appears to be a step forward, but at the same time leaves questions unanswered. As a contribution we introduce the concepts of pragmatic, ethical and moral. We show in what sense this conceptual framework provides a refinement of the discourse approach.
Introducting democracy in a Wuhan primary school: Please, vote for me (2007) directed by Weijun Chen
Margaret Sleeboom-Faulkner
In the film, Please Vote for Me (2007), director Weijun Chen illustrates how leadership ambitions allowed ‘undemocratic’ means of competition during a democratic election among primary school children. Parents encouraged and teachers allowed unscrupulous competition among preselected eight-year-old candidates. The competition led to classmates being manipulated and disappointed and a ‘dictatorship’ similar to that of previous years. This film shows that a ‘democratic election’ in a primary school in Wuhan was guided by native Chinese values of ‘good leadership’ in reformed China. However, the newly introduced discussions on democratic leadership could also be seen as initial steps towards reflection on democracy. The documentary has won prestigious international awards, including the Sterling Feature Award (2007) and the Adolf Grimme Award (2008).
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Kibbutz education: A sociological account
Yechezkel Dar
The ideal type of kibbutz education was characterised by six structural traits: unbalanced duality of communal institutions and family, centrality of the peer group in the socialisation process, merging of education and community, a multicoded and mullifaceted school, autonomous but task-orientated adolescence and a short passage to social adulthood. Although possibly taking a toll on individual autonomy, the “hidden curriculum” of this education facilitated the development of a prosocial orientation, emotional moderation and a strong sense of belonging–all important to the fulfilment of the role of kibbutz member. Rapid social change, culminating in the last decade, is eroding the structural uniqueness of kibbutz education and thus jeopardises its capacity for continuing to socialise children to communal life.
Some Effects of Teaching Designed to Promote Understanding of Racial Issues in Adolescence
Article
Christopher Bagley
Gajendra K. Verma
Teaching about race relations can be followed by small and sometimes significant changes in prejudiced attitudes. (DM)
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Children’s and adolescents’ moral emotion attributions and judgements about exclusion of peers with hearing impairments
Article
Jennifer Chilver-Stainer
Luciano Gasser
Pasqualina Perrig-Chiello
Children and adolescents with hearing impairments are at risk of being excluded from activities with hearing peers. Moral emotion attributions may represent important indicators for children’s identification with the moral norm not to exclude peers based on disability. Against this background, we investigated how 10-, 12- and 15-year-olds (N = 215) feel and judge about social exclusion of peers with hearing impairments. Emotion attributions and moral judgements were assessed using four different hypothetical scenarios about the exclusion of peers with hearing impairments (school vs. leisure time, group vs. dyad). Moreover, children’s and adolescents’ inclusive behaviour was assessed by a peer nomination procedure. Results revealed that moral emotion attributions differed as a function of exclusion context and grade. Moreover, participants with inclusive behaviour attributed moral emotions more often than participants with less inclusive behaviour. Implications of the results for moral education are discussed.
The Human Story at the Intersection of Ethics, Aesthetics and Social Justice
Article
Judith F. Baca
Murals tell specific stories, but, because they are created from many specific stories, they also tell a common story, a story of the things that connect people to each other. In this way, muralism is an antidote for the hatred and disconnectedness in society. Moral education is participatory. It is a creative, critical and analytical process. This document shares the authors' personal experiences of moral education.
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11 Citations
Promoting Ethical Reasoning, Affect and Behaviour Among High School Students: An Evaluation of Three Teaching Strategies
Robert DeHaan
Russell B Hanford
Kathleen Kinlaw
[...]
John Snarey
Ethics education should aim to promote students' maturity across a broad spectrum of moral functioning, including moral reasoning, moral affect and moral behaviour. To identify the most effective strategy for promoting the comprehensive moral maturity of high school students, we enrolled students in one of four groups: an introductory ethics class, a blended economics-ethics class, a role-model ethics class taught by graduate students and a non-ethics comparison class. Pretest and post-test instruments measured the ways students (a) reason, (b) feel and (c) act with regard to ethical-normative issues. The results indicated that the approaches to teaching ethics varied considerably in terms of their ability to promote significant positive changes in students' moral reasoning, empathy and behaviour.
Moral Decision-making in Real Life: Factors affecting moral orientation and behaviour justification
Article
Full-text available
Patrick Leman
Shira Haviv
The study addresses two separate but related issues in connection with people"s real-life moral decisions and judgements. First, the notion of moral orientation is examined in terms of its consistency across varying contexts, its relation to gender and to gender role. Secondly, a new aspect of moral reasoning is explored—the influence on moral decision-making of considering the consequences of an action. Fifty-eight undergraduate students were asked to discuss two personal and two impersonal real-life moral dilemmas. The results reveal a significant interaction between gender role and type of dilemma. However, moral orientation was not consistent across various dilemmas and gender was not related to any particular orientation. Also the results indicate a significant difference between the reasoning of consequences of personal-antisocial conflicts and impersonal-antisocial conflicts. These findings suggest that different moral orientations may be embedded in life experience and connect with an individual"s sense of his or her moral identity in real-life situations.
Ruled by hetero-norms? Raising some moral questions for teachers in South Africa
Deevia Bhana
Thirty-eight countries in Africa regard homosexuality as punishable by law with South Africa remaining a standout country advancing constitutional equality on the basis of sexual orientation. In the context of homophobic violence, however, concerns have been raised about schools’ potential to improve the educational, moral and social outcomes for young people. In examining how some South African teachers normalize heterosexuality the paper raises questions about moral education in addressing homophobia. By drawing on interviews conducted with teachers across different social contexts, the paper shows how rights are limited by dominant constructions of heterosexual privilege mediated by a range of interlocking social processes including gender, race and culture. The paper argues that attention to the social and cultural influences in teachers’ account of homosexuality must feature in local designs of moral education. The imperative of working with teachers is presented as a way forward to facilitate the broadening of moral education to include an interrogation of heteronormativity which has evaded the focus of South African moral education.
Unpacking (White) privilege in a South African university classroom: A neglected element in multicultural educational contexts
Sharlene Gale Swartz
Emma Arogundade
Danya Davis
Multiculturalism currently aims for the political accommodation of difference instead of the subversion of the resulting privileges of difference. In the South African context such a distinction is especially important since the economic and symbolic subjugation of the majority of Black South Africans continues despite political transformation, and is exacerbated by an unwillingness to reflect on privilege and inequality. Drawing on Biko and Soudien’s critique of multiculturalism and vision for anti-racist education, this paper describes a classroom activity set for 164 nationally and culturally diverse second year sociology students at a university in Cape Town, South Africa. The activity tasked students to reflect on texts by Peggy McIntosh and Khaya Dlanga (one canonical, the other contextual) and reports on these students’ nuanced understandings of personal biography, experiences of privilege and self-reflexivity that connects personal experience to social structure and historical contexts. It concludes by offering modest implications for moral education in a multicultural university classroom.
‘The good child’: Anthropological perspectives on morality and childhood
Anne-Meike Fechter
Currently, there is no clearly delineated field that could be described as ‘the anthropology of morality’. There exists, however, an increasingly visible and vocal interest in issues of morality among anthropologists. Although there has been a lack of explicit study, it has become clear that anthropologists have, in fact, been concerned with issues of moralities all along. The purpose of this special issue is to bring this interest to ethnographic studies of childhood, and explore how and why children or young people act in a particular way and are making certain choices, how these are valued or contested by their families, peers, and communities. The papers in this special issue highlight the contestations that arise as multiple moralities collide, and the effects this may have for the persons involved. Collectively, the papers illustrate a notion of moralities as multiple, contested, and mobile, and the consequences this may have in a globalising world.
Using forum theatre in organised youth soccer to positively influence antisocial and prosocial behaviour: A pilot study
Esther A. Rutten
Gert Biesta
Maja Deković
[...]
Paul Verweel
The aim of this pilot study was to examine the possible effects of a forum theatre intervention on moral team atmosphere, moral reasoning, fair play attitude and on- and off-field antisocial and prosocial behaviour in male adolescent soccer players from 10 to 18 years of age (n = 99). From pre-test to post-test, small but positive changes were found in moral atmosphere, but not in moral reasoning or fair play attitude. Changes were also found in on-field antisocial behaviour, which showed a significant decrease one month after the intervention. However, the changes in antisocial behaviour were not affected by the changes in moral team atmosphere. Off-field antisocial behaviour and both on- and off-field prosocial behaviour did not show a significant change. The results suggest that more extended efforts built on a similar approach are worth investigating.
Top-cited authors
Muriel J Bebeau
School of Dentistry, University of Minnesota Twin Cities
369 Citations
Thomas Lickona
State University of New York College at Cortland
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Gertrud Nunner‐Winkler
Max Planck Institute for Human Cognitive and Brain Sciences
Gustavo Carlo
University of California, Irvine
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Jonathan Haidt
New York University
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| https://www.researchgate.net/journal/Journal-of-Moral-Education-1465-3877 |
NOPR Collection:
<title> NOPR Collection: </title>
<link> http://nopr.niscpr.res.in/handle/123456789/37381 </link>
Propagation Characteristics of hf Signal over a Transequatorial Path
<link> http://nopr.niscpr.res.in/handle/123456789/37751 </link>
Title: Propagation Characteristics of hf Signal over a Transequatorial Path
Authors: Sen, A.K.; Trehan, S.K.
Abstract: The propagation characteristics of an hf radio signal (21.485 MHz, Radio Australia) over a transequatorial path viz. from Melbourne (37.5°8; 144.59°S) to Calcutta have been studied experimentally. A morning maximum is seen to occur in many cases.
Page(s): 334
<pubDate> Mon, 01 Dec 1975 00:00:00 GMT </pubDate>
Long Period Waves in the Upper Troposphere & Lower Stratosphere over the Indian Region
<link> http://nopr.niscpr.res.in/handle/123456789/37749 </link>
Title: Long Period Waves in the Upper Troposphere & Lower Stratosphere over the Indian Region
Authors: Rao, K. S. Raja; Thapliyal, V.; Patil, S. R.
Abstract: Long period waves in the upper troposphere and lower stratosphere in the Indian region have been identified using monthly mean data on the zonal and meridional winds and temperature over seven stations in the latitude range of 8-28°N. Four members of the wave family, viz. 2 month, 6 month, 12 month and 20-40 month periodicities, have been identified. The 2 month wave is masked by the more dominant Kelvin wave. The 6 month wave is confined to the equatorial stratosphere. The tilt of the line of maximum amplitude suggests transport of energy from the upper troposphere to lower stratosphere. The amplitude of the annual wave is a maximum below the tropopause. The prominent maximum near 200 mb, between 20 and 25°N is associated with the subtropical westerly jet. The quasi-biennial oscillation (QBO) present in the zonal wind and temperature is confined to 3D-month period. From the downward tilt from the equator to the sub-tropics in the line of maximum amplitude, it is inferred that the QBO originates in the equatorial stratosphere and travels to the upper troposphere over the subtropical latitudes.
Page(s): 328-334
<pubDate> Mon, 01 Dec 1975 00:00:00 GMT </pubDate>
<dc:date> 1975-12-01T00:00:00Z </dc:date>
<title> Satellite Tracking Systems </title>
<link> http://nopr.niscpr.res.in/handle/123456789/37748 </link>
Title: Satellite Tracking Systems
Authors: Saha, M. K.; Kalyanaraman, S.
Abstract: Satellite tracking systems which will provide range, range rate and angular information are being developed. The basic systems are Interferometry, Doppler and Tone Ranging. Data from these will be used to generate satellite ephemeris. Interferometry system uses two pairs of antennas each for north-south and east-west directions, providing coarse and fine data for direction cosines. The coarse data are used to resolve the ambiguity in the fine channel which provides the accuracy of approximately ±6'. Doppler system tracks the carrier frequency of the on-board telemetry transmitter with a tracking filter using phase-lock loop, to provide accuracy in radial velocity measurement within 10m/ sec. Tone ranging system uses four tones which are received in the satellite and retransmitted. The transmitted and received tones are processed in the ground to extract range data. This provides an accuracy of ± 375m and a maximum range capability of nearly 5000 km.
Page(s): 323-327
Prediction of the Occurrence of Sporadic E in the Indian Subcontinent
<link> http://nopr.niscpr.res.in/handle/123456789/37747 </link>
Title: Prediction of the Occurrence of Sporadic E in the Indian Subcontinent
Authors: Saksena, R. C.
Abstract: The contour diagrams (latitude versus time) for the occurrence of sporadic E have been drawn from the <i>f<sub>0</sub></i> Esdata from Indian stations and from Bangkok, Thailand (a neighbouring country). This has been done separately for equatorial and temperate latitudes during high and low solar activity. The Phillips' rule, which states that a straight line will fit a sporadic E cumulative distribution, appears to hold good only beyond the most probable<i> f<sub>0</sub></i> Esvalue for all latitudes. The contour diagrams of the gradient of these straight lines have been drawn. These two sets of contours, with the help of Phillips' rule, could be used for predicting the percentage occurrence of sporadic E above any specific value of <i>f<sub>0</sub></i> Es for any latitude, at any time of the day and for high and low solar activity.
Page(s): 318-322
| https://14.139.47.15/feed/rss_2.0/123456789/37381 |
Publications - Global Disability Innovation Hub
The GDI Hub brings together academic excellence, innovative practice and co-creation; harnessing the power of technology for good.
Type
Report
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Assistive & Accessible Technology
Assistive Technology Changes Lives: an assessment of AT need and capacity in England
Vicki Austin,Dilisha Patel,Jamie Danemayer,Kate Mattick,Anna Landre,Marketa Smitova,Maryam Bandukda, Aoife Healy, Nachiappan Chockalingam,Diane Bell,Cathy Holloway
This report was prepared by Global Disability Innovation (GDI) Hub for the Disability Unit in the Cabinet Office His Majesty’s Government (HMG). The report presents findings from a Country Capacity Assessment (CCA) of AT access in England. Findings illustrate a complex state of AT in England. While delivery systems tend to provide quality products that have a strong, positive impact on people’s lives, processes are often slow and stressful for users and providers alike. Startlingly, there is also an AT access gap of 31% of disabled people not having the assistive products they need to flourish, thrive, or even participate in daily life.
The Cabinet Office; 2023
Abstract
Assistive Technology Changes Lives: an assessment of AT need and capacity in England
The aim of this research was to undertake a Country Capacity Assessment (CCA) to inform a more integrated approach to Assistive Technology (AT) provision in England. The results aim to support policymakers in identifying actions to strengthen service delivery to better meet disabled people’s needs, improving outcomes for AT users and reducing inefficiencies in the current approach.
The research was undertaken from November 2022 to March 2023 and led by the Global Disability Innovation (GDI) Hub, which is the World Health Organization (WHO) Global Collaborating Centre on AT access, using WHO tools in the Assistive Technology Assessment (ATA) suite.
Cite
Assistive Technology Changes Lives: an assessment of AT need and capacity in England
Suggested Citation: Austin, V, Patel, D, Danemayer, J, Mattick, K, Landre, A, Smitova, M, Bandukda, M, Healy, A, Chockalingam, N, Bell D, and Holloway, C; Assistive Technology Changes Lives: an assessment of AT need and capacity in England; Cabinet Office, HMG; 2023
Assistive Technology Changes Lives: an assessment of AT need and capacity in England
Type
Workshop
Themes
Assistive & Accessible Technology
Research Group
Disability Interactions
Could AI Democratise Education? Socio-Technical Imaginaries of an EdTech Revolution
Sahan Bulathwela, María Pérez-Ortiz,Catherine Holloway, John Shawe-Taylor
This paper starts by synthesising how AI might change how we learn and teach, focusing specifically on the case of personalised learning companions, and then move to discuss some socio-technical features that will be crucial for avoiding the perils of these AI systems worldwide (and perhaps ensuring their success). This paper also discusses the potential of using AI together with free, participatory and democratic resources, such as Wikipedia, Open Educational Resources and open-source tools. We also emphasise the need for collectively designing human-centered, transparent, interactive and collaborative AI-based algorithms that empower and give complete agency to stakeholders, as well as support new emerging pedagogies.
Workshop on Machine Learning for the Developing World (ML4D) at the Conference on Neural Information Processing Systems 2021; 2021
Abstract
Could AI Democratise Education? Socio-Technical Imaginaries of an EdTech Revolution
Artificial Intelligence (AI) in Education has been said to have the potential for building more personalised curricula, as well as democratising education worldwide and creating a Renaissance of new ways of teaching and learning. Millions of students are already starting to benefit from the use of these technologies, but millions more around the world are not. If this trend continues, the first delivery of AI in Education could be greater educational inequality, along with a global misallocation of educational resources motivated by the current technological determinism narrative. In this paper, we focus on speculating and posing questions around the future of AI in Education, with the aim of starting the pressing conversation that would set the right foundations for the new generation of education that is permeated by technology. This paper starts by synthesising how AI might change how we learn and teach, focusing specifically on the case of personalised learning companions, and then move to discuss some socio-technical features that will be crucial for avoiding the perils of these AI systems worldwide (and perhaps ensuring their success). This paper also discusses the potential of using AI together with free, participatory and democratic resources, such as Wikipedia, Open Educational Resources and open-source tools. We also emphasise the need for collectively designing human-centered, transparent, interactive and collaborative AI-based algorithms that empower and give complete agency to stakeholders, as well as support new emerging pedagogies. Finally, we ask what would it take for this educational revolution to provide egalitarian and empowering access to education, beyond any political, cultural, language, geographical and learning ability barriers.
Could AI Democratise Education? Socio-Technical Imaginaries of an EdTech Revolution
Type
Workshop
Themes
Assistive & Accessible Technology
Towards Proactive Information Retrieval in Noisy Text with Wikipedia Concepts
Tabish Ahmed, Sahan Bulathwela
The informational needs of people are highly contextual and can depend on many different factors such as their current knowledge state, interests and goals [1, 2, 3]. However, an effective information retrieval companion should minimise the human effort required in i) expressing a human information need and ii) navigating a lengthy result set. Using topical representations of the user history (e.g. [4]) can immensely help formulating zero shot queries and refining short user queries that enable proactive information retrieval (IR). While the world has digital textual information in abundance, it can often be noisy (e.g. extracted through Automatic Speech Recognition (ASR), PDF text extraction etc.), leading to state-of-the-art neural models being highly sensitive to the noise producing sub-optimal results [5]. This demands denoising steps to refine both query and document representation. In this paper, we argue that Wikipedia, an openly available encyclopedia, can be a humanly intuitive knowledge base [6] that has the potential to provide the world view many noisy information Retrieval systems need.
Published at the First Workshop on Proactive and Agent-Supported Information Retrieval at CIKM 2022; 2022
Abstract
Towards Proactive Information Retrieval in Noisy Text with Wikipedia Concepts
Extracting useful information from the user history to clearly understand informational needs is a crucial feature of a proactive information retrieval system. Regarding understanding information and relevance, Wikipedia can provide the background knowledge that an intelligent system needs. This work explores how exploiting the context of a query using Wikipedia concepts can improve proactive information retrieval on noisy text. We formulate two models that use entity linking to associate Wikipedia topics with the relevance model. Our experiments around a podcast segment retrieval task demonstrate that there is a clear signal of relevance in Wikipedia concepts while a ranking model can improve precision by incorporating them. We also find Wikifying the background context of a query can help disambiguate the meaning of the query, further helping proactive information retrieval.
Towards Proactive Information Retrieval in Noisy Text with Wikipedia Concepts
Type
Article
Themes
Assistive & Accessible Technology
These tools help visually impaired scientists read data and journals
Alla Katsnelson
This article was featured in Nature and discusses tools that help visually impaired scientists read data and Journals. Innovation Manager, Daniel Hajas, was interviewed as part of this piece and highlights the need for an ecosystem approach, and access to data / visualisations for blind members of the research and science community.
Nature; 2023
These tools help visually impaired scientists read data and journals
Type
Book
Research Group
Disability Interactions
Disability Interactions Creating Inclusive Innovations
Catherine Holloway,Giulia Barbareschi
; 2021
Abstract
Disability Interactions Creating Inclusive Innovations
Disability interactions (DIX) is a new approach to combining cross-disciplinary methods and theories from Human Computer Interaction (HCI), disability studies, assistive technology, and social development to co-create new technologies, experiences, and ways of working with disabled people. DIX focuses on the interactions people have with their technologies and the interactions which result because of technology use. A central theme of the approach is to tackle complex issues where disability problems are part of a system that does not have a simple solution. Therefore, DIX pushes researchers and practitioners to take a challenge-based approach, which enables both applied and basic research to happen alongside one another. DIX complements other frameworks and approaches that have been developed within HCI research and beyond. Traditional accessibility approaches are likely to focus on specific aspects of technology design and use without considering how features of large-scale assistive technology systems might influence the experiences of people with disabilities. DIX aims to embrace complexity from the start, to better translate the work of accessibility and assistive technology research into the real world. DIX also has a stronger focus on user-centered and participatory approaches across the whole value chain of technology, ensuring we design with the full system of technology in mind (from conceptualization and development to large-scale distribution and access). DIX also helps to acknowledge that solutions and approaches are often non-binary and that technologies and interactions that deliver value to disabled people in one situation can become a hindrance in a different context. Therefore, it offers a more nuanced guide to designing within the disability space, which expands the more traditional problem-solving approaches to designing for accessibility. This book explores why such a novel approach is needed and gives case studies of applications highlighting how different areas of focus—from education to health to work to global development—can benefit from applying a DIX perspective. We conclude with some lessons learned and a look ahead to the next 60 years of DIX.
Disability Interactions Creating Inclusive Innovations
Type
PhD
Themes
Assistive & Accessible Technology
Research Group
Disability Interactions
Specifying a Hybrid, Multiple Material CAD System for Next Generation Prosthetic Design
Troy Bodkin
Doctoral Thesis. This work is one of four multidisciplinary research studies conducted by members of this research cluster, focusing on the area of Computer Aided Design (CAD) for improving the interface with Additive Manufacture (AM) to solve some of the challenges presented with improving prosthetic socket design, with an aim to improve and streamline the process to enable the involvement of clinicians and patients in the design process.
Loughborough University
Abstract
Specifying a Hybrid, Multiple Material CAD System for Next Generation Prosthetic Design
For many years, the biggest issue that causes discomfort and hygiene issues for patients with lower limb amputations have been the interface between body and prosthetic, the socket. Often made of an inflexible, solid polymer that does not allow the residual limb to breathe or perspire and with no consideration for the changes in size and shape of the human body caused by changes in temperature or environment, inflammation, irritation and discomfort often cause reduced usage or outright rejection of the prosthetic by the patient in their day to day lives. To address these issues and move towards a future of improved quality of life for patients who suffer amputations, Loughborough University formed the Next Generation Prosthetics research cluster. This work is one of four multidisciplinary research studies conducted by members of this research cluster, focusing on the area of Computer Aided Design (CAD) for improving the interface with Additive Manufacture (AM) to solve some of the challenges presented with improving prosthetic socket design, with an aim to improve and streamline the process to enable the involvement of clinicians and patients in the design process. The research presented in this thesis is based on three primary studies. The first study involved the conception of a CAD criteria, deciding what features are needed to represent the various properties the future socket outlined by the research cluster needs. These criteria were then used for testing three CAD systems, one each from the Parametric, Non Uniform Rational Basis Spline (NURBS) and Polygon archetypes respectively. The result of these tests led to the creation of a hybrid control workflow, used as the basis for finding improvements. The second study explored emerging CAD solutions, various new systems or plug-ins that had opportunities to improve the control model. These solutions were tested individually in areas where they could improve the workflow, and the successful solutions were added to the hybrid workflow to improve and reduce the workflow further. The final study involved taking the knowledge gained from the literature and the first two studies in order to theorise how an ideal CAD system for producing future prosthetic sockets would work, with considerations for user interface issues as well as background CAD applications. The third study was then used to inform the final deliverable of this research, a software design specification that defines how the system would work. This specification was written as a challenge to the CAD community, hoping to inform and aid future advancements in CAD software. As a final stage of research validation, a number of members of the CAD community were contacted and interviewed about their feelings of the work produced and their feedback was taken in order to inform future research in this area.
Cite
Specifying a Hybrid, Multiple Material CAD System for Next Generation Prosthetic Design
Bodkin, Troy L. (2017): Specifying a hybrid, multiple material CAD system for next-generation prosthetic design. Loughborough University. Thesis.https://hdl.handle.net/2134/25...;
Specifying a Hybrid, Multiple Material CAD System for Next Generation Prosthetic Design
Type
PhD
Themes
Assistive & Accessible Technology
Research Group
Disability Interactions
YouTransfer, YouDesign: A Participatory Approach to Design Assistive Technology for Wheelchair Transfers
Giulia Barbareschi
Doctoral Thesis. This thesis makes two contributions to facilitate wheelchair users’ engagement in the participatory design process for ATs, while being mindful of the burden of participation. The first contribution is a framework that provides a modular structure guiding the participatory design process from initial problem identification and analysis to facilitating collaborations between wheelchair users and designers. The framework identifies four factors determining the need and adoption process for ATs: (i) People focuses on the target population, (ii) Person includes personal characteristics, (iii) Activity refers to the challenges associated with the task, and (iv) Context encompasses the effect of the environment in which the activity takes place. The second contribution constitutes a rich picture of personal and external elements influencing real world wheelchair transfers that emerged from four studies carried out to investigate the effect of the framework factors on the design process for ATs.
UCL (University College London)
Abstract
YouTransfer, YouDesign: A Participatory Approach to Design Assistive Technology for Wheelchair Transfers
Transferring independently to and from their wheelchair is an essential routine task for many wheelchair users but it can be physically demanding and can lead to falls and upper limb injuries that reduce the person’s independence. New assistive technologies (ATs) that facilitate the performance of wheelchair transfers have the potential to allow wheelchair users to gain further independence. To ensure that users’ needs are addressed by ATs, the active involvement of wheelchair users in the process of design and development is critical. However, participation can be burdensome for many wheelchair users as design processes where users are directly involved often require prolonged engagement. This thesis makes two contributions to facilitate wheelchair users’ engagement in the participatory design process for ATs, while being mindful of the burden of participation. The first contribution is a framework that provides a modular structure guiding the participatory design process from initial problem identification and analysis to facilitating collaborations between wheelchair users and designers. The framework identifies four factors determining the need and adoption process for ATs: (i) People focuses on the target population, (ii) Person includes personal characteristics, (iii) Activity refers to the challenges associated with the task, and (iv) Context encompasses the effect of the environment in which the activity takes place. The second contribution constitutes a rich picture of personal and external elements influencing real world wheelchair transfers that emerged from four studies carried out to investigate the effect of the framework factors on the design process for ATs. A related outcome based on these contributions is a framing document to share knowledge between wheelchair users and designers to provide focus and promote an equal collaboration among participants.
Cite
YouTransfer, YouDesign: A Participatory Approach to Design Assistive Technology for Wheelchair Transfers
Barbareschi, Giulia. “YouTransfer, YouDesign : a Participatory Approach to Design Assistive Technology for Wheelchair Transfers / Giulia Barbareschi.” Thesis (Ph.D.)--University College London, 2018., 2018. Print.
YouTransfer, YouDesign: A Participatory Approach to Design Assistive Technology for Wheelchair Transfers
Type
PhD
Themes
Assistive & Accessible Technology
Research Group
Disability Interactions
Understanding wrist splint user needs and personalisation through codesign
Charlotte Pyatt
A Doctoral Thesis. Submitted in partial fulfilment of the requirements for the award of the degree of Doctor of Philosophy at Loughborough University.
Loughborough University
Abstract
Understanding wrist splint user needs and personalisation through codesign
Wrist splints are a common treatment for rheumatoid arthritis, however their effectiveness is compromised by patients not wearing splints as often as prescribed. Previous research has identified a number of reasons for non-compliance, but typically lacks insights that could lead to improved splint design.
This thesis investigates the motivators for patients to wear and not wear their wrist splints and, the impact of personalisation of splint appearance on patient wear. The work is based on the premise that digital design and manufacturing processes, such as Computer-Aided Design (CAD) and 3D Printing, can produce bespoke splints on demand.
The research begins with a literature review across the core areas of: splinting, additive manufacture, product appearance and personalisation. This literature review identifies gaps in knowledge from which research questions are established for the work.
The research employs a qualitative, generative design research approach and, follows a codesign framework employing telling, making and enacting tools. The thesis is made up of three studies. The first study is a sensitisation study and uses design probes to prepare the participants for the research and begin exploring the problem space. The second is a comprehensive study into participants splint wear behaviour and uses context mapping and scenario picture card tools to investigate the motivators for participants to wear and not wear wrist splints, along with positive and negative outcomes or wearing/not wearing splints. The final study uses a personalisation toolkit to elicit patient needs for a future wrist splint design and investigate self-reported expectations regarding compliance of patients who used the toolkit.
The research finds that patient compliance is affected by practical and aesthetic limitations of current splints. It identifies 4 motivating factors to wear a splint and 10 motivating factors to not wear a splint. Additionally, it identifies 6 positive outcomes of wearing splints, 6 negative outcomes of wearing splints, 3 positive outcomes of not wearing splints and 3 negative outcomes of not wearing splints. Requirements for an improved splint design are established and form the basis of the design for a prototype personalisation toolkit. Testing of this toolkit reveals that patients are keen to own more than one splint and personalise splints to match the scenario in which it is to be worn. Patients reported that they expected to be more compliant with a personalised splint when compared to their current splint.
Understanding wrist splint user needs and personalisation through codesign
Pyatt, Charlotte (2018): Understanding wrist splint user needs and personalisation through codesign. Loughborough University. Thesis.https://doi.org/10.26174/thesi...;
Understanding wrist splint user needs and personalisation through codesign
Type
PhD
Themes
Assistive & Accessible Technology
Shared Control for Wheelchair Interfaces
Dr Chinemelu Ejiamatu Muoma Ezeh
Doctoral Thesis. Independent mobility is fundamental to the quality of life of people with impairment. Most people with severe mobility impairments, whether congenital, e.g., from cerebral palsy, or acquired, e.g., from spinal cord injury, are prescribed a wheelchair. A small yet significant number of people are unable to use a typical powered wheelchair controlled with a joystick. Instead, some of these people require alternative interfaces such as a head- array or Sip/Puff switch to drive their powered wheelchairs. However, these alternative interfaces do not work for everyone and often cause frustration, fatigue and collisions. This thesis develops a novel technique to help improve the usability of some of these alternative interfaces, in particular, the head-array and Sip/Puff switch.
UCL (University College London)
Abstract
Shared Control for Wheelchair Interfaces
Independent mobility is fundamental to the quality of life of people with impairment. Most people with severe mobility impairments, whether congenital, e.g., from cerebral palsy, or acquired, e.g., from spinal cord injury, are prescribed a wheelchair. A small yet significant number of people are unable to use a typical powered wheelchair controlled with a joystick. Instead, some of these people require alternative interfaces such as a head- array or Sip/Puff switch to drive their powered wheelchairs. However, these alternative interfaces do not work for everyone and often cause frustration, fatigue and collisions. This thesis develops a novel technique to help improve the usability of some of these alternative interfaces, in particular, the head-array and Sip/Puff switch. Control is shared between a powered wheelchair user, using an alternative interface and a pow- ered wheelchair fitted with sensors. This shared control then produces a resulting motion that is close to what the user desires to do but a motion that is also safe. A path planning algorithm on the wheelchair is implemented using techniques in mo- bile robotics. Afterwards, the output of the path planning algorithm and the user’s com- mand are both modelled as random variables. These random variables are then blended in a joint probability distribution where the final velocity to the wheelchair is the one that maximises the joint probability distribution. The performance of the probabilistic approach to blending the user’s inputs with the output of a path planner, is benchmarked against the most common form of shared control called linear blending. The benchmarking consists of several experiments with end users both in a simulated world and in the real-world. The thesis concludes that probabilistic shared control provides safer motion compared with the traditional shared control for difficult tasks and hard-to-use interfaces.
Shared Control for Wheelchair Interfaces
Ezeh, Chinemelu Ejiamatu Muoma. Shared Control for Wheelchair Interfaces. UCL (University College London), 2018. Print.
Shared Control for Wheelchair Interfaces
Type
PhD
Themes
Assistive & Accessible Technology
Research Group
Disability Interactions
Materials For Facial Prostheses In Resource Limited Countries
Sophia Esther Liiba Tetteh
A Doctoral Thesis. Submitted in partial fulfilment of the requirements for the award of the degree of Doctor of Philosophy of Loughborough University
Loughborough University
Abstract
Materials For Facial Prostheses In Resource Limited Countries
Facial prostheses are artificial devices that replace a missing body part in the facial and neck regions of the body. Defects or deformities in these regions can lead to functional deficiencies; social and psychological effects in addition to cosmetic defects. Restoration or rehabilitation in resource limited countries is usually provided by charities and organisations volunteering assistance overseas, with some training of local staff in the fabrication of these prostheses. Furthermore, these countries typically lack technical knowhow and trained personnel. In industrialised nations maxillofacial prosthetics has developed into a sophisticated medical speciality requiring highly skilled staff and expensive facilities. In resource limited countries surgical procedures may be an option for rehabilitation of these deformities/defects however, they tend to be unavailable or unaffordable and donated prostheses are not suitable. Hence, this research explores, from first principles, the appropriate and affordable local provision of maxillofacial prostheses in resource constrained regions. The investigation provides knowledge on identifying requirements for resource limited areas, resulting in the creation of a guideline constituting priorities, requirements and specifications. It further explores the viability of potentially cheaper, locally available candidate materials via weathering and antimicrobial methods in ascertaining material longevity.
Materials For Facial Prostheses In Resource Limited Countries
Tetteh, Sophia (2019): Materials for facial prostheses in resource-limited countries. Loughborough University. Thesis.https://doi.org/10.26174/thesi...;
Materials For Facial Prostheses In Resource Limited Countries
Type
PhD
Themes
Assistive & Accessible Technology
Research Group
Disability Interactions
Exploring Thermal Discomfort Amongst Lower-Limb Prosthesis Wearers
Rhys James Williams
Thesis: Firstly, the research provides a methodological contribution showing how to conduct mixed-methods research to obtain rich insights into complex prosthesis phenomena. Secondly, the research highlights the need to appreciate psychological and contextual factors when researching prosthesis wearer thermal comfort. The research contributions are also converted into an implication for prosthesis design. The concept of 'regaining control' to psychologically mitigate thermal discomfort could be incorporated into technologies by using 'on-demand' thermal discomfort relief, rather than 'always-on' solutions, as have been created in the past.
UCL, ProQuest Dissertations Publishing
Abstract
Exploring Thermal Discomfort Amongst Lower-Limb Prosthesis Wearers
Amongst lower-limb prosthesis wearers, thermal discomfort is a common problem with an estimated prevalence of more than 50%. Overheating does not just create discomfort to the user, but it has been linked to excessive sweating, skin damage caused by a moist environment and friction. Due to impermeable prosthetic components and a warm moist environment, minor skin damage can result in skin infections that can lead to prosthesis cessation, increased social anxiety, isolation and depression. Despite the seriousness of thermal discomfort, few studies explore the issue, with research predominantly constrained to controlled laboratory scenarios, with only one out of laboratory study. In this thesis, studies investigate how thermal discomfort arises and what are the consequences of thermal discomfort for lower-limb prosthesis wearers. Research studies are designed around the principles of presenting lived experiences of the phenomenon and conducting research in the context of participants' real-life activities. A design exploration chapter investigates modifying liner materials and design to create a passive solution to thermal discomfort. However, this approach was found to be ineffective and unfeasible. Study 1 presents a qualitative study which investigates the user experience of a prosthesis, thermal discomfort and related consequences. Study 2 explores limb temperature of male amputees inside and outside the laboratory, with the latter also collecting perceived thermal comfort (PTC) data. Finally, Study 3 investigates thermal discomfort in the real-world and tracks limb temperature, ambient conditions, activities, and experience sampling of PTC. While there were no apparent relationships presented in sensor data, qualitative data revealed that in situations where prosthesis wearers perceived a lack of control, thermal discomfort seemed to be worse. When combined, the studies create two knowledge contributions. Firstly, the research provides a methodological contribution showing how to conduct mixed-methods research to obtain rich insights into complex prosthesis phenomena. Secondly, the research highlights the need to appreciate psychological and contextual factors when researching prosthesis wearer thermal comfort. The research contributions are also converted into an implication for prosthesis design. The concept of 'regaining control' to psychologically mitigate thermal discomfort could be incorporated into technologies by using 'on-demand' thermal discomfort relief, rather than 'always-on' solutions, as have been created in the past.
Cite
Exploring Thermal Discomfort Amongst Lower-Limb Prosthesis Wearers
Williams, Rhys James. “Exploring Thermal Discomfort Amongst Lower-Limb Prosthesis Wearers.” ProQuest Dissertations Publishing, 2020. Print.
Exploring Thermal Discomfort Amongst Lower-Limb Prosthesis Wearers
Type
PhD
Themes
Assistive & Accessible Technology
Research Group
Disability Interactions
Design rules for additively-manufactured wrist splints
Sarah Kelly
A Doctoral Thesis. Submitted in partial fulfilment of the requirements for the award of the degree of Doctor of Philosophy of Loughborough University.
Loughborough University
Abstract
Design rules for additively-manufactured wrist splints
Additive Manufacturing (AM) often known by the term three-dimensional printing (3DP) has been acknowledged as a potential manufacturing revolution. AM has many advantages over conventional manufacturing techniques; AM techniques manufacture through the addition of material - rather than traditional machining or moulding methods. AM negates the need for tooling, enabling cost-effective low-volume production in high-wage economies and the design & production of geometries that cannot be made by other means. In addition, the removal of tooling and the potential to grow components and products layer-by-layer means that we can produce more from less in terms of more efficient use of raw materials and energy or by making multifunctional components and products. The proposed Centre for Doctoral Training (CDT) in Additive Manufacturing and 3D Printing has the vision of training the next generation of leaders, scientists and engineers in this diverse and multi-disciplinary field. As AM is so new current training programmes are not aligned with the potential for manufacturing and generally concentrate on the teaching of Rapid Prototyping principles, and whilst this can be useful background knowledge, the skills and requirements of using this concept for manufacturing are very different. This CDT will be training cohorts of students in all of the basic aspects of AM, from design and materials through to processes and the implementation of these systems for manufacturing high value goods and services. The CDT will also offer specialist training on aspects at the forefront of AM research, for example metallic, medical and multi-functional AM considerations. This means that the cohorts graduating from the CDT will have the background knowledge to proliferate throughout industry and the specialist knowledge to become leaders in their fields, broadening out the reach and appeal of AM as a manufacturing technology and embedding this disruptive technology in company thinking. In order to give the cohorts the best view of AM, these students will be taken on study tours in Europe and the USA, the two main research powerhouses of AM, to learn from their international colleagues and see businesses that use AM on a daily basis. One of the aims of the CDT in AM is to educate and attract students from complementary basic science, whether this be chemistry, physics or biology. This is because AM is a fast moving area. The benefits of having a CDT in AM and coupling with students who have a more fundamental science base are essential to ensure innovation & timeliness to maintain the UK's leading position. AM is a disruptive technology to a number of industrial sectors, yet the CDTs industrial supporters, who represent a breadth of industrial end-users, welcome this disruption as the potential business benefits are significant. Growing on this industry foresight, the CDT will work in key markets with our supporters to ensure that AM is positioned to provide a real and lasting contribution & impact to UK manufacturing and provide economic stability and growth. This contribution will provide societal benefits to UK citizens through the generation of wealth and employment from high value manufacturing activities in the UK.
Cite
Design rules for additively-manufactured wrist splints
Kelly, Sarah (2020): Design rules for additively-manufactured wrist splints. Loughborough University. Thesis.https://doi.org/10.26174/thesi...;
Design rules for additively-manufactured wrist splints
Type
PhD
Themes
Assistive & Accessible Technology
Emotionally driven Prostheses: Exploring the Effects on Users’ Lives and Societies’ Attitudes in the UK and Greece
Anna Vlachaki
The literature shows that research into the aesthetic aspects of prostheses is limited. Although there are suggestions that prostheses with high levels of emotionally-driven design may improve users’ well-being, they are based only on theoretical findings. Therefore, in this thesis the effects of emotionally-driven prostheses on users’ lives and society’s attitudes were explored, with respect to culture and more specifically, the theories of individualism/ collectivism. In order to investigate the effects of culture, the research was conducted in two countries with different cultures; the UK (individualistic) and Greece (collectivistic). The thesis began with a literature review across three core areas: user, product and environment, and revealed the importance of investigating an additional area; that of prosthetists. The research employed a qualitative approach and consisted of four studies.
Loughborough University
Abstract
Emotionally driven Prostheses: Exploring the Effects on Users’ Lives and Societies’ Attitudes in the UK and Greece
The literature shows that research into the aesthetic aspects of prostheses is limited. Although there are suggestions that prostheses with high levels of emotionally-driven design may improve users’ well-being, they are based only on theoretical findings. Therefore, in this thesis, the effects of emotionally-driven prostheses on users’ lives and society’s attitudes were explored, with respect to culture and more specifically, the theories of individualism/ collectivism. In order to investigate the effects of culture, the research was conducted in two countries with different cultures; the UK (individualistic) and Greece (collectivistic). The thesis began with a literature review across three core areas: user, product and environment, and revealed the importance of investigating an additional area; that of prosthetists. The research employed a qualitative approach and consisted of four studies. Study I was an online questionnaire to explore users’ preferences towards prostheses, with respect to their culture. Study II consisted of semi-structured interviews and informational probes to comprehend the role of prostheses on users’ lives, with respect to prosthetic appearance. In Study III, the aim was to investigate prosthetists’ attitudes towards the needs of prosthetic users by conducting semi-structured interviews. Finally, Study IV was an online questionnaire to explore non-users’ attitudes towards the design of prostheses. The research showed that the use of prostheses for the completion of users’ body was not an adequate factor to improve their well-being, and a shift on users’ desires towards emotionally-driven prostheses has occurred. From the variables that were tested, sex, age, cause and area of limb-loss may affect people’s attitudes towards the design of prostheses. Furthermore, the results showed that prostheses with high emotionally-driven design evoked emotions, in both users and non-users, with higher levels of pleasantness and arousal than the emotions that were elicited by the prostheses of lower emotionally-driven designs and thus, they may trigger a greater behavioural reaction. This suggested that emotionally-driven prostheses may eliminate users’ stigmatisation by increasing their self-confidence and altering society’s attitudes. However, attention needs to be paid in collectivistic countries, as emotionally-driven prostheses may enhance users’ stigmatisation.
Emotionally driven Prostheses: Exploring the Effects on Users’ Lives and Societies’ Attitudes in the UK and Greece
Vlachaki, Anna (2020): Emotionally-driven prostheses: exploring the effects on users’ lives and societies’ attitudes in the UK and Greece. Loughborough University. Thesis.https://doi.org/10.26174/thesi...;
Emotionally driven Prostheses: Exploring the Effects on Users’ Lives and Societies’ Attitudes in the UK and Greece
Type
Workshop
Themes
Assistive & Accessible Technology
Culture and Participation
Rethinking the Senses: A Workshop on Multisensory Embodied Experiences and Disability Interactions
Maryam Bandukda, Aneesha Singh,Catherine Holloway,Nadia Berthouze, Emeline Brulé, Ana Tajadura-Jiménez, Oussama Metatla, Ana Javornik, and Anja Thieme
The emerging possibilities of multisensory interactions provide an exciting space for disability and open up opportunities to explore new experiences for perceiving one's own body, it's interactions with the environment and also to explore the environment itself. In addition, dynamic aspects of living with disability, life transitions, including ageing, psychological distress, long-term conditions such as chronic pain and new conditions such as long-COVID further affect people's abilities. Interactions with this diversity of embodiments can be enriched, empowered and augmented through using multisensory and cross-sensory modalities to create more inclusive technologies and experiences. To explore this, in this workshop we will explore three related sub-domains: immersive multi-sensory experiences, embodied experiences, and disability interactions and design.
CHI EA '21: Extended Abstracts of the 2021 CHI Conference on Human Factors in Computing Systems
Abstract
Rethinking the Senses: A Workshop on Multisensory Embodied Experiences and Disability Interactions
The emerging possibilities of multisensory interactions provide an exciting space for disability and open up opportunities to explore new experiences for perceiving one's own body, it's interactions with the environment and also to explore the environment itself. In addition, dynamic aspects of living with disability, life transitions, including ageing, psychological distress, long-term conditions such as chronic pain and new conditions such as long-COVID further affect people's abilities. Interactions with this diversity of embodiments can be enriched, empowered and augmented through using multisensory and cross-sensory modalities to create more inclusive technologies and experiences. To explore this, in this workshop we will explore three related sub-domains: immersive multi-sensory experiences, embodied experiences, and disability interactions and design. The aim is to better understand how we can re-think the senses in technology design for disability interactions and the dynamic self, constructed through continuously changing sensing capabilities either because of changing ability or because of the empowering technology. This workshop will: (i) bring together HCI researchers from different areas, (ii) discuss tools, frameworks and methods, and (iii) form a multidisciplinary community to build synergies for further collaboration.
Rethinking the Senses: A Workshop on Multisensory Embodied Experiences and Disability Interactions
Maryam Bandukda, Aneesha Singh, Catherine Holloway, Nadia Berthouze, Emeline Brulé, Ana Tajadura-Jiménez, Oussama Metatla, Ana Javornik, and Anja Thieme. 2021. Rethinking the Senses: A Workshop on Multisensory Embodied Experiences and Disability Interactions. Extended Abstracts of the 2021 CHI Conference on Human Factors in Computing Systems. Association for Computing Machinery, New York, NY, USA, Article 118, 1–5. DOI:https://doi.org/10.1145/341176...
Rethinking the Senses: A Workshop on Multisensory Embodied Experiences and Disability Interactions
Type
Workshop
Themes
Assistive & Accessible Technology
Research Group
Disability Interactions
Disability Design and Innovation in Low Resource Settings: Addressing Inequality Through HCI.
Giulia Barbareschi,Dafne Zuleima Morgado-Ramirez,Catherine Holloway, Swami Manohar Swaminathan, Aditya Vashistha, and Edward Cutrell.
Approximately 15% of the world's population has a disability and 80% live in low resource-settings, often in situations of severe social isolation. Technology is often inaccessible or inappropriately designed, hence unable to fully respond to the needs of people with disabilities living in low resource settings. Also lack of awareness of technology contributes to limited access. This workshop will be a call to arms for researchers in HCI to engage with people with disabilities in low resourced settings to understand their needs and design technology that is both accessible and culturally appropriate.
Extended Abstracts of the 2021 CHI Conference on Human Factors in Computing Systems.
Abstract
Disability Design and Innovation in Low Resource Settings: Addressing Inequality Through HCI.
Approximately 15% of the world's population has a disability and 80% live in low resource-settings, often in situations of severe social isolation. Technology is often inaccessible or inappropriately designed, hence unable to fully respond to the needs of people with disabilities living in low resource settings. Also lack of awareness of technology contributes to limited access. This workshop will be a call to arms for researchers in HCI to engage with people with disabilities in low resourced settings to understand their needs and design technology that is both accessible and culturally appropriate. We will achieve this through sharing of research experiences, and exploration of challenges encountered when planning HCI4D studies featuring participants with disabilities. Thanks to the contributions of all attendees, we will build a roadmap to support researchers aiming to leverage post-colonial and participatory approaches for the development of accessible and empowering technology with truly global ambitions.
Cite
Disability Design and Innovation in Low Resource Settings: Addressing Inequality Through HCI.
Giulia Barbareschi, Dafne Zuleima Morgado-Ramirez, Catherine Holloway, Swami Manohar Swaminathan, Aditya Vashistha, and Edward Cutrell. 2021. Disability Design and Innovation in Low Resource Settings: Addressing Inequality Through HCI. Extended Abstracts of the 2021 CHI Conference on Human Factors in Computing Systems. Association for Computing Machinery, New York, NY, USA, Article 124, 1–5. DOI:https://doi.org/10.1145/3411763.3441340
| https://www.disabilityinnovation.com/publications?page=4&type=book+workshop+phd+report+article |
IIH UK Research | IIH UK - (Idiopathic intracranial hypertension)
The IIH UK website is a source of information for IIH – Idiopathic Intracranial Hypertension
IIH UK Research
IIH UK funds, supports and promotes research that is informed by the priorities of people with IIH and health care professionals. IIH UK facilitates research into IIH, its treatments and possible cures.
IIH UK not only works with internationally renowned teams of researchers but also carries out and disseminates its own research projects working with our membership. IIH UK has 3 research representatives Amanda Denton, Dr Krystal Kirkby and Nisha Raval (Click here for profiles)
Recent projects are detailed in descending date order below:
Obesity Stigma in people with IIH
In 2021, IIH UK carried out a survey in response to members of IIH UK to see if they were experiencing stigma related to their weight in consultations with health professionals.
To find out more about the results of this survey and what IIH UK plan to do in response click here.
2020 Report into the effects of Lockdown on those people living with IIH.
In March 2020 the UK and world experienced an unprecedented event of a global pandemic Covid-19. In the UK lockdown started on March the 23rd and IIH UK was keen to capture the impact on the lives of people with IIH. A great response was received to the IIH UK short survey about lockdown. 121 people responded to the survey which ran from 24/05/2020 to 24/06/2020. 120/121 who responded added additional comments to explain their response.
2019 What is the lived experience of headache in the words of people with IIH?
In November 2019 IIH UK carried out a piece of research to capture the experience of living with headache in people with IIH in their words. Previously research reports of headache in IIH show that it affects quality of life (SF-36); causes disability (HIT-6) and is daily in most (86%)(4–6). The James Lind Alliance Research Priority Setting Partnership also highlighted that headache is an unmet need in IIH(3). However the voice of people with IIH describing their experience has not been reported previously.
2018 Physical activity, quality of life and headache impact in people with Idiopathic Intracranial Hypertension
Research Reps Amanda Denton and Dr Krystal Hemmings (University of Derby) and a Physiotherapy researcher from Plymouth University Dr Hilary Gunn carried out and analysed this survey. An online survey was sent to people with IIH to complete. The survey contained measures of physical activity, quality of life and headache impact. 164 pwIIH took part and their information was analysed. The results showed that pwIIH have low levels of physical activity and take little exercise. Physical activity is related to quality of life in pwIIH. Physical activity was not related to age, current or diagnosis BMI (Body Mass Index) or headache impact score in pwIIH.
Conclusion
The results suggest that improving physical activity in pwIIH could positively impact on quality of life. Ways to increase physical activity such as exercise should be explored in pwIIH.
2016 and 2018 Barriers to Weight Loss and Exercise
Research reps Krystal Hemmings and Amanda Denton put together two surveys to people with IIH to firstly identify perceived barriers to weight loss and exercise and then to rank these in order of importance. The survey highlighted that exercise exacerbates symptoms of IIH for many and that there was a mismatch between researchers perceived benefits of weight loss and participants perceptions of the effect of weight loss on their symptoms.
Top 3 perceived barriers to weight loss – Fatigue, Pain and Mood
Top 3 perceived barriers to exercise – Fatigue, Headache and Dizziness
The results show that further research is needed to understand why some people with IIH experience exacerbations of their IIH symptoms with exercise. Explore what type of exercise is best for pwIIH and that there is a need to explore the barriers to weight loss and exercise with pwIIH at greater depth.
2016 Illuminating the Patient experience of Lumbar Puncture:
A survey carried out by IIH UK, which exposed the toll on patients of undergoing repeated Lumbar Puncture, has spurred a collaborative research project and paved the way for improved clinical management.Illuminating the Patient Experience of LP
Characterising the patient experience of diagnostic lumbar puncture in idiopathic intracranial hypertension: a cross-sectional online survey. This patient initiated research aimed to guide future clinical practice of Lumbar Puncture.
http://bmjopen.bmj.com/content/8/5/e020445
| https://www.iih.org.uk/product/82/5/iih_uk_research/bd81bf9e8b45526e62cd2166f5159344 |
KoreaMed Synapse
Chest Radiology
Case Report
Journal of the Korean Society of Radiology 2011; 64(3): 249-252.
Published online:31 March 2011
DOI:https://doi.org/10.3348/jksr.2011.64.3.249
MR Imaging Features of Primary Cutaneous Diffuse Large B-cell Lymphoma: A Case Report
Jae il Park, M.D. , Jae Woon Kim, M.D.
1Department of Diagnostic Radiology, College of Medicine, Yeungnam University, Korea.
Address reprint requests to: Jae Woon Kim, M.D., Department of Diagnostic Radiology, College of Medicine, Yeungnam University, 317-1, Daemyung-dong, Nam-gu, Daegu 705-717, Korea. Tel. 82-53-620-3046, Fax. 82-53-653-5484,[email protected]
Received 12 September 2010 Accepted 3 January 2011
Copyright © 2011 The Korean Society of Radiology
Abstract
Here we report magnetic resonance (MR) imaging findings for a case of primary cutaneous diffuse large B-cell lymphoma (PCDLBCL) located in the chest wall, a rare type of lymphoma, occurring in a 67-year-old woman. Although rare, PCDLBCL may be one of the diagnostic inclusions for a soft tissue mass in the subcutaneous layer of the trunk, especially when the mass shows hyperintensity in relation to the muscle on T2-weighted MR images and peripheral enhancement on contrast enhanced T1-weighted MR images.
Keywords:Lymphoma, Large B-cell, Diffuse,Soft Tissue Neoplasms,Magnetic Resonance Imaging,Epidermoid Cyst
Primary cutaneous lymphomas are defined as a subtype that are restricted to the dermal or epidermal region and are without any signs of systemic lymphoma. Most skin non-Hodgkin's lymphomas (NHL) originate from T cells, and primary cutaneous diffuse large B cell lymphomas (PCDLBCLs) are uncommon ( 1 ). PCDLBCLs appear clinically as non-specific multiple palpable nodules or plaques in the subcutaneous tissue ( 2 ). PCDLBCLs localized in the head and trunk have good outcome compared to PCDLBCLs involving the leg ( 3 4 ). The clinical and pathological features of PCDLBCLs have been well described, but MR imaging features of PCDLBCLs have not been reported. Herein we report such features.
Case Report
A 67-year-old woman presented with fever and a subcutaneous mass on the left posterior chest wall. She had had a small non-tender palpable nodule on her left posterior chest wall for 20 years, and it had recently increased in size. Palpable lymphadenopathy or organomegaly was not found on physical examination. Laboratory tests disclosed anemia (a hemoglobin level of 10.8 g/dL), but white blood cell and platelet counts were within the normal ranges.
To diagnose the mass and assess its extent, MRI was performed using a 1.5 T MR system (Symphony Vision®, Siemens Medical Solutions, Erlangen, Germany). MR images included T2-weighted turbo spin echo sequences (TR/TE, 3700-4400/99 msec; echo train length, 13; 4 mm slice thickness; 448 × 252 matrix; 20 cm field of view) and T1-weighted turbo spin echo (TR/TE, 700/11 msec; 448 × 233 matrix; 4 mm slice thickness; 20 cm field of view) sequences. Three minutes after injection of contrast material (0.1 mmol/kg at a rate of 2-3 mL/sec; Gd-diethylenetriaminepentaacetic acid, Magnevist; Bayer Schering Pharma, Berlin, Germany), post-contrast images were obtained using spin echo sequences (TR/TE=640/11 msec) with a fat suppression technique.
T1-weighted images showed a 3 × 2.5 × 2 cm, lobulated subcutaneous mass of low signal intensity with a high signal rim and infiltration of the overlying skin ( Fig. 1A ) in her left posterior chest wall. T2-weighted images showed a hyperintense mass with thin septa ( Fig. 1B ). On gadolinium-enhanced, fat-suppressed, T1-weighted images, a thick irregular peripheral rim and septal enhancement were seen. Fuzzy enhancement of overlying skin was also seen ( Fig. 1C ). The differential diagnoses included a ruptured epidermoid cyst, a cutaneous abscess, and, less likely, solid mass.
On general anesthesia, excisional biopsy was performed. A yellowish, 2 cm diameter, soft, and movable mass was seen in the subcutaneous layer of the left posterior chest wall. It was easily separated from adjacent soft tissue.
Fig. 1D
). An immunohistochemical study showed positivity of lymphocytes for CD20, CD99, CD10, BCL6 and Ki-67 LI (
Fig. 1E
). However, tumor cells were negative for CD3, CD30, BCL2, EMA, CD56, Cytokeratin (AE1/AE3), Cyclin D1, ALK and MUM 1. Combined morphologic and immunohistochemical features supported a diagnosis of diffuse large B-cell lymphoma. To assess extracutaneous manifestations of lymphoma, CT of the chest, abdomen, and whole-body F-18-deoxyglucose positron emission tomography (FDG-PET) were performed. Neither abnormal lymphadenopathy nor visceral involvement was noted. The patient has been periodically monitored in our hospital over the last 6 months without any recurrence of the lymphoma.
DISCUSSION
Nearly half of NHLs arise in extranodal sites, most commonly affecting the gastrointestinal tract and skin. The annual incidence of primary cutaneous lymphomas (PCLs) is 0.5 to 1 per 10,000 people (5, 6). Mycosis fungoides is the most common subtype of PCLs in the West. It is thought that 20 to 25% of these cases are of B-cell origin. PCDLBCLs represent a heterogeneous group of NHLs that present in the skin without evidence of extracutaneous disease at presentation and within 6 months after diagnosis. In the most recent (2005) classification of the World Health Organization/European Organization for Research and Treatment of Cancer, four main types of PCDLBCLs are recognized: primary cutaneous marginal zone B-cell lymphoma, primary cutaneous follicle-center lymphoma, primary cutaneous diffuse large B-cell lymphoma-leg type and primary cutaneous diffuse large B-cell lymphoma, other (
7
). PCDLBCLs usually affect elderly patients, in particular females, and characteristically present as solitary or multiple persistent red to violaceous papules, plaques, or non-scaly, non-ulcerated smooth cutaneous nodules on the head, trunk and leg. Therefore, PCDLBCLs are often confused with other entities including subcutaneous inflammatory panniculitis, cystic masses, solid tumors and vascular lesions (
6
8
).
Imaging tools such as ultrasound (US), computed tomography (CT), FDG-PET and MRI have an advantage over physical examination for detection and follow up (
3
4
). US is useful for evaluating a superficially located lesion. However, it is generally used for regional evaluation rather than to evaluate the extent of disease. CT has been useful in staging the lymphoma and in defining the extent of adenopathy. Although it is associated with limited soft tissue delineation and radiation, CT is still the first choice for soft tissue evaluation. FDG-PET can detect most low-grade lymphomas, but some types of indolent lymphoma are not well visualized on FDG-PET. Moreover, the spatial resolution of FDG-PET is not perfect: lesions smaller than 1 cm in diameter often go undetected. However, further studies are needed to assess the diagnostic ability of FDG-PET to detect PCDLBCLs. MRI is the radiologic technique of choice for preoperative evaluation of the extent and depth of primary and recurrent skin tumors.
The key point that enables the diagnosis of primary extranodal soft tissue lymphoma to be made is the extension of the tumor with preservation of the surrounding structures. In this patient, muscles and ribs were closely contacted by, but not invaded by the lymphoma, which is not a specific finding. On MR imaging, extranodal soft tissue lymphomas are homogeneously isointense or slightly hypointense relative to normal muscle on T1-weighted spine echo images, and are hyperintense to muscle on T2-weighted spin echo images. They uniformly enhance after intravenous administration of contrast material (
9
). Our case showed a well-defined lobulating lesion of high signal intensity on T2-weighted images, and low signal intensity with a peripheral high signal intensity rim on T1-weighted images in the subcutaneous layer of the chest wall. After gadolinium enhancement, we observed a central non-enhancement area with a thick irregular peripheral rim enhancing nodule and patchy enhancement of overlying skin. In correlation with the histopathology, the peripheral rim reflected a myxoid tissue, and the central area reflected necrosis and atypical lymphocytic infiltration of overlying skin. MR imaging features of PCDLBCLs are not definitively diagnostic because benign inflammatory lesions such as abscesses, complicated ganglia, bursitis, and ruptured epidermoid cysts also show septa and demonstrate thick and irregular rim enhancement after gadolinium enhancement (
10
).
A cutaneous T-cell lymphoma generally appears as eczema-like skin rashes or plaque-like lesions affecting any part of the body. Unlike cutaneous T cell lymphoma, cutaneous B cell lymphoma often shows nodule-like lesions ( 2 ). Imaging features of cutaneous lymphoma are non-specific and include soft tissue thickening, infiltration, or a mass. MR imaging features of PCDLBCLs have not been reported.
Inclusion of extranodal soft tissue lymphoma in the clinical differential diagnosis affects surgical decision making because lymphoma is not treated with surgery. In general, complete resection is not indicated because it would require the removal of a marker of disease response to chemotherapy, radiation therapy, or both.
Figures and Tables
Fig. 1
67-year-old woman with painful primary cutaneous diffuse large B-cell lymphoma in the left posterior chest wall.
A. This Axial T1-weighted image shows a hypointense lesion and a peripheral high signal intensity rim on the chest wall.
B. An axial T2-weighted image showing a lobulating subcutaneous mass with a central high signal intensity and peripheral low signal intensity rim.
C. A gadolinium-enhanced, fat-suppressed, T1-weighted image that shows a mass with thick and irregular peripheral enhancement. Subtle subcutaneous and overlying skin enhancements (arrow) are present near the mass.
D. Photomicrography of the skin shows diffuse dermal infiltration by large atypical lymphocytes (H & E stain, ×40).
E. Immunohistochemical staining of tumor cells showing expression of CD20.
References
1. Narimatsu H, Morishita Y, Shimada K, Ozeki K, Kohno A, Kato Y, et al. Primary cutaneous diffuse large B cell lymphoma: a clinically aggressive case. Intern Med. 2003; 42:354–357.
2. Hwang S. Imaging of lymphoma of the musculoskeletal system. Radiol Clin North Am. 2008; 46:379–396.
3. Goodlad JR, Krajewski AS, Batstone PJ, Mckay P, White JM, Benton EC, et al. Primary cutaneous diffuse large B-cell lymphoma: prognostic significance of clinicopathological subtypes. Am J Surg Pathol. 2003; 27:1538–1545.
4. Hallermann C, Niermann C, Fischer RJ, Schulze HJ. New prognostic relevant factors in primary cutaneous diffuse large B-cell lymphomas. J Am Acad Dermatol. 2007; 56:588–597.
5. Chen YF, Li YC, Chen LM, Tu CC, Chang CC, Kuo SY, et al. Primary cutaneous diffuse large B cell lymphoma relapsed solely as a huge lung tumor mimicking a primary pulmonary lymphoma. Int J Hematol. 2010; 91:112–116.
6. Sharon V, Mecca PS, Steinherz PG, Trippett TM, Myskowski PL. Two pediatric cases of primary cutaneous B-cell lymphoma and review of the literature. Pediatr Dermatol. 2009; 26:34–39.
7. Willemze R, Jaffe ES, Burg G, Cerroni L, Berti E, Swerdlow SH, et al. WHO-EORTC classification for cutaneous lymphomas. Blood. 2005; 105:3768–3785.
8. Hembury TA, Lee B, Gascoyne RD, Macpherson N, Yang B, House N, et al. Primary cutaneous diffuse large B-cell lymphoma: a clinicopathologic study of 15 cases. Am J Clin Pathol. 2002; 117:574–580.
9. ter Braak PM, Guit GL, Bloem JL. Case 111: Soft-tissue lymphoma. Radiology. 2007; 243:293–296.
10. Hong SH, Chung HW, Choi JY, Koh YH, Choi JA, Kang HS. MRI findings of subcutaneous epidermal cysts: emphasis on the presence of rupture. AJR Am J Roentgenol. 2006; 186:961–966.
Copyright © 2023. Korean Association of Medical Journal Editors.E-mail:[email protected]
| https://synapse.koreamed.org/articles/1086909 |
E-Library - Information At Your Fingertips: Printer Friendly
EN BANC
[ G.R. No. 258456 [Formerly UDK 17252]. July 26, 2022 ]
GIORGIDI B. AGGABAO AND AMELITA S. NAVARRO, PETITIONERS, VS. COMMISSION ON ELECTIONS (COMELEC) AND LAW DEPARTMENT, RESPONDENTS.
D E C I S I O N
LAZARO-JAVIER, J.:
In this Petition for Certiorari
under Rule 64 of the Rules of Court, Giorgidi B. Aggabao (Aggabao) and Amelita S. Navarro (Navarro) seek to nullify the following documents issued by respondent Commission on Elections (COMELEC) through its Law Department: a)
Document No. 21-3973 [1]
dated November 10, 2021
, declaring Navarro as an independent candidate; b)
Document No. 21-7467
[2]
dated December 22, 2021
, denying Aggabao's Certificate of Candidacy (COC) as substitute candidate for petitioner Navarro; and c)
Document No. 222-0176 dated January 5, 2022
, denying Aggabao's motion for reconsideration. Petitioners also pray that the Court restrain his exclusion from the ballot pending final resolution of the case.
On October 4, 2021, Navarro filed her COC [3]
for Mayor of Santiago City, Isabela for the May 9, 2022 National and Local Elections. She stated in her COC that she was officially nominated by the Partido para sa Demokratikong Reporma (Partido Reporma) for the mayoralty race. She attached to her COC a notarized copy of her Certificate of Nomination and Acceptance (CONA) dated September 23, 2021 signed by Senator Panfilo M. Lacson (Senator Lacson), the Chairperson of Partido Reporma. [4]
On October 8, 2021, one Christopher G. Ayson (Ayson) also filed a COC for Mayor of Santiago City, Isabela. He, too, declared in his COC that he was nominated by Partido Reporma. [5]
He submitted a CONA of even date which he claimed was also signed by Senator Lacson. [6]
When Senator Lacson learned of Ayson's aforesaid declaration, he sent COMELEC through its Law Department a Letter [7]
dated November 6, 2021, disclaiming that Partido Reporma issued any CONA in favor of Ayson. Senator Lacson emphasized that for purposes of the May 9, 2022 elections, Navarro was the official candidate of Partido Reporma for Mayor of Santiago City, Isabela, thus: [8]
ATTY. MARIA NORINA S. TANGARO-CASINGAL
Direcror , Law Department
Commission on Elections
Palacio Del Gobernador, Postigo Street
Intramuros Manila
Re: Official Candidate of Partido Reporma for Mayor in the City of Santiago, Isabela
Dear Director Tangaro-Casingal,
On behalf of PARTIDO PARA SA DEMOKRATIKONG REPORMA (PARTIDO REPORMA), I am writing to inform your good office and the Honorable Commission that
Partido Reporma has not issued any Certificate of Nomination and Acceptance (CONA) in favor of a certain CHRISTIAN GAMBOA [AY]SON supposedly nominating him as the party's purported candidate for the position of Mayor in Santiago City, Isabela
. A Certification issued by the undersigned is attached herein for your immediate reference.
It must be emphasized that for purposes of the May 9, 2022 National and Local Elections,
the official candidate of Partido Reporma for the aforementioned position is Ms. AMELITA S. NAVARRO .
Considering the foregoing, Partido Reporma respectfully requests that the necessary correction/s be made in the Honorable Commission's Certified List of Candidates.
Kind consideration and immediate action regarding this matter is much appreciated. Thank you. [9]
Sincerely yours,
[ original signed
]
Sen. Panfilo "Ping" M. Lacson
Chairman
, PARTIDO REPORMA
Attached to the letter was a notarized Certification of Senator Lacson, viz
.:
CERTIFICATION
To Whom it may Concern:
This is to certify that our party,
PARTIDO PARA SA DEMOKRATIKONG REPORMA (Partido Reporma), has not issued any Certificate of Nomination and Acceptance (CONA) to a certain Christopher Gamboa [Ay]son who is purportedly running for Mayor in the City of Santiago, Province of Isabela under Partido Reporma .
This Certification is being issued for any legal purpose it may serve.
Done this 6
th
day of November 2021, in Pasig City. (Emphasis supplied)
[ original signed
]
SEN. PANFILO LACSON
Chairman
[10]
On November 9, 2021, Navarro withdrew her candidacy and opted to run for Vice-Mayor of Santiago City, Isabela instead. In her Statement of Withdrawal, [11]
she declared that she would be substituted by Aggabao who is also a member of Partido Reporma. On even date, Aggabao filed his COC as Mayor of Santiago City, Isabela. [12]
He stated in his COC that he was officially nominated by Partido Reporma as evidenced by his CONA dated November 8, 2021 signed by Senator Lacson. [13]
Dispositions of the COMELEC
By Document No. 21-3973
[14]
dated November 10, 2021
, respondent COMELEC through its Law Department Director Maria Norina TangaroCasingal informed Navarro that she was deemed to be an independent candidate pursuant to Section 15 of COMELEC Resolution No. 10717 because Partido Reporma nominated two (2) candidates for the same mayoralty post, more than the number allowed to be voted for the elective position ( i.e.
, one [1]). Section 15 reads:
Section 15. Allowed Number of Nominations.
– No duly registered [Political Party] or Coalition shall be allowed to nominate more than the number of candidates required to be voted for in a particular elective position.
If the [Political Party] or Coalition nominated more than the number of candidates required to be voted for in a particular elective position, all of the nominations shall be denied due course by the Commission, and the aspirants shall be declared
independent candidates .
[15]
By Letter
[16]
dated November 12, 2021 addressed to the COMELEC Law Department, Aggabao clarified that on November 9, 2021, Navarro already withdrew her COC for Mayor of Santiago City, Isabela. On even date, he filed his COC as substitute candidate. It was indicated in his CONA that he was the official candidate of Partido Reporma for the mayoralty post, in lieu of Navarro. He called the attention of the COMELEC to the Letter and Certification both dated November 6, 2021 of Senator Lacson, the Chairperson of Partido Reporma stating that the Partido Reporma never issued a CONA in favor of Ayson.
Thereafter, on December 2, 2021, Senator Lacson sent another Letter addressed to COMELEC Chairperson Sheriff Abas reiterating his November 6, 2021 Letter that: (a) for purposes of the May 9, 2022 elections, the official candidate of Partido Reporma for Mayor of Santiago City, Isabela was Navarro prior to her withdrawal; and (b) Partido Reporma never issueda CONA to Ayson. Senator Lacson stressed that Ayson was not even a member of Partido Reporma as confirmed by Partido Reporma Regional Chairperson Michael John C. Delmendo, thus: [17]
x x x x
xxx I, as Chairman of Partido Reporma, categorical1y declared and emphasized that
for purposes of the May 9, 2022 National and Local Elections, the official candidate of Partido Reporma for the position of Mayor of Santiago City is Ms. Amelita S. Navarro
. xxx
the party has not issued any CONA to a certain Christopher Gamboa [Ay]son who is running for mayor of Santiago City .
I disowned Ayson's CONA as it is illogical, if not absurd for Partido Reporma to have issued a CONA to said Christopher Gamboa Ayson when
he is not even a member of Partido Reporma
. Attached hereto as Annex "F" is the Affidavit of
Atty. Michael John C. Delmendo, Regional Chairman of Partido Reporma, Region 2 where Santiago City belongs, stating that Christopher Gamboa Ayson, is not a member of the Party .
Yet despite all the foregoing Party declaration and certification denying the genuineness and authenticity of Mr. Ayson's CONA, the Law Department issued the subject Document No. 21-3973, obviously without exercising due diligence
, and declared Ms. Navarro as an independent candidate, using as an expedient basis the existence of two (2) candidates from the same party. To allow this to happen will set a dangerous precedent that any ill-motivated person can just file his candidacy and claim to have been nominated by a certain party to sow confusion, dislodge a viable candidate and make a mockery of the elections.
I ask the C[OMELEC] to carefully consider this problem.
x x x x
[ original signed
]
PANFILO "PING LACSON"
Senator
Chairman, Partido Para sa Demokratikong Reporma [18]
On December 22, 2021, the COMELEC Law Department issued
Document No. 21-7467
,
[19]
reflecting the following disposition of the COMELEC
En Banc
, thus:
Pursuant to Sections 39 and 40 of COMELEC Resolution No. 10717 promulgated on August 18, 2021, please be advised that the Certificate of Candidacy filed by
Amelita Sison Navarro is hereby WITHDRAWN effective 09 November 2021. Consequently, her name will be deleted/removed/cancelled from the Official Ballot and the Certified List of Candidates for the May 9, 2022 National and Local Elections.
Please be informed that the COMELEC En Banc during the regular meeting held on 22 December 2021 has maintained that Amelita Sison Navarro as INDEPENDENT
pursuant to Section 15 of the COMELEC Resolution No. 10717 because your political party nominated more than the number of candidates required to be voted for in a particular elective position. Hence, the COC of
Giorgidi Buza Aggabao who filed as a substitute cannot be given due course.
For your information and guidance. [20]
Meantime, on December 23, 2021, the COMELEC posted a Certified List of Candidates for the May 9, 2022 National and Local Elections. Navarro's name did not appear under the column "Mayor" but under the column "Vice Mayor." As for Ayson, his name was included as an Independent candidate for "Mayor." On the other hand, Aggabao's name was not included in the list of candidates for "Mayor" as seen in the list provided below:
Certified List of Candidates
(Municipal)
ISABELA – CITY OF SANTIAGO
ISABELA – CITY OF SANTIAGO
MAYOR
#
NAME TO APPEAR ON THE BALLOT
SEX
NAME
POLITICAL PARTY
1 AYSON, CHRISTOPHER (IND) MALE AYSON, CHRISTOPHER GAMBOA INDEPENDENT [21]
2 CORNEL, MAUI
MALE CORNEL, MANUEL ESTARIJA
INDEPENDENT
3 LUCUDINE, MAR22 (IND)
MALE LUCUDINE, MARCELINO ACOSTA
INDEPENDENT
4 MIGUEL, WALTER JAY (PFP)
MALE MIGUEL, WALTER JAY AGGABAO
PARTIDO FEDERAL NG PILIPINAS
5 MIRANDA, OTEP (PROMDI)
MALE MIRANDA, JOSEPH GUTIERREZ
PROGRESSIVE MOVEMENT FOR THE DEVOLUTION OF INITIATIVES
6 ROQUE, NAP (IND)
MALE ROQUE, NAPOLEON HERMOSURA
INDEPENDENT
7 TAN, SHEENA (PDPLBN)
FEMALE TAN, ALYSSA SHEENA PUA
PARTIDO DEMOKRATIKO PILIPINO LAKAS NG BAYAN
8 TESORO, GENALYN (LAKAS)
FEMALE TESORO, GENALYN APOLTO
LAKAS CHRISTIAN MUSLIM DEMOCRATS
9 VALDEZ, ARTHUR (IND)
MALE VALDEZ, ARTHUR MERCADO
INDEPENDENT
ISABELA – CITY OF SANTIAGO
VICE-MAYOR
#
NAME TO APPEAR ON THE BALLOT
SEX
NAME
POLITICAL PARTY
1 ABAYA, ALVIN (PDPLBN)
MALE ABAYA, ALVIN NAVARRO
PARTIDO DEMOKRATIKO PILIPINO LAKAS NG BAYAN
2 BARTOLOME, BONIFACIO (PDDS)
MALE BARTOLOME, BONIFACIO PADIERNOS
FEDERALISMO NG DUGONG DAKILANG SAMAHAN
3 LIM, ANGELO (IND)
MALE LIM, ANGELO MIRANDA
INDEPENDENT
4 NAVARRO, AMELITA (PDR) FEMALE NAVARRO, AMELITA SISON PARTIDO PARA SA DEMOKRATIKONG REPORMA [22]
5 NAVARRO, SOC (PROMDI)
MALE NAVARRO, SOCORRO BERMISA
PROGRESSIVE MOVEMENT FOR THE DEVOLUTION OF INITIATIVES
Consequently, Aggabao filed a motion for reconsideration which was denied under Document No. 22-0176
[23]
dated January 5, 2022
. The COMELEC reiterated that both Ayson and Navarro were independent candidates, hence, Aggabao's COC as substitute of Navarro cannot be given due course. The COMELEC also held that Aggabao's motion for reconsideration was a prohibited pleading under Rule 13, Section 1(d) of the COMELEC Rules of Procedure.
[24]
The COMELEC though admitted that it received the twin letters
from Senator Lacson dated November 6, 2021 and December 2, 2021, respectively, disowning the CONA of Ayson and requesting the immediate rectification of Document No. 21-3973 dated November 10, 2021. [25]
The Present Petition
Aggabao and Navarro now charge the COMELEC and its Law Department with grave abuse of discretion in declaring Navarro as an independent candidate and in denying Aggabao's substitution of Navarro as the official candidate for Mayor of Santiago City, Isabela of Partido Reporma. They essentially assert:
First.
The COMELEC violated their right to due process. Specifically, it denied Aggabao's COC as substitute of Navarro, without prior proceedings before any of its Divisions. [26]
Second.
Respondents incorrectly applied Section 15 of COMELEC Resolution No. 10717. Partido Reporma did not nominate more than one (1) candidate for Mayor of Santiago City, Isabela. Ayson's supposed CONA from Partido Reporma was fake as repeatedly disavowed by its Chairperson Senator Lacson himself. [27]
Third.
Since Navarro was the official candidate of Partido Reporma for Mayor of Santiago City, Isabela prior to her withdrawal, she could be validly substituted by Aggabao who has complied with all the legal requirements as substitute candidate.
[28]
Petitioners further seek the issuance of a temporary restraining order (TRO) and/or writ of status quo ante order against the implementation of Document No. 21-7467 [29]
dated December 22, 2021. [30]
Under Order
[31]
dated January 25, 2022
, the Court, after due consideration, issued a TRO
, enjoining COMELEC from enforcing
Document No. 21-7467
:
x x x x
NOW, THEREFORE, respondent COMELEC is hereby required to
COMMENT on the petition within a NON-EXTENDABLE period of ten (10) days from notice hereof. Meanwhile, a
TEMPORARY RESTRAINING ORDER is
ISSUED , effective immediately and continuing until further orders from this Court, enjoining You, respondent COMELEC, your agents, representatives, or persons acting in your place or stead, from enforcing the assailed Doc. No. 21-7467 dated December 22 2021. [32]
x x x x
In its Comment
[33]
dated February 2, 2022, the COMELEC, through the Office of the Solicitor General (OSG) informed the Court that it had received two (2) separate COCs with attached CONAs issued by Partido Reporma for the position of Mayor of Santiago City, Isabela, i.e.
, one from petitioner Navarro and another from Ayson. Pursuant to Section 15 of the COMELEC Resolution No. 10717, both Navarro and Ayson were declared independent candidates. [34]
The COMELEC, thus, argued that since Navarro was an independent candidate, Aggabao could not have substituted her for the mayoralty post pursuant to Section 77 of the Omnibus Election Code (OEC) in relation to Section 40 of COMELEC Resolution No. 10717, thus:
Section 77, Omnibus Election Code :
Candidates in case of death, disqualification or withdrawal of another. — If after the last day for the filing of certificates of candidacy, an official candidate of a registered or accredited political party dies, withdraws or is disqualified for any cause, only a person belonging to, and certified by, the same political party may file a certificate of candidacy to replace the candidate who died, withdrew or was disqualified. The substitute candidate nominated by the political party concerned may file his certificate of candidacy for the office affected in accordance with the preceding sections not later than mid-day of the day of the election. If the death, withdrawal or disqualification should occur between the day before the election and mid-day of election day, said certificate may be filed with any board of election inspectors in the political subdivision where he is candidate or, in case of candidates to be voted for by the entire electorate of the country, with the Commission.
Section 40, COMELEC Resolution No. 10717 :
Substitution of Aspirants/Official Candidates in Case of Death, Disqualification or Withdrawal of Another. – An aspirant/official candidate of a duly registered PP or Coalition who dies, withdraws or is disqualified for any cause after the last day for the filing of COCs may be substituted by an aspirant/official candidate belonging to, and nominated by, the same PP or Coalition.
No substitute shall be allowed for any independent candidate.
The substitute of an aspirant who died, withdrew his candidacy, or was disqualified may file a COC for the Office affected on or before November 15, 2021 (Monday) so that the name of the substitute will be reflected on the official ballots.
No substitution due to withdrawal shall be allowed after November 15, 2021.
x x x x
The COMELEC underscored the provision of law which does not allow substitution where the original candidate is an independent candidate. It only allows substitution where the original candidate and the latter's substitute belong to and are certified by the same political party.
[35]
Too, the COMELEC asserted that it was merely exercising its ministerial duty when it received Ayson's COC and CONA both of which it had accorded the presumption of regularity for having been notarized
.
[36]
It prayed that the TRO issued by the Court on January 25, 2022 be lifted. [37]
On February 24, 2022, petitioners filed a
Manifestation with Grave Concern [38]
stating that they received a copy of Document No. 22-1924 (LAW 22-02663) dated February 16, 2022 from the COMELEC Law Department. This document reiterated the status of Navarro as an independent candidate. But the issuance of this document violated the TRO issued by the Court on January 25, 2022 enjoining the enforcement of Document No. 21-7467 which considered Navarro as an independent candidate. [39]
By Resolution
[40]
dated April 19, 2022, the Court directed the COMELEC to explain why it did not comply with the TRO issued by the Court per Order dated January 25, 2022. [41]
In its Manifestation
[42]
dated June 10, 2022, the COMELEC called the attention of the Court to its Minute Resolution [43]
No. 22-0079 dated January 26, 2022 entitled "
In the Matter of the Temporary Restraining Orders (TROs) Issued by the Supreme Court on Various SPA and SPP Cases
,"
viz
.:
After due deliberation, the Commission RESOLVED , as it hereby RESOLVES , to adopt Minute Resolution 22-0019, wherein the Commission resolved to include in the publication and ballots the abovenamed party-lists groups who obtained temporary restraining orders ( TROs ) from the Supreme Court and the same was
received by the Commission prior to January 9, 2022 which is the date of the generation of the final ballot face for the 2022 NLE
as a judicial courtesy and recognition of the authority of the Supreme Court. However, TROs received after January 9, 2022 the date for the generation of the final ballot face is already technically impossible to comply as the process of generating another ballot face will leave little time for the Commission to complete the preparation for the 2022 NLE putting at much risk the holding thereof. [44]
The COMELEC informed the Court that as early as January 9, 2022, it already initiated preparatory activities as regards the printing of the machinereadable official ballots. Thus, it had to comply with a very strict timeline, [45]
thus:
PREPARATORY ACTIVITY DATE
Generation of the Final Ballot Face Templates
January 9, 2022
Loading of the Finalized List of Candidates in the Election Management System Database (EMS)
January 15, 2022
Generation of the Serialized Machine-Readable Official Ballots
January 15, 2022
The COMELEC further averred that the tedious processes involving the various preparatory activities and printing of the official machine-readable ballots compelled it to adopt a cut-off date within which to comply with the TROs issued by the Court. This meant that beyond this cut-off date, the act or acts sought to be restrained would have already become fait accompli
.
[46]
The COMELEC then claimed that it received the subject TRO only on January 25, 2022 far beyond its cut-off date of January 9, 2022. Hence, the matters sought to be restrained –
the declaration of petitioner Navarro as an independent candidate and denial of due course to petitioner Aggabao 's candidacy for Mayor of lsabela City as a substitute for petitioner Navarro
– had themselves become fait accompli
. This meant that the final ballot face templates were already generated, and the machine-readable official ballots were already being printed. It gave notice that any adjustment, postponement, or suspension of these activities would prejudice the timely conduct of its constitutional duties. [47]
Our Ruling
Mootness of the Petition
The conclusion of the May 9, 2022 National and Local Elections and the subsequent proclamation of one Sheena Tan as the Mayor-elect of Santiago City, Isabela [48]
have undoubtedly rendered the petition moot insofar as it seeks to nullify the denial of Aggabao's COC as substitute of Navarro, the non-inclusion of Aggabao's name as a mayoralty candidate, and Navarro's declaration as an independent candidate. A case is moot when it ceases to present a justiciable controversy by virtue of supervening events, so that an adjudication of the case or a declaration on the issue would be of no practical value or use. [49]
Here, the election of Tan to the contested mayoralty post has put an end to the dispute, and none of the complained actions by COMELEC ( i.e.
, the denial of Aggabao's COC as substitute of Navarro, the non-inclusion of Aggabao's name as a mayoralty candidate, and Navarro's declaration as an independent candidate) even if wrong will not undo the outcome of the election to this office.
Despite the mootness of a case, however, the Court may still render a decision if it finds that: (a) there is a grave violation of the Constitution
; (b) the case involves a situation of exceptional character and is of paramount public interest; (c)
the issues raised require the formulation of controlling principles to guide the Bench, the Bar and the public
; and (4) the case is capable of repetition yet evading review. [50]
As eruditely explained by Associate Justice Maria Filomena D. Singh during the deliberation, the third exception applies here. Left unchecked, the COMELEC may repeat the underlying questionable acts or omissions which resulted in the assailed dispositions,
albeit not necessarily against petitioners themselves
again but against some other individuals in elections to come. These
underlying questionable acts or omissions
include: (a)
ignoring
the clear and repeated certifications
and letters
of a particular political party about the identity of the candidate it seeks to endorse and
the falsity of a candidate's claim of endorsement
by that particular political party; (b)
failing to conduct a summary hearing
on the candidates'
conflicting claims
pertaining to their party membership and endorsement; and (c) emasculating
the TRO issued by the Court by perpetuating the erroneous COC cancellation and improperly denying one's right to be substituted as a candidate.
As the final guardian and arbiter of the Constitution, the Court deems it necessary to lay down principles on the observance of the right to due process, particularly the right to hearing of candidates to whom conflicting CONAs have been issued, in view of the seeming vacuum in the COMELEC's rules. [51]
Powers and functions of the COMELEC
The Constitution and the Omnibus Election Code confer the powers and functions of the COMELEC which may be classified into administrative quasi-legislative, and quasi-judicial.
[52]
Bedol v. COMELEC
[53]
expounds:
The powers and functions of the COMELEC, conferred upon it by the 1987 Constitution and the Omnibus Election Code, may be classified into administrative, quasi-legislative, and quasi-judicial. The
quasi-judicial power of the COMELEC embraces the power to resolve controversies arising from the enforcement of election laws, and to be the sole judge of all pre-proclamation controversies; and of all contests relating to the elections, returns, and qualifications . Its quasi-legislative power refers to the issuance of rules and regulations to implement the election laws and to exercise such legislative functions as may expressly be delegated to it by Congress. Its administrative function refers to the enforcement and administration of election laws. In the exercise of such power, the Constitution (Section 6, Article IX-A) and the Omnibus Election Code (Section 52 [c]) authorize the COMELEC to issue rules and regulations to implement the provisions of the 1987 Constitution and the Omnibus Election Code.
The quasi-judicial or administrative adjudicatory power is the power to hear and determine questions of fact to which the legislative policy is to apply, and to decide in accordance with the standards laid down by the law itself in enforcing and administering the same law.
[54]
(Emphases supplied)
The administrative powers of the COMELEC are found in Section 2 (1), (3), (4), (5), (6), (7), (8), and (9) of Article IX-C of the Constitution, [55]
thus:
SECTION 2. The Commission on Elections shall exercise the following powers and functions:
(1) Enforce and administer all laws and regulations relative to the conduct of an election, plebiscite, initiative, referendum, and recall.
x x x x
(3) Decide, except those involving the right to vote, all questions affecting elections, including determination of the number and location of polling places, appointment of election officials and inspectors, and registration of voters.
(4) Deputize, with the concurrence of the President, law enforcement agencies and instrumentalities of the Government, including the Armed Forces of the Philippines, for the exclusive purpose of ensuring free, orderly, honest, peaceful, and credible elections.
(5) Register, after sufficient publication, political parties, organizations, or coalitions which, in addition to other requirements, must present their platform or program of government; and accredit citizens' arms of the Commission on Elections. Religious denominations and sects shall not be registered. Those which seek to achieve their goals through violence or unlawful means, or refuse to uphold and adhere to this Constitution, or which are supported by any foreign government shall likewise be refused registration.
Financial contributions from foreign governments and their agencies to political parties, organizations, coalitions, or candidates related to elections constitute interference in national affairs, and, when accepted, shall be an additional ground for the cancellation of their registration with the Commission, in addition to other penalties that may be prescribed by law.
(6) File, upon a verified complaint, or on its own initiative, petitions in court for inclusion or exclusion of voters; investigate and, where appropriate, prosecute cases of violations of election laws, including acts or omissions constituting election frauds, offenses, and malpractices.
(7) Recommend to the Congress effective measures to minimize election spending, including limitation of places where propaganda materials shall be posted, and to prevent and penalize all forms of election frauds, offenses, malpractices, and nuisance candidacies.
(8) Recommend to the President the removal of any officer or employee it has deputized, or the imposition of any other disciplinary action, for violation or disregard of, or disobedience to its directive, order, or decision.
(9) Submit to the President and the Congress a comprehensive report on the conduct of each election, plebiscite, initiative, referendum, or recall.
As for its quasi-judicial powers, Section 2 (2) of Article IX-C ordains:
[56]
Section 2. The Commission on Elections shall exercise the following powers and functions:
xxx
(2) Exercise exclusive original jurisdiction over all contests relating to the elections, returns, and qualifications of all elective regional, provincial, and city officials, and appellate jurisdiction over all contests involving elective municipal officials decided by trial courts of general jurisdiction, or involving elective barangay officials decided by trial courts of limited jurisdiction.
Decisions, final orders, or rulings of the Commission on election contests involving elective municipal and barangay offices shall be final, executory, and not appealable.
When the COMELEC receives or acknowledges receipt of COCs and CONAs filed in due form, it performs the administrative function of enforcement and administration of all laws and regulations pertaining to the conduct of an election. [57]
Section 76 of the Omnibus Election Code in relation to Section 32 of Resolution No. 10717 provides:
Omnibus Election Code, Section 76:
Sec. 76. Ministerial duty of receiving and acknowledging receipt. - The Commission, provincial election supervisor, election registrar or officer designated by the Commission or the board of election inspectors under the succeeding section shall have the ministerial duty to receive and acknowledge receipt of the certificate of candidacy.
COMELEC Resolution No. 10717, Section 32:
Section 32. Ministerial Duty of Receiving and Acknowledging Receipt of Certificates of Candidacy/Nomination and Acceptance. – The Receiving Officer has the ministerial duty to receive and acknowledge the receipt of the COC and CONA; Provided that they are filed in conformity with the rules and regulations. [58]
Based thereon, the COMELEC must
receive COCs and CONAs provided they are filed in conformity with the rules and regulations. Thus, we agree with the COMELEC when it asserted that up to the point when it received Ayson's COC and CONA (which it accorded with the presumption of regularity for having been notarized), it merely performed its
ministerial function
under the foregoing provisions.
A ministerial act is one which an officer or tribunal performs in a given state of facts, in a prescribed manner, in obedience to the mandate of legal authority, without regard to or the exercise of his or her own judgment upon the propriety or impropriety of the act done. [59]
To repeat, because Ayson's COC and CONA appeared to be regular on their face, the COMELEC had no recourse but to accept them. [60]
Up to that point, no grave abuse of discretion could be ascribed to the COMELEC simply because there was no occasion for the exercise of such discretion to come into play. [61]
But following the acceptance of Ayson's COC and CONA, supervening events took place which necessarily called for the COMELEC's exercise of its discretionary power vis-à-vis
the performance of its quasi-judicial functions, viz
.: Senator Lacson, Chairperson of Partido Reporma, disclaimed the CONA allegedly issued by Partido Reporma to Ayson; and he sought the COMELEC's "immediate action" and requested that "the necessary correction/s be made in the [COMELEC's] Certified List of Candidates." [62]
In fine, Senator Lacson was seeking a resolution of a controversy which affected the candidacy of Ayson and Navarro, and subsequently, Aggabao.
As astutely observed by Associate Justice Alfredo Benjamin S. Caguioa (Justice Caguioa) during our deliberation, [63]
when Senator Lacson sent his letters to the COMELEC challenging the validity or authenticity of the CONA of Ayson,
a legal controversy had then come to fore, i.e. , which of the respective CONAs of Ayson and Navarro should prevail?
To be sure, this legal controversy required the COMELEC to look beyond the face of these CONAs. On this score, Section 2 of Article IX-C of the 1987 Constitution empowers the COMELEC to exercise jurisdiction over all contests relating to the elections, returns and qualifications of all elective officials, and to decide all questions affecting elections. [64]
It is mandated to "investigate and, where appropriate, prosecute cases of violations of elections laws, including acts or omissions constituting election frauds, offenses and malpractices." [65]
Thus, even after its acceptance of Ayson's CONA, which initially appeared to be regular, the COMELEC became duty bound to take cognizance of, and investigate, the material information coming from Senator Lacson that Partido Reporma had not issued any CONA in favor of Ayson. [66]
In this regard, where the situation calls
for the power of the COMELEC to
exercise its judgment or discretion involving a determination of fact, or resolution of controversies [67]
where parties adduce evidence in support of their contentions
,
[68]
the COMELEC ought to perform its quasi-judicial functions. [69]
In
Francisco v. COMELEC
,
[70]
we pronounced:
The COMELEC's adjudicative function over election contests is quasi-judicial in character since the COMELEC is a governmental body, other than a court, that is vested with jurisdiction to decide the specific class of controversies it is charged with resolving. In adjudicating the rights of persons before it, the
COMELEC is not just empowered
but is in fact required
to investigate facts or ascertain the existence of facts, hold hearings, weigh evidence, and draw conclusions from them as basis for their official action and exercise of discretion in a judicial nature.
This is simply in congruence with the concept of due process that all administrative adjudicatory bodies are enjoined to observe.
The COMELEC is, thus, fully-clothed with authority to make factual determinations in relation to the election contests before it.
This has been the thrust of the decades worth of constitutional revisions that transformed the COMELEC from a purely administrative body whose scope of decision-making is limited to those incidental to its duty to enforce election laws, to a polling commission that also exercises original and exclusive, as well as appellate, jurisdiction over election contests. (Emphases and underscoring supplied)
Baytan v. COMELEC
[71]
echoed the rule that in the exercise of its quasijudicial power, the COMELEC should reckon with Section 3 of Article IX-C [72]
of the Constitution. This provision requires all election cases, including pre-proclamation controversies,
to be decided by the COMELEC in Division
; and the motion for reconsideration, by the COMELEC En Banc
.
Again, as correctly pointed out by Justice Caguioa, the COMELEC
En Banc
had, in several instances, referred matters to its Divisions for hearing. [73]
The COMELEC, therefore, should have similarly referred the administrative matter in this case to a Division and docketed the same as an election case, heard the parties thereon, and thereafter resolved the material issue as to who between Ayson and Navarro, and subsequently Aggabao was the real mayoralty candidate of Partido Reporma.
That the COMELEC rules may be silent on how these conflicting CONAS and the disavowals of the concerned political party may be resolved did not justify its inaction. [74]
All it needed to do was adhere to the due process requisites of notice and hearing attendant to every adjudication it does in the exercise of its quasijudicial functions. In Engle v. COMELEC
,
[75]
we held that in the exercise of its quasi-judicial functions, the COMELEC is mandated to hear and decide cases first by Division and, on motion for reconsideration, by the COMELEC
En Banc
. The Court further stressed that the opinion of the COMELEC Law Department is not binding and at most, is merely recommendatory. [76]
The COMELEC En Banc
cannot short cut proceedings by acting without prior action by a Division because this deprives the candidate of due process. [77]
In Cerafica v. COMELEC
,
[78]
which involved the cancellation of COCs via
minute resolutions simply adopting the recommendations of the COMELEC Law Department, the Court ruled that the COMELEC gravely abused its discretion because such situations properly called for the referral of the case to a Division for summary hearing. [79]
The COMELEC acted with grave abuse of discretion
Grave abuse of discretion is defined as arbitrary or despotic exercise of power due to passion, prejudice, or personal hostility; or the whimsical, arbitrary, or capricious exercise of power that amounts to an evasion or refusal to perform a positive duty enjoined by law or to act at all in contemplation of law. [80]
Going by the undisputed facts, the COMELEC effectively aided the winning mayoralty candidate by refusing to resolve the respective status of Ayson and Navarro, and later on of Aggabao, as candidates. It opted to rely solely on the recommendation of its Law Department, sans
the benefit of its own independent confirmation which could have been done by referring the case to the COMELEC Division for a summary hearing. Had the COMELEC performed its adjudicative duty required under the Constitution and the law, Ayson or Aggabao could have given the winning candidate a run for her money. But as things turned out, both were denied the opportunity to run as the official mayoralty candidate of Partido Reporma. The party itself was deprived of the right to prove who its official mayoralty candidate was, and the electorate, consequently, was deprived of the opportunity to choose either of these two candidates as their duly elected leader.
The lack of hearing precludes the Court from resolving who between Ayson and Aggabao was the real official candidate of Partido Reporma
The Court once more agrees with the keen observation of Justice Caguioa that because the COMELEC failed to exercise its quasi-judicial functions, conduct hearings, weigh evidence, and draw conclusions therefrom, [81]
let alone, resolve once and for all the issue of party endorsement or representation between Ayson and Aggabao, the Court itself in this
certiorari
proceeding cannot do either one or the other. The Court is not a trier of facts. [82]
Nor can it draw conclusions or resolve the issue of party endorsement or representation where the facts had not been established on record before the COMELEC at the first instance.
But as for the assailed Document No. 21-3973 [83]
dated November 10, 2021
, declaring Navarro as an independent candidate; (b)
Document No. 21- 7467
[84]
dated December 22, 2021
, denying Aggabao's Certificate of Candidacy (COC) as substitute candidate for petitioner Navarro; and (c)
Document No. 222-0176 dated January 5, 2022
, denying Aggabao's motion for reconsideration, the Court nullifies and sets them aside for non-compliance with the due process requirements as discussed above.
The Court accepts the explanation of the COMELEC why it went ahead with the printing of ballots despite the TRO issued by the Court.
Although we find the COMELEC to have acted with grave abuse of discretion when it failed to afford due process to the contending parties and rule on the controversy between Ayson, on one hand, and Navarro, Aggabao and Partido Reporma, on the other, it has sufficiently demonstrated that it was not impelled by a desire to disrespect the authority of the Court when it proceeded with the election preparations, which included the printing of ballots, despite the TRO issued by the Court. Rather, the COMELEC only sought to ensure that the May 9, 2022 National and Local Elections would take place on the second Monday of May as decreed in the Constitution
:
After due deliberation, the Commission RESOLVED , as it hereby RESOLVES , to adopt Minute Resolution 22-0019, wherein the Commission resolved to include in the publication and ballots the abovenamed party-lists groups who obtained temporary restraining orders
(TROs) from the Supreme Court and the same was
received by the Commission prior to January 9, 2022 which is the date of the generation of the final ballot face for the 2022 NLE
as a judicial courtesy and recognition of the authority of the Supreme Court. However, TROs received after January 9, 2022 the date for the generation of the final ballot face is already technically impossible to comply as the process of generating another ballot face will leave little time for the Commission to complete the preparation for the 2022 NLE putting at much risk the holding thereof. [85]
The Court, therefore, accepts the explanation of the COMELEC on the matter. It defers to the wisdom of the COMELEC, after all, it is Constitutional body charged with the power of enforcement and administration of all laws and regulations relative to the conduct of an election. [86]
It possesses indubitable expertise in the field of elections [87]
and was in the best position to determine what preparations were needed to ensure that the 2022 national and local elections would promptly, as it did, take place.
Conclusion
As ordained in the recent case of
Marquez v. COMELEC
,
[88]
the Court recognizes that the COMELEC is time-pressed in its preparatory activities especially during an election year. Thus, we strongly urge the COMELEC to promptly resolve substitution cases and similar cases which may result in the inclusion or exclusion of candidates so that it can devote its time to ensuring the conduct of free, fair, and honest elections. A balanced policy which guarantees promptness, on one hand, and the fair exercise of discretion on the other, will not only aid in the noble mandate of the COMELEC but also prevent cases from becoming moot, as here.
To avoid a recurrence of similar undesirable incidents in the future, the COMELEC is likewise strongly urged to adopt a practicable plan and timeline to ensure that all these cases are resolved at the earliest possible time. In formulating these measures and plans, the COMELEC should bear in mind that its dispositions are subject to review by the Court and that the Court also needs ample time to resolve these cases prior to election day. It should further consider that the aggrieved party will likely seek injunctive relief from the Court which might affect its pre-set timeline for necessary election preparations.
Whatever practicable measures or plans may be formulated by the COMELEC in this regard should ensure that election cases are promptly decided to prevent them from becoming moot as what happened here.
ACCORDINGLY
, the petition is
PARTLY GRANTED
. Document No. 21-3973 dated November 10, 2021, Document No. 21-7467 dated December 22, 2021, and Document No. 22-0176 dated January 5, 2022 issued by respondent Commission on Elections are NULLIFIED
.
As for petitioners' prayer to admit the Certificate of Candidacy of Giorgidi B. Aggabao as substitute candidate for Mayor of Santiago City and to include his name in the list of candidates for the post, the same is
DECLARED MOOT
.
The Manifestation
dated June 10, 2022 of the Commission on Elections bearing its explanation why the Temporary Restraining Order under Order dated January 25, 2022 was not complied with is
NOTED and ACCEPTED
.
To avoid a recurrence of similar incidents in the future, the Commission on Elections is strongly urged to adopt a practicable plan and timeline to ensure that all cases which involve substitution cases or similar cases which may result in the inclusion or exclusion of a candidate from the ballot are resolved at the earliest possible time.
SO ORDERED.
Gesmundo, C.J., Leonen, SAJ., Hernando, Inting, Zalameda, M. Lopez, Gaerlan, Rosario, J. Lopez, Dimaampao, Marquez
, and Singh, JJ.
, concur.
Caguioa, J.
, see separate concurring.
Kho
,
*
Jr., J.
, no part.
*
Not participating due to previous post as Commission on Elections Commissioner.
[1]
Rollo
, p. 51.
[2]
Id.
at 38.
[3]
Id.
at 41.
[4]
Id.
at 42.
[5]
Id.
at 43.
[6]
Id.
at 44.
[7]
Id.
at 45-46.
[8]
Id.
at 15-16.
[9]
Emphases supplied.
[10]
Id.
[11]
Rollo
, p. 48.
[12]
Id.
at 49.
[13]
Id.
at 50.
[14]
Id.
at 51.
[15]
Emphases in original.
[16]
Rollo
, p. 52.
[17]
Id.
at 61.
[18]
Id.
at 61, emphases supplied.
[19]
Id.
at 38-39.
[20]
Id.
, emphases in the original.
[21]
Id.
at 40, emphasis supplied.
[22]
Id.
, emphasis provided.
[23]
Id.
at 72-73.
[24]
Id.
at 73.
[25]
Id.
at 72.
[26]
Rollo
, pp. 22-24.
[27]
Id.
at 25.
[28]
Id.
at 28.
[29]
Id.
at 38-39.
[30]
Rollo
, pp. 30-32.
[31]
Id.
at 82-84.
[32]
Id.
, emphases in the original.
[33]
Id.
at 121-139.
[34]
Id.
at 125.
[35]
Id.
at 129-130.
[36]
Id.
at 128.
[37]
Id.
at 138.
[38]
Id.
at 113-115.
[39]
Id.
at 113.
[40]
Id.
at 145.
[41]
Id.
at 82-84.
[42]
Id.
at 162-171.
[43]
Id.
at 172-174.
[44]
Id.
at 173, emphases in the original.
[45]
Id.
at 163.
[46]
Id.
at 163-167.
[47]
Id.
at 167.
[48]
Santiago City, Isabela 2022 Election Results. Accessed at
https://stgocity.com/city-of-santiago-electionresults-2022/
on June 23, 2022.
[49]
Marquez v. Commission on Elections, G.R. No. 238274 (Notice)
, November 9, 2021.
[50]
International Service for the Acquisition of Agri-Biotech Applications, Inc. v. Greenpeace Southeast Asia (Philippines)
, 791 Phil. 243, 259 (2016), citing
Belgica v. Ochoa
, 721 Phil. 416 (2013).
[51]
Separate Opinion of Justice Caguioa, pp. 2-3.
[52]
Bedol v. COMELEC
, 621 Phil. 498, 510 (2009).
[53]
Id.
[54]
Id.
[55]
Baytan v. COMELEC
, 444 Phil. 812 (2003).
[56]
Id.
[57]
1987 Constitution, Article IX-C, Section 2(1); See
Cipriano v. COMELEC
, 479 Phil. 677, 688 (2004).
[58]
Emphasis omitted.
[59]
Department of Education v. Rizal Teachers Kilusang Bayan for Credit, Inc., G.R. No. 202097
, July 3, 2019, citing
Umali v. Judicial and Bar Council
, 814 Phil. 253, 293-294 (2017).
[60]
Omnibus Election Code, Section 76; COMELEC Resolution No. 10717, Section 32.
[61]
See Department of Education v. Rizal Teachers Kilusang Bayan for Credit, Inc., G.R. No. 202097
, July 3, 2019, citing
Umali v. Judicial and Bar Council
, supra
at 294; Sps. Espiridion v. Court of Appeals
, 523 Phil. 664, 668 (2006).
[62]
Rollo
, pp. 15-16.
[63]
Separate Opinion of Justice Caguioa, p. 6.
[64]
1987 Constitution, Article IX-C, SECTION 2(2) and (3).
[65]
1987 Constitution, Article IX-C, SECTION 2(6).
[66]
Rollo
, pp. 15-16.
[67]
Emmanuel Tipon and Artemio Tipon, Election Laws, (2010), p. 95.
[68]
Cipriano v. COMELEC
, supra
57 at 691.
[69]
Sandoval v. COMELEC
, 380 Phil. 375, 392 (2000).
[70]
Francisco v. COMELEC
, 831 Phil. 106, 121 (2018).
[71]
Supra
note 52 at 825.
[72]
1987 Constitution, Article IX-C, SECTION 3. The Commission on Elections may sit en banc
or in two divisions, and shall promulgate its rules of procedure in order to expedite disposition of election cases, including pre-proclamation controversies. All such election cases shall be heard and decided in division, provided that motions for reconsideration of decisions shall be decided by the Commission En Banc
.
[73]
Separate Opinion of Justice Caguioa, p. 10.
[74]
Id.
[75]
778 Phil. 568 (2016).
[76]
Id.
at 581.
[77]
Bautista v. COMELEC
, 460 Phil. 459, 477 (2003).
[78]
749 Phil. 80 (2014).
[79]
Id.
at 91.
[80]
Beluso v. COMELEC
, 635 Phil. 436, 443 (2010).
[81]
Separate Opinion of Justice Caguioa, p. 11.
[82]
See Cacho v. Manahan
, 823 Phil. 1011, 1021 (2018), citing
Maglana Rice and Corn Mill, Inc. v. Tan
, 673 Phil. 532, 539 (2011).
[83]
Rollo
, p. 51.
[84]
Id.
at 38.
[85]
Id.
at 173, emphases in the original.
[86]
Cayetano v. COMELEC
, 515 Phil. 485, 492-493 (2006), citing
Buac v. COMELEC
, 465 Phil. 800 (2004).
[87]
Id.
[88]
See Marquez v. COMELEC, G.R. No, 258435
, June 28, 2022.
G.R. No. 258456 (Formerly UDK 17252) – GIORGIDI B. AGGABAO *
and AMELITA S. NAVARRO,
**
petitioners
, versus COMMISSION ON ELECTIONS EN BANC and LAW DEPARTMENT, respondents
.
SEPARATE CONCURRING OPINION
CAGUIOA, J .:
The ponencia
resolves to partly grant the instant Petition for Certiorari
[1]
(Petition) thereby nullifying the assailed Commission on Elections (COMELEC) issuances [2]
but declaring moot the prayer to admit the Certificate of Candidacy (CoC) of petitioner Giorgidi B. Aggabao (Aggabao) as a substitute candidate for Mayor of Santiago City, Isabela in view of the conclusion of the May 9, 2022 National and Local Elections. [3]
Per the ponencia
's narration of facts, the COMELEC received two (2) Certificates of Nomination and Acceptance (CONAs) from the Partido para sa Demokratikong Reporma (Partido Reporma) issued in favor of petitioner Amelita Navarro (Navarro) and a certain Christopher G. Ayson [4]
(Ayson), respectively, who were both running for Mayor of Santiago City. In view of the multiple nominations made by the Partido Reporma, Navarro and Ayson were declared as independent candidates, pursuant to Section 15 [5]
of COMELEC Resolution (Com Res) No. 10717. [6]
As such, when Navarro withdrew her CoC for the position of Mayor and Aggabao filed his CoC as Navarro's substitute, the COMELEC denied due course to Aggabao's CoC in accordance with Section 40 [7]
of the same Com Res which disallows substitution for independent candidates. Prior to the cancellation of Aggabao's CoC, Senator Panfilo Lacson (Sen. Lacson), the Chairman of Partido Reporma, sent letters dated November 6, 2021 and December 2, 2021, to the COMELEC disowning Ayson's CONA, maintaining that Navarro is the official candidate of Partido Reporma for Mayor of Santiago City, and stating that Ayson is not even a member of the party; hence, it was absurd for Partido Reporma to have issued a CONA in his favor. However, the COMELEC failed to act on these letters. [8]
Hence, the present Petition which charges respondents COMELEC
En Banc
and its Law Department with grave abuse of discretion in declaring Navarro as an independent candidate and in denying Aggabao's substitution of Navarro's candidacy as Mayor of Santiago City, Isabela.
On January 25, 2022, the Court issued a temporary restraining order (TRO) against the assailed COMELEC issuances. [9]
Nevertheless, the COMELEC, on February 16, 2022, reiterated that Navarro is an independent candidate. However, it later explained its defiance of the TRO in that as early as January 9, 2022, the preparatory activities with respect to the printing of the official ballots had begun; hence, the matter sought to be restrained had become
fait accompli
.
[10]
The ponencia
, in partly granting the instant Petition, ruled, among others, that: (1) while the COMELEC was c01Tect in receiving the CoCs and CONAs of Navarro and Ayson upon finding that they were filed in due form pursuant to its ministerial duty, it committed grave abuse of discretion when it failed to act on the letters of Sen. Lacson which challenged the validity or authenticity of Ayson's CONA; (2) upon the emergence of a legal controversy on the CONAs requiring the COMELEC to look beyond its face, the COMELEC became duty-bound to perform its quasi-judicial functions, which mandated the requisites of notice and hearing; (3) the lack of hearing precludes the Court from resolving who between Ayson and Aggabao was the real official candidate of Partido Reporma as the Court is not a trier of facts; and (4) nevertheless, the assailed COMELEC issuances are nullified for noncompliance with the due process requirements. [11]
I concur with the ponencia
's finding of grave abuse of discretion on the COMELEC's part and, thus, the disposition of the case. I write this Separate Concurring Opinion to stress that: (1) the COMELEC's exercise of its quasijudicial powers requires the observance of notice and hearing upon the concerned parties; (2) thus, in failing to accord the parties due process, it gravely abused its discretion when it completely ignored the letters of Sen. Lacson which gave rise to a legal controversy; (3) despite the seeming vacuum in its rules, the COMELEC should have referred the case for hearing to one of its divisions; and (4) the present case shows a need to enjoin political parties to be more circumspect in issuing CONAs.
When the COMELEC exercises its quasi-judicial powers, notice and hearing is necessary. There is an exercise of quasi-judicial powers when investigation and ascertainment of facts, as well as judgment and discretion, are crucial. Administrative powers, on the other hand, require merely an application of policies and enforcement of orders.
Pursuant to Section 3,
[12]
Article IX-C of the Constitution, the COMELEC need only hear and decide, first through its divisions, and then, upon motion for reconsideration, sitting as an en banc
, when it is exercising its adjudicatory or quasi-judicial powers. It may act in either division or directly as an en banc
when it is in the exercise of its administrative powers.
[13]
Crucial, therefore, to the present controversy is the determination of the nature of the power exercised by the COMELEC when it issued the assailed resolutions.
The case of Bedol v. COMELEC
[14]
is instructive on the three (3) powers of the COMELEC:
The powers and functions of the COMELEC, conferred upon it by the 1987 Constitution and the Omnibus Election Code, may be classified into administrative, quasi-legislative, and quasi-judicial.
The quasijudicial power of the COMELEC embraces the power to resolve controversies arising from the enforcement of election laws, and to be the sole judge of all
pre-proclamation controversies; and of all
contests relating to the elections, returns, and qualifications
. Its quasi-legislative power refers to the issuance of rules and regulations to implement the election laws and to exercise such legislative functions as may expressly be delegated to it by Congress.
Its administrative function refers to the enforcement and administration of election laws. In the exercise of such power, the Constitution (Section 6, Article IX-A) and the Omnibus Election Code (Section 52 [c]) authorize the COMELEC to issue rules and regulations to implement the provisions of the 1987 Constitution and the Omnibus Election Code.
The quasi-judicial or administrative adjudicatory power is the power to hear and determine questions of fact to which the legislative policy is to apply, and to decide in accordance with the standards laid down by the law itself in enforcing and administering the same law.
x x x [15]
(Emphasis and underscoring supplied)
In Cipriano v. COMELEC
[16]
( Cipriano
), the COMELEC En Banc
, as recommended by its Law Department, disallowed the CoCs of therein petitioners as they were not registered voters. As in the present case, petitioners therein cried deprivation of their due process rights, with the COMELEC interposing the defense that its assailed resolutions were issued in the exercise of its administrative powers; hence, did not require notice and hearing. In ruling for petitioners, the Court elaborated on the distinction between the COMELEC's power to administer election laws and its quasijudicial powers, viz
.:
Contrary to the submission of the COMELEC, the denial of due course or cancellation of one's certificate of candidacy is not within the administrative powers of the Commission, but rather calls for the exercise of its quasi-judicial functions.
Administrative power is concerned with the work of applying policies and enforcing orders as determined by proper governmental organs. We have earlier enumerated the scope of the Commission's administrative functions. On the other hand, where a power rests in judgment or discretion, so that it is of judicial nature or character, but does not involve the exercise of functions of a judge, or is conferred upon an officer other than a judicial officer, it is deemed quasi-judicial. [17]
(Emphasis supplied)
The Court in Jalosjos v. COMELEC
,
[18]
citing Villarosa v. COMELEC
,
[19]
pertinently ruled:
[T]he term ' administrative' connotes, or pertains
, to 'administration, especially management, as by managing or conducting, directing or superintending, the execution, application, or conduct of persons or things
.[']
It does not entail an opportunity to be heard, the production and weighing of evidence, and a decision or resolution thereon.
While a ' quasi-judicial function ' is a term which applies
to the action, discretion, etc., of public administrative officers or bodies, who are required to investigate facts, or ascertain the existence of facts, hold hearings, and draw conclusions from them, as a basis for their official action and to exercise discretion of a judicial nature . x x x
[20]
(Additional emphasis supplied; underscoring in the original)
From the foregoing, there is an exercise of quasi-judicial powers when investigation and ascertainment of facts, as well as judgment or discretion, are crucial. More specifically, when the body is required to ascertain facts to which the law shall apply so that discretion of judicial character is necessary, adjudicatory powers are in play. On the other hand, where what is involved is the mere application of policies and enforcement of orders as determined by proper governmental organs, there is a mere exercise of administrative powers. The latter does not entail the production and weighing of evidence, hence, an opportunity to be heard is not necessary.
The COMELEC, in the exercise of its administrative powers, properly applied its rules in receiving both Navarro's and Ayson's CONAs and declaring them independent candidates. However, it gravely abused its discretion in failing to accord notice and hearing to the parties when a legal controversy arose after Sen. Lacson sent his letters thereby requiring the COMELEC to exercise its quasi-judicial powers.
Under Section 76
[21]
of Batas Pambansa Blg. 881, [22]
otherwise known as the "Omnibus Election Code of the Philippines" (OEC) and Section 32 [23]
of Com Res No. 10717, it is the
ministerial
duty of the COMELEC to receive and acknowledge receipt of the CoCs and CONAs filed before it, provided that these were filed in due form and in conformity with the rules and regulations, respectively. Conversely, the Court, in several occasions, has ruled that the COMELEC, may not, by itself, without the proper proceedings, deny due course to or cancel a CoC
filed in due form
.
[24]
In Cipriano
, citing Sanchez v. Del Rosario
,
[25]
the Court held that the duty of the COMELEC to give due course to a CoC filed in due form is ministerial in character and that while it may look into patent defects
therein, it may not go into matters not appearing on its face. [26]
In the present case, the COMELEC received the CoCs of both Navarro and Ayson, pursuant to its ministerial duty to receive and give due course to CoCs filed in due form. The CONAs attached to both CoCs, likewise being regular on their faces and compliant with the COMELEC rules, were likewise received and given due course, again, pursuant to the COMELEC's ministerial duty. Finally, there being two (2) CONAs issued by the same political party in favor of two (2) nominees for the same position, the COMELEC treated these nominees as independent candidates and disallowed both nominations, pursuant to Section 15 of Com Res No. 10717, which mandates that in case of such excessive nominations, "all of the nominations shall be denied due course by the Commission, and the aspirants shall be declared independent candidates."
[27]
To emphasize, these actions by the COMELEC were done pursuant to its administrative functions, there being no need to admit evidence, ascertain facts and render conclusions thereon.
Nevertheless, when Sen. Lacson sent letters to the COMELEC challenging the validity or authenticity of the CONA of Ayson issued by Partido Reporma, there arose a legal controversy which required the COMELEC to look beyond the face of the certificates. At this point, the COMELEC was already required to investigate, receive evidence and examine and weigh the same to arrive at factual conclusions to which the law shall apply. Specifically, it was called upon to ascertain whether Ayson's CONA was not authentic, as claimed by Sen. Lacson, so that Section 15 of Com Res No. 10717 on multiple nominations would be inapplicable, leaving Navarro as the lone nominee of Partido Reporma. If so found, then the substitution of Navarro by Aggabao should be valid under Section 40 of the same Com Res.
To stress, where only an application of the law is required without having to investigate and ascertain facts beyond the face of the certificates and other uncontroverted documents, administrative functions are exercised. This is thus involved when the COMELEC examines, upon filing of the CoC, the attached CONA, and ascertain, on its face
, whether it was filed in due form and within the filing period, properly and completely filled-out, signed by the authorized signatories (by simple comparison of such signatures to those in the pertinent list submitted by the party to the COMELEC ahead of the filing of CoCs) and compliant with the requirements under the rules. [28]
Once found that the CONA is filed in conformity with the rules and regulations, it becomes the ministerial duty of the COMELEC to receive and acknowledge receipt of the CONAs filed with them, in accordance with Section 76 of the OEC and Section 32 of Com Res No. 10717.
However, when there arises an issue or controversy with the certificates not appearing on their faces, such as when extrinsic evidence is offered to prove an allegedly fraudulent CONA, the COMELEC cannot merely ignore the same — as what it apparently did with respect to Sen. Lacson's letters — especially where, as in this case, such non-action inevitably led to the cancellation of the CoC of the substitute candidate, Aggabao.
The cancellation of a CoC on the ground of invalidity of the candidate's substitution requires notice and hearing.
On this note, the Court has held that both denial of due course to and cancellation of CoCs are adjudicatory proceedings which need to be first heard by the COMELEC division, as a matter of jurisdiction. The COMELEC
En Banc
can only act on the same upon a motion for reconsideration of its division's decision. [29]
In Luna v. COMELEC
,
[30]
the Court voided the COMELEC's disallowance of a substitution of an underaged candidate and the consequent cancellation of the CoC of his substitute. The Court even went further as to suggest that a petition to deny due course to or cancel the CoC of the substituted
candidate was necessary because ineligibility of a candidate for non-age is beyond the usual and proper cognizance of the COMELEC outside of a petition under Section 78 [31]
of the OEC, owing to its ministerial duty to give due course to CoCs filed in due form
.
In Cipriano
, the Court categorically held that the denial of due course or cancellation of a CoC "is not within the administrative powers of the [COMELEC], but rather calls for the exercise of its quasi-judicial functions." [32]
Hence, the Court annulled the COMELEC's Resolution, adopting the recommendation of its Law Department and cancelling or denying due course to CoCs of several candidates, including petitioners, for not being registered voters. It ruled that outside of patent defects, the COMELEC may only deny due course to or cancel a CoC in accordance with the procedure laid down in Section 78, which affords all parties notice and an opportunity to present evidence, albeit through a summary procedure. [33]
In Bautista v. COMELEC
,
[34]
the Court held that the COMELEC denied a candidate of his due process rights when its en banc
, upon its Law Department's recommendation, cancelled the candidate's CoC for the latter's failure to register as a voter. The Court ruled that a division of the COMELEC should have first heard the case, so that the COMELEC En Banc
acted without jurisdiction when it ordered such cancellation of the CoC.
[35]
The COMELEC contended that there was no need for presentation and evaluation of evidence because the issue of whether Bautista was a registered voter is easily resolved by looking at the COMELEC registrations records. The Court nevertheless ruled that such reasoning fails to consider instances where a voter may be excluded through inadvertence or registered with an erroneous or misspelled name. Indeed, a COMELEC rule allows candidates who are not registered voters to be included in the certified list of candidates until the COMELEC directs otherwise. The Court declared that the COMELEC should have observed the summary proceeding outlined in Rule 23 [36]
of its Rules of Procedures [37]
in relation to petitions to deny due course to or cancel CoCs. [38]
In Engle v. COMELEC En Banc
[39]
( Engle
), while the Court ruled that the matter of validity of petitioner's substitution is not a proper subject of a Rule 78 petition to deny due course to or cancel a CoC as it does not relate to a qualification of the candidate, it nonetheless held that the denial of due course to the CoCs of both the substituted candidate and his substitute calls for the exercise of the COMELEC's quasi-judicial functions, and therefore, must first be heard and decided by the COMELEC's divisions, thus:
First, the COMELEC Law Department's "ruling" was issued only after the filing of petitioner's COC. Second, with respect to the denial of due course to James L. Engle's COC as a nominee of Lakas-CMD and to petitioner's COC as his substitute, the COMELEC Law Department's letter is not binding and at most, recommendatory. It is settled in jurisprudence that the denial of due course [to] or cancellation of one's COC is not within the administrative powers of the COMELEC, but rather calls for the exercise of its quasi-judicial functions. We have also previously held that the COMELEC, in the exercise of its adjudicatory or quasi-judicial powers, is mandated by the Constitution to hear and decide such cases first by Division and, upon motion for reconsideration, by the En Banc . In resolving cases to deny due course to or cancel certificates of candidacy, the COMELEC cannot merely rely on the recommendations of its Law Department but must conduct due proceedings through one of its divisions. Returning to the case at bar, the COMELEC Second Division only formally ruled on the status of James L. Engle as an independent candidate and the invalidity of petitioner's substitution on July 5, 2013, months after the May 13, 2013 Elections. [40]
Hence, it appears that although Engle held against the propriety of a Section 78 petition to adjudicate the issue of validity of substitution because the same does not relate to the qualifications of a candidate, it still held the stance that cancellation of CoC's on the ground of invalidity of substitution demands the exercise of quasi-judicial powers of the COMELEC, hence, must first be heard and decided by its division. Engle
merely failed to specify the remedy therefor under the COMELEC Rules or any statute.
Nevertheless, the Court in Tagolino v. House of Representatives Electoral Tribunal [41]
( Tagolino
), appears to have taken the position that an invalid substitution may be a ground to remove a winning candidate from office as the same still relates to the expanded meaning of "qualifications."
Tagolino
involved the cancellation of CoC of Richard Gomez (for noncompliance with the pertinent residency requirement) and the consequent removal from office in a
quo warranto
action of his substitute, his wife, Lucy Torres-Gomez (Lucy). The Court, through the masterful
ponencia
of Senior Associate Justice Estela Perlas-Bernabe (SAJ Bernabe), held that as a person whose CoC was denied due course or cancelled ( i.e.
, Richard Gomez) cannot be substituted, Lucy, the substitute, never became a bona fide
candidate.
Tagolino
occasioned to define "qualifications" and the word "eligible" as used in Section 74 [42]
of the OEC, thus:
Notably, the phrase "election, returns, and qualifications" should be interpreted in its totality as referring to all matters affecting the validity of the contestee's title. More particularly, the term "qualifications" refers to matters that could be raised in a
quo warranto
proceeding against the proclaimed winner, such as his disloyalty or ineligibility, or the inadequacy of his certificate of candidacy. As used in Section 74 of the OEC, the word "eligible" means having the right to run for elective public office, that is, having all the qualifications and none of the ineligibilities to run for the public office. In this relation, private respondent's own qualification to run for public office — which was inextricably linked to her husband's own qualifications due to her substitution — was the proper subject of quo warranto
proceedings falling within the exclusive jurisdiction of the HRET and independent from any previous proceedings before the COMELEC, lest the jurisdictional divide between the two be blurred. [43]
To stress, Section 74 lays down the contents of a CoC, one of which is a declaration that the candidate is eligible for the office sought. It appears that, proceeding from
Tagolino
, an invalid substitution may be the proper subject of a false material declaration under Section 78 of the OEC.
The COMELEC should have endorsed the matter to one of its divisions for hearing despite the seeming vacuum in its rules treating of a remedy to challenge its administrative allowance or disallowance of substitutions.
To recall, under the Constitution, the COMELEC must hear and decide election cases pursuant to its quasi-judicial powers sitting, first, as a division and then as an en banc
, on motion for reconsideration. While there appears to be nothing in the COMELEC's rules expressly and categorically authorizing it to endorse a matter to its division for hearing and decision, the Court takes notice of several cases wherein the COMELEC En Banc
referred a matter to its divisions for hearing. [44]
In the present case, the COMELEC should have similarly referred the administrative matter to its division and docketed the same as an election case, heard the parties thereon and, only after such hearing, decided the case.
Further, the COMELEC's rules likewise appear devoid of any remedy to challenge its administrative allowance or disallowance of substitution or CONAs or its declaration of candidates as independent candidates pursuant to its rules. There is no explicit avenue to contest such actions, i.e.
, where a party can file a petition and thereafter can present evidence. To recall, the remedy against an administrative action of the COMELEC, through the COMELEC
En Banc
, is a petition for certiorari
with the Court alleging grave abuse of discretion. [45]
However, the Court is generally not a trier of facts and does not receive and evaluate evidence. This is why Sen. Lacson, in disclaiming the CONA issued in Ayson's favor, merely wrote letters to the COMELEC. Again, upon receipt of the letters, the COMELEC should have docketed the matter as an election case with its division and then heard the parties thereon.
However, as it turned out, the COMELEC failed to act on the letters. Instead, it merely declared in Document No. 21-7467 that it maintains its position that Navarro was an independent candidate without any explanation why Aggabao and Sen. Lacson's allegations did not deserve any credence. At the risk of being repetitive, when COMELEC was confronted with Sen. Lacson's letters, there arose a controversy requiring the COMELEC to afford the parties notice and hearing. As the COMELEC failed in this, I agree therefore with the ponencia
that it gravely abused its discretion in failing to observe the constitutional requirement of hearing and deciding election cases at the first instance with the COMELEC divisions.
Nevertheless, it must be stressed that while the COMELEC erred in ignoring altogether the letters of Sen. Lacson, it could not have likewise validly and properly dishonored Ayson's CONA on the basis solely of said letters. As mentioned, it was positively required to accord all the parties notice and hearing, especially in light of the following circumstances surrounding the letters:
First
, Sen. Lacson's letters, quite intriguingly, did not specifically refute the genuineness of his signature on Ayson's CONA and are silent as to how Ayson may have obtained the same.
Second
, the letters seek to avoid the CONA issued in favor of Ayson, who was neither heard by the COMELEC nor a party to the present case.
Third
, to recall, Ayson's CONA, as found by the COMELEC Law Department and En Banc
, was regular on its face, conformed with the prescribed form and bore the signature of Sen. Lacson as appearing on Partido Reporma's List of Authorized Signatories with Specimen Signatures submitted to the COMELEC. Further and, perhaps, more importantly, the CONA is notarized, hence, presumed regular.
Fourth
, the fact that Ayson is not a member of Partido Reporma, as alleged in Sen. Lacson's letters, lacks legal bearing on his alleged nomination because the OEC allows political parties to nominate guest candidates. [46]
Neither is it irregular that Navarro's nomination was seemingly allowed by the COMELEC when she filed her CoC as Vice Mayor of Santiago City after withdrawing as a Mayoralty candidate. Unlike in the Mayoralty race where Ayson filed a CONA supposedly likewise issued by Partido Reporma, Navarro is indisputably the lone candidate nominated by the party in the Vice Mayoralty race (assuming she filed a CONA along with her CoC as Vice Mayor). There is no occasion to apply Section 15 of Com Res No. 10717 in the latter.
Political parties are enjoined to be more circumspect in issuing CONAs.
It is well to point out that the present case does not appear to be unique or even rare. There seems to be a significant number of election cases involving the issue of multiple CONAs, appearing in due form and notarized, but issued to more than the maximum number of candidates prescribed in the rules, resulting in the treatment of all such candidates as independent pursuant to Section 15 of Com Res No. 10717.
It is, indeed, curious why the authorized signatory of a CONA, which appears regular and conforms with pertinent rules and regulations, cannot categorically refute the authenticity of his or her own signature thereon, although claiming the same to have been fraudulently issued. Perhaps, a possibility is that such CONA likewise hears authentic signatures and was duly-issued.
One can imagine a large-sized political party such as a national party whose leadership from the national level understandably lacks familiarity with the political climate in every locality in the country. Perhaps because it is more practical, the leadership, who is likewise authorized to issue and sign CONAs, simply releases blank but duly-signed CONAs, to be filled-up by the parties' local chapters with the names of party nominees for local positions. However, a problem arises when both the national and local leaderships (by filling up the pro-forma and pre-signed CONAs) decide to nominate different candidates for the same positions, without duly communicating with each other. This now results in multiple CONAs, appearing in due form, bearing authentic signatures of the authorized signatory and duly-notarized, issued in favor of more than the maximum number of candidates allowed by law, consequently rendering all concerned candidates as independent. In other words, such problem arises when there is lack of communication and coordination within the political party.
Thus, as a parting note, the Court reminds political parties to be more circumspect in signing and issuing CONAs, as it is the State, and even the Court, that gets burdened with having to settle their internal controversies which could have been easily avoided with due coordination and communication among its members and officers. The preparations for, and conduct of, a national and local elections are gargantuan tasks which the COMELEC must undertake in the context of rapidly-moving timelines. Therefore, the same must not be hampered by party politics and blunders easily remediable by observing due diligence in the party's conduct of its business.
To conclude, I vote to GRANT
the instant Petition for Certiorari
as the COMELEC committed grave abuse of discretion in failing to accord the parties notice and hearing in exercising its quasi-judicial functions.
*
Also Giorgidi Buza Aggabao in some parts of the rollo
.
**
Also Amelita Sison Navarro in some parts of the rollo
.
[1]
Rollo
, pp. 12-37.
[2]
Ponencia
, pp. 1-2. These issuances are: (a) Document No. 21-3973 dated November 10, 2021, declaring Navarro as an independent candidate; (b) Document No. 21-7467 dated December 22, 2021, denying Aggabao's CoC as substitute candidate for Navarro; and (c) Document No. 22-0176 dated January 5, 2022, denying Aggabao's motion for reconsideration.
[3]
Id
. at 20.
[4]
Also Christian Gamboa Ison in some parts of the rollo
.
[5]
SECTION 15. Allowed Number of Nominations .
– x x x
If the [political parties] or [coalition of political parties] nominated more than the number of candidates required to be voted for in a particular elective position, all of the nominations shall be denied due course by the Commission, and the aspirants shall be declared
independent candidates
. (Emphasis in the original)
[6]
RULES AND REGULATIONS GOVERNING: 1) POLITICAL CONVENTIONS; 2) SUBMISSION OF NOMINEES OF GROUPS OR ORGANIZATIONS PARTICIPATING UNDER THE PARTY-LIST SYSTEM OF REPRESENTATION; AND 3) FILING OF CERTIFICATES OF CANDIDACY AND NOMINATION OF AND ACCEPTANCE BY OFFICIAL CANDIDATES OF REGISTERED POLITICAL PARTIES OR COALITIONS OF POLITICAL PARTIES IN CONNECTION WITH THE MAY 9, 2022 NATIONAL AND LOCAL ELECTIONS, August 18, 2021.
[7]
SECTION 40. Substitution of Aspirants/Official Candidates in Case of Death, Disqualification or Withdrawal of Another .
— x x x
No substitute shall be allowed for any independent candidate.
x x x x
[8]
Ponencia
, pp. 2-6.
[9]
Id
. at 8.
[10]
Id
. at 10-11.
[11]
See id
. at 14-18.
[12]
SEC. 3. The Commission on Elections may sit en banc
or in two divisions, and shall promulgate its rules of procedure in order to expedite disposition of election cases, including pre-proclamation controversies. All such election cases shall be heard and decided in division, provided that motions for reconsideration of decisions shall be decided by the Commission en banc
.
[13]
See Cipriano v. COMELEC
, 479 Phil. 677 (2004).
[14]
621 Phil. 498 (2009).
[15]
Id
. at 510. Citation omitted.
[16]
Cipriano v. COMELEC
, supra
note 13.
[17]
Id
. at 690-691. Citations omitted.
[18]
711 Phil. 414 (2013).
[19]
377 Phil. 497, 506-507 (1999).
[20]
Jalosjos v. COMELEC
, supra
note 18, at 423-424.
[21]
SEC. 76. Ministerial duty of receiving and acknowledging receipt
. — The Commission, provincial election supervisor, election registrar or officer designated by the Commission or the board of election inspectors under the succeeding section shall have the ministerial duty to receive and acknowledge receipt of the certificate of candidacy.
[22]
Approved on December 3, 1985.
[23]
SECTION 32. Ministerial Duty of Receiving and Acknowledging Receipt of Certificates of Candidacy/Nomination and Acceptance .
– The Receiving Officer has the ministerial duty to receive and acknowledge the receipt of the COC and CONA;
Provided that they are filed in conformity with the rules and regulations
. (Emphasis in the original)
[24]
See Luna v. COMELEC
, 550 Phil. 284, 292 (2007) and
Cipriano v. COMELEC
, supra
note 13, at 689.
[25]
111 Phil. 733, 736-737 (1961).
[26]
Cipriano v. COMELEC
, supra
note 13, at 689.
[27]
Emphasis omitted.
[28]
See Sections 13 and 14 of COMELEC Resolution No. 10717.
[29]
See Bautista v. COMELEC
, 460 Phil. 459, 475-476 (2003).
[30]
Supra
note 24.
[31]
SEC. 78 Petition to deny due course to or cancel a certificate of candidacy
. — A verified petition seeking to deny due course or to cancel a certificate of candidacy may be filed by the person exclusively on the ground that any material representation contained therein required under Section 74 hereof is false. The petition may be filed at any time not later than twenty-five days from the time of the filing of the certificate of candidacy and shall be decided, after due notice and hearing, not later than fifteen days before the election.
[32]
Cipriano v. COMELEC
, supra
note 13, at 690.
[33]
See id
. at 689-690.
[34]
Supra
note 29.
[35]
Id
. at 475.
[36]
SECTION 1. Grounds for Denial of Certificate of Candidacy
. — A petition to deny due course to or cancel a certificate for any elective office may be filed with the Law Department of the Commission by any citizen of voting age or a duly registered political party, organization, or coalition or political parties on the exclusive ground that any material representation contained therein as required by law is false.
SECTION 2. Period to File Petition
. — The petition must be filed within five (5) days following the last day for the filing of certificate of candidacy.
SECTION 3. Summary Proceeding
. — The petition shall be heard summarily after due notice.
SECTION 4. Delegation of Reception of Evidence
. — The Commission may designate any of its officials who are the members of the Philippine Bar to hear the case and to receive evidence.
[37]
COMELEC RULES OF PROCEDURE, approved on February 15, 1993.
[38]
Bautista v. COMELEC
, supra
note 29, at 480.
[39]
778 Phil. 568 (2016).
[40]
Id
. at 583-584. Citations omitted.
[41]
706 Phil. 534 (2013).
[42]
SEC. 74. Contents of certificate of candidacy
. — The certificate of candidacy shall state that the person filing it is announcing his candidacy for the office stated therein and that he is eligible for said office; if for Member of the Batasang Pambansa
, the province, including its component cities, highly urbanized city or district or sector which he seeks to represent; the political party to which he belongs; civil status; his date of birth; residence; his post office address for all election purposes; his profession or occupation; that he will support and defend the Constitution of the Philippines and will maintain true faith and allegiance thereto; that he will obey the laws, legal orders, and decrees promulgated by the duly constituted authorities; that he is not a permanent resident or immigrant to a foreign country; that the obligation imposed by his oath is assumed voluntarily, without mental reservation or purpose of evasion; and that the facts stated in the certificate of candidacy are true to the best of his knowledge.
x x x x
[43]
Tagolino v. House of Representatives Electoral Tribunal
, supra
note 41, at 560-561. Citations omitted.
[44]
E.g., Sunga v. COMELEC
, 351 Phil. 310, 324 (1998) wherein a letter-complaint for disqualification was referred by the COMELEC En Banc
to its Second Division for hearing.
[45]
See Rule 64 in relation to Rule 65 of the Rules of Court.
[46]
SEC. 70. Guest candidacy
— A political party may nominate and/or support candidates not belonging to it.
Source: Supreme Court E-Library
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Molecules | Free Full-Text | Overview of the Biological Activity of Anthraquinons and Flavanoids of the Plant Rumex Species
Rumex confertus belongs to the genus Rumex and is classified as an invasive parasitic plant in agriculture. Despite other Rumex species being widely used in herbal medicine due to their antimicrobial, antioxidant, antitumor, and anti-inflammatory effects, there are almost no information about the potential of Rumex confertus for the treatment of various diseases. In this review we analyzed scientific articles revealing properties of Rumex plant& rsquo;s substances against cancer, diabetes, pathogenic bacterial invasions, viruses, inflammation, and oxidative stress for the past 20 years. Compounds dominating in each composition of solvents for extraction were discussed, and common thin layer chromatography(TLC) and high performance liquid chromatography(HPLC) methods for efficient separation of the plant& rsquo;s extract are included. Physico-chemical properties such as solubility, hydrophobicity (Log P), pKa of flavonoids, anthraquinones, and other derivatives are very important for modeling of pharmacokinetic and pharmacodynamics. An overview of clinical studies for abounded selected substances of Rumex species is presented.
Overview of the Biological Activity of Anthraquinons and Flavanoids of the Plant Rumex Species
by Dmitriy Berillo 1,2,* , Marzhan Kozhahmetova 1,2 and Lina Lebedeva 3
Department of Pharmaceutical and Toxicological Chemistry, Pharmacognosy and Botany School of Pharmacy, Asfendiyarov Kazakh National Medical University, Almaty 050040, Kazakhstan
Department of Biotechnology, Al-Farabi Kazakh National University, Almaty 050040, Kazakhstan
Author to whom correspondence should be addressed.
Molecules 2022 , 27 (4), 1204; https://doi.org/10.3390/molecules27041204
Received: 31 December 2021 / Revised: 30 January 2022 / Accepted: 7 February 2022 / Published: 10 February 2022
Abstract
:
Rumex confertus
belongs to the genus
Rumex
and is classified as an invasive parasitic plant in agriculture. Despite other
Rumex
species being widely used in herbal medicine due to their antimicrobial, antioxidant, antitumor, and anti-inflammatory effects, there are almost no information about the potential of
Rumex
confertus for the treatment of various diseases. In this review we analyzed scientific articles revealing properties of
Rumex
plant’s substances against cancer, diabetes, pathogenic bacterial invasions, viruses, inflammation, and oxidative stress for the past 20 years. Compounds dominating in each composition of solvents for extraction were discussed, and common thin layer chromatography(TLC) and high performance liquid chromatography(HPLC) methods for efficient separation of the plant’s extract are included. Physico-chemical properties such as solubility, hydrophobicity (Log P), pKa of flavonoids, anthraquinones, and other derivatives are very important for modeling of pharmacokinetic and pharmacodynamics. An overview of clinical studies for abounded selected substances of
Keywords:
Rumex confertus
;
herbal medicine
;
anthraquinone derivatives
;
flavonoids
;
epigallocatechin gallate
;
epigallocatechin
;
emodin
Graphical Abstract
1. Introduction
1.1. Rumex Confertus Chemical Composition and Prospects for Use
The genus Rumex is presented by approximately 200 edible and medicinal species worldwide, including Rumex abyssinicus Jacq, Rumex acetosa L., Rumex lunaria L., Rumex beringensis , Rumex crispus L., and others [ 1 ]. Although these plants are enriched by biologically important secondary metabolites, such as anthraquinones, flavonoids, stilbenoids, naphthalene, and phenylpropanoids, only 50 species have been used for biomedical and pharmacological investigations [ 1 , 2 ]. According to the results of these studies, representatives of the genus Rumex demonstrated antibacterial, bacteriostatic, antiviral, antitumor, antioxidant, and anti-inflammatory effects, and radiation protection, and might be used for treatment of various diseases [ 3 , 4 , 5 ]. Although Rumex confertus Willd. (Russian dock, Asiatic dock, or mossy sorrel) is characterized by the presence of anthracene derivatives and has even been included on the list of prospective herbs, it is mainly known as a severe invasive alien in Russia, Kazakhstan, China, and eastern and central Europe [ 6 , 7 ]. Thus, there is almost no information about its therapeutic potential, which is partly related to the incomplete study of its chemical composition.
Rumex confertus
Willd. is a perennial plant up to 50 cm in height, growing in meadows, forests, and forelands. The composition includes eight polyphenol anthracene derivatives such as chrysophanol, physcion, emodin, aloe-emodin, rhein, barbaloin, and sennoside A and B, which were all confirmed using HPLC analysis (
Figure 1
). According to the Smolarz study, the largest concentration of these compounds is detected in roots (163.42 mg/g), whereas fruits and leaves contain 0.52 mg/g and 0.67 mg/g, respectively [
8
]. Also a main criterion of preparation of the plant’s extract is the monitoring of content of heavy metals and other potentially toxic compounds in the plant.
The plant accumulates various compounds over the year; therefore, if researchers want to replicate published results obtaining therapeutically active extract, it is better to collect roots in spring or autumn, as stated in the protocol. To save maximum biologically active substances, it is essential to carefully wash them and dry them at room temperature. Micro and macro pharmacognostic analysis as well as conditions for extraction and TLC analysis are presented in pharmacopeia article 2.5.0052.15 [
9
]. Qualitative and quantitative analyses of aloe-emodin, rhein, and emodin can be also carried out using high-performance thin-layer chromatography (HPTLC) utilizing the stationary phase of a petroleum ether–ethyl acetate–formic acid (15.5:5:1,
v
/
v
) [
10
].
R. confertus
Willd. total amount of anthracene derivatives can be estimated via UV spectrum at 520 nm. Dry material should contain more than 3% of 8-O-β-D-glycoside emodin. The chromatographic separation of ethanol extract on silicagel can be done using chloroform ethanol systems such as 97:1, 97:2, 97:3, 95:5, 93:7, 90:10, 85:15, 80:20, 70:30, 60:40, 50:50. Kurkin et al. reports that
R. confertus
Willd. contains the following derivatives: emodin (1,6,8-Trihydroxy-3-methyl-anthraquinone); emodin 8-O-D-glucopyranoside; chrysophanol (1,8-Dihydroxy-3-methylanthraquinone); chrysophanol (chrysophanein-8-O-D-glucopyranoside); physcion (1,8-Dihydroxy-6-methoxy-3-methylanthraquinone); nepodin (1,8-Dihydroxy-2-acetyl-3-methylnaphthalene); neposide (nepodin 8-O-D-gluco-pyranoside); and torachrysone 8-O-D-glucopyranoside (1,8-Dihydroxy-6-methoxy-2-acetyl-3-methylnaphthalene 8-O-D-glucopyranoside) [
11
].Litvinenko et al. investigated roots of seven
Rumex
species and suggested using 50% acetone to extract a wider range of compounds and microelements (K, Na, Ca, Mg, Fe, Zn, Ni, Mn, etc.) with efficiency of 30% from the plant. It contained tannins (22%), anthraquinones (2.8%), flavonoids (2.9%), and polyphenolic compounds (4.3%), among others [
12
].
Even high concentrations of these derivatives do not provoke toxic effect or mortality of animals. Guerra et al. states that oxalic acid presenting in high concentrations in Rumex induratus Boiss. & Reuter resulted in several cases of intoxication in children [ 13 ]. Crews et al. also proves that oxalic acid can cause kidney damage [ 14 ].
1.2. Rumex Confertus Anticancer Properties
Cancer is currently the second leading cause of death in the world. Despite progress in developing new therapeutic approaches for cancer, its occurrence increases day by day. According to WHO, almost 10 million people died from cancer in 2020 [ 15 ]. Therefore, it is necessary to discover new effective and inexpensive drugs that can improve the antitumor effects and reduce the side effects of commonly recommended chemotherapeutic drugs [ 16 ].
One of milestones of the prediction of biological activity is the hydrophilicity and hydrophobicity balance of the substance, which is represented as Log P characteristic [ 17 ]. Log P is the octanol:water partition coefficient (log P ) of the substance. Some research revealed the structure-activity relationship correlated with Log P coefficient; therefore, we highlighted this characteristic along with pKa and solubility. For example, in the illumination of cancer cells in the presence of various substances, activities were minimal with log P ≤ 5, whereas it increased dramatically with log P in the range 5–6, and reached maximum with log P in the range 5.6–6.6, However, anticancer activities gradually declined with higher log P . The deficiency of activity of the least-lipophilic homologs of substances was explained due to their poor biodistribution characteristics, yielding insignificant tumor and plasma drug concentrations at the time of treatment with light [ 18 ]. The hydrophobicity for natural substances is a significant descriptor of bioactivity for the entire group of phenolics, for example, in decreasing order: p-courmaric acid > ferulic acid > quercetin > quercetin 3-O-glucoside > rutin. Yang et al. established correlation that the DNA cleavage activity was in a decreasing order: quercetin = rutin > p-courmaric acid > ferulic acid > quercetin 3-O-glucoside, whereas NADPH prooxidation activity was quercetin 3-O-glucoside > p-courmaric acid > rutin > quercetin > ferulic acid [ 19 ]. Such a significant difference between LD50 for rhein at oral and intraperitoneal administration is related to metabolism of the substance to rhein glucuronide and rhein sulfate as well as binding with proteins of plasma ( Table 1 ) [ 20 ]. The value of Log P for most of compounds is in the range 2.2–4.12, and this correlates with their high antitumor activity, as was noted above. These substances are characterised by poor solubility in water, and, as expected, introducing glycoside residue leads to substantial enhance of solubility and decrease of Log P.
The anthracene derivative emodin is known as an anticancer agent [
34
]. Very often, separating a complex mixture of compounds is not feasible due to cost, and therefore it is convenient to test and use plant extracts that may act in a synergetic way. Thus, as shown in
Figure 2
, ethanoic extract from leaves of
R. confertus
illustrated better activity against Ehrlich ascites carcinoma cells compares to the model drug emodin. Antonyan et al. studied the influence of various concentrations of ethanol extract and pure emodin obtained from
R. confertus
Willd. leaves at concentrations that varied from 0.04 to 400 μg/mL on Ehrlich ascites carcinoma (EAC) cells and non-cancerous mouse blood leukocytes (MBL). As a positive control, 1.3 μg/mL of the antitumor drug cyclophosphamide (CPA) was used [
35
].
The influence of various concentrations of the plant extracts
R. confertus
Willd. strongly affect the cells: the suppression of the growth of malignant EAC cells was proved by high IC
50
values: 0.3 ± 0.04 μg/mL for ethanol extract and 40 ± 10 μg/mL for pure emodin (
Figure 2
). The better result of the extract usage might be related to its rich chemical composition (anthracene derivates, flavonoids, tannins, coumarins, phenol glucosides, and alkaloids). In the case of the experiments with MBL cell lines, neither pure emodin nor plant extract showed any effect at the same concentrations. MBL growth was suppressed at 25 ± 10 mg/mL (ethanol extract) and 0.2 ± 0.1 mg/mL (pure emodin), respectively.
Chun-Guang et al. also found that emodin has antitumor activity against human K562 (chronic myelocytic leukemia cell lines). Cell growth of K562 was decreased to 60% after the treatment with emodin at a concentration of 100 μmol/L, as cell cycle was terminated in phase G (0)/G (1). It was found that apoptosis-associated protein Bcl-2 decreased in a dose-dependent manner, and Bax increased after treatment with emodin. In addition, caspase-3, -8, and -9 activations have been demonstrated in vitro and in vivo. An increase in Bax along with a decrease in Bcl-2 indicates that the treatment with emodin can lead to apoptosis of K562 cells. Early apoptosis occurred in cells treated with 25, 50, and 100 µmol/L of emodin incubated for 12 h. The cell death rates in the treated groups were 8.9%, 22.9%, and 36.1%, respectively; whereas the level of apoptosis in the control group was no more than 2.1% [
36
].
It was observed that treatment of breast cancer cells Bcap-37 and ZR-75-30 with emodin inhibits growth and induces apoptosis. The highest growth rates were observed when cells were exposed to at least 10 μmol/L of emodin for 72 h. The highest apoptotic rate was registered at a dose of 40 mM/L. Emodin treatment inhibited Bcl-2 expression and increased caspase-3 activation, PARP, p53, and Bax levels in breast cancer cells in a concentration-dependent manner [ 23 ].
Weigelt et al. reported that although breast cancer can be classified as a local tumor, it is able to metastasize to the distant organs via blood and lymph [ 37 ]. Emodin treatment in vitro suppressed epithelial-mesenchymal transition and cancer stem cell formation by inactivation of TGF-β1-metiated interactions between tumor-associated macrophages (TAM) and breast cancer cells, and reduced cancer cells migration and metastasis formation [ 38 ].
A major factor stimulating angiogenesis in cancer tumors is vascular endothelial-derived growth factor A (VEGFA) [ 39 ]. Transcriptional factor SerRS has a potency to repress VEFGA by binding to its promoter region [ 40 ]. Zou et al. reported that emodin demonstrated the highest anti-angiogenesis activity at a concentration of 10 µM by increasing SeRS mRNA and blocking transcription of VEGFA after 48 h incubation [ 34 ]. Bai et al. also proved that emodin reduced VEGFA expression in liver cancer cells (HepG2) in vitro and inhibited tumorigenesis in BALB/c nude mice in vivo at concentrations of 1 mg/kg or 10 mg/kg [ 41 ]. Gu et al. tested emodin efficiency against colon cancer both in vitro and in vivo and found that emodin significantly suppressed migration of cancer cells and decreased the expression of VEGFA [ 42 ]. Dai et al. reported similar results after emodin treatment that decreased the levels of expression of VEGFR2, PI3K, and p-AKT in colorectal cancer HCT116 cell line [ 43 ].
Another anthracene derivative, aloe-emodin, has been reported to be an anti-cancer agent with selective activity against neuroectodermal tumors [ 44 ]. The treatment with aloe-emodin demonstrated specific dose-dependent cytotoxic effects on neuroblastoma, pPNET, and Ewing’s sarcoma cells [ 22 ]. Cell line growth of neuroectodermal tumors was specifically inhibited, and the ED50s ranged from 1 to 13 μm for neuroblastoma and Ewing sarcoma, respectively. Moreover, it induced apoptosis in human T24 bladder cancer cells via the p53-dependent apoptosis pathway [ 24 ].
Activation of mitochondrial pathways by aloe-emodin can induce the apoptosis of colon cancer cells. MTT assays were used to as measure the effect of aloe-emodin on HCT116 and NCM460 cell viability. The colony formation experiments demonstrated interesting results: in the case of increasing drug concentration and time, the cell mass extensively decreased, which shows that aloe-emodin inhibits cell proliferation in a dose-dependent way. An analysis of the assessment of cellular apoptosis showed that caspase-3 is activated and participates in the process of apoptosis induced by aloe-emodin, followed by the release of caspase-dependent members of the Bcl-2 family and cytochrome C. Using Western blotting, it was determined that the expression of the protein of the pro-apoptotic factor of the Bcl-2 Bax family increased, in contrast to the anti-apoptotic factor Bcl-2, the expression of which decreased after treatment with aloe-emodin. In addition, the results show that cytochrome C protein expression was upregulated in the cytosol but decreased in mitochondria. In the mitochondrial pathway of apoptosis, the release of cytochrome C plays a key role in the beginning of the pathway and activation of caspases [
45
].
Aloe-emodin, rhein, and physcion inhibit the proliferation of SCC15 cells, and the order of inhibition level are aloe-emodin > rhein > physcion; the half maximal inhibitory concentrations (IC 50 ) value of aloe-emodin was 60.90 μM at 48 h of treatment. Aloe-emodin treatment resulted in a time- and dose-dependent decrease in cell viability and increased the apoptotic cell ratio. The results of Western blotting showed the expression levels of caspase-9 and caspase-3 proteins increased following aloe-emodin treatment [ 46 ].
Po-Lin Kuo et al. found that aloe-emodin inhibited cell proliferation and induced apoptosis in two human liver cancer cell lines, Hep G2 and Hep 3B. In Hep G2 cells, aloe-emodin induced p53 expression and was accompanied by induction of p21 expression, which was associated with cell cycle arrest in phase G1. In addition, aloe-emodin had a marked increase in Fas/APO1 receptor and Bax expression. On the contrary, in Hep 3B cells, in which p53 deficiency is detected, the process of inhibition of the proliferation of aloe-emodin is expressed in a p21-dependent manner, during which the cell life cycle does not stop and the number of Fas/APO1 receptors does not increase; on the contrary, it affects the increase in Bax expression and at the onset of apoptosis [
31
]. It was also revealed that this anthracene derivative contributes to cell death in the cell line of squamous cell carcinoma of the human lung CH27. The concentration of aloe-emodin that was lethal for 50% of CH27 cells was approximately 25 mM. Anthracene derivative-induced CH27 cell death was significant at 50 mM aloe-emodin concentration [
32
]. Chen et al. determined that aloe-emodin is an inhibitor of two human gastric cancer cell lines, AGS and NCI-N87. The IC
50
value for AGS cells after 72 h of exposure was below 0.07 mM, for NCI-N87 cells it was between 0.15 and 0.19 mM, which indicates that AGS cells are more sensitive to aloe-emodin than are NCI-N87 cells [
33
].
It is known that telomerase enzyme plays a critical role in cancer cell proliferation. Wang et al. tested aloe-emodin on three types of breast cancer cells lines: MDA-MB-453, MDA-MB-231, and MCF-7. Aloe-emodin increased its activity in a dose-dependent manner, reducing telomerase activity to 30.5%, 26.7%, and 34.1%, respectively, at concentration of 50 μM [ 47 ].
Cheng et al. showed that aloe-emodin at concentrations of 10, 20, and 40 μM induced endoplasmic reticulum stress-dependent apoptosis in SW620 and HT29 cell lines and recommended this anthracene derivative as a potential candidate in the treatment of colorectal cancer [ 48 ]. The similar results were obtained by Shen et al. from testing in vivo the rate of caspase-dependent apoptosis induced by aloe-emodin at a concentration of 20 μM in lung cancer A549 and NCI-H1299 cell lines. The authors stated that aloe-emodin inhibited the Akt/mTOR signaling pathway [ 49 ].
Rhien suppressed the cell cycle and viability of hormone-dependent breast cancer cells (MCF-7) and hormone-independent breast cancer cells (MDA-MB-435s) under normal conditions. Rhein treatment was more effective against MDA-MB-435 cells only at a concentration of 12.5 mM, whereas at 100 mM it was more toxic for MCF-7 cells. The IC
50
value of rhein after 48 h of incubation under normal or hypoxic conditions was 81.3 or 71.3 mM for MCF-7 cells and 52.1 or 127.3 mM for MDA-MB-435s cells [
25
]. Rhein inhibited proliferation of human hepatocelluar carcinoma BEL-7402 cells and increased the apoptosis rate at concentrations of 50–200 μM in 46 h. It has been reported that cell cycle S-phase was arrested via decreasing of expression of oncogene c-Myc and increasing of concentration of caspase-3 [
50
]. Rhein decreased the half-life of β-catenin in HepG2 cells two-fold. Moreover, it induced cell cycle arrest at S phase, which repressed proliferation of cells and further tumor growth [
51
]. You et al. proved that this anthraquinone induced apoptosis in HepaRG cells and cell cycle arrest at S phase by mitochondrial-mediated pathways but noted that the cytotoxicity of rhein in humans is still not clear [
52
].
According to the studies, Rumex contain gallic acid and flavan-3-ols, i.e., epigallocatechin gallate (EGCG), epigallocatechin (EGC), catechin and epicatechin (EC). [
53
,
54
,
55
] Galloylated catechins showed a stronger antiproliferative effect and apoptotic effect than non-halogenated catechins. EGCG is the most effective in the Hs578T breast cancer cell line. EGCG contains two gallate groups that can explain the highest antiproliferative effect observed in this study. EGCG, EGC, or EC can inhibit cell proliferation and modulate apoptosis. Flavan-3-ols can have a dual function, both as antioxidants and prooxidants, depending on their concentration and time of exposure to cell culture [
26
].
It was shown that roots of
R. confertus
contains large amounts of chrysophanol and related anthracene derivatives and are therefore considered for use in pharmaceutical practice [
56
]. Chrysophanol induced necrosis in J5 liver cancer cells, depending on dose and time. Cells exposed to 100 and 120 μM chrysophanol concentrations for 48 h showed S-phase arrest and cell death [
27
]. Analysis of cytotoxicity showed that chrysofanol nanoparticles kill prostate cancer cells compared to normal cells. Chrysophanol nanoparticles reduce histone deacetylase (HDAC) by inhibiting cell proliferation and inducing apoptosis by stopping the cell cycle in the sub-G phase. In addition, proteins associated with the cell cycle, including p27, CHK1, cyclin D1, CDK1, p-AMP activated protein kinase (AMPK), and p-protein kinase B (AKT), are regulated by chrysofanol nanoparticles to prevent human prostate cancer in vivo [
57
].
Caffeic acid induces apoptosis in cancer cells of the cervix, inhibiting the activity of Bcl-2, leading to the release of cytochrome c and subsequent activation of caspase-3, which indicates that caffeic acid induces apoptosis via the mitochondrial apoptotic pathway. This also suggests that caffeic acid has a strong antitumor effect [ 58 ].
1.3. Rumex Exctracts Anti-Inflammatory and Antioxidant Properties
Inflammation is an immediate reaction of the body to tissue injury caused by pathogens and toxic stimuli, such as biological, physical, or chemical damage. Although the inflammatory response is a protective mechanism, if it persists it can lead to multiple pathological conditions such as cancer, allergies, atherosclerosis, autoimmune diseases, and even death [
59
]. In mammals, heart attack results in a large amount of necrotic cardiomyocytes and an intense inflammatory response, leading to a cytokine storm [
60
]. It is known that cytokine storms are related to high concentrations of reactive oxygen species (ROS), which act as a chemoattractant.
Both emodin and aloe-emodin treatment inhibit oxidative stress, significantly reduce the size of infarct, and reduce the number of apoptotic cells in vivo in mice hearts due to presence of phenolic hydroxyl groups [ 61 , 62 ]. At a concentration of 30 mg/kg, emodin suppresses the expression of tumor necrosis factor-α (TNF-α) and the activation of NF-κB at the site of injury, preventing severe inflammation [ 63 ].
Postoperative intra-abdominal adhesions are the main complication after abdominal surgery. Emodin affects the prevention of postoperative adhesion formation compared to the control group. Such indicators of inflammation as interleukin-6 (IL-6) and transforming growth factor-β1 (TGF-β1) as well as gastrin and motilin levels were reduced after 48 h of treatment within 7 days after surgery in experimental groups in rats [
64
]. Emodin suppressed in vitro TNF-alpha-induced stimulation of the pro-inflammatory response. MCP-1 is a chemoattractant expressed by various types of cells, including fibroblasts. Its activation leads to the recruitment of macrophages, which, in turn, causes fibrotic reactions through their expression of TGF-β. As TNF-α is a pro-inflammatory cytokine expressed by corneal epithelial cells and macrophages, changes in its level, along with TGF-β levels, serve as indicators of the pathophysiological changes resulting from damage. Emodin at the concentration range from 1 to 5 μg/mL suppressed a dose-dependent increase in TNF-α on the expression of MCP-1 mRNA and the concentration of MCP-1 protein [
65
].
Lee et al. reported that emodin treatment at a concentration of 10 μM (whereas EC
50
> 3 μM) inhibited cell death exposed by arachidonic acid and iron in vitro. Also, emodin restored mitochondria membrane that was previously destroyed by ROS [
66
]. Emodin also positively affected oxidative stress and apoptosis in HK-2 human renal tubular cells after hypoxia. In addition, emodin pre-treatment inhibited the process of phosphorylation of extracellular kinases [
67
]. Waly et al. also published results proving that emodin at a concentration of 0.5 µM significantly reduced oxidative stress in HEK 293 human kidney cells [
68
]. At the same time, Xie et al. reported that emodin can induce apoptosis in human colon cancer HCT116 cells by provoking oxidative stress. Emodin induced mitochondrial transmembrane potential loss, increased Bax, and decreased Bcl-2 expression. After emodin treatment, the concentration of ROS rapidly increased, which resulted in p53 overexpression [
69
].
Aloe-emodin dose-dependently inhibits mRNA expression induced by nitric oxide synthase (iNOS) and the production of nitric oxide (NO) at 5–40 MKM, thereby inhibiting inflammatory reactions [ 70 ].
Increased reactive oxygen species (ROS) production can also result in inflammation and pain.
1.4. Rumex Compounds with Antibacterial, Antimicrobial, and Antiviral Properties
Although antibiotics are widely used against bacterial infections, they have severe side effects and, in addition, bacteria are characterized by high rates of mutations and become more and more resistant to antibiotics [ 71 ]. Thus, plant extracts replace antibiotics in traditional medicine because of the absence of toxicity; moreover, they act as a complex of compounds via various pathways, providing synergistic effects of treatment and minimizing development of resistance.
Orbán-Gyapai et al. tested various fractions of Rumex species as potential agents against such bacteria as Staphylococcus epidermidis, Staphylococcus aureus, MRSA, Bacillus subtilis, Moraxella catarrhalis, Streptococcus pyogenes, Streptococcus pneumoniae, and Escherichia coli and proved that n-hexane and chloroform extracts from roots demonstrated significant antibacterial activity (inhibition zones > 15 mm) [ 72 ]. Ginovyan et al. recommended using acetone extracts from Rumex as the most efficient agent (76.24 µg Catechin equivalent/mg of dry weight) [ 73 ].
Ghosh et al. reported that the extract of
Rumex nepalensis
possesses some antimicrobial activity against tested microorganisms (
Staphylococcus aureus
,
Bacillus subtilis
,
Escherichia coli
,
Shigella dysenteriae
,
and
Vibrio cholerae
) at all tested concentrations (200, 400, 800, and 1000 μg/disc). The inhibitory effect of the extract was observed against
Shigella dysenteriae
and comparable to the effect of chloramphenicol (10 μg/disc). Aloe-emodin is mostly responsible for the activity against
Shigella dysenteriae
[
74
]. Aloe-emodin, rhein, and emodin showed significant antibacterial effects on four strains of methicillin-resistant
Staphylococcus aureus
at concentrations of 2–64 μg/mL [
75
]. John et al. also described that the epimerized form of gallocatechin gallate had a high antagonistic effect against
E.
c
oli
and
Staphylococcus aureus
accompanied by epigallo-catechin, whereas catechin gallate and (+) catechin showed lower activity against microbes [
76
].
Kengne et al. used ethanol and methanol as extractants for isolate active compounds from Rumex abyssinicus . Anthracene derivative physcion is responsible for disruption of the cytoplasmic membrane and inhibition of the microbial respiratory chain in P . aeruginosa and S. flexneri [ 77 ].
Rumex japonicus Houtt
extract exhibited good antibacterial activity against MDR
Staph. aureus
having minimum inhibitory concentrations (MIC) ranging from 0.8 to 6.2 mg/mL and minimum bactericidal concentrations ranging from 3.1 to 12.5 mg/mL. A strong 82% inhibition of biofilm formation at sub-MIC value and eradication of biofilm at higher concentrations was observed. The motility of
Staph. aureus
was efficiently suppressed by the extract containing mainly emodin, chrysophanol, and physcion. Kim et al. stated that the extract was nontoxic to human epithelial cell lines (Caco-2 and HT-29 cell lines) at concentrations ranging from 0.1 to 0.5 mg/mL and from 0.1 to 0.75 mg/mL, respectively [
78
].
Noshad et al. studied antimicrobial property of methanolic extract of Rumex alveollatus L (disk diffusion agar, well diffusion agar, and minimum inhibitory/bactericidal concentration) against
Enterobacter aerogenes
,
Staphylococcus aureus, Salmonella typhi
, and
Streptococcus pyogenes
. It was stated that the extract contains 92 mg of gallic acid/g total phenols and 48.6 mg quercetin/g total flavonoids. It was evaluated that the extract was able to scavenge DPPH and ABTS free radicals by 69.6 and 80.6%, respectively, indicating good antioxidant activity. The growth of microorganisms was supressed in the presence of high concentrations of the extract, and
E. aerogenes and S. aureus
were the most resistant and sensitive bacterial species to the methanolic extract of
Rumex alveollatus
[
79
].
Emodin isolated from Japanese knotweed ( Polygonum cuspidatum ) at concentrations of 32 and 64 μg/mL has shown a potent inhibitory effect against Haemophilus parasuis , the causative agent of Glässer’s disease in pigs. At concentrations below 64 μg/mL exposure, it was found to have abnormal cell shape, plasmolysis, destroyed cell wall and membrane, and cytoplasmic vacuolation [ 71 ].
The effect of emodin on specific virulence factors of Streptococcus mutans ( S. mutans ) was studied in vitro and the development of caries in vivo. The growth and production of S. mutans acid was significantly inhibited by emodin at concentrations of 0.5–2 mg/mL. In addition, topical administration of emodin reduced the frequency and severity of carious lesions in rats [ 80 ].
It was proposed that emodin can be used as a natural alternative method for the prevention of brucellosis in animals. Brucella (B.) abortus is a pathogenic microorganism that results in chronic infections with multiple pathologies such as arthritis, endocarditis, and meningitis in humans, and spontaneous abortions in domestic animals. Among used concentrations of emodin, the highest non-toxic dose was 0.3 µg/mL, but higher concentrations of 3, 6, and 15 µg/mL significantly reduced survival rates of Brucella (B.) abortus [ 81 ].
Sennosides A, B, C, and D and rhein isolated from
Cassia pumila
Lamk demonstrated antibacterial activity against
Streptococcus pneumoniae
and
Rhizoctonia bataticola
at concentrations ranging from 100 to 400 µg/mL with the result compared to antibiotics [
82
]. Friedman et al. studied antimicrobial activity of seven green tea catechins and four black tea theaflavins, generally belonging to flavonoids against
Bacillus cereus
(strain RM3190). The results also show that (-)-gallocatechin-3-gallate, (-)-epigallocatechin-3-gallate, (-)-catechin-3-gallate, (-)-epicatechin-3-gallate, theaflavin-3, 3′-digallate, theaflavin-3′-gallate, and theaflavin-3-gallate showed antimicrobial activity at nanomolar concentrations; most compounds were more active than drug antibiotics such as tetracycline or vancomycin in comparable concentrations [
83
]. The mechanism of catechin action was described by Gradisar et al. Catechins were found to inhibit bacterial DNA gyrase by binding to the ATP binding site of a subunit of gyrase B. Epigallocatechin gallate (EGCG) was the most active in the group of four catechins, followed by epicatechin gallate (ECG) and epigallocatechin (EGC) regarding antimicrobial activity [
84
].
Chrysophanol (1,8-dihydroxy-3-methylanthracenedione) showed activity against Bacillus cereus, Bacillus subtilis, Staphylococcus aureus, Micrococcus kristinae, Staphylococcus epidermidis, Escherichia coli, Proteus vulgaris, Enterobacter aerogenes, and Shigella sonnei at concentrations >250 µg/mL [ 85 ].
RmlC (dTDP-6-deoxy-D-xylo-4-hexulose 3,5-epimerase) is a critical enzyme for cell wall biosynthesis in Mycobacterium tuberculosis . Chrysophanol is a leading inhibitor against the RmlC target with binding affinity of −9.24 kcal/mole to the RmlC active site [ 86 ].
Agarwal et al. manifested significant antifungal activity of anthraquinone derivatives such as rhein, physcion, aloe-emodin, and chrysophanol extracted from
Rheum emodi
against
Candida albicans
,
Cryptococcus neoformans
,
Trichophyton mentagrophytes
, and
Aspergillus fumigatus
. According to the results, MIC of crude MeOH extract was 250 mg/mL, whereas MIC of the pure compounds varied from 25 to 50 mg/mL, which makes them more prospective antifungal candidates [
87
]. Similar results on
Trichophyton mentagrophytes
(strain SM-110) have been demonstrated by Kawai et al.. Miller et al. showed antifungal activity of Barbaloin compared to lanoconazole, a commercial agent, at a minimum concentration of 75 mg/mL and 200 μg/mL in vivo and in vitro, respectively [
88
].
CVB3 (Coxsackie 3 virus) is the main causative agent of viral myocarditis. The study established that emodin inhibits CVB3 replication in vitro in mice. Emodin treatment at a concentration of 20 μM for 30 min inhibited mTOR signaling and activated 4EBP1 (eukaryotic initiation factor 4R-binding protein 1), resulting in suppression of translation of ribosomal protein L32. Emodin also differentially influenced several signal cascades, including Akt/mTORC1/p70(S6K) (p70 S6 kinase), ERK1/2 (extracellular-signal-regulated kinase 1/2)/p90(RSK) (p90 ribosomal S6 kinase), and Ca(2+)/calmodulin, which activate eEF2K (eukaryotic elongation factor 2 kinase) and eEF2 (eukaryotic elongation factor 2), respectively, which stop synthesis of VP1 (viral protein 1) [
89
].
The antiviral activity of aloe-emodin against Japanese encephalitis virus (JEV) and enterovirus 71 (EV71) was detected. The IC
50
of aloe-emodin ranged from 0.50 mcg/mL to 1.51 mcg/mL for JEV and from 0.14 mcg/mL to 0.52 mcg/mL for EV71 [
90
]. Chang et al. obtained results that aloe-emodin, chrysophanol, rhein, emodin, and physcion negatively influenced JEV. The inhibitory effect of methanol extract was higher than water extract (IC
50
= 15.04 μg/mL and IC₅₀ = 51.41 μg/mL, respectively). Separately, IC
50
values determined by a plaque reduction assay for chrysophanol and aloe-emodin were 15.82 μg/mL and 17.39 μg/mL, respectively [
91
]. Derivatives of anthraquinone, such as aloe-emodin, emodin, and chrysofanol, have been stated to exhibit antiviral activity, with their inhibition mechanism and anti-influenza A activity decreasing the cytopathic effect caused by the virus and inhibition of influenza A virus replication. The IC
50
value of aloe-emodin was less than 0.05 μg/mL [
92
].
The IC 50 values were found to be 100 μg/mL and 7.3 μg/mL for abscisic acid and aloe-emodin, respectively, which indicate more potency of aloe-emodin over the abscisic acid [ 93 ].
1.5. Antidiabetic Activity of the Plant’s Extract Rumex
Diabetes mellitus is characterized by hyperglycemia caused by deficiency in the action or production of insulin [ 94 ]. Currently available antidiabetic agents, such as hypoglycemic drugs and insulin, have their own limitations. Natural bioactive chemicals such as flavonoids, terpenoids, alkaloids, and phenolic compounds have been described as antidiabetic agents [ 95 ].
Westermark et al. noted that amyloid peptide, which is secreted by β-cells of the pancreatic islets of Langerhans, has cytotoxic effects related to type 2 diabetes mellitus in humans and diabetes in other mammalian species [ 96 ]. Ten independent experiments showed that the number of living β-cells after three days of cultivation in the presence of 2 μM of pre-aggregated amylin significantly decreased to 20% and lower (from 40.2 × 10 5 ± 2.6 to 7.8 × 10 5 ± 0.8) compared with a positive control ( p value < 0.0001).
It was found that the cultivation of primary hippocampal cells of aggregated amyloid Aβ (1-40/42) peptides leads to their death or degradation [
97
,
98
]. Avetisyan et al. detected that the number of living cells decreased to 22.7% (from 59.8 × 10
5
± 4.0 to 13.6 × 10
5
± 1.9) in 3 days exposure in a medium containing 2 μM Aβ (1-40), pre-aggregated during 7 days. In another case, when using peptides 0.2 μM Aβ (1-42), which were aggregated under identical conditions with a duration of 5 days, the amount decreased by approximately 79.8% (from 59.8 × 10
5
± 4.0 to 12.1 × 10
5
± 1.5;
p
value < 0.0001) (
Figure 3
).
It has been noted that even in the absence of amyloid peptides, pure emodin at a concentration of 13.5 μg/mL decreased the number of living cells to 60%, which proves that emodin is also toxic for neuronal cells [
99
]. However, compared to aggregated Aβ (1-40) and Aβ (1-42) peptides, emodin is less poisonous. After the exposure of both the
R. confertus
leaves extract and pure emodin at concentrations of 3.5 μg/mL and 30 μg/mL, respectively, in the presence of Aβ (1-40), the viability of cells increased to 74%, in the presence of Aβ (1-42) increased to 61%. The IC
50
values in the presence of Aβ (1-40) and Aβ (1-42) for the plant extract were 14.03 ± 0.13 μg/mL and for the pure emodin was 2.6 ± 0.8 μg/mL, respectively.
Anand et al. investigated in vitro the efficiency of aloe-emodin-8-O-glycoside in enhancing glucose transport by modulating the proximal and distal markers involved in glucose uptake and its conversion into glycogen even in the absence of insulin [
100
]. The α-glucosidase inhibition assay revealed significant activity of various samples of
R. hastatus
. Among the test samples, Rumex chloroform extract showed the highest activity of 49, 55, 61, 64, 71, and 77 at concentrations of 31.25, 62.5, 125, 250, 500, and 1000 μg/mL, respectively. The IC
50
value was 42 μg/mL. Flavonoids and saponins also exhibited significant enzyme inhibition, with IC
50
values of 89 and 105 μg/mL, respectively [
101
]. Xue at al. has shown that emodin demonstrated an activating effect on peroxisomal proliferator-activated receptor-gamma (PPARgamma) both in vitro and in vivo. Intraperitoneal injections of emodin for 3 weeks improved the symptoms in diabetic mice (serum glucose level in the experimental group was significantly lower than in the control,
p
value < 0.01), and this effect was probably associated with the regulation of the PPARγ pathway [
102
].
Malaguti et al. explained that rhein increases insulin sensitivity to glucose regulation in a dose-dependent manner in NOD mice [ 103 ]. Based on a rat model, it is known that 37% of rhein is excreted in urine and 53% in faeces, with a half-life of 4–10 h. Ninety-nine percent of rhein binds to plasma proteins and metabolizes primarily to rhein glucuronide and rhein sulfate. Its antidiabetic potential might be explained by suppressing the expression of dynamin-related protein 1 [ 20 ].
Rhein in cooperation with angiotensin-converting enzyme inhibitor (ACEI) can prevent the progression of diabetic nephropathy (DN) in mice suffering from type 2 diabetes. Normally DN causes kidney destruction, but after 8 weeks of rhein (150 mg/kg/day) with benazepril (10 mg/kg/day) treatment, plasma creatinine levels decreased significantly, compared with the diabetic control group by the end of the treatment period [
104
]. Moreover, ethanol extracts of Rhei Rhizoma containing rhein and sennosides attenuated DN, hypercholesterolemia, and platelet aggregation—the possible consequences of diabetes—in vitro via enhancing glucose uptake in 3T3-L1 adipocytes, decreasing triglyceride accumulation, and inhibiting alpha-glucoamylase activity [
105
].
Nepodin (Log P 3.1) isolated from Rumex roots was examined for the ability to stimulate protein kinase (AMPK) phosphorylation. In in vivo experiments, nepodin decreased the level of glucose in blood, increased the glucose intolerance in mice, and increased glucose uptake in a dose-dependent manner. In in vitro studies on L6 myotubes, it was detected that nepodin stimulated the process of 5′-adenosine monophosphate-activated and also improved AMPK phosphorylation in skeletal muscle cells [ 106 ].
As a result of the evaluation of the inhibitory potential of COX-1 and COX-2 using molecular docking and the theoretical evaluation of the absorption, distribution, metabolism, excretion, and toxicity in pharmacokinetics properties of eighteen nepodine derivatives isolated from the roots of Rumex nepalensis , it was found that four of them indicated enhanced inhibition of COX -2 as well as anti-inflammatory activity using rat paw edema induced by carrageenan [ 107 ].
Barbaloin (C-glucoside of aloe-emodin) also has a beneficial effect on type 2 diabetes. In mice treated by barbaloin at concentrations of 20 mg/kg and 50 mg/kg, the level of blood sugar decreased, whereas the insulin level increased [ 108 ].
Diabetic retinopathy occurs due to diabetes and is one of the most common causes of vision loss. Hyperglycemia leads to overexpression of many biological effectors, such as vascular endothelial growth factor (VEGF), which is very important for the development of diabetic retinopathy. Astragaline, the flavonoid presented in many Rumex species, has a beneficial effect on hyperglycemia: it helps to prevent diabetic retinopathy by reducing the excessive expression of VEGF in cultured Muller cells and weakening the effects caused by a high concentration of glucose in the blood [ 109 ].
Aldose reductase is involved in the development of secondary complications of diabetes, including cataracts, and, therefore, is the main drug target for the development of methods for treating diabetic diseases. A bioanalysis was performed based on the isolation and clarification of the structure of phloroglucinol derivative that can be isolated from
Rumex acetosa
L. 1-O-galloyl-β-D-glucose (β-glucogallin, which exhibits both selective and relatively strong inhibition (IC) 50 = 17 μM) of AKR1B1 in vitro. Molecular docking results find that this inhibitor is able to bind favorably at the active site, and β-glucogallin effectively inhibits sorbitol accumulation by 73% at 30 μM under hyperglycemia in an ex vivo organ cultivation model for lenses excised in transgenic mice with overexpression of human aldose reductase in the lens [
110
].
Pao-Hsuan Huang et al. established that MCF-7 cell growth was eliminated by administration of 12.5 μM aloe-emodin over 6 days, and only 50% of cells survived at 25 μM aloe-emodin treatment for 4 days. Some other nonclinical study illustrated that the IC
50
of aloe-emodin was 46 μM for MCF-7 cells. At a concentration of 25 μM, aloe-emodin significantly inhibited proliferation in human skin epidermoid carcinoma cells compared to in noncancerous cells. Nonetheless, aloe-emodin did not significantly affect the proliferation of MDA-MB-453 ERα-negative cells. The overexpression of ERα in MCF-7 cells enlarged the sensitivity to aloe-emodin treatment. Thus, aloe-emodin has a higher cytotoxic potential to MCF-7 (ERα-positive) cells than to MDA-MB-231 (ERα-negative) cells. Moreover, even a relatively low dose of 10 μM of aloe-emodin revealed that both cell growth and ERα activation were significantly repressed by aloe-emodin in a dose-dependent manner [
111
]. We have summarised all available information about completed clinical trials of individual compounds that was found in Rumex plant’s in
Table 2
.
Rumex acetosa considerably prevents the adhesion of Porphyromonas gingivalis (P.g.) to eukaryotic host cells in vitro. The randomized placebo-controlled pilot-trial established that mouth wash by 0.8% of proanthocyanidin-enriched extract from the plant effect microbiological, clinical, and cytological parameters [
117
]. Supragingival debridement was followed by mouth washing (3 times per day) with the extract or placebo (control) for 7 days as adjunct to routine oral hygiene. Intergroup assessments illustrated no meaningful microbiological, cytological, and clinical differences at any timepoint. Nevertheless, significant reductions in sulcular bleeding index at day 14 (
p
= 0.003) and approximal plaque index at day 7 (
p
= 0.02) and day 14 (
p
= 0.009) were observed in the test group by intragroup comparison. There were no severe side effects. The results indicate that the plant extract mouth rinse is safe but does not seem to inhibit colonization of Porphyromonas gingivalis or improve periodontal health following supragingival debridement [
117
].
1.6. Metabolism of Plant Derivatives In Vivo
Adsorption, distribution, metabolism, and excretion are among the most important parameters, along with pharmacological activity, during drug development preclinical and clinical trials and the standardisation process of a substance. Investigation of metabolism is an extremely difficult task, which can be solved using modern physicochemical equipment such as an HPLC equipped with C18 column and mass detector and radiation isotope analysis [ 118 ].
It was observed that emodin after a single oral administration of 50 mg/kg to rats indicated urinary excretion of 18% dose in one day and up to 22% in 3 days. Metabolites evaluated in pooled urine (0–3 days) were mostly free anthraquinones (emodin and emodic acid, 16% dose), and 3% was conjugated. Thus, 48% and 68% of the dose of emodin was excreted in the faeces mostly in unchanged anthraquinone over observation time, respectively. In cannulated rats, biliary discharge achieved a maximum after 6 h and eliminated 49% of the dose after 15 h; 70% of biliary activity was in conjugated emodin. Interestingly, radioactive labelled derivative of emodin in most organs decline significantly in 72–120 h. The
14
C activity of the substance in kidneys was estimated of 4.3 ppm after 120 h; in the mesenterium and fat tissue, an increase in
14
C activity from 72 to 120 h was noticed [
21
].
The metabolism of 1,3,8-trihydroxy-6-methylanthraquinone was calculated analysing rat liver microsomes. It was found that emodin metabolites omega-hydroxyemodin and 2-hydroxyemodin were detected. It was established that formation of omega-hydroxyemodin happens in cytochrome P450 [
119
]. It is known that the phenolic group is sensitive to oxidation. Emodin is sensitive to prolonged exposure to light due to the phenolic functional group oxidation. Novel derivatives of aloe-emodin, with an N-heterocyclic fragment in the composition, were isolated. The structure-activity relationship (SAR) is a powerful tool to predict probability of pharmacological activity of novel substances in silico. SAR software predicted that when some groups are replaced, i.e., hydroxyethyl and benzhydryl piperazine groups, the efficiency of their application increases. Compared to the activity of aloe-emodin and corresponding benzhydryl piperazine derivatives showed a substantial inhibitory effect (IC
50
5.66 ± 0.47 μM) on LPS-induced nitric oxide production in macrophage cells. The emodin derivatives exhibited high bioavailability (55%). The in vivo experiments on mice with induced ulcerative colitis showed a suppressive effect on the inflammatory process, indicating the superiority of novel derivative of emodin for the design of an anti-inflammatory drug based on it [
120
].
2. Conclusions and Future Prospects
We summarised systems of solvents used for extraction of therapeutically active compounds from
Rumex
. The main focus on pharmacological activity of extracted anthracene and flavonoid derivatives obtained from the
Rumex
species is due to its wide area of growth and large quantities. A great number of studies focus on substances that can be obtained from
Rumex
species devoted to the evaluation of anticancer activity of glycosylated anthraquinones and flavonoids.
Rumex
confertus and other species contain rhein glucuronide, barbaloin, sennoside, leucocyanidin, chrysophanol, physcion, nepodin, aloe-emodin, and other derivatives that have been proven to have antibacterial, antimicrobial, antiviral, antidiabetic, anti-inflammatory, and antioxidant properties. The gap in the research related to herbal plants is the limited information about optimization of cultivation conditions at artificial conditions. Currently, special attention is given to liquid soil supplements and growth stimulants for plants along with artificial light with programmed spectral characteristics. It is known that the method of the plant cultivation, amount of sun light, and microclimate can significantly change the chemical composition of the plant extract. Therefore, there is great potential for research to optimize conditions of cultivation with a purpose to achieve the highest yield of valuable biologically active ingredients. Another area of interest is the chemical modification of extracted complex compounds for development of novel drugs. The presence of diverse functionalities in the structure of anthraquinones and flavonoid derivatives provides the possibility of modification via a linker with synthetic drugs or precursors in order to create a combinatorial library of hybrid compounds in a search for novel substances with high efficiency of treatment of serious diseases. There are not many clinical studies of prepared plant extracts that have been tested successfully in vitro. Moreover, during the clinical studies, special attention should be given to metabolites of natural compounds that might reveal unique pharmacological properties and therefore motivate researchers to explore novel substances.
Author Contributions
Conceptualization, D.B.; methodology, D.B.; software, L.L.; formal analysis, D.B., M.K. and L.L.; investigation, D.B. and L.L.; data curation, D.B.; writing—original draft preparation, D.B.; writing—review and editing, D.B., M.K. and L.L.; visualization, D.B. and M.K.; supervision, D.B.; funding acquisition D.B. All authors have read and agreed to the published version of the manuscript.
Funding
Acknowledgments
D.B. greatly thanks the Best Teacher of University 2020 grant by the Science Committee of the Ministry of Education and Science of the Republic of Kazakhstan for covering the publication fee.
Conflicts of Interest
The authors declare no conflict of interest.
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Figure 1. Chromatogram (RP-HPLC) of methanolic extracts from the leaves of R. confertus reproduced with the permission of Smolarz [ 8 ].
Figure 1. Chromatogram (RP-HPLC) of methanolic extracts from the leaves of R. confertus reproduced with the permission of Smolarz [ 8 ].
Figure 2. Influence of different concentrations of ethanol extract and emodin of leaves of R. confertus on the viability of EAC cells in vitro, adapted from Antonyan et al. [ 35 ].
Figure 2. Influence of different concentrations of ethanol extract and emodin of leaves of R. confertus on the viability of EAC cells in vitro, adapted from Antonyan et al. [ 35 ].
Figure 3. Correlation between emodin and ethanol extract of leaves of Rumex Confertus on the viability hippocampal cells, adapted from Antonyan et al. [ 35 ].
Figure 3. Correlation between emodin and ethanol extract of leaves of Rumex Confertus on the viability hippocampal cells, adapted from Antonyan et al. [ 35 ].
Table 1. Physico-chemical and toxicity data of extractive substances.
Table 1. Physico-chemical and toxicity data of extractive substances.
Emodin 6-methyl-1,3,8-trihydroxyanthraquinone Logp 2.7 water solubility less than 1 mg/mL at 66 °F. Solubility at 25 °C (g/100 mL of saturated solution): ether 0.140; chloroform 0.071 [ 16 ]; Ld 50 mouse intraperitoneal 35 mg/kg [ 21 ]. Aloe-emodin 1,8-dihydroxy-3-(hydroxymethyl) anthraquinone LogP 3.25 [ 22 ], water solubility 5.5 × 10 −5 mole/L LD 50 mouse intraperitoneal 35 mg/kg [ 23 ]. Rhein 4,5-dihydroxy-9,10-dioxo-anthracene-2-carboxylic acid LogP 2.2 water solubility less than 1 mg/mL at 66 °F LD 50 mouse oral 5000 mg/kg LD 50 mouse intraperitoneal 25 mg/kg [ 24 ]. Leucocyanidin (2R,3S,4S)-2-(3,4-dihydroxyphenyl)-3,4-dihydro-2H-chromene-3,4,5,7-tetrol Water Solubility 2.22 g/L pKa 8.95 LD50 2110 mg/kg Rat Oral admin [ 25 ]. Chrysophanol or chrysophanic acid (1,8-dihydroxy-3-methylanthracene-9,10-dione) Water Solubility 0.12 g/L logP 4.12 pKa 9.14 [ 26 ]. Physcion (1,8-Dihydroxy-6-methoxy-3-methylanthraquinone) or emodin monomethyl ether Water Solubility 0.087 g/L logP 3.97 pKa 7.89 LD50 mouse intraperitoneal 10 mg/kg [ 27 ]. Epigallocatechin gallate (EGCG) water solubility 32.77 mg/L at 25 °C LogP 0.639 pKa 7.75 LD 50 2170 mg/kg at oral administration [ 28 ]. Epigallocatechin (EGC) water solubility 0.871 mg/mL LogP 0.71 pKa 8.73 LD 50 1.87 mol/kg = 857 mg/kg [ 29 ]. Barbaloin or Aloin A 1,8-dihydroxy-3-(hydroxymethyl)-10-[3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]-10 H -anthracen-9-one water solubility 2.63 g/mL [ 30 ] Log P 0.42 pKa 9.51 LD50 cat oral 500 mg/kg LD50 mouse intraperitoneal 200 mg/kg [ 31 ]. Sennoside (-)-(9R*,9′R*)-5,5′-bis(β-D-gluco-pyranosyloxy)-4,4′-dihydroxy-10,10′-dioxo-9,9′,10,10′-tetrahydro-9,9′-bianthracene-2,2′-dicarboxylic acid water solubility 0.753 mg/mL LogP1.2 The LD50 value in rats was 5000 mg/kg [ 32 ] pka 3.23 [ 33 ].
Table 2. Clinical trials of plant’s extractive substances.
Table 2. Clinical trials of plant’s extractive substances.
Compound Effect Action Clinical Experiment Epigallocatechin gallate [ 112 ] neuroprotective and neurorescue effects modulation of cell survival and cell cycle genes A randomised, double-blind, placebo-controlled, balanced crossover study the effects of 135 mg and 270 mg pure EGCG in 24 healthy, young adults (18–35) Emodin [ 113 ] antiproliferative effect inhibits the activity of the 26S proteasome in vitro and in vivo HEK293A-luciferase-cODC cells were seeded in 96-well plates and treated in the presence of emodin Sennoside [ 114 ] laxative increasing cyclic 3′,5′-adenosine monophosphate it alter permeability of cell walls in the colon, which regulates the process of active ion secretion Participants aged 10–18 years were randomly assigned to receive either PEG 60 mL/kg/day or PEG 30 mL/kg/day plus oral bisacodyl 10–15 mg/day or sennosides 2 mg/kg/day for 2 days prior to the colonoscopy Aloe-emodin [ 115 ] Triptolide Woldifii for Autosomal Dominant Polycystic Kidney Disease MRI calculated kidney volume, eGFR [Time Frame: Every 3–6 months] End-stage kidney disease (ESRD) [Time Frame: every 2 months] Interventional 300 participants from 15 to 70 years (child, adult, older adult) Randomized administration of Emodin (Frangula emodin, Frangulic acid) at concentration 100 mg/d Epigallocatechin anticancer drug [ 116 ] To determine whether the daily consumption of decaffeinated green tea catechins (Polyphenon E ® ) for 1 year reduces the rate of progression to prostate cancer (PCa) in men diagnosed with HGPIN or ASAP Study of Polyphenon E in Men with High-grade Prostatic Intraepithelial Neoplasia 240 (120 men/arm) men 30 Years to 80 Years (adult, older adult) diagnosed with the prostate condition HGPIN or ASAP with a capsule form of standardized green tea extract called Polyphenon E (200 mg epigallocatechin gallate (EGCG) twice a day) or placebo for a 12-month period and see if it can prevent progression of the prostate condition to prostate cancer. Investigators wanted to see if Polyphenon E reduces lower urinary tract symptoms and if this can be taken safely over one year
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BUBLITZ v. E.I. DUPONT DE | 171 F.Supp.2d 906 (2001) | pp2d9061987 | Leagle.com
MEMORANDUM OPINION AND ORDER PRATT District Judge. The Court has before it Defendants Motion for Partial Summary Judgment. In their...pp2d9061987
BUBLITZ v. E.I. DUPONT DE NEMOURS AND CO.
Nos. 4-00-CV-90247, 4:00-CV-90286, 4:00-CV-90375.
View Case
Cited Cases
171 F.Supp.2d 906 (2001)
Ann E. BUBLITZ and Dorothy A. Pierce, Individually and on Behalf of Themselves and All Persons Similarly Situated, Plaintiffs,
v.
E.I. duPONT de NEMOURS AND COMPANY and Pioneer Hi-Bred International, Inc., Defendants.
Jeanne Foster, Plaintiff,
v.
E.I. duPont de Nemours and Company and Pioneer Hi-Bred International, Inc., Defendants.
William Pennington, Plaintiff,
v.
E.I. duPont de Nemours and Company and Pioneer Hi-Bred International, Inc., Defendants.
United States District Court, S.D. Iowa, Central Division. https://leagle.com/images/logo.png
November 5, 2001.
November 5, 2001.
Attorney(s) appearing for the Case
Michael Thrall, Frank B. Harty, Des Moines, IA, for Plaintiffs.
Michael A. Giudicessi, Des Moines, IA, John B. Gordon, Minneapolis, MN, for Defendants.
United States District Court, S.D. Iowa, Central Division.
MEMORANDUM OPINION AND ORDER
PRATT, District Judge.
The Court has before it Defendants' Motion for Partial Summary Judgment. In their motion, Defendants request summary judgment with respect to two aspects of Plaintiffs' First Amended Recast and Substituted Complaint: (1) that the Severance Committee has the power to review the reasonableness and good faith of a Plan Participant's statement; and (2) that changes to one or all of Pioneer's compensation, bonus, or benefit plans which were made prior to the merger on October 1, 1999 did not trigger the conclusive presumptions of "Stated Good Reason" under the Plan. Plaintiffs resist on various grounds. For the reasons set forth below, the Court grants Defendants' motion in its entirety.
I. BACKGROUND
This is a class action involving a benefit plan that is covered by the Employee Retirement Income Security Act ("ERISA"), 29 U.S.C. § 1001 et seq. The Plaintiffs are a group of current and former executives of Pioneer Hi-Bred International, Inc. ("Pioneer"). They are suing Pioneer and the company that took over Pioneer, E.I. duPont de Nemours and Company ("DuPont"). In their First Amended Recast and Substituted Complaint, Plaintiffs allege four counts: Count I is a claim for enforcement and declaration of plan benefits against Pioneer and DuPont; Count II is a breach of fiduciary claim against Pioneer and DuPont; Count III is a claim
[171 F.Supp.2d 908]
against DuPont for interference with protected rights; and Count IV is an equitable relief claim against Pioneer and DuPont asking the Court to toll the three year period during which participants are entitled to exercise their rights under the Plan for the pendency of this action.
The benefit plan at issue is called the Change in Control Severance Compensation Plan for Management Employees ("Plan"). Essentially, the Plan provides that certain management-level employees of Pioneer who are "Participants" in the Plan are entitled to specified "Severance Benefits" if they experience an "Involuntary Termination of Employment" within three years after a "Change in Control." "Involuntary Termination of Employment" is defined in relevant part as "the termination of employment of a Participant by the Company other than Termination for Cause, [or] the resignation or retirement of a Participant for Stated Good Reason. ..." Plan § 2.1(k).
At issue in the current motion is the interpretation of the term "Stated Good Reason." The Plan defines "Stated Good Reason" as follows: "Stated Good Reason" means a written determination by a Participant that he reasonably and in good faith cannot continue to fulfill the responsibilities for which he was employed. Plan § 2.1(t). The Plan then goes on to set forth five specific circumstances under which the Participant's determination will be "conclusively presumed" to be "reasonable and in good faith" and thus constitute Stated Good Reason:
The Participant's determination will be conclusively presumed to be reasonable and in good faith if, without the Participant's express written consent, the Company
(a) reduces the Participant's base salary or rate of compensation as in effect immediately prior to the Change in Control, or as the same may have been increased thereafter,
(b) fails to continue any bonus plans in which the Participant was entitled to participate immediately prior to the Change in Control, substantially in the form then in effect,
(c) fails to continue in effect any benefit or compensation plan in which the Participant is participating immediately prior to the Change in Control (or plans providing substantially similar benefits),
(d) assigns to the Participant any duties inconsistent with the Participant's duties, responsibilities or status immediately prior to the Change in Control, or changes the Participant's reporting responsibilities, titles or offices, or
(e) requires the Participant to change the location of his job or office, so that the Participant will be based at a location more than thirty (30) miles distant by public highway from the location of his job or office immediately prior to the Change in Control.
Plan § 2.1(t). The parties disagree over the meanings of "Stated Good Reason" and "Change in Control."
II. LEGAL STANDARD
Federal Rule of Civil Procedure 56(c) provides that summary judgment "shall be rendered forthwith if the pleadings, depositions, answers to interrogatories, and admissions on file, together with the affidavits, if any, show that there is no genuine issue as to any material fact and that the moving party is entitled to a judgment as a matter of law." An issue is "genuine," "if the evidence is such that a reasonable jury could return a verdict for the nonmoving party."
Anderson v. Liberty Lobby, Inc.,
477 U.S. 242
, 248, 106 S.Ct. 2505, 91
[171 F.Supp.2d 909]
L.Ed.2d 202 (1986). A fact is "material" if the dispute over it might affect the outcome of the suit under the governing law. Id. In order to survive a motion for summary judgment, the nonmoving party must present enough evidence for a reasonable jury to return a verdict in his or her favor. Anderson, 477 U.S. at 257, 106 S.Ct. 2505.
On a motion for summary judgment, the Court is required to "view the evidence in the light most favorable to the nonmoving party and give that party the benefit of all reasonable inferences." United States v. City of Columbia,914 F.2d 151, 153 (8th Cir.1990). The Court does not weigh the evidence or make credibility determinations. See Anderson,477 U.S. at 252, 106 S.Ct. 2505. The Court only determines whether there are any disputed issues and, if so, whether those issues are both genuine and material. Id.
III. DISCUSSION
Defendants request summary judgment with respect to two aspects of Count I of Plaintiffs' First Amended Recast and Substituted Complaint. First, Defendants argue that each Plan Participant is not the sole arbiter of whether Stated Good Reason exists and does not have sole discretion to "pull his or her own chute," as Plaintiffs contend. Rather, Defendants argue, the Severance Committee has the power to review the reasonableness and good faith of a participant's statement. Second, Defendants argue that the changes to Pioneer's compensation, bonus, or benefit plans that were made prior to the merger on October 1, 1999 did not trigger the conclusive presumptions of Stated Good Reason under the Plan. They argue that these changes could not have triggered the conclusive presumptions because they occurred prior to the Change of Control as that term is defined in the Plan. Plaintiffs resist Defendants' requests on various grounds.
A. The Severance Committee's Power to Review the Reasonableness and Good Faith of a Participant's Statement
Plaintiffs claim that a Plan Participant's statement "that he reasonably and in good faith cannot continue to fulfill the responsibilities for which he was employed" is intended to be a totally subjective determination. They state that this determination is by design, intention, and historical interpretation a "hair trigger." It is the Plaintiffs' position that the Severance Committee has no right to review the reasonableness and good faith of a Participant's statement.
1. Discretionary Authority
Plaintiffs argue that the Plan does not grant the Severance Committee any discretionary authority to review the reasonableness and good faith of a Participant's statement. They argue that without explicit discretion-granting language, the Severance Committee has no authority to review a Participant's statement. Plaintiffs also argue that the Plan prohibits Defendants' attempt to effectively amend it, that the Severance Committee's responsibilities under the Plan are merely administrative, and that the Defendants' attempt to secure discretionary authority should be rejected where DuPont controls the Severance Committee and the Plan is unfunded.
Plaintiffs' argument that Defendants are attempting to invoke discretionary authority is misguided. Defendants admit that the Plan contains no discretion-granting language. However, they maintain that the Severance Committee still has the power to make a determination under the Plan, even though that determination will then be subject to a de novo review. The Court agrees. Whether a plan administrator or fiduciary has discretionary authority only relates to whether the reviewing court
[171 F.Supp.2d 910]
is required to apply the abuse of discretion standard as opposed to the de novo standard. It does not relate to whether the plan administrator or fiduciary has any power to make a determination under the plan. In other words, the benefit-determination issue and the standard-of-review issue are distinct concepts under ERISA.
In Firestone Tire and Rubber Co. v. Bruch,489 U.S. 101, 115, 109 S.Ct. 948, 103 L.Ed.2d 80 (1989), the Court recognized that "the validity of a claim to benefits under an ERISA plan is likely to turn on the interpretation of terms in the plan at issue." The Court held that "a denial of benefits challenged under § 1332(a)(1)(B) is to be reviewed under a de novo standard unless the benefit plan gives the administrator or fiduciary discretionary authority to determine eligibility for benefits or to construe the terms of the plan." Id.The import of that holding is that while a plan administrator or fiduciary may interpret a term in a plan to deny a participant benefits, the reviewing court will give no deference to that interpretation unless the plan gives the plan administrator or fiduciary discretionary authority to interpret it. The existence or nonexistence of discretion-granting language goes not to the ability of a plan administrator or fiduciary to interpret the plan or make a determination under the plan, but rather to the weight a reviewing court must give that interpretation or determination.
This distinction is evident in Walke v. Group Long Term Disability Ins.,256 F.3d 835(8th Cir.2001). In Walke,the parties disagreed over whether the phrase "submits satisfactory proof of Total Disability to us" amounted to discretion-granting language. Id.at 839. The district court found that it did provide the defendant with some discretion and reviewed its determination under the abuse of discretion standard. Id.at 840. Under this standard the district court upheld the defendant's determination, finding no evidence to support the contrary. Id.The Eighth Circuit disagreed with the district court on the standard to be applied, and applied the de novo standard after concluding that the phrase did not amount to discretion-granting language. Id.The Eighth Circuit then proceeded to review the defendant's determination under that more rigorous standard and agree with the district court on the conclusion to deny benefits. Id.at 840-41. This exemplifies how the determination and the review of the determination are two separate processes. Plaintiffs' interpretation of the discretionary authority cases collapses these two processes into one-concluding that if a plan administrator or fiduciary has no discretion in its interpretation of or determination under a plan, then it has no power to interpret or make a determination under the plan at all.
Plaintiffs' other arguments concerning discretionary authority are equally misguided. Defendants are not attempting to amend the Plan to give the Severance Committee broad discretionary authority. Nor is the Severance Committee's responsibilities under Plan relevant to its lack of discretionary authority. Finally, whether DuPont controls the Severance Committee and whether the Plan is unfunded are also irrelevant; those issues pertain to the abuse of discretion standard of review. See Firestone,489 U.S. at 115, 109 S.Ct. 948.
2. Extrinsic Evidence
Plaintiffs also argue that extrinsic evidence shows that the Plan was not intended to grant to the Severance Committee the authority to review the reasonableness and good faith of a Participant's statement. In their resistance to Defendants' motion, Plaintiffs discuss Pioneer's past conduct and historical interpretation of Stated
[171 F.Supp.2d 911]
Good Reason. They cite to a "Blue Book," which is a collected history of the Plan put together by Pioneer. They also cite to deposition testimony from several high ranking Pioneer executives. This evidence demonstrates that some key individuals, including some of Pioneer's counsel, thought Stated Good Reason was intended to be a hair trigger, or totally subjective determination on the part of the Plan Participant.
Plaintiffs's attempted use of extrinsic evidence is improper though. Extrinsic evidence is generally not admissible to aid in the interpretation of an ERISA plan unless the plan is ambiguous. See Barker v. Ceridian Corp.,122 F.3d 628, 633 (8th Cir.1997); Jensen v. SIPCO, Inc.,38 F.3d 945, 950 (8th Cir.1994); Farley v. Benefit Trust Life Ins. Co.,979 F.2d 653, 657 (8th Cir.1992). The steps in interpreting an ERISA plan have been outlined by the Eighth Circuit as follows:
That intent [of the settlor] is first sought by careful examination of the trust clause in question, giving the words in that clause their ordinary meanings. If the construction question cannot be resolved by reference to the clause alone, the court will examine the entire trust instrument to determine the creator's intent and purposes.... The third step becomes necessary when the intent or meaning of the settlor ... cannot be determined by reference to the provisions of the trust instrument itself. Extrinsic evidence will be admitted by the court to assist it in determining the meaning and effect of the particular clause.
Jensen,38 F.3d at 950 (quotation omitted). Thus, it is only where the meaning of an ERISA plan cannot be gleaned from the disputed provision itself or the plan as a whole that extrinsic evidence is admissible.
The Plan is not patently ambiguous. Black's Law Dictionary defines patent ambiguity as "[a]n ambiguity that clearly appears on the face of a document, arising from the language itself...." Black's Law Dictionary (7th Ed.). The disputed phrase reads: "Stated Good Reason" means a written determination by a Participant that he reasonably and in good faith cannot continue to fulfill the responsibilities for which he was employed. Plan § 2.1(t). While the Court cannot say from a mere reading of this phrase alone that no ambiguity exists, as discussed infra,the rest of the plan document makes the meaning of the phrase clear.
Nor are the Plaintiffs properly attempting to establish a latent ambiguity. Black's Law Dictionary defines latent ambiguity as "an ambiguity that does not readily appear in the language of a document, but instead arises from a collateral matter when the document's terms are applied or executed.... Black's Law Dictionary (7th Ed.)." The real thrust of Plaintiffs' argument concerning extrinsic evidence is that they may use it to demonstrate that the Plan is latently ambiguous.
Plaintiffs rely on the Eighth Circuit's decision in
Landro v. Glendenning Motorways, Inc.,
625 F.2d 1344
(8th Cir.1980). In
Landro,
the plaintiffs were all employees of Glendenning Motorways, Inc. ("Glendenning"); before that they were all employees of Moland Brothers Trucking, Inc. ("Moland"), which was bought out by Glendenning.
Id.
at 1346. The main issue was whether the plaintiffs were entitled to credit toward their pensions under the Glendenning pension plan for the years they worked for Moland.
Id.
Using extrinsic evidence, the district court had determined that the plan was silent or ambiguous on the question of credit for years of service with a predecessor employer like Moland.
Id.
at 1353. The defendants argued that the district court erred in looking
[171 F.Supp.2d 912]
to extrinsic evidence, and the Eighth Circuit disagreed. Id.
The Eighth Circuit held as follows:
While is is true that the Plan by its terms allowed credited service only for periods of employment by Glendenning, it nowhere excluded the possibility that periods of employment by predecessor employers like Moland were meant to be included within the definition of credited service as periods of employment by Glendenning. The district court properly considered evidence extrinsic to the Plan itself for the purpose of determining whether it was open to this construction whether, in effect, the Plan was latently ambiguous on this point.
Id.(emphasis added). It concluded that "[t]he extrinsic evidence considered by the district court demonstrated that in fact the Plan could be construed as including periods of service with Moland as periods of service with Glendenning." Landro,625 F.2d at 1353. The extrinsic evidence showed that defendants had acted as though they would give credit for years of service with Moland and even said as much when asked. Id.
The Plaintiffs are not attempting to use extrinsic evidence for the same purpose as the defendants used it for in Landro.In Landro,the extrinsic evidence was used to demonstrate that the plan was silent as to whether "employment by Glendenning" included employment by employers that Glendenning bought out. Id.In this case, at least from looking at the Plan as a whole, the Plan is not silent on the issue of whether the Severance Committee has the power to review the reasonableness and good faith of a Plan Participant's decision. As will be shown infra,the Plan is clear that the Severance Committee does have that power. And Plaintiffs are attempting to use extrinsic evidence to contradict that interpretation. Such a use of extrinsic evidence is impermissible. See McPeek v. Beatrice Co.,936 F.Supp. 618, 630 n. 14 (N.D.Iowa 1996) (stating " `extrinsic evidence may not be used to create an ambiguity in a pension or welfare agreement subject to ERISA' ") (quoting Central States, Southeast and Southwest Areas Pension Fund v. Joe McClelland, Inc.,23 F.3d 1256, 1259 (7th Cir.1994)).
3. The Text of the Plan
The text of the Plan makes it clear that the Severance Committee has the power to review the reasonableness and good faith of a Plan Participant's statement. First and foremost, there is the definition of Stated Good Reason in the Plan. The definition of Stated Good Reason begins, " `Stated Good Reason' means a written determination by a Participant that he reasonably and in good faith cannot continue to fulfill the responsibilities for which he was employed." Plan § 2.1(t). Admittedly, this particular phrase, standing alone, is subject to more than one reasonable interpretation. However, when read in conjunction with the entire definition of Stated Good Reason, it is subject to only one reasonable interpretation.
The next sentence in the definition states, "The Participant's determination will be conclusively presumed to be reasonable and in good faith if,...." Plan § 2.1(t). The definition then goes on to identify certain circumstances, such as reduction in pay and change in duties. The conclusive presumptions of Good Faith make it clear that a Participant's determination of reasonableness and good faith is not totally subjective, that rather the Severance Committee would review it. Plaintiffs' interpretation that a Participant's determination is totally subjective contradicts the notion that the determination may be conclusively presumed. That a
[171 F.Supp.2d 913]
definition may be conclusively presumed implies that someone will be reviewing the determination. Otherwise, it would make no sense to have conclusive presumptions. Plaintiffs' argument that they merely provided objective examples does not square with the wording in the definition.
Beyond the conclusive presumptions, the definition is still laced with content-laden language. The mere fact that it is called Stated Good Reason is contrary to an interpretation wherein the Participant could "pull his or her own chute" at his or her sole discretion; in other words, if there was no check on whether the Participant's reason was a good one, then the Participant could really pull the trigger for any reason or even no reason. Similarly, the use of the terms "reasonable" and "good faith" suggests that there is more to the determination than Plaintiffs contend.
The rest of the Plan provides further support for Defendants' interpretation. For example, Defendants point out that the Plan is a double trigger plan: the first trigger being a change in control and the second trigger being something else, such as a good reason for leaving. Yet, if Plaintiffs were correct, it makes sense that Pioneer would have made it a single trigger plan wherein all that was required is a change in control. Also, it must be remembered that under the Plan a termination of employment for Stated Good Reason is a species of "Involuntary Termination of Employment." Plan § 2.1(k). Plaintiffs interpretation comes very close to making Stated Good Reason a voluntary termination.
In addition, the review process intimates a much more searching inquiry than is suggested by Plaintiffs. The Plan outlines the review process as follows:
Any claim for benefits shall be made in writing to the Severance Committee. The claim for benefits shall be reviewed by the Severance Committee. If any part of the claim is denied, the Severance Committee shall provide a written notice ... setting forth: (a) the specific reasons for the denial; (b) specific reference to the provision of this Plan upon which the denial is based; (c) any additional information the claimant should furnish to perfect the claim; and (d) the steps to be taken if a review of the denial is desired.
Plan § 4.7. However, there would be very little point to this complicated review process if all that was necessary was that the Participant write down on a piece of paper that he or she cannot reasonably and in good faith continue to fulfill the duties for which he or she was employed. Moreover, the Severance Committee that is in charge of this review process is made up of high level executives.
1
It would make very little sense for a company to have high level
[171 F.Supp.2d 914]
executives performing the clerical tasks Plaintiffs suggest the Severance Committee performs.
It is therefore clear that Stated Good Reason is not a totally subjective trigger. The Severance Committee has the power to review whether a Plan Participant's determination is in fact reasonable and in good faith. And Defendants are entitled to summary judgment on this interpretation.
B. Changes to Pioneer's Compensation, Bonus, or Benefit Plans Made Prior to October 1, 1999
Plaintiffs claim that the changes in one or all of Pioneer's compensation, bonus, or benefit plans made prior to October 1, 1999 triggered Stated Good Reason. Specifically, Plaintiffs' claim concerns two of the conclusive presumptions. The Plan provides that a conclusive presumption of Stated Good Reason exists if, "without the Participant's express written consent, the Company ..."
(b) fails to continue any bonus plans in which the Participant was entitled to participate immediately prior to the Change in Control, substantially in the form then in effect, [or]
(c) fails to continue in effect any benefit or compensation plan in which the Participant is participating immediately prior to the Change in Control (or plans providing substantially similar benefits. ....)
Plan § 2.1(t). In order to determine whether one of these two conclusive presumptions applies, it is necessary to compare the compensation, bonus, and benefit plans in effect prior to the Change in Control with the compensation, bonus, and benefit plans in effect after the Change in Control.
Essentially, Plaintiffs assert that DuPont was in effective control of Pioneer prior to October 1, 1999, the official date of the merger, and that Defendants cannot interpret the Plan in such a way so as to allow them to make the changes they did prior to that date without triggering the conclusive presumptions. Plaintiffs state that such an interpretation is at odds with other provisions in the Plan specifically designed to protect Pioneer's upper-level management team from the conduct of an acquiring company. They point to the purpose of the Plan, which is to attract and retain "highly qualified individuals" and to "reduce the distractions ... inherent in a takeover threat." Plan § 1.2. They point to the fact that the Plan vests the Participants with a contractual right to benefits. 2Plaintiffs also point to Section 8.1 of the Plan, which states that "any amendment which reduces Severance Benefits or any termination of the Plan shall be disregarded for all purposes if such amendment or termination is adopted during the one year period immediately preceding a Change in Control." Finally, they claim that the fact that the drafters sought to prevent an acquiring company from having the ability to force a reduction in benefits is also demonstrated by Sections 5.2 and 5.3 of the Plan. Those sections require that as soon as a "Potential Change in Control" occurs, Pioneer shall fund a trust in "an amount that is no less than one hundred (100%) of the Severance Benefits" potentially payable to all Participants.
[171 F.Supp.2d 915]
the members of the Board of Directors of Pioneer. Plan § 2.1(d). It is clear that in this case the Change in Control occurred when DuPont acquired twenty-five percent of Pioneer's stock on October 1, 1999. The conclusive presumptions all require changes to the Plan after a Change in Control. Therefore, the changes to one or all of Pioneer's compensation, bonus, or benefit plans that occurred prior to October 1, 1999 could not have triggered the conclusive presumptions, and Defendants are entitled to summary judgment on that fact.
IV. CONCLUSION
Defendants' Motion for Partial Summary Judgment (Clerk's No. 237) is granted.
IT IS SO ORDERED.
FootNotes
1. The Plan states that the Severance Committee is comprised of:
the Compensation Committee of the Board of Directors or such other person or persons appointed by the Board of Directors to administer the Plan. If the Severance Committee is not the Compensation Committee and the Board does not appoint a Severance Committee, the Board of Directors shall be the Severance Committee.
Before the Change in Control, the Pioneer Board had appointed the five highest ranking executives at Pioneer to serve on the Severance Committee. After the Change in Control, Pioneer replaced the members of the Severance Committee with similarly senior executives. The Severance Committee consisted of the Director of Human Resources for Pioneer, the Director of Human Resources for DuPont Agricultural Enterprise, and the Director of Corporate Compensation and Benefits for DuPont. The Authorization Committee, which was appointed by the Board to hear appeals, consisted of the President, Chief Executive Officer, and Secretary of Pioneer, a Senior Vice President of DuPont Agricultural Enterprise, and the Executive Vice-President and Chief Operating Officer of DuPont.
2. Section 1.3 of the Plan, entitled, "Contractual Rights to Benefits," states: "This Plan establishes and vests in each Participant a contractual right to the benefits to which he is entitled hereunder, enforceable by the Participant against the Company."
| https://www.leagle.com/decision/20011077171fsupp2d9061987 |
Modular vehicle electronic system Patent Grant Suman , et al. August 20, 1 [Prince Corporation]
Modular vehicle electronic system
Suman , et al. August 20, 1
Patent Grant 5040990
U.S. patent number 5,040,990 [Application Number 07/535,337] was granted by the patent office on 1991-08-20 for
modular vehicle electronic system
.
This patent grant is currently assigned to Prince Corporation. Invention is credited to Michael J. Suman, Sheldon J. Watjer.
United States Patent 5,040,990 Suman , et al. August 20, 1991
**Please see images for: ( Certificate of Correction ) **
Modular vehicle electronic system
Abstract
A modular interchangeable electronic system for providing a
number of different options for a vehicle which can be selectively
plugged into a base unit. The base unit can receive or be replaced
by selected optional units which interface with vehicle controls or
provide desired control or display functions.
Inventors: Suman; Michael J. (Holland,
MI) , Watjer; Sheldon J. (Holland, MI) Assignee: Prince Corporation (Holland,
MI) Family
ID: 26996447 Appl.
No.: 07/535,337 Filed: June 8, 1990
Related U.S. Patent Documents
Application
Number Filing Date Patent Number Issue Date 350014 May 9, 1989
Current U.S.
Class: 439/34 ; 307/10.1;
439/49; 361/729; 296/37.7 Current CPC
Class: B60R
11/00 (20130101); H01R 31/08 (20130101) Current International
Class: B60R
11/00 (20060101); H01R 31/00 (20060101); H01R
31/08 (20060101); H01R 031/08 () Field of
Search: ;439/34,35,36,43,49,53
;296/37.7 ;307/10.1 ;361/352,395,393
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4818010 April 1989 Dillon
4844533 July 1989 Dowd et al.
4869670 September 1989 Ueda et al.
Foreign Patent Documents
219440 Sep 1988 JP
Primary Examiner:
Paumen; Gary F.
Attorney, Agent or Firm:
Price, Heneveld, Cooper, DeWitt
& Litton
Parent Case Text
This is a continuation of copending application Ser. No. 07/350,014
filed on May 9, 1989, now abandoned.
Claims
The embodiments of the invention in which an exclusive property or
privilege is claimed are defined as follows:
1. A vehicle accessory system comprising a base module mounted to a
vehicle, said base module including a first accessory and further
including first electrical connecting means and further including
first electrical connecting means to the vehicle's electrical
system, said base module further including means for receiving a
select one of a plurality of accessory modules; and
at least one accessory module including means for mechanically
coupling said accessory module to said base module and further
including second electrical connecting means for coupling said
accessory module to said first electrical connecting means and
wherein said means for electrically coupling said first electrical
connecting means to the vehicle's electrical system comprises first
conductors coupled to said first electrical connecting means,
second electrical conductors coupled to said vehicle's electrical
system, and means for selectively coupling said first electrical
conductors to said second electrical conductors to interface with a
selected one of said accessory modules such that said means for
selectively coupling interconnects selected ones of said first
conductors to selected ones of said second conductors for
selectively changing said first and second conductors which are
interconnected to be when different accessory modules are received
in said base module.
2. The system as defined in claim 1 wherein said system includes a
plurality of accessory modules.
3. The system as defined in claim 2 wherein said means for
selectively coupling includes a universal connector having first
terminals coupled to said first electrical conductors and second
terminals coupled to said second electrical conductors and a
plurality of programming connectors with one of said programming
connectors associated with each one of said accessory modules for
interconnecting selected first and second terminals whereby at
least one first terminal can be coupled to different second
terminals by changing said programming connectors.
4. The system as defined in claim 3 wherein said universal
connector comprises a socket including said first terminals and
said second terminals, and said programing connectors comprise a
plurality of plugs for selectively coupling selected ones of said
first terminals to selected ones of said second terminals using a
plug unique to a selected said accessory module.
5. The system as defined in claim 4 wherein a first said accessory
module comprises light means.
6. The system as defined in claim 5 wherein said base module is
mounted to the roof area of the vehicle.
7. The system as defined in claim 1 wherein said at least one
accessory module is a compass module.
8. The system as defined in claim 1 wherein said at least one
accessory module is a garage door opening module.
9. The system as defined in claim 1 wherein said at least one
accessory module is a systems check module.
10. The system as defined in claim 1 wherein said at least one
accessory module is a door-lock control module.
11. The system as defined in claim 1 wherein said at least one
accessory module is a 2-wheel/4-wheel drive control and display
module.
12. The system as defined in claim 1 wherein said means for
selectively coupling couples said first connecting means to the
vehicle's electrical system in accordance with a control or display
option of a selected accessory module.
13. The system as defined in claim 1 wherein said means for
coupling said first electrical connector to the vehicle's
electrical system further includes a ribbon-like substrate of
insulating material including a plurality of spaced generally
parallel conductors mounted therein, said substrate mounted to
extend across a module receiving recess in the vehicle, and wherein
said base module is shaped to be mounted in said recess and
includes contact means for engaging at least predetermined ones of
said spaced conductors.
14. The system as defined in claim 13 wherein said substrate
includes elongated grooves for receiving inlaid conductors and
wherein said contact means comprises spring contacts which extend
into said grooves to contact said conductors.
15. The system as defined in claim 13 wherein said substrate
includes a plurality of openings for exposing sections of said
conductors and wherein said contact means comprises spring clips
aligned with said openings to engage said conductors when said
module is mounted within said recess.
16. A vehicle accessory system comprising:
a base module for attaching to the vehicle for receiving a selected
one of a plurality of accessory modules and including a first
electrical connector having conductors;
at least one accessory module including means for connecting to the
first electrical connector; and
a selective electrical connector coupled between the first
electrical connector and the vehicle's electrical system, the
vehicle's electrical system including the vehicle's fuse box and
conductors, said selective connector for selectively providing a
plurality of connections between the first electrical connector and
the vehicle's electrical system including the vehicle's fuse box
for selectively coupling at least one conductor of said first
electrical connector to different conductors of the vehicle's
electrical system according to display or control options of the
plurality of accessory modules.
17. The system as defined in claim 16 wherein said base module
further includes a light means for illuminating the interior of the
vehicle.
18. The system in claim 16 wherein the selective connector provides
a respective unique connection for each of the plurality of the
accessory modules.
19. The system as defined in claim 16 wherein said plurality of
accessory modules comprise a compass module, a garage door opening
module, a systems check module, a door-lock control module or a
2-wheel/4-wheel drive control and display module.
20. The system as defined in claim 16 wherein one of said
conductors of said first electrical connector is switchingly
connected to the vehicle's fuse box by said selective
connector.
21. The system as defined in claim 16 wherein said selective
connector connects some of the conductors of said first electrical
connector to some of the conductors of said vehicle's electrical
system, and the conductors of said first electrical connector
connected to the conductors of said vehicle's electrical system can
be changed by said selective connector to program said system for
different selected accessory modules.
22. A vehicle accessory system comprising:
a base mounted to a vehicle, said base including means for
receiving an accessory module, said means for receiving including a
first electrical connecting means for coupling to said accessory
module and means for coupling said first electrical connecting
means to said vehicle's electrical system;
at least one accessory module adapted to be inserted into said
means for receiving and adapted to be coupled to said first
electrical connecting means; and
a programming means including first terminals coupled to the first
electrical connecting means and second terminals coupled to said
vehicle's electrical system, said programming means programming a
connection between said first and second terminals by selectively
interconnecting different ones of said first and second terminals
whereby different ones of said first and second terminals can be
interconnected when different respective accessory modules are
received in said base.
23. The accessory system as defined in claim 22 wherein said
programming means includes a socket including said terminals and a
respective plug for each of said different respective accessory
modules, whereby a respective plug is inserted into said socket to
connect a respective said accessory module to said vehicle's
electrical system.
24. The accessory system as defined in claim 23 wherein said
programming means can connect at least one of said first terminals
to different ones of said second terminals for coupling said
different accessory modules to different vehicle electrical
circuits.
25. The system as defined in claim 22 wherein said means for
coupling said first electrical connector to the vehicle's
electrical system includes a ribbon-like substrate of insulating
material including a plurality of spaced generally parallel
conductors mounted therein, said substrate mounted to extend across
a module receiving recess in the vehicle, and wherein said base
module is shaped to be mounted in said recess and includes contract
means for engaging at least predetermined ones of said spaced
conductors.
26. The system as defined in claim 25 wherein said substrate
includes elongated grooves for receiving inlaid conductors and
wherein said contact means comprises spring contacts which extend
into said grooves to contact said conductors.
27. The system as defined in claim 25 wherein said substrate
includes a plurality of openings for exposing sections of said
conductors and wherein said contact means comprises spring clips
aligned with said openings to engage said conductors when said
module is mounted within said recess.
Description
BACKGROUND OF THE INVENTION
The present invention pertains to an electronic modular display and
control system for use in a vehicle and particularly one which
allows installation of several optional modular units for different
control and display functions.
In recent years, vehicles such as automobiles, have begun using
display systems located in areas different than the typical
dashboard area. One such installation is a console mounted in the
center roof area between the vehicle visors and which includes both
an electronic compass and a garage door opening transmitter
housing. Such a system is shown in U.S. Pat. No. 4,505,054 issued
Mar. 19, 1985 to the present assignee. This unit can be purchased
by the vehicle owner as an optional accessory or comes as standard
equipment on some vehicles.
Although vehicles have included these types of displays as well as
other overhead counsel displays for providing for example, a
systems check for a variety of control functions and engine
operating parameters; systems today have not allowed either the
user or the vehicle dealer to provide optional accessories after
the purchase of the vehicle without major installation
requirements.
SUMMARY OF THE PRESENT INVENTION
The system of the present invention provides a modular
interchangeable electronic system for providing a number of
different options which can be plugged into a base unit to provide
selected options for the vehicle purchaser either at the time of
purchase of later. Systems embodying the present invention include
a base unit which is mounted to a socket which is standard on all
vehicles. The base unit can receive or be replaced by selected
optional units which interface with vehicle controls or provide
desired display functions. Each unit includes means for programming
the unit for interfacing with the vehicle once installed.
With such a system, vehicles can be made with a base level overhead
module which can be upgraded with selected options and which
options can be selectively changed subsequent to the purchase of
the vehicle by plugging in different modules.
These and other features, objects and advantages of the present
invention will become apparent upon reading the following
description thereof together with reference to the accompanying
drawings, in which:
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a fragmentary perspective view partly exploded of a
vehicle including a socket with an elementary plug-in module;
FIG. 2 is a block diagram illustrating a variety of optional
plug-in modules which can be used with the system shown in FIG.
1;
FIG. 3 is a fragmentary perspective view of a vehicle showing a
systems check module with a courtesy lamp option installed
therein;
FIG. 4 is a fragmentary perspective view of a vehicle showing a
compass module and courtesy lamp option installed therein;
FIG. 5 is a top perspective view of the base housing shown in FIG.
2 and 3;
FIG. 6 is a fragmentary perspective view of a programming jumper
system for connecting the vehicle wiring system to the selective
module;
FIG. 7 is an electrical circuit diagram partially in block and
schematic form showing the wiring of the system of the present
invention;
FIG. 8 is a perspective exploded view of an alternate mounting
system for the modules of the present invention;
FIG. 9 is a fragmentary cross-sectional view taken along section
lines IX--IX of FIG. 8;
FIG. 10 is an exploded fragmentary view of an other alternate
mounting system for the modules of the present invention; and
FIG. 11 is a fragmentary cross-sectional view of the structure
shown in FIG. 10 taken along section lines XI--XI of FIG. 10;
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
Referring initially to FIG. 1, there is shown a vehicle 10 having a
roof 12 and windshield 14 to which a rearview mirror 16 is attached
in a conventional manner. Attached to the vehicle roof are a pair
of visors 11 and 13 on either side of the center area of the roof
which includes a recess 18 including a socket 22 for receiving a
variety of plug-in modules such as a base module 20 shown. Recess
18 accordingly includes both mechanical and electrical
interconnection means with the system illustrated in FIG. 1
including a plug-in electrical socket 22, a pair of guide apertures
24 and 26, and a mechanical latch 28 which mates with
correspondingly shaped and configured electrical and mechanical
connectors included in the base unit 20. Thus unit 20 will include
an electrical plug 27 (FIG. 5) which is aligned with and mates with
the electrical socket 22, a pair of posts (not shown) which
mechanically align and interfit within circular apertures 24 and 26
in the roof structure and a resilient or moveable latch member
which interlocks with latch 28 for snap fitting module 20 within
recess 18. A few of the various different modules which can either
be incorporated in the base unit or plugged into the base unit
which in turn is plugged into socket 22 are shown pictorially in
FIG. 2.
In FIG. 2, the base unit 20 may include a simple dome lamp 21 as
seen in FIG. 1 or individually operated courtesy lamps 23 as seen
in the FIGS. 3, 4 and 5 embodiments of the invention. In addition,
the base unit 20 may include a base module housing 21 (FIGS. 4 and
5) with an opening 25 for receiving plug-in modules such as a
systems check module 34 (FIG. 3), a compass module 30 (FIG. 4), a
garage door opening module 32, a door-lock control module 36, or a
2-wheel/4-wheel drive control and display module 38. It is
understood that each of these modules of the embodiment shown in
FIG. 2-7 plug into the base unit housing 21 which in turn plugs
into the recess 18 and electrically plugs into socket 22 as seen in
FIG. 1.
In order to provide a universal interface between the selected
optional module and the vehicle power supply, vehicle device being
controlled, or parameter being displayed; program means is provided
which in the preferred embodiment is a typical automotive fuse box
50 which is modified to be programmable by insertion of a selected
plug-in program module 56 as shown in FIG. 6. The fuse box 50
includes a multiple pin electrical socket 52 mounted therein which
is connected by a multiple conductor cable 54, as shown in greater
detail in FIG. 7, to various vehicle supply and control units as
well as to electrical socket 22 of recess 18 in the vehicle roof
12. The various pins of socket 52 in fuse box 50 are shown in
detail in FIG. 7 and receive a predetermined programming plug-in
programming member 56 which includes a corresponding number of pins
which mate with socket 52 and which are interconnected to connect
predetermined ones of the socket connections to each other as
described in greater detail in connection with FIG. 7.
Referring now to FIG. 7, cable 54 includes 10 conductors numbered 1
through 10 which extend to and are coupled to a variety of vehicles
supply and control circuits such as circuits 60, 80, 82, 84, 86 and
88. Cable 54 also includes, within the outer sheath thereof, output
conductors 40, 41, 42, 43 and 44 which are selectively programmably
coupled to ones of the input conductors 1-10 through the
programming module 56. Module 56 in the preferred embodiment
therefore essentially comprises a selective shorting bar which
plugs into socket 52 for coupling conductors of cable 54
together.
As an example, with respect to the FIG. 4 embodiment utilizing the
compass module 30, the aligned top three pins 91, 93 and 95 are
shorted to pins 92, 94 and 96 respectively of program module 56 by
conductors 97, 98 and 99. When module 56 is plugged into fuse box
50, the ignition conductor 1, the courtesy power conductor 2, and
the battery power conductor 3 from a part of the vehicle's fuse box
50 show schematically as block 60 in FIG. 7 are thus coupled to
conductors 40, 41 and 42 of cable 54 which in turns are coupled to
pins 2, 3 and 4 on socket 70 contained within a base unit 20. The
compass module 30 which plugs into the base unit housing 21
includes a corresponding plug 72 corresponding to socket 70 such
that when interconnected with the corresponding pin numbers
indicated in FIG. 6, the pins 2, 3 and 4 will be coupled to
conductors 40, 41 and 42 in turn coupled to conductors 1-3 of cable
54 through programmed connector 56 identified as the compass
connector. Module 56 also has pin 101 electrically coupled to pin
103 by conductor 102 to couple conductor 8 of cable 54 to conductor
43 and thus provide a dimming control signal to the compass module
through interconnected pins plug 72 and socket 70.
Other modules such as the systems check module 34 illustrated in
FIG. 3 will have different programmed connectors 56 programmed to
similarly connect the conductors of cable 54 to one another for
supplying either power to or signals to and from their respective
module and associated vehicle control unit. The vehicle units
include a relay board 80 for the power locks, a control relay for
82 controlling the 2-wheel/4-wheel drive unit, a dimmer circuit
control 84, a trunk unlocking relay control board 86 and a
regulated 12 volt control circuit 88.
The base module 20 as seen in FIGS. 1, 5 and 7 may include a pair
of courtesy lamps 110 and 112 (FIG. 7) controlled by a first or
second electrical control circuit such as a simplified circuit 114
used for activating the FIG. 1 embodiment lights or a more
sophisticated control circuit 116 shown in the embodiments of FIGS.
5 and 7 whereby independent map lamps are provided with slow on and
off capability. Typically the base unit will include one or the
other of circuits 114 and 116 and more typically circuit 116 with
the ability to receive the optional modules such as modules 30, 32,
34, 36 or 38 each of which includes a plug which correspondingly
aligns with and electrically couples the individual module to
socket 70 in the base unit 20 within housing 21 thereof. Each of
the modules are thus shaped as seen in FIGS. 3 and 4 to fit within
the generally rectangular aperture 25 of the base unit housing 21
which housing can be attached to the vehicle headliner in a variety
of manners including a rear snap fitting latch 31 and snap fitting
front tabs 33 and 35 as seen in FIG. 5 which mate with
corresponding brackets mounted within recess 18 as an alternative
to the structure shown in FIG. 1. There are also a variety of
manners in which the base units can be coupled to conductors 40-44
and two examples of such interconnections are shown in the
remaining FIGS. 8-11 now described. It is understood that the
ground conductor connection for the various modules is typically
made through connection to the sheet metal structure of the vehicle
and is not separately described.
Referring initially to FIGS. 9 and 10, the base module 20 shown
therein may include for example a dome light 115 of the type
controlled by a circuit 114 associated with the base unit and a
housing 21 which includes a longitudinally recessed track 120
having a plurality of curved spaced aligned contacts 121, 122, 123
and 124 extending outwardly from the upper surface of recess 120.
Contacts 121-124 can be made of beryllium copper or other
spring-like conductive material and are coupled to the courtesy
lamps 110 and 112 contained within dome light 115 or pins of a
connector 70 contained within a base module if the module is
designed for receiving a plurality of display and control modules
such as 30, 32, 34, 36 or 38. Housing 21 shown in FIG. 8 includes
latch means 130 and 132 shown schematically in FIG. 8 for snap
locking the base unit 20 within a recess 134 in the vehicle roof
12. Extending longitudinally across recess 134 is a ribbon-like
connector 140 made of a generally rectangular (in cross-section)
piece of flexible polymeric non-conductive material 142 (FIG. 9)
having longitudinally extending slots 141, 143, 145 and 147 formed
therein into which there is inlaid elongated electrical contact
strips 144, 146, 148 and 150. Strips 144, 146, 148 and 150 engage
as illustrated in FIG. 9 when base unit 20 is snapped into position
within recess 134, the spaced electrical contacts 121, 122, 123 and
124 for transferring power to or signals to and from the vehicle
control to which the contacts strips 144, 146, 148 and 150 are
coupled and the base unit 20. In FIGS. 8 and 9 only four contacts
and contact strips are shown it being understood that the unit may
include as many as necessary for intercoupling the base unit to the
socket defined by recess 134 and connector strip 140. Strip 140 may
extend from the front windshield area of the vehicle to the back
window for also applying power to rear seat accessories such as
overhead drop down vanity mirrors, and rear window brake
lights.
An alternate method of coupling the housing 21 of base unit 20 is
shown in FIGS. 10 and 11 in which the housing 21 includes a
plurality of electrical spring clips 160, 162, 164 and 166 which
are spaced in staggered relationship along the longitudinal axis of
the recess 120 formed in base housing 21. The clips snap fit over
conductors 170, 172, 174 and 176. Which are embedded in a polymeric
base 180 which is cut away in rectangular areas aligned with
connector clips 160, 162, 164 and 166 as illustrated by recesses
179, 182, 184 and 186. The spring clips thus fit within the base
180 and electrically and mechanically engage the conductors when
housing 21 is snapped fitted within recess 1 34 in the headliner
12. Again as with conductor strip 140, connector 179 may include a
greater number of conductors extending in parallel relationship and
aligned with a greater number of contact clips associated with base
housing 21.
These and other modifications to the preferred embodiments of the
invention as described herein can be made by those skilled in the
art without departing from the spirit or scope of the invention as
defined by the appended claims.
* * * * *
| https://uspto.report/patent/grant/5040990 |
Sulfur Vacancy Engineering of MoS2 via Phosphorus Incorporation for Improved Electrocatalytic N2 Reduction to NH3 | Request PDF
Request PDF | Sulfur Vacancy Engineering of MoS2 via Phosphorus Incorporation for Improved Electrocatalytic N2 Reduction to NH3 | Electrocatalytic N2 reduction reaction (NRR) serves as a promising approach for converting N2 to NH3 in a sustainable way to replace the... | Find, read and cite all the research you need on ResearchGate
Sulfur Vacancy Engineering of MoS2 via Phosphorus Incorporation for Improved Electrocatalytic N2 Reduction to NH3
September 2021
Applied Catalysis B: Environmental300:120733
DOI: 10.1016/j.apcatb.2021.120733
Authors:
<here is a image f2f62089ad6ff61c-d19572ff1996375a>
Hao Fei
Hao Fei
<here is a image f2f62089ad6ff61c-d19572ff1996375a>
Ting Guo
Ting Guo
<here is a image f2f62089ad6ff61c-d19572ff1996375a>
Yue Xin
<here is a image f2f62089ad6ff61c-d19572ff1996375a>
Liangbing Wang
Liangbing Wang
Abstract
Electrocatalytic N2 reduction reaction (NRR) serves as a promising approach for converting N2 to NH3 in a sustainable way to replace the energy-intensive Haber-Bosch process. MoS2-based electrocatalysts hold great potentials in catalyzing N2 reduction due to their similarity with active MoFe-co in biological nitrogenase. In this work, we reported a sulfur vacancy-rich MoS2 as an excellent electrocatalyst for NRR, where the sulfur vacancies (SVs) were easily controlled by regulating the amount of P dopants. MoS2 with abundant SVs (P-M-1) achieved a large NH3 yield rate of 60.27 µg h⁻¹ mg⁻¹cat. and high Faradaic efficiency of 12.22% towards NRR. Further mechanistic study revealed that P dopants not only created SVs as the active centers but also modulated the electronic structure for the enhanced adsorption and activation of N2 molecules, thus immensely promoting the catalytic performance of NRR.
<here is a image 175d1bd4b7439d95-754927124da715c1>
... was reported
[155]
. Both experimental and theoretical analysis showed that the doping of P not only generates SVs that become a catalytic site for the N 2 adsorption and hydrogenation but also regulates the charge exchange between the catalyst and the adsorbed nitrogen gas molecules, further easing the molecular N 2 adsorption on the catalytic site of the catalyst (Fig. 14d). ...
... (d) Schematic representation of N 2 adsorption, the difference in charge density of P incorporation, and the first hydrogenation step over P-SV-MoS 2 , respectively. Reproduced with permission from
[155]
. Copyright 2022 Elsevier. ...
Recent progress in electrocatalytic nitrogen reduction to ammonia (NRR)
Article
Mar 2023
COORDIN CHEM REV
Zanling Huang
<here is a image 53229a6039e6d909-90bf31dda4ca8e69> Madiha Rafiq
<here is a image 879b9a7668043b1b-c0e2547d6693ecff> Abebe Reda Woldu
<here is a image 0c74a79a4faba3c7-b9567a1298db3355> Liangsheng Hu
Ammonia is an essential raw ingredient for fertilizers, a carbon-free hydrogen carrier, and an alternative fuel. The natural process of producing ammonia cannot meet the rapidly growing global demand. On the other hand, the conventional industrial Haber-Bosch process for ammonia production demands high energy and generates massive greenhouse gases. Recently, the research community has focused on designing environmentally friendly nanocatalysts for the electrocatalytic N 2 reduction reaction (NRR) that involves less energy consumption. However, the NRR is still far from industrial implementation because of the low faradic efficiency and ammonia formation rate. In this comprehensive review, we start with a brief overview of the fundamentals of NRR related to thermodynamic perspectives and discuss the reaction mechanisms for ammonia synthesis. We then critically introduce the research methods for elec-trocatalytic NRR and various nanocatalysts, including transition metals, non-metals, main group elements , and noble-metal-based NRR electrocatalysts. Finally, some outlooks are provided on the research progress of the NRR electrocatalytic nanomaterials, methods and techniques toward ammonia production.
... [10] Therefore, more Mo-based heterogeneous N 2 precatalysts have been proposed. Various strategies have been adopted to further enhance the NRR performance, mainly including single-metal atom coordination [11][12][13], structural manipulation [14][15], defect engineering [16][17], and heteroatom doping [18]
[19]
, etc. ...
MOF-derived Fe2O3/MoSe2 Heterostructure for Promoted Electrocatalytic Nitrogen Fixation
Full-text available
Mar 2023
Liming Huang
Leiming Tao
Kui Pang
Hongbing Ji
Due to the low activity and poor selectivity of current artificial nitrogen fixation catalysts, there is an urgent need to develop efficient and environmentally friendly Electrochemical ammonia synthesis (EAS) electrocatalysts. Electrochemical ammonia synthesis is considered an environmentally friendly and sustainable method for artificial nitrogen fixation. Herein, Fe 2 O 3 nanoparticles assembled on MoSe 2 (Fe 2 O 3 /MoSe 2 ) were first developed and regarded as an efficient electrocatalytic nitrogen fixation catalyst with high electroactive. The Fe 2 O 3 /MoSe 2 composites exhibited excellent NRR activity with an NH 3 yield of 55.52 µg∙h − 1 ∙mg − 1 at -0.5 V and Faradaic efficiency of 9.6% at -0.6 V vs . RHE. Notably, the Fe 2 O 3 /MoSe 2 composites exhibited excellent stability and durability in recycling tests. Density functional theory (DFT) calculations revealed that the interfacial charge transport from Fe 2 O 3 to MoSe 2 could significantly enhance the Electrochemical nitrogen reduction reaction (NRR) activity of Fe 2 O 3 /MoSe 2 by promoting the conductivity of Fe 2 O 3 /MoSe 2 and reducing the free energy barrier for the rate-determining of *N 2 to *N 2 H formation step. This work provides a promising avenue for the green synthesis of NH 3 .
... redox and phase change) should be clarified. And innovative strategies can be combined to simultaneously enhance the intrinsic HER activity, boost the electronic conductivity, and increase the number of active sites [175,
176]
. Fabricating high-entropy compositions and introducing single atoms may be promising strategies to further modulate MoS 2 and improve the performance. Well-designed configurations, such as the core-shell structure, may be helpful to protect MoS 2 from the influences of impure ions from the electrolytes. ...
Extending MoS2-based materials into the catalysis of non-acidic hydrogen evolution: challenges, progress, and perspectives
Full-text available
Mar 2023
Hao Fei
Ruoqi Liu
Yunze Zhang
<here is a image e7a31e71197eef22-e7df74967756044d> Jian Wang
Water splitting is regarded among the most prospective methods of generating green hydrogen. Switching electrolytes of water electrolysis from acidic to non-acidic ones will enable the use of noble-metal-free electrocatalysts and mitigate material corrosion, thus lowering the capital cost of water electrolyzers and improving their operational stability. However, increasing electrolyte pH will degrade the hydrogen evolution reaction (HER) activity because of the reduced concentration of H3O+ as reactants, making non-acidic HER sluggish. To accelerate HER, MoS2-based materials with the advantages of unique atomistic structure, low cost, and high abundance, have been considered prospective electrocatalysts to substitute for Pt in acid. Great efforts are being spent on extending MoS2-based materials into the catalysis of non-acidic HER, and their further development requires clarification of the existing challenges and current progress. However, it has not been systematically discussed yet for non-acidic HER on MoS2-based electrocatalysts. To mitigate the disparity, we systematically overview MoS2-based electrocatalysts for non-acidic HER, covering catalytic mechanisms, modulation strategies, materials development, current challenges, research progress, and perspectives. This review will contribute to the rational design of MoS2-based materials for high-performance HER in non-acidic conditions.
... To enhance the catalytic performance, researchers studied the synthesis of defect-rich MoS2, in which a sulfur vacancy that created the edge sites plays an important role [16][17][18]. Indeed, at the sulfur vacancy sites, the surrounding under-coordinated Mo atoms introduce gap states that facilitate N2 absorption or hydrogen bonding, which improves the performance of the nitrogen reduction reaction (NRR)
[19]
, hydrogen evolution reaction (HER) [20,21], as well as sensing [22][23][24]. ...
Enhanced NH3 Sensing Performance of Mo Cluster-MoS2 Nanocomposite Thin Films via the Sulfurization of Mo6 Cluster Iodides Precursor
The high-performance defect-rich MoS2 dominated by sulfur vacancies as well as Mo-rich environments have been extensively studied in many fields, such as nitrogen reduction reactions, hydrogen evolution reactions, as well as sensing devices for NH3, which are attributed to the under-coordinated Mo atoms playing a significant role as catalytic sites in the defect area. In this study, the Mo cluster-MoS2 composite was creatively synthesized through a one-step sulfurization process via H2/H2S gas flow. The Mo6 cluster iodides (MIs) coated on the fluorine-doped tin oxide (FTO) glass substrate via the electrophoretic deposition method (i.e., MI@FTO) were used as a precursor to form a thin-film nanocomposite. Investigations into the structure, reaction mechanism, and NH3 gas sensing performance were carried out in detail. The results indicated that during the gas flowing, the decomposed Mo6 cluster iodides played the role of template and precursor, forming complicated Mo cluster compounds and eventually producing MoS2. These Mo cluster-MoS2 thin-film nanocomposites were fabricated and applied as gas sensors for the first time. It turns out that after the sulfurization process, the response of MI@FTO for NH3 gas increased three times while showing conversion from p-type to n-type semiconductor, which enhances their possibilities for future device applications.
... Oxygen, nitrogen and sulphur vacancy are the most common type of defects observed in metal oxides, nitrides and sulphides, respectively [114]
[115]
[116]. The vacancy defects are principally improving the charge trapping center and hence improves the efficiency of photocatalysts by providing active sites as reaction center [117,118]. ...
Visible light active titanate perovskites: An overview on its synthesis, characterization and photocatalytic applications
The two-dimensional (2D) graphitic carbon nitride skeleton offers rich hollow sites for stably anchoring transition-metal (TM) atoms to promote single-atom catalysis, which is expected to overcome the great challenges of low activity and selectivity for ammonia synthesis resulting from the sluggish activation of inert N2 and the competitive hydrogen evolution reaction (HER). Very recently, a novel holey graphitic carbon nitride monolayer with the C7N3 stoichiometric ratio (g-C7N3) was proposed, whose Dirac dispersion located at the Fermi level rightly provides excellent electric conductivity for achieving the high-performance nitrogen reduction reaction (NRR). Herein, first-principles calculations within the density-functional theory were performed to examine the feasibility of a single TM-atom (from Sc to Au) supported on g-C7N3 as π-d conjugated single-atom catalysts (SACs) for NRR. Through a “Five-step Procedure” screening strategy, Hf, Ta, W and [email protected]7N3 were highlighted from 27 [email protected]7N3 as the best SACs for NRR with low limiting potentials of −0.06 to −0.46 V. Particularly, the two systems, [email protected]7N3 and [email protected]7N3, possess well-HER-suppressed ability due to smaller NRR-kinetic barriers as compared with those of HER and, impressively, together with their rather low limiting potentials of −0.27/−0.27 and −0.22/−0.06 V under end-on/side-on pattern, respectively, they may exceed most NRR catalysts reported previously. Moreover, multiple-level descriptors have been developed to uncover the origins of NRR activity, among which a 3D volcano plot (screening strategies, limiting potentials, and electronic origins) shows the activity trends of NRR, achieving a fast prescreening among various candidates. This work not only accelerates the discovery of catalysts for nitrogen fixation but also contributes to broadening the understanding of single-atom catalysis.
| https://www.researchgate.net/publication/354701490_Sulfur_Vacancy_Engineering_of_MoS2_via_Phosphorus_Incorporation_for_Improved_Electrocatalytic_N2_Reduction_to_NH3 |
Campbell ex rel. Herself & Similarly Situated Equity Units Holders of Am. Int'l Grp., Inc. v. Am. Int'l Grp., Inc., No. 13–7041. - Federal Cases - Case Law - VLEX 892851245
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Campbell ex rel. Herself & Similarly Situated Equity Units Holders of Am. Int'l Grp., Inc. v. Am. Int'l Grp., Inc., No. 13–7041.
Court United States Courts of Appeals. United States Court of Appeals (District of Columbia) Writing for the Court Opinion for the Court filed PER CURIAM. Citation 760 F.3d 62 Parties Kathryn Lynn CAMPBELL, on behalf of herself and similarly situated Equity Units Holders of American International Group, Inc., Appellant v. AMERICAN INTERNATIONAL GROUP, INC., et al., Appellees. Docket Number No. 13–7041. Decision Date 10 September 2014
760 F.3d 62
Kathryn Lynn CAMPBELL, on behalf of herself and similarly situated Equity Units Holders of American International Group, Inc., Appellant v. AMERICAN INTERNATIONAL GROUP, INC., et al., Appellees.
No. 13–7041.
United States Court of Appeals, District of Columbia Circuit.
Aug. 1, 2014. Rehearing En Banc Denied Sept. 10, 2014.
Appeal from the United States District Court for the District of Columbia (No. 1:12–cv–00115). Wendu Mekbib was on the briefs for appellant.
[760 F.3d 63]
Before: GARLAND, Chief Judge, and SRINIVASAN and PILLARD, Circuit Judges. Opinion for the Court filed PER CURIAM.PER CURIAM:
Kathryn Lynn Campbell contends that the American International Group, Inc. (AIG) and its board of directors wrongfully reduced the value of certain securities issued by AIG. The district court dismissed Campbell's securities class action for lack of subject matter jurisdiction, holding that the Securities Litigation Uniform Standards Act of 1998 (SLUSA) does not confer federal jurisdiction over Campbell's state-law claims.We agree. *
I.
In 2008, AIG issued 78.4 million “Equity Units,” a type of security that included a stock purchase contract obligating holders to purchase AIG common stock. AIG, Annual Report (Form 10–K) (Fiscal Year 2008). According to Campbell, an Equity Unit holder, AIG and its directors depleted the investment value of the Equity Units by improperly reducing the number of common shares each Equity Unit holder was entitled to receive. Campbell filed a securities class action in federal district court on behalf of herself and similarly situated investors. Her complaint stated claims for unjust enrichment and breaches of the covenant of good faith and fair dealing under both Delaware and New York law. Although she alleged violations of state law, Campbell did not invoke the district court's diversity jurisdiction. Instead, she asserted subject matter jurisdiction principally under SLUSA, codified in relevant part at 15 U.S.C. §§ 77p(d) and 78bb(f) (3). SeeSLUSA, Pub.L. No. 105–353, 112 Stat. 3227 (1998) (codified as amended at scattered sections of 15 U.S.C.).
AIG moved to dismiss for lack of federal jurisdiction over Campbell's state law claims. The district court granted the motion. Campbell v. AIG, 926 F.Supp.2d 178 (D.D.C.2013). We review the dismissal for lack of subject matter jurisdiction de novo, Nat'l Air Traffic Controllers Ass'n v. Fed.Serv. Impasses Panel, 606 F.3d 780 , 786 (D.C.Cir.2010), and we now affirm.
II.
Campbell's principal contention, below and on appeal, is that SLUSA confers federal jurisdiction over her class action. Congress enacted SLUSA in 1998, closely on the heels of the Private Securities Litigation Reform Act of 1995 (the Reform Act), Pub.L. No. 104–67, 109 Stat. 737 (codified as amended at scattered sections of 15 U.S.C.). See Merrill Lynch, Pierce, Fenner & Smith Inc. v. Dabit, 547 U.S. 71 , 82, 126 S.Ct. 1503 , 164 L.Ed.2d 179 (2006). The Reform Act aimed to curb “perceived abuses of the class-action vehicle in litigation involving nationally traded securities” by imposing a number of limitations on federal securities class actions. Id.at 81,126 S.Ct. 1503. To avoid the “special burdens” associated with federal securities fraud class actions established by the Reform Act, plaintiffs “began bringing class actions under state law, often in state court.” Id.at 82,126 S.Ct. 1503(emphasis added). Congress then enacted SLUSA to stem the migration from federal to state court and “to prevent certain State private securities class action lawsuits alleging fraud from being used to frustrate the objectives”of the Reform Act. 112 Stat. at 3227.
[760 F.3d 64]
SLUSA amends the Securities Act of 1933 and the Securities Exchange Act of 1934 “in substantially identical ways.” Dabit, 547 U.S. at 82 n. 6, 126 S.Ct. 1503 ; compare 15 U.S.C. § 77p (codifying amendments to the 1933 Act), with 15 U.S.C. § 78bb(a) (2), (f) (codifying amendments to the 1934 Act). To simplify the analysis, we, like the district court, focus our discussion on the amendments to the Securities Act of 1933. See Kircher v. Putnam Funds Trust, 547 U.S. 633 , 637 n. 3, 126 S.Ct. 2145 , 165 L.Ed.2d 92 (2006); Dabit, 547 U.S. at 82 n. 6, 126 S.Ct. 1503 . Those amendments begin by clarifying that, “[e]xcept as provided in subsection (b), the rights and remedies provided by this title shall be in addition to any and all other rights and remedies that may exist at law or in equity.”112 Stat. at 3227–28 (codified at 15 U.S.C. § 77p(a) ). As a general matter, then, SLUSA leaves state-law claims in place except as set forth in subsection (b).
Subsection (b) is SLUSA's “core provision.” Dabit, 547 U.S. at 82, 126 S.Ct. 1503 . Referred to as the “preclusion provision,” Kircher, 547 U.S. at 636, 126 S.Ct. 2145 , subsection (b) bars the bringing of certain state-law securities fraud claims as class actions, in either state or federal court.It provides:
No covered class action based upon the statutory or common law of any State or subdivision thereof may be maintained in any State or Federal court by any private party alleging—
(1) an untrue statement or omission of a material fact in connection with the purchase or sale of a covered security; or
(2) that the defendant used or employed any manipulative or deceptive device or contrivance in connection with the purchase or sale of a covered security.
112 Stat. at 3228 (codified at 15 U.S.C. § 77p(b) ). A “covered class action” refers to a lawsuit seeking damages on behalf of more than fifty persons. See 15 U.S.C. § 77p(f) (2). A “covered security” refers to a nationally traded security listed on a national exchange. See 15 U.S.C. §§ 77p(f) (3), 77r(b).
The next provision, subsection (c), “ensur[es] that federal courts will have the opportunity to determine whether a state action is precluded.” Madden v. Cowen & Co., 576 F.3d 957 , 965 (9th Cir.2009). It authorizes defendants to remove to federal district court “[a]ny...
8 cases
North v. Smarsh, Inc., Civil Action No. 15-494 (RMC) United States United States District Courts. United States District Court (Columbia) December 4, 2015 ...no supplemental jurisdiction under 28 U.S.C. § 1367. See Campbell v. American Int'l Grp. Inc. , 926 F.Supp.2d 178, 182 (D.D.C.2013), aff'd 760 F.3d 62 (D.C.Cir.2014).2. Diversity Jurisdiction Smarsh contends that Plaintiffs' claims must be dismissed because the Complaint failed to establish......
Campbell ex rel. Equity Units Holders of Am. Int'l Grp. Inc. v. Am. Int'l Grp. Inc., 1:14CV1320 LMB/IDD. United States United States District Courts. 4th Circuit. United States District Court (Eastern District of Virginia) January 20, 2015 ...Inc., 926 F.Supp.2d 178 (D.D.C.2013). Campbell appealed, and the D.C. Circuit affirmed the dismissal. Campbell v. Am. Intern. Grp., Inc., 760 F.3d 62 (D.C.Cir.2014), reh'g en banc denied (Sept. 10, 2014).II. DISCUSSIONCampbell filed the instant complaint less than one month after the D.C. C......
Cyan, Inc. v. Beaver Cnty. Emps. Ret. Fund, 15–1439. United States United States Supreme Court March 20, 2018 ...that § 77p(c) allows removal of only class actions falling within § 77p(b)'s prohibition. See Campbell v. American Int'l Group, Inc ., 760 F.3d 62 , 64 (C.A.D.C.2014) ; Hidalgo–Velez v. San Juan Asset Management, 758 F.3d 98, 103 (C.A.1 2014) ; Appert v. Morgan Stanley Dean Witter, Inc ., 67......
Anwar v. Fairfield Greenwich Ltd., 09 Civ. 118(VM). United States United States District Courts. 2nd Circuit. United States District Courts. 2nd Circuit. Southern District of New York July 29, 2015 ...dismissals for lack of subject-matter jurisdiction de novo." (citing Rowinski, 398 F.3d at 298 )); Campbell v. Am. Int'l Grp., Inc., 760 F.3d 62 , 64 (D.C.Cir.2014) ("Removal [under SLUSA] is for a specific purpose: when a case is removed to federal district court under that provision, the c......
| https://case-law.vlex.com/vid/campbell-ex-rel-herself-892851245 |
UNIPROT:Q9H9Z2 - FACTA Search
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434 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The ability to derive neural progenitors, differentiated neurons and glial cells from human embryonic stem cells (hESCs) with high efficiency holds promise for a number of clinical applications. However, investigating the temporal events is crucial for defining the underlying mechanisms that drive this process of differentiation along different lineages. We carried out quantitative proteomic profiling using a multiplexed approach capable of analyzing eight different samples simultaneously to monitor the temporal dynamics of protein abundance as human embryonic stem cells differentiate into motor neurons or astrocytes. With this approach, a catalog of approximately 1200 proteins along with their relative quantitative expression patterns was generated. The differential expression of the large majority of these proteins has not previously been reported or studied in the context of neural differentiation. As expected, two of the widely used markers of pluripotency, alkaline phosphatase
(ALPL) and LIN28 , were found to be downregulated during differentiation, while S-100 and tenascin C were upregulated in astrocytes. Neurofilament 3 protein, doublecortin and CAM kinase-like 1 and nestin proteins were upregulated during motor neuron differentiation. We identified a number of proteins whose expression was largely confined to specific cell types, embryonic stem cells, embryoid bodies and differentiating motor neurons. For example, glycogen phosphorylase (PYGL) and fatty acid binding protein 5 (FABP5) were enriched in ESCs, while beta spectrin (SPTBN5) was highly expressed in embryoid bodies. Karyopherin, heat shock 27 kDa protein 1 and cellular retinoic acid binding protein 2 (CRABP2) were upregulated in differentiating motor neurons but were downregulated in mature motor neurons. We validated some of the novel markers of the differentiation process using immunoblotting and immunocytochemical labeling. To our knowledge, this is the first large-scale temporal proteomic profiling of human stem cell differentiation into neural cell types highlighting proteins with limited or undefined roles in neural fate.
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PMID:Temporal analysis of neural differentiation using quantitative proteomics. 1917 12
Currently worldwide attention has focused on the derivation of human embryonic stem cells (hESCs) for future therapeutic medicine. However, the majority of existing hESCs are directly or indirectly exposed to non-human materials during their derivation and/or propagation, which greatly restrict their therapeutic potential. Besides the efforts to improve culture systems, the derivation procedure, especially blastocyst manipulation, needs to be optimized. We adopted a non-contact laser-assisted hatching system in combination with sequential culture process to obtain hatched blastocysts as materials for hESC derivation, and derived a hESC line ZJUhES-1 of a Chinese population without exposure to any non-human materials during blastocyst manipulation. ZJUhES-1 satisfies the criteria of pluripotent hESCs: typically morphological characteristics; the expression of
alkaline phosphatase
, human telomerase reverse transcriptase and multiple hESC-specific markers including SSEA-3, SSEA-4, TRA-1-60, TRA-1-81, OCT-4, Nanog, Rex-1, Sox-2, UTF-1, Connexins 43 and 45, TERF-1 and TERF-2, Glut-1, BCRP-1/ABCG-2, GDF3, LIN28 , FGF4, Thy-1, Cripto1/TDGF1, AC133 as well as SMAD1/2/3/5; extended proliferative capacity; maintenance of a stable male karyotype after long-term cultivation; and robust multiple-lineage developmental potentials both in vivo and in vitro. Moreover, ZJUhES-1 has distinct identity revealed from DNA fingerprinting. Our xeno-free blastocyst manipulation procedure may promote the progression toward clinical-grade hESC derivation.
...
PMID:Derivation, characterization and differentiation of a new human embryonic stem cell line from a Chinese hatched blastocyst assisted by a non-contact laser system. 2097 34
The aim of this study was to confirm the presence of stem cells in the ovarian surface epithelium of patients with premature ovarian failure and no mature follicles and oocytes. In these patients, small round cells of unknown origin expressing SOX-2 marker of pluripotency were observed among the epithelial cells just after the ovarian surface epithelium scraping. These cells were an integral part of the ovarian surface epithelium. When the scraped cells were cultured in a medium with added follicular fluid to provide some ovarian niche, primitive oocyte-like cells and typical round-shaped cell clusters positively stained on
alkaline phosphatase , and markers of pluripotency, such as SOX-2 and SSEA-4, were developed. These markers were expressed early and also later in the culture. Single oocyte-like cells expressed genes OCT4A, SOX-2, NANOG, NANOS, STELLA, CD9, LIN28 , KLF4, GDF3, and MYC, characteristic for pluripotent stem cells. The results of this study confirmed the presence of putative stem cells in the ovarian surface epithelium of these patients and provided some basis to create a stem cell line in the future.
...
PMID:Ovarian surface epithelium in patients with severe ovarian infertility: a potential source of cells expressing markers of pluripotent/multipotent stem cells. 2218 24
In mice and humans, it has been shown that embryonic and adult fibroblasts can be reprogrammed into pluripotency by introducing 4 transcription factors, Oct3/4, Klf4, Sox2, and c-Myc (OKSM). Here, we report the derivation of induced pluripotent stem cells (iPSCs) from adult canine fibroblasts by retroviral OKSM transduction. The isolated canine iPSCs (ciPSCs) were expanded in 3 different culture media [fibroblast growth factor 2 (FGF2), leukemia inhibitory factor (LIF), or FGF2 plus LIF]. Cells cultured in both FGF2 and LIF expressed pluripotency markers [POU5F1 (OCT4), SOX2, NANOG, and LIN28 ] and embryonic stem cell (ESC)-specific genes (PODXL, DPPA5, FGF5, REX1, and LAMP1) and showed strong levels of alkaline phosphatase
expression. In vitro differentiation by formation of embryoid bodies and by directed differentiation generated cell derivatives of all 3 germ layers as confirmed by mRNA and protein expression. In vivo, the ciPSCs created solid tumors, which failed to reach epithelial structure formation, but expressed markers for all 3 germ layers. Array comparative genomic hybridization and chromosomal fluorescence in situ hybridization analyses revealed that while retroviral transduction per se did not result in significant DNA copy number imbalance, there was evidence for the emergence of low-level aneuploidy during prolonged culture or tumor formation. In summary, we were able to derive ciPSCs from adult fibroblasts by using 4 transcription factors. The isolated iPSCs have similar characteristics to ESCs from other species, but the exact cellular mechanisms behind their unique co-dependency on both FGF2 and LIF are still unknown.
...
PMID:Growth requirements and chromosomal instability of induced pluripotent stem cells generated from adult canine fibroblasts. 2301 47
Regenerative medicine is in need of solid, large animal models as a link between rodents and humans to evaluate the functionality, immunogenicity, and clinical safety of stem cell-derived cell types. The common marmoset (Callithrix jacchus) is an excellent large animal model, genetically close to humans and readily used worldwide in clinical research. Until now, only two groups showed the generation of induced pluripotent stem cells (iPSCs) from the common marmoset using integrating retroviral vectors. Therefore, we reprogrammed bone marrow-derived mesenchymal cells (MSCs) of adult marmosets in the presence of TAV, SB431542, PD0325901, and ascorbic acid via a novel, excisable lentiviral spleen focus-forming virus (SFFV)-driven quad-cistronic vector system (OCT3/4, KLF4, SOX2, C-MYC). Endogenous pluripotency markers like OCT3/4, KLF4, SOX2, C-MYC,
LIN28 , NANOG, and strong alkaline phosphatase
signals were detected. Exogenous genes were silenced and additionally the cassette was removed with a retroviral Gag precursor system. The cell line could be cultured in absence of leukemia inhibitory factor (LIF) and basic fibroblast growth factor (bFGF) and could be successfully differentiated into embryoid bodies and teratomas with presence of all three germ layers. Directed differentiation generated neural progenitors, megakaryocytes, adipocytes, chondrocytes, and osteogenic cells. Thus, all criteria for fully reprogrammed bone marrow-MSCs of a nonhuman primate with a genetically sophisticated construct could be demonstrated. These cells will be a promising tool for future autologous transplantations.
...
PMID:Induced pluripotent stem cells generated from adult bone marrow-derived cells of the nonhuman primate (Callithrix jacchus) using a novel quad-cistronic and excisable lentiviral vector. 2319 52
Primordial germ cells (PGCs) are precursors of gametes and share several features in common with pluripotent stem cells, such as
alkaline phosphatase
activity and the expression of pluripotency-associated genes such as OCT4 and NANOG. PGCs are able to differentiate into oocytes and spermatogonia and establish totipotency after fertilization. However, our knowledge of human germ cell development is still fragmentary. In this study, we have carried out genome-wide comparisons of the transcriptomes and molecular portraits of human male PGCs (mPGCs), female PGCs (fPGCs) and unfertilized oocytes. We detected 9210 genes showing elevated expression in fPGCs, 9184 in mPGCs and 9207 in oocytes, with 6342 of these expressed in common. As well as known germ cell-related genes such as BLIMP1/PRDM1, PIWIL2, VASA/DDX4, DAZL, STELLA/DPPA3 and LIN28 , we also identified 465 novel non-annotated genes with orthologs in the mouse. A plethora of olfactory receptor-encoding genes were detected in all samples, which would suggest their involvement not only in sperm chemotaxis, but also in the development of female germ cells and oocytes. We anticipate that our data might increase our meagre knowledge of the genes and associated signaling pathways operative during germ cell development. This in turn might aid in the development of strategies enabling better differentiation and molecular characterisation of germ cells derived from either embryonic or induced pluripotent stem cells. Ultimately, this would have a profound relevance for reproductive as well as regenerative medicine.
...
PMID:Comparative molecular portraits of human unfertilized oocytes and primordial germ cells at 10 weeks of gestation. 2341 1
Human embryonic stem (hES) cells are considered to be a potential source for the therapy of human diseases, drug screening, and the study of developmental biology. In the present study, we successfully derived hES cell lines from blastocysts developed from frozen and fresh embryos. Seventeen- to eighteen-year-old frozen embryos were thawed, cultured to the blastocyst stage, and induced to form hES cells using human foreskin fibroblasts. The Chula2.hES cell line and the Chula4.hES and Chula5.hES cell lines were derived from blastocysts developed from frozen and fresh embryos, respectively. The cell lines expressed pluripotent markers, including alkaline phosphatase (AP), Oct3/4, stage-specific embryonic antigen (SSEA)-4, and tumor recognition antigen (TRA)-1-60 and TRA-1-81 as detected with immunocytochemistry. The real-time polymerase chain reaction (RT-PCR) results showed that the cell lines expressed pluripotent genes, including OCT3/4, SOX2, NANOG, UTF, LIN28 , REX1, NODAL, and E-Cadherin. In addition, the telomerase activities of the cell lines were higher than in the fibroblast cells. Moreover, the cell lines differentiated into all three germ layers both in vitro and in vivo. The cell lines had distinct identities, as revealed with DNA fingerprinting, and maintained their normal karyotype after a long-term culture. This study is the first to report the successful derivation of hES cell lines in Thailand and that frozen embryos maintained their pluripotency similar to fresh embryos, as shown by the success of hES cell derivation, even after years of cryopreservation. Therefore, embryos from prolonged cryopreservation could be an alternative source for embryonic stem cell research.
...
PMID:Eighteen-year cryopreservation does not negatively affect the pluripotency of human embryos: evidence from embryonic stem cell derivation. 2351 52
Pluripotent stem cells are still generally accepted not to exist in adult human ovaries, although increasing studies confirm the presence of pluripotent/multipotent stem cells in adult mammalian ovaries, including those of humans. The aim of this study is to isolate, characterize and differentiate in vitro stem cells that originate from the adult human ovarian cortex and that express markers of pluripotency/multipotency. After enzymatic degradation of small ovarian cortex biopsies retrieved from 18 women, ovarian cell cultures were successfully established from 17 and the formation of cell colonies was observed. The presence of cells/colonies expressing some markers of pluripotency (
alkaline phosphatase
, surface antigen SSEA-4, OCT4, SOX-2, NANOG, LIN28 , STELLA), germinal lineage (DDX4/VASA) and multipotency (M-CAM/CD146, Thy-1/CD90, STRO-1) was confirmed by various methods. Stem cells from the cultures, including small round SSEA-4-positive cells with diameters of up to 4 μm, showed a relatively high degree of plasticity. We were able to differentiate them in vitro into various types of somatic cells of all three germ layers. However, these cells did not form teratoma when injected into immunodeficient mice. Our results thus show that ovarian tissue is a potential source of stem cells with a pluripotent/multipotent character for safe application in regenerative medicine.
...
PMID:Isolation, characterization and differentiation of cells expressing pluripotent/multipotent markers from adult human ovaries. 2382 Jul 36
Embryonic stem cells (ESCs) are a powerful model for genetic engineering, studying developmental biology, and modeling disease. To date, ESCs have been established from the mouse (Evans and Kaufman, 1981, Nature 292:154-156), non-human primates (Thomson et al., , Proc Nat Acad Sci USA 92:7844-7848), humans (Thomson et al., 1998, Science 282:1145-1147), and rats (Buehr et al., , Cell 135:1287-1298); however, the derivation of ESCs from domesticated ungulates such as goats, sheep, cattle, and pigs have not been successful. Alternatively, induced pluripotent stem cells (iPSCs) can be generated by reprogramming somatic cells with several combinations of genes encoding transcription factors (OCT3/4, SOX2, KLF4, cMYC, LIN28 , and NANOG). To date, iPSCs have been isolated from various species, but only limited information is available regarding goat iPSCs (Ren et al., 2011, Cell Res 21:849-853). The objectives of this study were to generate goat iPSCs from fetal goat primary ear fibroblasts using lentiviral transduction of four human transcription factors: OCT4, SOX2, KLF4, and cMYC. The goat iPSCs were successfully generated by co-culture with mitomycin C-treated mouse embryonic fibroblasts using medium supplemented with knockout serum replacement and human basic fibroblast growth factor. The goat iPSCs colonies are flat, compact, and closely resemble human iPSCs. They have a normal karyotype; stain positive for alkaline phosphatase , OCT4, and NANOG; express endogenous pluripotency genes (OCT4, SOX2, cMYC, and NANOG); and can spontaneously differentiate into three germ layers in vitro and in vivo.
...
PMID:Induced pluripotent stem cells from goat fibroblasts. 2412 1
The generation and application of porcine induced pluripotent stem cells (iPSCs) may enable the testing for safety and efficacy of therapy in the field of human regenerative medicine. Here, the generation of iPSCs from the Massachusetts General Hospital miniature pig (MGH minipig) established for organ transplantation studies is reported. Fibroblasts were isolated from the skin of the ear of a 10-day-old MGH minipig and transduced with a cocktail of six human factors: POU5F1, NANOG, SOX2, C-MYC, KLF4, and LIN28 . Two distinct types of iPSCs were generated that were positive for
alkaline phosphatase
activity, as well as the classical pluripotency markers: Oct4, Nanog, Sox2, and the surface marker Ssea-1. Only one of two porcine iPSC lines differentiated into three germ layers both in vitro and in vivo. Western blot analysis showed that the porcine iPSCs were dependent on LIF or BMP-4 to sustain self-renewal and pluripotency. In conclusion, the results showed that human pluripotent factors could reprogram porcine ear fibroblasts into the pluripotent state. These cells may provide a useful source of cells that could be used for the treatment of degenerative and genetic diseases and agricultural research and application.
...
PMID:Generation of leukemia inhibitory factor-dependent induced pluripotent stem cells from the Massachusetts General Hospital miniature pig. 2437 15
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ROBERTS, RICHARD (1789 - 1864), inventor | Dictionary of Welsh Biography
ROBERTS, RICHARD (1789 - 1864), inventor
Name: Richard Roberts Date of birth: 1789 Date of death: 1864 Child: Elizabeth Roberts Parent: Mary Roberts (née Jones) Parent: Richard Roberts Gender: Male Occupation: inventor Area of activity: Business and Industry; Engineering, Construction, Naval Architecture and Surveying Author: Robert Thomas Jenkins
Born 22 April 1789 at Carreg-hwfa toll-gate-house, Llanymynech, second of the seven children of the gate-keeper (and shoemaker) Richard Roberts and his wife Mary (Jones, of Meifod). In the parish school the curate noted and fostered the mechanical instinct which had led the boy of 10 to construct a spinning-wheel for his mother. After a spell as barge-man on the canal, the lad worked in the Llanymynech limestone quarries; when about 20 he was a pattern-maker in a Bilston iron-works; in 1814, after working at Liverpool and Manchester (to evade enlistment in the militia), he walked to London to work in iron-works at Lambeth; but in 1816 he returned to Manchester and took a small workshop in Deansgate. About 1822-3 he took a partner named Hill (for two of the subsequent years he was at Mulhouse in France), but in 1828 he was in partnership with Thomas Sharpe. Sharpe died in 1842, and Roberts was on his own till 1845; from 1845 till 1851 he was joined by a Fothergill, but the partnership was not successful, and Roberts then set up as a consulting engineer, subsequently (1861) removing to London (Adam Street, Adelphi), where he died 11 March 1864; he was buried in Kensal Green. He was twice married; his daughter, Elizabeth (1835 - 1869), tended him in his last years. He had latterly fallen into adversity; at the time of his death a subscription for him had been set up, and the proceeds were handed over to his daughter, who was also granted a Civil List pension of £200. He was a tall and burly man, curt in speech, pronouncedly Welsh in accent, and possessed of a phenomenal memory.
Roberts was purely and simply an inventor. For one thing, money was for him a secondary matter; he invented instinctively without troubling overmuch whether the invention was commercially practicable - though in fact he took out a patent almost annually for twenty-eight years, be did not bother to patent many of his inventions. In the second place, he never specialized - inventions occurred to his mind wherever he looked. A dictionary is no place for detail in this matter (the authorities cited below describe some of his inventions fairly fully), but it may be mentioned here that he made improvements in textile machinery, steam-engines, railways, ships and ships' gear, lighthouses, clocks, etc. - he even devised a steam motor-car, which however did not run a prosperous course. One authority avers that ' he was one of the greatest mechanical inventors of the [19th] century.' Nor did he hold aloof from the public life of Manchester : he was at ' Peterloo ' in 1819, was one of the founders of the Manchester Mechanics' Institute, was a member of the famous Philosophical and Literary society of the city, and became a member of the Borough Council when Manchester was incorporated in 1838.
Author
Emeritus Professor Robert Thomas Jenkins , (1881 - 1969)
Sources
The fullest account is the paper by H. W. Dickinson, read to the Newcomen Society, 13 November 1946, and printed in its Transactions of the Newcomen Society (1770), xxv (1946-7)
| https://biography.wales/article/s-ROBE-RIC-1789 |
JPM | Free Full-Text | A Personalized Approach to Radical Cystectomy Can Decrease Its Complication Rates
The aim of this study was to assess the influence of a patient’s general status on perioperative morbidity and mortality after radical cystectomy, and to assess which of the used scales is best for the prediction of major complications. The data of 331 patients with muscle-invasive bladder cancer, who underwent radical cystectomy, were analyzed. The general status was assessed according to the American Society of Anesthesiologists (ASA), Charlson Comorbidity Index (CCI), Eastern Cooperative Oncology Group (ECOG), and Geriatric-8 (G-8) scales. Complications were classified according to the Clavien–Dindo classification system. In a group of patients with the highest complication rate according to the Clavien–Dindo scale, (i) statistically more patients rated high according to the ASA and ECOG scales, (ii) patients had significantly higher CCI scores (minor complications (I-II), and (iii) there were significantly more patients rated as frail with G8—predominantly those with 11 points or fewer in the scale. A patient’s general status should be assessed before the start of therapy because patients with a high risk of death or serious complications (evaluated with any rating scale) should be offered conservative treatment. None of the scales can describe the risk of cystectomy, because the percentage of patients with major complications among those who achieved worse score results on any scale was not significantly different from the percentage of patients with major complications in the general group.
A Personalized Approach to Radical Cystectomy Can Decrease Its Complication Rates
Mateusz Kadlubowski 1 ,
Witold Mikolajczak 1 ,
Tomasz Drewa 1,3 and
Kajetan Juszczak 3
Department of General and Oncologic Urology, Nicolaus Copernicus Hospital, 87-100 Torun, Poland
Department of Oncological Urology, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, 31-115 Krakow, Poland
*
Author to whom correspondence should be addressed.
J. Pers. Med. 2022 , 12 (2), 281; https://doi.org/10.3390/jpm12020281
Received: 19 December 2021 / Revised: 7 February 2022 / Accepted: 11 February 2022 / Published: 14 February 2022
(This article belongs to the Special Issue Postoperative Complications and Personalized Medicine )
Abstract
:
The aim of this study was to assess the influence of a patient’s general status on perioperative morbidity and mortality after radical cystectomy, and to assess which of the used scales is best for the prediction of major complications. The data of 331 patients with muscle-invasive bladder cancer, who underwent radical cystectomy, were analyzed. The general status was assessed according to the American Society of Anesthesiologists (ASA), Charlson Comorbidity Index (CCI), Eastern Cooperative Oncology Group (ECOG), and Geriatric-8 (G-8) scales. Complications were classified according to the Clavien–Dindo classification system. In a group of patients with the highest complication rate according to the Clavien–Dindo scale, (i) statistically more patients rated high according to the ASA and ECOG scales, (ii) patients had significantly higher CCI scores (minor complications (I-II), and (iii) there were significantly more patients rated as frail with G8—predominantly those with 11 points or fewer in the scale. A patient’s general status should be assessed before the start of therapy because patients with a high risk of death or serious complications (evaluated with any rating scale) should be offered conservative treatment. None of the scales can describe the risk of cystectomy, because the percentage of patients with major complications among those who achieved worse score results on any scale was not significantly different from the percentage of patients with major complications in the general group.
Keywords:
bladder cancer
;
radical cystectomy
;
complications
;
ASA scale
;
CCI scale
;
ECOG scale
;
G-8
;
Clavien–Dindo scale
1. Introduction
Bladder cancer is the fourth most common cancer in men and the twelfth most common cancer in women [ 1 ]. At presentation, around 30% of cases are muscle-invasive bladder cancer. Radical cystectomy (RC) with neoadjuvant or adjuvant chemotherapy remains the standard treatment in these cases [ 2 ], performed as an open (ORC), laparoscopic (LRC), or robot-assisted surgery (RARC) with ileal conduit (IC), orthotopic neobladder (ON), or simple ureterocutaneostomy (UCS) as the urinary diversion. The mortality rates among patients who undergo operations are estimated at 1.2–32% after 30 days, and 2.3–8.0% after three months in the case of RARC. Early postoperative complications (<90 days after surgery) were reported in 58% of patients, which can be linked to the type of urinary diversion [ 3 ]. However, the risk of major complications of radical cystectomy is greater in older patients due to frequent comorbidities and general frailty, but considerable improvements in perioperative management and the use of minimally invasive procedures offer a favorable risk-benefit profile for elderly adults who were previously disqualified from surgery [ 4 , 5 ].
Until recently, only age and standard clinical assessment were used to guide treatment decisions, but several scoring systems have been developed to recognize patients’ general status before RC. From those, Geriatric-8 (G8), the Eastern Cooperative Oncology Group (ECOG) scale, and the Charlson Comorbidity Index (CCI) are commonly used. To assess the risk of anesthesia prior to surgery, the American Association of Anesthesiology (ASA) scale is usually applied [ 6 , 7 , 8 , 9 ].
Platinum-based chemotherapy, which is commonly used in bladder cancer patients, is effective, but its use is limited by its severe, dose-limiting side effects [ 10 ]. Therefore, the use of those agents is personalized and usually given to younger patients with favorable prognoses [ 10 ].
The personalized approach also depends on the histopathological result of tissue taken during transurethral resection of the tumor before radical treatment. The majority of bladder cancers are classified as pure urothelial carcinoma, and the rest are assessed as other histological variants [
11
], including adenocarcinoma, which usually derives from bladder urachus. Several patterns of this cancer exist, and differentiating urachal and non-urachal subtypes of adenocarcinoma is essential in the personalized approach to the management of this disease because partial cystectomy can be performed in patients with pure urachal adenocarcinoma [
12
]. The same applies to the treatment of patients with other histopathological variants. Bladder SCC is usually treated with palliative chemotherapy based on neuroendocrine-type regimens using a platinum drug (cisplatin in healthy patients) because it is usually found in the advanced stage [
13
].
Besides histology, a personalized approach should also include assessment of general and nutritional status, because low albumin levels can have a negative impact on the risk of perioperative morbidity, and hypoalbuminemia is a recognized risk factor of postoperative complications (e.g., surgical wound healing and/or gastrointestinal complications) and infection [ 14 ]. However, the precise impact of patients’ nutritional status or clinical factors on the complication rates after RC remain unclear [ 15 ].
The patient’s general status should be assessed before surgery, using specially designed scales to adjust the type of treatment to the patient’s fragility status. The most common is the ECOG scale. Another scale is the CCI, which is an independent risk factor for postoperative mortality [ 7 ]. It considers 19 general conditions, and the results are used to calculate the Charlson Probability Index of 10-year mortality risk.
The G8 is a simple eight-item screening scale, which considers seven factors from the Mini Nutritional Assessment tool [ 16 ]. It was developed to identify healthy older adult cancer patients who can receive standard therapy. The G8 may also have predictive value for patient outcomes after radical cystectomy. Even in patients with high scores, and in whom a full geriatric assessment may not yet be indicated, G8 might still predict poor outcomes [ 17 ]. A previous study revealed in multivariable analysis that patients with neoplasmatic disease with a low G8 score had significantly shorter overall survival [ 18 ].
This study aimed to explore the influence of the patient’s general status, measured by four designed scales (ASA, G8, ECOG, and CCI), on perioperative morbidity and mortality related to RC. We also assessed which of the four scales is best in terms of prediction of major complications after RC.
2. Materials and Methods
2.1. Study Design and Patients
This retrospective study included data from 331 consecutive patients from three institutions who underwent RC between 2013 and 2021. Of these, 80 underwent operations by ORC, 61 by LRC, and 190 by RARC. The choice of surgical technique depended on availability in the department and the surgeon’s decision. Indications for RC were in accordance with the guideline of the European Association of Urology (EAU) [
19
]. Neoadjuvant chemotherapy was administered according to the decision of the multidisciplinary team. During RC (which included resection of the prostate in men and the reproductive system in women), the obturator, external, internal, common iliac, and presacral lymph nodes were dissected.
Surgery was performed by four different surgeons, but most laparoscopic and all robot-assisted surgeries were performed by the same operator. All consecutive patients that qualified for surgery in one center were operated by the same method, irrespective of any clinical variables (age, general status, disease stage, etc.).
2.2. Data Collection
All patients underwent a preoperative examination, including routine laboratory tests, a chest radiogram, an abdominal ultrasonography scan, a computed tomography (CT) scan, and/or magnetic resonance imaging (MRI). Oncological variables and results were noted, and neoplasm staging was performed according to the TNM classification system [ 20 ].
Anesthesia risk was assessed and scored according to the ASA physical status classification system. General status was assessed according to the CCI, ECOG, and G8 scales. Complications were classified according to the Clavien–Dindo classification system. Major complications were defined as a Clavien–Dindo score of grades 3–4, and minor as grades 1–2 [ 21 ]. Groups were divided into subgroups according to the method of urinary diversion: ileal conduit, orthotopic neobladder, and simple UCS. Complications were stratified according to urinary deviation.
2.3. Ethical Considerations
Because this study was a retrospective chart review, informed consent was not required. All procedures were performed in accordance with the ethical standards of the Ethics Committee of the Nicolaus Copernicus University (number 439/2013) and with the Declaration of Helsinki (1964) and its later amendments or comparable ethical standards.
2.4. Statistical Analysis
The normality of the data was checked by the Shapiro–Wilk test. The chi-square test was used to identify associations between dichotomous and categorical data. The Kruskal–Wallis test was used to compare the patients’ results among the categories followed by the post hoc Dunn multiple comparisons test. Statistical significance was considered at p < 0.05 for all tests.
3. Results
Women accounted for 20.8% of the study population. The median age was 68.5 (range 17–91) years (Q1–Q3: 62.0–74.0), the mean age 67.82 (SD 9.32).
3.1. Frequency of ASA, ECOG, G8, and CCI
Patients from the study group were scored according to the ASA, ECOG, and G8 scales. The details are presented in Table 1 .
3.2. Ten-Year Survival According to the CCI
It was observed that according to the CCI, 106 patients (32%) had no chance of 10-year survival. In the rest of the group, the chance of 10-year survival was between 2% and 98% ( Figure 1 ).
3.3. Complication Rates in the Study Group and Subgroups According to the Type of Urinary Diversion
In the whole group, the most frequent were Clavien–Dindo grades 1 and 2 (82% of patients), and the grades were dependent on the type of urinary diversion; when more complex urinary derivation is applied, a significantly higher percentage of patients suffer higher grades of complications ( Figure 2 ).
3.4. Evaluation of the Relationship between Preoperative Status and Number of Complications
3.4.1. ASA Scale vs. Clavien–Dindo Scale
The percentage of minor complications was highest in patients with ASA 1 and lowest in those with ASA 4. Death (Clavien–Dindo grade 5) was only noted in patients assessed as ASA 4 and ASA 3 ( Figure 3 ).
3.4.2. ECOG Scale vs. Clavien–Dindo Scale
In the group of patients with the highest complication rate according to the Clavien–Dindo scale, there were statistically more patients rated high according to the ECOG scale ( p = 0.021) ( Figure 4 ).
At the same time, there were no significant differences in subgroups according to the type of urinary diversion ( p > 0.05).
3.4.3. CCI Scale vs. Clavien–Dindo Scale
Patients with the highest complication rate according to the Clavien–Dindo scale had significantly higher CCI scores (H = 9.41, p < 0.01 vs. minor complications (1–2)— p < 0.01 and vs. major complications (3–4) p < 0.05) ( Figure 5 ). In relation to the urinary derivation, the study group was divided according to the CCI level. In the group of patients with Clavien–Dindo 5 complications, there were significantly more patients with higher CCI scores (this applies to patients with UCS p = 0.0134; in the ileal conduit and Studer neobladder group, there were no such complications).
3.4.4. G8 Scale vs. Clavien–Dindo Scale
In the group with Clavien–Dindo grade 5, there were significantly more patients rated as frail with the G8 scale, predominantly those with 11 points or fewer in the scale, whereas in the group of patients with minor and major complications, there were predominantly those with a cut-off level above 14 (H = 17.35, p < 0.01; comparison vs. minor and vs. major p < 0.001) ( Figure 6 ). When divided into groups according to the urinary derivation, the relationship is similar. In the UCS group with Clavien–Dindo grade 5 complications, patients with G8 score of 11 and lower— p < 0.001 dominated (in IC and SN, there were no Clavien–Dindo grade 5 complications).
3.5. Co-Morbidities vs. Complication Rate
The study group was evaluated according to the nourishing status (measured by protein concentration, renal insufficiency, and diabetes in relation to the type of urine derivation, with no significant difference between study groups (respectively, p = 0.233, p = 0.404, and p = 0.165)). The same applies to the subgroups according to the urinary derivation (for USC, IL, and SN, respectively, p = 0.067 p = 0.753, and p = 0.891).
4. Discussion
Radical cystectomy in patients with advanced urothelial carcinoma combined with pre- or postoperative chemotherapy provides good outcomes regarding short-term survival; however, around two-thirds of patients suffer one or more complications within 90 days of surgery [
22
]. A significant group of patients who require aggressive oncological treatment are older adults, who are seen more frequently now than in previous years. Bladder cancer can be considered an age-dependent neoplasm because prolonged exposure to carcinogenic agents for many years makes it more frequent in older age. A personalized approach to the surgical treatment of such patients must be adapted not only to the cancer histology but also to the stage of the disease and the patient’s general status.
The current, classical approach to radical cystectomy, based on histology and imaging studies, can be misleading. During pre-operative staging, tumors classified on a pathological basis as low risk show highly invasive biological behavior, with a high risk of local progression and metastasis. Additionally, from observational studies, it can be seen that some tumors respond strongly to intravesical Bacillus Calmette–Guerin (BCG) therapy, while others with similar pathological grading are BCG refractory. Some tumors respond well to chemotherapy, and some are not chemosensitive. This suggests that urothelial carcinoma cannot be distinguished only on the basis of pathological examination, and outcomes of treatment cannot be predicted with the traditional classification system. The currently used pathological parameters of the tumor cannot fully reflect the true biological characteristics of bladder cancer. Therefore, a personalized approach to treatment according to the new findings of cancer biology and genetics is necessary to improve the outcomes of therapy and to distinguish those patients who require aggressive treatment.
Current findings, based on transcriptional analysis, assign bladder cancer to one of two main molecular types: luminal and basal. With gene expression profiling, six subtypes were distinguished: luminal papillary, luminal non-specified, luminal unstable, stroma-rich, basal/squamous, and neuroendocrine-like [ 23 ].
Luminal cancers arise in the superficial layer of the urothelium, and they show up-regulation of PARγ target genes with enrichment of FGFR3, ELF3, CDKN1A, and TSC1 mutations. However, basal tumors arise in deeper parts of the urothelium and show up-regulation of p63 target genes with enrichment of TP53 and RB1 mutations. It is also interesting that both types exhibit similarities to the basal and luminal subtypes identified in breast cancers. The recognition of those variants with an estimation of expression of only two markers, GATA3 (for luminal subtype) and KRT5/6 (for basal), is important because both types show different clinical outcomes and lead to different therapeutic approaches. Both types show different responses to frontline chemotherapy, with the basal subtype exhibiting more aggressive behavior with shorter survival than luminal cancers, but with much better response to platinum-based chemotherapy [
24
].
Proteins, which are synthesized from mutated genes and are overexpressed in luminal and basal subtypes of molecular subtypes of bladder cancer, may represent attractive therapeutic targets. They include E-Cadherin, HER2/3, Rab-25, and Src in luminal tumors and CD49, Cyclin B1, and FGFR in basal ones. Studies are ongoing on the use of specific agents personalized to the type of mutation present in the tumor cell. FGFRs are a family of receptor tyrosine kinases that are involved in tumor cell differentiation, proliferation, and angiogenesis. They can be upregulated in various tumor cell types, including bladder cancer. Erdafitinib, an oral pan-fibroblast growth factor receptor (FGFR) tyrosine kinase inhibitor, was approved for second-line treatment of patients who progressed following platinum-based chemotherapy. Its use is currently under investigation, and future implementation in bladder cancer treatment will be significant.
Another way to personalize treatment would be to incorporate modern immunotherapy into the clinical setting, possibly combining it with cisplatin chemotherapy. These include atezolizumab (blocking anti-PDL1 antibody) [ 25 ] and atezolizumab in combination with [ 26 ]. However, the most desirable would be a combination of pre-operative immunotherapy (possibly combined with chemotherapy) and its linking with surgery.
New discoveries in the field of molecular bladder cancer subtypes can improve treatment pathways of bladder cancer patients, not only in the advanced urothelial disease, but also in non-muscle invasive disease initially treated with transurethral resections and BCG installations. In the near future, various anti-tumor agents will be added to the treatment (currently, pembrolizumab studies are most promising) [ 27 , 28 , 29 ].
Clinical use of molecular subtyping is under investigation, so the decision about the type of treatment in patients with advanced urothelial carcinoma is currently based on clinical data only. For this purpose, it is necessary to divide patients into risk groups, using the most reliable and safe method possible. For clinical assessment, designated scales have been developed, which divide patients into those with moderate, high, and very high risk of post-operative complications.
Older adults generally have a worse prognosis and a higher postoperative complication rate. Therefore, radical treatment was proposed only to a small group of patients, and for the rest, only palliative treatment was used [ 4 ]. Currently, it is known that radical treatment in older patients can be safe when the type of treatment is personally adjusted to their state. With precise preoperative preparation, meticulous intraoperative hemostasis, a minimally invasive method of surgery (laparoscopic or robot-assisted), and the correct post-operative management, it is possible to significantly reduce surgery complication rates. In our previous study, older age alone did not increase the risk of major postoperative complications, prolonged hospital stays, or blood loss among patients who were subjected to radical cystectomy [ 30 ]. This concurs with other studies [ 31 , 32 , 33 ].
In the current study, we aimed to establish whether the personalized approach based on assessing risk with designed scales can be used, and whether the risk of complications can be determined before surgery. We also aimed to assess which of the four scales is best in terms of predicting major complications after radical cystectomy. It is interesting that the highest number of patients (58%) were screened as ECOG 0–1 and 35.2% as ASA 1–2. Self-reported results of the ECOG scale tended to present patients in better condition than the real situation, as seen by anesthesiologists (with use of the ASA scale). The G-8 is a short report scale, which should be used as a screening tool to identify patients in need of further assessment and appropriate geriatric assessment, with a threshold value of 14. Patients with a total score of 14 or lower are considered frail, and their radical treatment should be reconsidered. Indeed, in the group of patients with major complications, and in those who died, there were significantly more patients rated as frail [
6
]. On the other hand, the reduced complication rates in older patients in more recent studies might be explained by the greater availability of minimally invasive operations and better perioperative management.
In our study, the complication rate depended on the type of urinary derivation, which concurs with reports from other authors. In contrast, the presence of diabetes, renal insufficiency class III or more, and lower levels of albumins did not have a negative prognostic value in terms of the complication rate (in relation to urinary derivation). This proves the importance of good nutritional preparation before surgery as well as controlled diabetes. In our previous studies, we have shown that the type of approach had an impact on complication rates, with a shift towards more frequent, higher-grade complications in the open approach than the minimally invasive ones (laparoscopic and robot assisted) [
34
]. It was also demonstrated that the type of approach (ORC, LRC or RARC) had no impact on oncological safety in terms of positive surgical margins or number of lymph nodes removed. The significance of the PSM ratio was interestingly revealed in an article by Bongiolatti et al. [
35
].
Modern minimally invasive methods of approach (LRC or RARC) reduce the number of minor and hemorrhagic complications [
36
]. However, the type of approach must be adapted to the specific physiological limitations of the patient. Laparoscopic CO
2
retention and hypoventilation with decreased venous return can result in metabolic acidosis. Additionally, the Trendelenburg position with peritoneal gas insufflations increases the intraabdominal pressure and can cause increased intracranial pressure during lower abdominal procedures. Therefore, laparoscopy in elderly adults was contraindicated because of pneumoperitoneum in cardiac and pulmonary physiology. With improved anesthetic and operating techniques, these contraindications are not valid in most cases. Moreover, several studies have confirmed the benefits of laparoscopy in elderly adults, including reduced hospital stays, lower rates of pulmonary complications, and fewer wound-healing problems compared to traditional operative approaches [
37
,
38
].
The use of LRC and RARC also decreases complication rates in terms of surgical site infections [ 39 ].
To conclude, evaluation of the patient’s frailty level and personalized geriatric assessment can lower the risk of complications.
5. Conclusions
It is possible to safely modify the treatment of patients with advanced neoplasmatic disease even when the 10-year survival rate is very low. In our study group, even in older and frail patients, the risk of fatal complications was low, probably due to the use of a minimally invasive surgical approach with short operation time and low blood loss. The patient’s general status should be assessed before the start of therapy because patients with a high risk of death or serious complications (evaluated with any rating scale) should be offered conservative treatment.
In a clinical setting, it seems that none of the scales can ascertain the risk of cystectomy because the percentage of patients with major complications among those who achieved worse score results on any scale is not different from the percentage of patients with major complications in the general group ( Table 2 ).
When more complex urinary derivation is applied, a significantly higher percentage of patients suffer higher grades of complications, so the patient’s general status should be assessed to personalize the type of urinary derivation.
Precise pre-operative preparation of patients results in a significant reduction of complications; well-prepared patients in our study group did not show any differences in complication rates in relation to hypoalbuminemia, uncontrolled diabetes, or renal insufficiency.
Author Contributions
Research conception and design: P.A.; data acquisition: P.P.; statistical analysis: J.A.; data analysis and interpretation: P.A. and C.M.; drafting of the manuscript: P.A.; critical revision of the manuscript: W.M. and K.J.; obtaining funding: P.P.; administrative, technical, or material support: M.K.; supervision: T.D. and C.M.; approval of the final manuscript: P.A. and K.J. All authors have read and agreed to the published version of the manuscript.
Funding
This research received no external funding.
Institutional Review Board Statement
The study was conducted in accordance with the Declaration of Helsinki, and approved by the Ethics Committee of the Nicolaus Copernicus University (number 439/2013).
Informed Consent Statement
Patient consent was waived due to retrospective character of the study.
Data Availability Statement
The data presented in this study are available on request from the corresponding author.
Acknowledgments
Authors would like to thank Karolina Beda-Maluga (Proper Medical Writing) for her support.
Conflicts of Interest
The authors declare no conflict of interest.
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Figure 1. Chance of 10-year survival in the studied group according to the CCI scale. Number of cases: Number of patients with the indicated chance of 10-year survival. Chance expressed as a percentage.
Figure 1. Chance of 10-year survival in the studied group according to the CCI scale. Number of cases: Number of patients with the indicated chance of 10-year survival. Chance expressed as a percentage.
Figure 2. Complications in the study group according to Clavien–Dindo grades (1,2—minor complications, 3,4—major complications) depending on the urinary derivation.
Figure 2. Complications in the study group according to Clavien–Dindo grades (1,2—minor complications, 3,4—major complications) depending on the urinary derivation.
Figure 3. Relationship between ASA-assessed preoperative status and complications (number and percentage of patients).
Figure 3. Relationship between ASA-assessed preoperative status and complications (number and percentage of patients).
Figure 4. Relationship between ECOG-assessed preoperative status and complications (number and percentage of patients).
Figure 4. Relationship between ECOG-assessed preoperative status and complications (number and percentage of patients).
Figure 5. Relationship between CCI-assessed preoperative status and complications (number and percentage of patients).
Figure 5. Relationship between CCI-assessed preoperative status and complications (number and percentage of patients).
Figure 6. Relationship between G8-assessed preoperative status and complications (number and percentage of patients).
Figure 6. Relationship between G8-assessed preoperative status and complications (number and percentage of patients).
Table 1. Percentage of patients scored according to the appropriate scale.
Table 1. Percentage of patients scored according to the appropriate scale.
ASA ECOG G8 CCI Score % of Patients Score % of Patients Score % of Patients Score % of Patients 1 1 0 71 14–17 75 ≥5 63 2 34 1 15 10–13 22 <5 32 3 54 2 3 0–9 3 4 11 3 4 4 2 No Data 5 No Data 5
ASA-American Society of Anesthesiologists scale; CCI-Charlson Comorbidity Index; ECOG-Eastern Cooperative Oncology Group scale; G8-Geriatric-8 scale.
Table 2. Percentage of patients with a worse score according to the appropriate scale with major complications.
Table 2. Percentage of patients with a worse score according to the appropriate scale with major complications.
ASA ≥ 3 ECOG ≥ 3 G8 ≤ 14 CCI ≥ 5 General N % N % N % N % N % Clavien 3–5 37/215 17 4/19 17 26/152 17 42/209 20 55/331 17
MDPI and ACS Style
Adamczyk, P.; Poblocki, P.; Michalik, C.; Kadlubowski, M.; Adamowicz, J.; Mikolajczak, W.; Drewa, T.; Juszczak, K. A Personalized Approach to Radical Cystectomy Can Decrease Its Complication Rates. J. Pers. Med. 2022, 12, 281.
https://doi.org/10.3390/jpm12020281
AMA Style
Adamczyk P, Poblocki P, Michalik C, Kadlubowski M, Adamowicz J, Mikolajczak W, Drewa T, Juszczak K. A Personalized Approach to Radical Cystectomy Can Decrease Its Complication Rates. Journal of Personalized Medicine. 2022; 12(2):281.
https://doi.org/10.3390/jpm12020281
Chicago/Turabian Style
Adamczyk, Przemyslaw, Pawel Poblocki, Cyprian Michalik, Mateusz Kadlubowski, Jan Adamowicz, Witold Mikolajczak, Tomasz Drewa, and Kajetan Juszczak. 2022. "A Personalized Approach to Radical Cystectomy Can Decrease Its Complication Rates" Journal of Personalized Medicine12, no. 2: 281.
https://doi.org/10.3390/jpm12020281
| https://www.mdpi.com/2075-4426/12/2/281 |
Historical Markers and War Memorials in James City County, Virginia
A list of Historical Markers and War Memorials in .
Historical Markers and War Memorials in James City County, Virginia
image/svg+xml
U.S. Census Bureau, Abe.suleiman; Lokal_Profil; HMdb.org; J.J.Prats/dc:title>
https://commons.wikimedia.org/wiki/File:Usa_counties_large.svg
James City County, VA (209) Charles City County, VA (75) Gloucester County, VA (95) Isle of Wight County, VA (51) King and Queen County, VA (27) New Kent County, VA (56) Newport News Ind. City, VA (272) Surry County, VA (36) Williamsburg Ind. City, VA (54) York County, VA (168) James City County (209) James City County (209) Charles City County (75) Charles City County (75) Gloucester County (95) Gloucester County (95) Isle of Wight County (51) Isle of Wight County (51) King and Queen County (27) King and Queen County (27) New Kent County (56) New Kent County (56) Newport News (272) Newport News (272) Surry County (36) Surry County (36) (54) Williamsburg (54) York County (168) York County (168)
Williamsburg is the county seat for James City County
Adjacent to James City County, Virginia
Charles City County
(75)
►
Gloucester County
(95)
►
Isle of Wight County
(51)
►
King and Queen County
(27)
►
New Kent County
(56)
►
Newport News
(272)
►
Surry County
(36)
►
Williamsburg
(54)
►
York County
(168)
►
101 ► Virginia, James City County, Williamsburg — Ace Roller Coaster Landmark — _link_
The American Coaster Enthusiasts recognize Loch Ness Monster as an ACE Roller Coaster Landmark, a designation reserved for rides of historic significance. Acknowledged as the world's first continuous track interlocking loop roller coaster, the . . . — — Map (db m220463) HM
102 ► Virginia, James City County, Williamsburg — An Upper-Class Neighborhood 1630s-1699 — _link_
From the 1630s to the end of the 17th century, this area along Backstreete boasted some of the finest dwellings in Jamestown. Governors, councilmen, burgesses, and lawyers all made this neighborhood home. Richard Kemp, an ardent supporter of . . . — — Map (db m17357) HM
103 ► Virginia, James City County, Williamsburg — Archers Hope — _link_
The great Indian massacre of March 22, 1622, during which a quarter of the population of Virginia was slain came nearest to Jamestown here in a community known as Archer's Hope. At the house of Ensign William Spence five persons were killed-- John . . . — — Map (db m31085) HM
104 ► Virginia, James City County, Williamsburg — At Jamestown Began: — 1607 – 1957 — _link_
At Jamestown began: the Expansion overseas of the English speaking peoples; the Commonwealth of Virginia; the United States of America; the British Commonwealth of Nations — — Map (db m17006) HM
105 ► Virginia, James City County, Williamsburg — Attempted Settlement — _link_
A small group of Spanish Jesuits attempted a settlement in Virginia in September, 1570. They are said to have entered James river and landed along this creek and crossed the peninsula to establish a mission near York River. Six months later all were . . . — — Map (db m30732) HM
106 ► Virginia, James City County, Williamsburg — Backstreet – Jamestown’s Main Street 1620-1699 — _link_
As Jamestown expanded beyond the fort, the Virginia Company sent William Claiborne to survey lots in New Towne. There Ralph Hamor patented an acre and a half lot in 1624. Hamor’s deed made it clear that at least three streets already existed – . . . — — Map (db m17115) HM
107 ► Virginia, James City County, Williamsburg — Bacon's Rebellion — Greensprings Greenway — Interpretive Trail — _link_
In 1676 the colony became embroiled in the popular uprising known as Bacon's Rebellion. Frontier settlers
whose homesteads were attacked by hostile Indians, asked Governor Berkeley's government for protection. Fearful and frustrated by the lack of . . . — — Map (db m99078) HM
108 ► Virginia, James City County, Williamsburg — Barracks — "a homely thing, like a barn" - John Smith — _link_
Like this experimental frame structure before you, most buildings found at James Fort were of earthfast or post-in-ground construction. Main structural posts were seated directly in the ground without the use of footings. Once the building . . . — — Map (db m100109) HM
109 ► Virginia, James City County, Williamsburg — Battle of Green Spring — July 6, 1781 — _link_
Hear the crack of flintlock muskets and smell the smoke from cannon fire! On this site, on July 6, 1781, 5,000 British troops under General Charles Cornwallis and Colonel Banastre Tarleton clashed with 900 American soldiers led by the Marquis de . . . — — Map (db m30651) HM
110 ► Virginia, James City County, Williamsburg — V-39 — Battle Of Green Spring — _link_
Nearby, late in the afternoon of 6 July 1781, Gen. Charles Cornwallis and cavalry commander Col. Banastre Tarleton with 5,000 British and Hessian troops clashed with 800 American troops commanded by Brig. Gen. “Mad” Anthony Wayne and the Marquis de . . . — — Map (db m194748) HM
111 ► Virginia, James City County, Williamsburg — Battle of Green Spring Memorial — _link_
In memory of the 6 Virginia & 22 Pennsylvania Line Patriots who died in The Battle of Green Spring on July 6, 1781 & are buried near here.
By their sacrifices they made possible the establishment of a free United States of America. — — Map (db m99079) WM
112 ► Virginia, James City County, Williamsburg — W-43 — Battle of Williamsburg — Reported permanently removed
To the east of the road here, centering at Fort Magruder, was fought the Battle of Williamsburg on May 5, 1862. The Union General McClellan was pursuing General Johnston’s retiring army, the rearguard of which was commanded by General Longstreet. . . . — — Map (db m130379) HM
113 ► Virginia, James City County, Williamsburg — Captain John Smith — _link_
John Smith was born about 1580 the son of a yeoman farmer of modest means. As a young man he traveled throughout Europe and fought as a soldier in the Netherlands and in Hungary. There he was captured, taken to Turkey and sold into slavery in . . . — — Map (db m11367) HM
114 ► Virginia, James City County, Williamsburg — Captain John Smith — _link_
. . . — — Map (db m11368) HM
115 ► Virginia, James City County, Williamsburg — W-50 — Carter's Grove — _link_
During the 17th century Carter's Grove was part of the Martin's Hundred Plantation. In the early 1720's, Robert "King" Carter purchased it and later named the tract Carter's Grove. Between 1730 and 1735 Carter Burwell, grandson of Robert "King" . . . — — Map (db m9503) HM
116 ► Virginia, James City County, Williamsburg — Church On The Main — History — _link_
The Church on the Main, which lies ahead, was built of brick in about 1750, along the main road connecting Jamestown and Williamsburg. It replaced the fifth church at Jamestown and was used by James City Parish, the community in this vicinity. . . . — — Map (db m99084) HM
117 ► Virginia, James City County, Williamsburg — Church On The Main — Church Plan — _link_
This 30 x60' brick church, marked by the remnants of a builder’s trench, was constructed in a simple rectangular plan with doors on the west and the south. Holes marking the location of scaffolding employed during construction flank the perimeter of . . . — — Map (db m99085) HM
118 ► Virginia, James City County, Williamsburg — Church On The Main — Site Plan — _link_
This archaeological site consists of the remains of the church, the cemetery, and the surrounding fences. All that remains to indicate the location and size of the church below grade is a small remnant of the foundation builder's trench. The 30' x . . . — — Map (db m99086) HM
119 ► Virginia, James City County, Williamsburg — V-46 — Church on the Main — _link_
Less than one mile to the east is the site of the Church on the Main, a brick Anglican church built by the 1750s to serve James City Parish as replacement for the church on Jamestown Island, which had become difficult for communicants to reach. The . . . — — Map (db m194711) HM
120 ► Virginia, James City County, Williamsburg — College Creek — _link_
On May 12, 1607 the colonists who were the next day to establish Jamestown, landed at the mouth of this creek. Captain Gabriel Archer, one of the councilors, liked the spot and would have settled here but was outvoted. For more than a century the . . . — — Map (db m30730) HM
121 ► Virginia, James City County, Williamsburg — Colonial Highway — _link_
The James River was a lifeline. Ships from England brought tools, seeds, cloth, food, more settlers – and hope. The colonists sent back timber, tobacco, pitch, potash, furs, iron ore – and stories. By 1650, wharves reached out to the . . . — — Map (db m17119) HM
122 ► Virginia, James City County, Williamsburg — Colonial Parkway — _link_
In 1930, Congress established Colonial National Monument (designated Colonial National Historical Park in 1936) to preserve and interpret the beginning and end of the British colonial experience in North America. The park included Jamestown, the . . . — — Map (db m89336) HM
123 ► Virginia, James City County, Williamsburg — Colonist on Neck of Land — _link_
Early in the 17th century, colonists began settling beyond Jamestown Island. In 1619, for example, Reverend Richard Buck received a patent of land here at Neck of Land, between Mill and Powhatan creeks.
When Buck and his wife died, their . . . — — Map (db m31058) HM
124 ► Virginia, James City County, Williamsburg — WT-4 — Community of Grove — _link_
After the Civil War, in the area that later became known as the Community of Grove, the Freedmen’s Bureau confiscated land for displaced newly freed slaves and free blacks. In 1867, the government restored the land to its previous owners. Some . . . — — Map (db m66911) HM
125 ► Virginia, James City County, Williamsburg — Confederate Earthworks — _link_
These earthworks were erected by Confederate troops in 1861 as part of the defense system to block Union penetration of the James River. — — Map (db m17052) HM
126 ► Virginia, James City County, Williamsburg — Confederate Soldiers and Sailors Monument — 1861 - 1865 — _link_
(front) 1861-1865
To the
Confederate Soldiers and
Sailors of Williamsburg
and James City County (left) Erected by the United Daughters
of the Confederacy and the
Citizens of Williamsburg and
James City . . . — — Map (db m185422) WM
127 ► Virginia, James City County, Williamsburg — Ditch and Mound — _link_
Dozens of open ditches crisscrossed Jamestown. A ditch and its mound could mark a property boundary, line the edge of a road, or drain swampy soil. Ditches also served as handy trash dumps. Two major ditches, several feet wide and hundreds of feet . . . — — Map (db m17316) HM
128 ► Virginia, James City County, Williamsburg — Eastern State Hospital — Williamsburg, Virginia — 1768 - 1925 — _link_
This hospital is the oldest institution of its kind in America. Francis Fauquier was Governor in 1768. In November, 1769, the tenth year of the reign of George the Third an act was passed by the House of Burgesses confirming the establishment of . . . — — Map (db m66918) HM
129 ► Virginia, James City County, Williamsburg — W 40-b — Eastern State Hospital — _link_
Eastern State Hospital is the oldest psychiatric hospital in the United States. It was established on 12 Oct. 1773, when Virginia was still a British colony, with the mission of treating and discharging the curable mentally ill. In 1841, under the . . . — — Map (db m58354) HM
130 ► Virginia, James City County, Williamsburg — Efforts of a Virginia Tradesman 1670s — _link_
The early English settlers came to Virginia looking for gold, silver, and precious gems, but never found them. Some of the artifacts they left behind, however, are highly valuable to the archaeologists who excavated Jamestown centuries later. . . . — — Map (db m17204) HM
131 ► Virginia, James City County, Williamsburg — Efforts to Build a Town 1660-1699 — _link_
The foundations of the multi-dwelling structure that stood here match the dimensions called for in legislation passed by the General Assembly in September 1662. This row rouse was standing by September 1668 when the justices of James City . . . — — Map (db m17320) HM
132 ► Virginia, James City County, Williamsburg — Engagement at Spencer's Ordinary — June 26, 1781 — _link_
In the summer of 1781, thousands of troops crisscrossed the James City County countryside, foraging for food and strategically moving toward Yorktown. Although neither side knew the other’s strength, Lafayette saw an opportunity to attack. . . . — — Map (db m194749) HM
133 ► Virginia, James City County, Williamsburg — Fences and Livestock — _link_
Jamestown had a large number of four-footed and feathered residents. A chronicler wrote of “two hundred … cattle, as many goats, infinite hogs in herds all over the woods.” The government required fences to keep the free-roaming . . . — — Map (db m17200) HM
134 ► Virginia, James City County, Williamsburg — WT-1 — First Africans in English America — _link_
The first documented Africans in English America arrived at Jamestown in August 1619. A Dutch man-of-war captured them from the Spanish, who had enslaved them, and sold them to the Virginia colonists. The “twenty and odd” Africans, some . . . — — Map (db m97319) HM
135 ► Virginia, James City County, Williamsburg — WT-2 — First Germans at Jamestown — _link_
The first Germans to land in Jamestown, the first permanent English settlement in Virginia, arrived aboard the vessel Mary and Margaret about 1 October 1608. These Germans were glassmakers and carpenters. In 1620, German mineral specialists . . . — — Map (db m194640) HM
136 ► Virginia, James City County, Williamsburg — Fort Magruder — An Ugly Place to Have to Attack — 1862 Peninsula Campaign — _link_
Here are the remains of Fort Magruder, an earthen redoubt built in 1861 at the center of the Confederate defensive line. The “Williamsburg Line” stretched between the James and York rivers and consisted of fourteen forts, commonly called . . . — — Map (db m10371) HM
137 ► Virginia, James City County, Williamsburg — Foundations at Jamestown — _link_
The remains of Jamestown now lie buried beneath the ground. Archeologists have unearthed some of the known town site, but the original foundations of structures would erode quickly if left exposed to wind, weather, and acid rain. The foundations . . . — — Map (db m17220) HM
138 ► Virginia, James City County, Williamsburg — Gardens and Crops — _link_
Tobacco, sassafras – the Jamestown gardener was distracted by quick-money crops for export to Europe. Tobacco was even grown in the streets. In 1624 the General Assembly tried to aid the struggling silk and wine industries by ordering each . . . — — Map (db m17317) HM
139 ► Virginia, James City County, Williamsburg — Glebe Land — _link_
After 1619 these 100 acres of land were set aside for the benefit of the Jamestown parish church and minister. Richard Buck was the first clergyman to have use of it. Later on Francis Bolton became minister at "James Citty" and he, too, had "leave . . . — — Map (db m31079) HM
140 ► Virginia, James City County, Williamsburg — Governor Harvey’s House 1630s — _link_
John Harvey served as a member of a royal commission investigating conditions in Virginia in 1624. As a reward, he received land at the east end of New Towne. There he probably built a residence and a wharf. A temperamental sea captain, Harvey . . . — — Map (db m17215) HM
141 ► Virginia, James City County, Williamsburg — Governor Yeardley’s Lot 1620’s — _link_
George Yeardley arrived in Jamestown in 1610, was appointed captain of the guard, and eventually lieutenant governor. Later knighted and appointed governor of Virginia in 1618, he issued the Great Charter in 1619, establishing the first . . . — — Map (db m17027) HM
142 ► Virginia, James City County, Williamsburg — V-41 — Governor’s Land — _link_
Situated near Jamestown, Governor’s Land originally was a 3,000-acre tract encompassing open fields between the James River and Powhatan Creek. The Virginia Company of London set the parcel aside in 1618 to seat tenants who worked the land, giving . . . — — Map (db m2438) HM
143 ► Virginia, James City County, Williamsburg — Governor's Land — _link_
In November 1618, The Virginia Company instructed Governor George Yeardley to set aside 3,000 acres of land “in the best and most convenient place of the territory of Jamestown” to be “the seat and land of the Governor of . . . — — Map (db m99077) HM
144 ► Virginia, James City County, Williamsburg — W-36 — Green Spring — _link_
On this road, five miles south, is Green Spring, home of Governor Sir William Berkeley. Bacon the Rebel occupied it in 1676. Cornwallis, after moving from Williamsburg by this road on July 4, 1781, was attacked by Lafayette near Green Spring on July . . . — — Map (db m20810) HM
145 ► Virginia, James City County, Williamsburg — V-42 — Green Spring Road — _link_
The 17th century road to Green Spring, home of Governor Sir William Berkeley, was the eastern part of the Great Road, the earliest-developed English thoroughfare in Virginia. The Great Road ran from Jamestown Island toward the falls of the James . . . — — Map (db m2441) HM
146 ► Virginia, James City County, Williamsburg — History of Fort Magruder — _link_
On May 4th, 1862 Union Division’s of Generals Hooker, Hancock, and “Baldy” Smith encountered units of the Southern Army east of Williamsburg. When the Confederate Army Commander General Joseph E. Johnston became aware of the engagement, . . . — — Map (db m15716) HM
147 ► Virginia, James City County, Williamsburg — V-47 — Hot Water / Centerville — _link_
Royal Governor William Berkeley, owner of nearby Green Spring Plantation, purchased the land here by 1652, then known as Hot Water. After Berkeley's death, the Hot Water tract passed to the Ludwell and Lee families. William Ludwell Lee inherited the . . . — — Map (db m23614) HM
148 ► Virginia, James City County, Williamsburg — In Memory of Early Settlers — _link_
To the glory of God and in grateful memory of those early settlers, the founders of this Nation who died at Jamestown during the first perilous years of the colony. Their bodies lie along the ridge beyond this cross, in the earliest known burial . . . — — Map (db m11377) HM
149 ► Virginia, James City County, Williamsburg — Inside a Home — _link_
All that was left of this home was the foundation of a fireplace and two rows of stains in the soil. The house was built on wood posts sunk directly into the ground. Changes in the color of the soil show where the holes were dug to sink the posts. . . . — — Map (db m17358) HM
150 ► Virginia, James City County, Williamsburg — Interpreting Jamestown — _link_
In 1934, the National Park Service acquired 1,500 acres of Jamestown Island, including New Towne. Since then, the NPS has used different methods to tell visitors about the town. After archaeologists unearthed numerous structures with brick . . . — — Map (db m17211) HM
151 ► Virginia, James City County, Williamsburg — Iron and Industry — _link_
The raw materials for the smelting of iron were all found here: lime from oyster shells, bog ore from the swamp, charcoal from burned trees. A circular kiln, 10 feet across and lined with baked clay, sat over a pit with an air vent to the surface. . . . — — Map (db m17218) HM
152 ► Virginia, James City County, Williamsburg — Jackson Home 1620s — _link_
Jackson the smith was at work in his shop . . . Minutes of the General Court, 1623 Protection was of the utmost importance in the early years of Virginia. Gunsmiths like Jamestown resident, assemblyman, and churchwarden John Jackson, were . . . — — Map (db m17212) HM
153 ► Virginia, James City County, Williamsburg — Z-266 — James City County / York County — _link_
James City County. Area 164 Square Miles. One of the original shires formed in 1634, and named for Jamestown, the first settlement in Virginia, 1607. Williamsburg is in this county.
York County. Area 186 Square . . . — — Map (db m73950) HM
154 ► Virginia, James City County, Williamsburg — James Fort Site 1607 – 1624 — _link_
You are about to enter the site of 1607 James Fort, the heart of the first, permanent English settlement in North America. The sections of log walls stand above archaeological remains of the original palisades. The walls enclosed about one acre, in . . . — — Map (db m11470) HM
155 ► Virginia, James City County, Williamsburg — James River — _link_
Indians knew this as the Powhatan River, the colonists renamed it in honor of their sovereign, James I. It is one of Virginia's longest and broadest rivers. Rising in the Appalachians it flows eastward, often soil laden, 340 miles to the Chesapeake . . . — — Map (db m31087) HM
156 ► Virginia, James City County, Williamsburg — Jamestown — National Historic Site — _link_
This part of old “James Towne” has been owned and preserved since 1893 by the Association for the Preservation of Virginia Antiquities. Founded May 13, 1607, “James Towne” was the first permanent English settlement in . . . — — Map (db m10262) HM
157 ► Virginia, James City County, Williamsburg — Jamestown — _link_
Across the swamp lies Jamestown Island. Powhatan Creek below you, takes its name from the Indian Chief. To the right is Glasshouse Point, place of early glassmaking and later a part of the suburb of "James Cittie". — — Map (db m30733) HM
158 ► Virginia, James City County, Williamsburg — V-44 — Jamestown — _link_
Nearby to the east is Jamestown, the original site of the first permanent English colony in North America. On 14 May 1607, a group of just over 100 men and boys recruited by the Virginia Company of London came ashore and estblished a settlement at . . . — — Map (db m2443) HM
159 ► Virginia, James City County, Williamsburg — Jamestown Island — _link_
The woodland and marsh beyond the water is Jamestown Island, a pear-shape area of some 1,500 acres, being about 2½ miles in length. It is separated from the mainland by Back Creek. In more recent times the wide mouth of this creek, which you . . . — — Map (db m31077) HM
160 ► Virginia, James City County, Williamsburg — W-38 — Jamestown Road — _link_
The ancient road that linked Jamestown, the original colonial capital, with Middle Plantation (later Williamsburg) followed a meandering course. It departed from Jamestown Island and then turned northeast, crossing Powhatan and Mill Creeks. As it . . . — — Map (db m194909) HM
161 ► Virginia, James City County, Williamsburg — Jamestown Settlement — Rededicated April 24, 2007 — _link_
This plaque marks the rededication of Jamestown Settlement on the eve of the Jamestown Quadricentennial and upon the occasion of its 50th anniversary and completion of its comprehensive facilities master plan, executed between 1997 and 2007. . . . — — Map (db m98077) HM
162 ► Virginia, James City County, Williamsburg — Jamestown Tercentenary Monument — _link_
East Side of Monument:
Virginia Company of London Chartered April 10, 1606 Founded Jamestown and sustained Virginia 1607 – 1624
North Side of Monument:
Jamestown The first permanent colony of the English people. The birthplace . . . — — Map (db m11467) HM
163 ► Virginia, James City County, Williamsburg — Jamestown’s Churches — _link_
The First and Second Churches Captain John Smith reported that the first church services were held outdoors “under an awning (which was an old sail)” fastened to three or four trees. Shortly thereafter the colonists built the first . . . — — Map (db m17053) HM
164 ► Virginia, James City County, Williamsburg — W-47 — Kingsmill — _link_
Kingsmill Plantation, the home of Col. Lewis Burwell, was built in the mid-1730s and consisted of a mansion, outbuildings, garden, and 1,400 acres. The house burned in 1843. Only the office and the kitchen still stand; they are among the earliest . . . — — Map (db m165422) HM
165 ► Virginia, James City County, Williamsburg — Loch Ness Coaster — _link_
The Loch Ness Monster opened in Busch Gardens Williamsburg in 1978 as the World's tallest coaster, standing at a height of 130ft. With a layout as a twisting as the beast that lends it its name, the Loch Ness Monster features the world's first and . . . — — Map (db m220461) HM
166 ► Virginia, James City County, Williamsburg — W-44 — Magruder’s Defenses — _link_
Here is a redoubt in the line of Confederate defenses, built across the James-York Peninsula in 1861-62 by General John B. Magruder. — — Map (db m10540) HM
167 ► Virginia, James City County, Williamsburg — W-51 — Martin's Hundred — _link_
This plantation was allocated to the London-based Society of Martin's Hundred by 1618 and was later assigned 21,500 acres. It was initially settled in 1620 around Wolstenholme Town, its administrative center, located near the James River. . . . — — Map (db m9495) HM
168 ► Virginia, James City County, Williamsburg — W-52 — Martin's Hundred Church — _link_
The first Martin's Hundred Parish church was probably built at Wolstenholme Town, an early 17th-century settlement that was located a mile southeast of here. None of the structures excavated there have been identified as a church; it may have been . . . — — Map (db m9497) HM
169 ► Virginia, James City County, Williamsburg — May-Hartwell Site 1660-1699 — _link_
Evidence from wills, deeds, land plats, patents, and court cases helps to identify structures excavated by archaeologists. When historians digitalized two 17th-century land plats and superimposed them on a modern map of Jamestown, they matched a . . . — — Map (db m17310) HM
170 ► Virginia, James City County, Williamsburg — Neck of Land — near "James Citty" — _link_
This area, like a peninsula and bounded on three sides by a marsh, is just across Back River from Jamestown Island. In 1625 there were a number of houses and 25 people living here. The settlement had close community ties to “James Citty” . . . — — Map (db m31073) HM
171 ► Virginia, James City County, Williamsburg — V-63 — Norge Depot — _link_
The Chesapeake and Ohio Railway Company constructed the Norge Depot 600 feet north of here in 1907-1908. Several years earlier, Norwegian-born railway agent Carl M. Bergh had recruited Scandinavian immigrants who lived in the American Midwest to . . . — — Map (db m194686) HM
172 ► Virginia, James City County, Williamsburg — W-28 — Olive Branch Christian Church — _link_
In 1833 the founders of Olive Branch Christian Church (Disciples of Christ) met for worship at Hill Pleasant Farm. By 1835, the congregation had built a brick church on land donated by Dr. Charles M. Hubbard and Mary Henley. During the Civil War, . . . — — Map (db m23598) HM
173 ► Virginia, James City County, Williamsburg — Oyster Shells to Mortar — _link_
Brick, lime, and pottery kilns operated throughout Jamestown. A small paved pit here, filled with oyster shells and moistened lime, marked a kiln where mortar or plaster was made. Different pits produced varying qualities of mortar and plaster. . . . — — Map (db m17314) HM
174 ► Virginia, James City County, Williamsburg — Palisades — _link_
“our extreme toil in bearing and planting palisades so strained and bruised us, and our continual labor in the extremity of heat had so weakened us” – John Smith
These replicated sections of James Fort’s palisades are . . . — — Map (db m100110) HM
175 ► Virginia, James City County, Williamsburg — Paspahegh — _link_
When the English colonists arrived in 1607, they landed in Paspahegh Country, which extended westward along the shore of the James River to the Chickahominy River and beyond.
The Native Americans who lived here were Algonquin speakers that fished, . . . — — Map (db m90951) HM
176 ► Virginia, James City County, Williamsburg — W-37 — Peninsula Campaign — _link_
During the Peninsula Campaign of 1862, both Confederate Gen. Joseph E. Johnston and Union Maj. Gen. George B. McClellan had their armies west toward Richmond on this road. Johnston evacuated Yorktown on 3-4 May and withdrew up the Peninsula, with . . . — — Map (db m10118) HM
177 ► Virginia, James City County, Williamsburg — Pitch and Tar Swamp — _link_
To the north, Jamestown Island is ringed with slow moving water and a marsh of reeds, cypress, and pine. One of the first industries attempted at Jamestown was the extraction of pitch and tar from the pine trees in this swampy area. Pitch, tar, and . . . — — Map (db m17219) HM
178 ► Virginia, James City County, Williamsburg — Pocahontas — _link_
Erected in 1922, this statue by William Ordway Partridge, honors Pocahontas, the favorite daughter of Paramount Chief Wahunsenacawh (better known as Powhatan), ruler of the Powhatan Paramount Chiefdom. Pocahontas was born around 1595, probably at . . . — — Map (db m11371) HM
179 ► Virginia, James City County, Williamsburg — V-45 — Pocahontas — _link_
Matoaka, nicknamed Pocahontas (“mischievous one”), the daughter of Powhatan, was born about 1597. She served as an emissary for her father and came to Jamestown often in 1608. In 1613, Samuel Argall kidnapped Pocahontas while she visited the . . . — — Map (db m194910) HM
180 ► Virginia, James City County, Williamsburg — Powhatan’s Headquarters — Captain John Smith Chesapeake National Historic Trail — National Park Service, U.S. Department of the Interior — _link_
(panel 1) Powhatan's Headquarters
At the time Captain John Smith traveled the York River, several Eastern Virginia Algonquian tribes paid tribute to a spiritual and political leader named Powhatan. In return, he provided . . . — — Map (db m97289) HM
181 ► Virginia, James City County, Williamsburg — W-42 — Quarterpath Road — _link_
James Bray owned land nearby in Middle Plantation by the 1650s, and Quarterpath Road probably began as a horse path to one of Bray’s quarters or farm units. Over the years, the road was improved; it extended to Col. Lewis Burwell’s landing on the . . . — — Map (db m130380) HM
182 ► Virginia, James City County, Williamsburg — Real Estate — _link_
Early records tell of a land sale in 1636 being these 500 acres with “all howses...gardens, orchards, tenements.” The property passed from Thomas Crompe “of the Neck of Land” to Gershon Buck son of the Rev
| https://www.hmdb.org/results.asp?County=James%20City%20County&Page=2&Search=County&State=Virginia&Want=1&nu=2 |
Nutrients | Free Full-Text | Serine Phosphorylation of IRS1 Correlates with Aβ-Unrelated Memory Deficits and Elevation in Aβ Level Prior to the Onset of Memory Decline in AD
The biological effects of insulin signaling are regulated by the phosphorylation of insulin receptor substrate 1 (IRS1) at serine (Ser) residues. In the brain, phosphorylation of IRS1 at specific Ser sites increases in patients with Alzheimer& rsquo;s disease (AD) and its animal models. However, whether the activation of Ser sites on neural IRS1 is related to any type of memory decline remains unclear. Here, we show the modifications of IRS1 through its phosphorylation at etiology-specific Ser sites in various animal models of memory decline, such as diabetic, aged, and amyloid precursor protein (APP) knock-in NL-G-F (APPKINL-G-F) mice. Substantial phosphorylation of IRS1 at specific Ser sites occurs in type 2 diabetes- or age-related memory deficits independently of amyloid-& beta; (A& beta;). Furthermore, we present the first evidence that, in APPKINL-G-F mice showing A& beta;42 elevation, the increased phosphorylation of IRS1 at multiple Ser sites occurs without memory impairment. Our findings suggest that the phosphorylation of IRS1 at specific Ser sites is a potential marker of A& beta;-unrelated memory deficits caused by type 2 diabetes and aging; however, in A& beta;-related memory decline, the modifications of IRS1 may be a marker of early detection of A& beta;42 elevation prior to the onset of memory decline in AD.
Serine Phosphorylation of IRS1 Correlates with Aβ-Unrelated Memory Deficits and Elevation in Aβ Level Prior to the Onset of Memory Decline in AD
Daisuke Tanokashira 1,† ,
Yusuke Fukui 1 ,
Megumi Maruyama 1 ,
Chiemi Kuroiwa 1 ,
Takashi Saito 2,3 ,
Takaomi C. Saido 2 and
Akiko Taguchi 1,*
1
Department of Integrative Aging Neuroscience, National Center for Geriatrics and Gerontology, Obu, Aichi 474-8511, Japan
2
Laboratory for Proteolytic Neuroscience, RIKEN Center for Brain Science, Wako, Saitama 351-0106, Japan
3
Department of Neurocognitive Science, Nagoya City University Graduate School of Medical Science, Nagoya, Aichi 467-8601, Japan
*
Author to whom correspondence should be addressed.
†
These authors contributed equally.
Nutrients 2019 , 11 (8), 1942; https://doi.org/10.3390/nu11081942
Received: 23 July 2019 / Revised: 3 August 2019 / Accepted: 14 August 2019 / Published: 17 August 2019
(This article belongs to the Special Issue Nutrition and Central Nervous System )
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Abstract
The biological effects of insulin signaling are regulated by the phosphorylation of insulin receptor substrate 1 (IRS1) at serine (Ser) residues. In the brain, phosphorylation of IRS1 at specific Ser sites increases in patients with Alzheimer’s disease (AD) and its animal models. However, whether the activation of Ser sites on neural IRS1 is related to any type of memory decline remains unclear. Here, we show the modifications of IRS1 through its phosphorylation at etiology-specific Ser sites in various animal models of memory decline, such as diabetic, aged, and amyloid precursor protein (APP) knock-in
NL-G-F
(APPKI
NL-G-F
) mice. Substantial phosphorylation of IRS1 at specific Ser sites occurs in type 2 diabetes- or age-related memory deficits independently of amyloid-β (Aβ). Furthermore, we present the first evidence that, in APPKI
NL-G-F
mice showing Aβ42 elevation, the increased phosphorylation of IRS1 at multiple Ser sites occurs without memory impairment. Our findings suggest that the phosphorylation of IRS1 at specific Ser sites is a potential marker of Aβ-unrelated memory deficits caused by type 2 diabetes and aging; however, in Aβ-related memory decline, the modifications of IRS1 may be a marker of early detection of Aβ42 elevation prior to the onset of memory decline in AD.
Keywords:
IRS1
;
serine phosphorylation
;
hippocampus
;
diabetes
;
aging
;
Alzheimer’s disease
;
memory decline
;
Aβ
;
AMPK
;
energy depletion
Graphical Abstract
1. Introduction
Insulin signaling mediated by insulin receptor substrates 1 and 2 (IRS1 and IRS2) is involved in the regulation of growth, glucose homeostasis, energy metabolism, and lifespan [ 1 , 2 , 3 , 4 ]. The biological effects of insulin signaling are regulated by the modulation of IRS proteins through serine (Ser) and threonine (Thr) phosphorylation [ 5 , 6 ]. Notably, IRS1 is known to be abundantly phosphorylated at Ser and Thr residues regardless of insulin or IGF1 stimulation [ 5 , 7 ]. In vitro studies have demonstrated the relationship between IRS1 Ser/Thr phosphorylation and canonical downstream signaling components, including Akt/protein kinase B, glycogen synthase kinase 3 beta (GSK3β), and ribosomal protein S6 kinase (S6K) [ 5 ]. Under physiological and pathological conditions, Ser/Thr phosphorylation of IRS1 is potentially mediated by multiple kinases, including AMP-activated protein kinase (AMPK), conventional and novel protein kinase C (PKC), and c-Jun N-terminal kinases (JNKs), in response to intracellular energy status, nutritional conditions, and inflammatory stimulation [ 5 , 6 , 8 ].
Among the numerous Ser residues on IRS1, a few sites, including human(h)Ser312/mouse(m)Ser307, hSer616/mSer612, hSer636/mSer632, hSer639/mSer635, and hSer1101/mSer1097, have been studied because a limited number of phosphospecific antibodies were previously commercially available.
Nonetheless, hSer312/mSer307 has been widely investigated and implicated in insulin resistance under metabolic stress conditions and in inflammatory conditions such as obesity, hyperinsulinemia, and dyslipidemia [ 5 , 9 , 10 ]. However, IRS1 mSer307 knock-in mice display insulin resistance rather than increased insulin sensitivity, suggesting that IRS1 mSer307 is a positive regulatory site and is essential for normal insulin signaling [ 11 ]. IRS1 mSer612 and mSer632/635 have been cited as negative regulatory sites for IRS1 signaling through tyrosine phosphorylation [ 5 ], and mSer1097, regarded as a potential mammalian target of rapamycin (mTOR) /S6K signaling pathway, is activated in the liver of model animals of obesity [ 12 ]. However, the roles of these sites remain largely unknown because they have been examined in different context.
In the central nervous system, studies on postmortem brain tissues of patients with Alzheimer’s disease (AD) have revealed increased phosphorylation of IRS1 at hSer312/mSer307, hSer616/mSer612, hSer636/mSer632, and hSer639/mSer635 compared with that in non-AD control subjects [ 13 , 14 , 15 , 16 ]. The phosphorylation levels of IRS1 at hSer312/mSer307 and hSer616/mSer612 are considerably elevated in the brains of patients with AD [ 15 ]. In animal studies, multiple AD mouse models display increased phosphorylation of IRS1 at mSer307 and/or mSer632 or mSer612 [ 16 , 17 , 18 ]. However, whether the modifications of IRS1 via Ser phosphorylation are involved in memory decline in amyloid precursor protein (APP) knock-in (KI) NL-G-F (APPKI NL-G-F ) mice, a novel AD mouse model, remains unclear [ 19 ]. Meanwhile, animals with diet-induced obesity (DIO), a model of type 2 diabetes mellitus (T2DM), that were fed a 40% or 60% high-fat diet (HFD) during different periods displayed cognitive impairment accompanied by increased phosphorylation of neural IRS1 at different Ser residues (mSer1097, mSer307, or mSer612) at different ages [ 20 , 21 , 22 ]. Few studies have reported the relationship between streptozotocin (STZ)-induced type 1 diabetes-related cognitive impairment and phosphorylation of neural IRS1 at Ser sites. Similarly, in aged animals, the phosphorylation of IRS1 at mSer307 has been shown to increase in the cortex; however, whether this alteration is correlated with age-related decline in cognitive function has not been explored [ 23 ].
In the present study, we investigated whether the modification of hippocampal IRS1 by Ser phosphorylation is commonly associated with different types of memory decline in DIO, STZ, aged, and APPKI
NL-G-F
mice and whether it occurs before or after the onset of memory decline in APPKI
NL-G-F
mice. We demonstrate that the concomitant activation of specific Ser sites on hippocampal IRS1 with amyloid-β (Aβ)-unrelated memory decline occurs in DIO and aged mice, whereas STZ mice exhibit memory deficits independent of IRS1 activity. We further show that increased phosphorylation of hippocampal IRS1 at Ser sites is already observed in young APPKI
NL-G-F
mice showing normal memory function despite increased Aβ42 level. These data suggest that the activation of Ser residues on hippocampal IRS1 is associated with non-AD-related memory impairment in T2DM and aging and with Aβ42 level, which is related to the onset of cognitive decline in AD.
2. Materials and Methods
2.1. Animals
C57BL/6J male mice (4 weeks of age) supplied by Japan SLC, Inc. (Shizuoka, Japan) were used to establish type 1 and 2 diabetes mellitus (T1DM, T2DM) mice and their respective control mice. Generation of high-fat-diet (HFD)-induced type 2 diabetes mice (DIO mice) was carried out as previously described [
20
]. Briefly, C57BL/6J mice were assigned to control wild-type (WT) mice] and HFD (DIO mice) groups, and were fed a normal diet (CE-2; CLEA Japan Inc., Tokyo, Japan) or a HFD (D12492, 60% kcal from fat; Research Diets, Inc., New Brunswick, NJ, USA) for 32 weeks, respectively. To generate Streptozotocin (STZ)-induced type 1 diabetes mice (STZ mice), eight-week-old C57BL/6J mice were intraperitoneally administered with 150 mg/kg STZ (Wako Pure Chemical Industries, Ltd., Osaka, Japan) dissolved in sodium citrate (pH 4.5) after overnight fasting, and control mice were injected with the sodium citrate buffer alone. Young and aged WT male mice, which were all pure C57BL/6J strains, were purchased from Charles River Inc., Kanagawa, Japan, or/and bred within our animal facility. APPKI
NL-G-F
(Swedish (NL), Arctic (G), and Beyreuther/Iberian (F) mutations) homozygous mice were obtained from Dr. Saido at the Laboratory for Proteolytic Neuroscience, RIKEN Brain Science Institute, Saitama, Japan [
19
]. Age-matched WT mice of a similar strain (C57BL/6J) were used in the control experiments. All experiments were performed using DIO, STZ, and young and middle-aged APPKI
NL-G-F
mice, and their respective age-matched control mice (DIO mice: 34–36 weeks, WT mice: 34–36 weeks; STZ mice: 10 weeks, WT mice: 10 weeks; young APPKI
NL-G-F
mice: 12 weeks, WT mice: 12 weeks; middle-aged APPKI
NL-G-F
mice: 34–36 weeks, WT mice: 34–36 weeks; young WT mice: 8–13 weeks, aged WT mice: 84 weeks). All mice were housed in a standard 12 h light–dark cycle with free access to water and food (room temperature: 25 ± 2 °C). Animal experiments were performed in compliance with the guidelines and with the approval of the ethics committee in Animal Care and Use of the National Center for Geriatrics and Gerontology in Obu, Aichi, Japan (Approval ID: 31-5).
2.2. Western Blotting
The protocol of western blotting used has been previously described [
20
]. In brief, hippocampal tissue was isolated on ice and homogenized in lysis buffer with a pellet mixer. The aliquot of hippocampal lysates was boiled for 5 min in Laemmli sodium dodecyl sulfate (SDS) sample buffer [60 mm Tris-Cl (pH 6.8), 2% sodium dodecyl sulfate, 10% glycerol, 4% β-mercaptoethanol, and 0.01% bromophenol blue]. A total of 10 μg of each SDS protein sample was loaded per lane, separated by 7.5% sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), and transferred to polyvinylidene difluoride membranes. Membranes were blocked using 4% Block Ace (Yukijirushi Ltd., Sapporo, Japan), incubated with the indicated primary antibodies, followed by incubation with horseradish peroxidase-conjugated secondary antibodies. Primary antibodies were rabbit anti-phospho-IRS1 [mouse Ser307/human Ser312 (mSer307/hSer312), mouse Ser612/human Ser616 (mSer612/hSer616), mouse Ser632/Ser635/human Ser636/Ser639 (mSer632/Ser635/hSer636/Ser639), mouse Ser1097/human Ser1101 (mSer1097/hSer1101)] (1:500; Cell Signaling Technology(CST)), rabbit anti-IRS1 (1:1000; CST), rabbit anti-phospho-Akt (Ser473) (1:1000; CST), rabbit anti-Akt (1:1000; CST), rabbit anti-phospho-p70S6K (Thr389) (1:1000; CST), rabbit anti-p70S6K (1:1000; CST), rabbit anti-phospho-AMPK (Thr172) (1:1000; CST), rabbit anti-AMPK (1:1000; CST), rabbit anti-phospho-GSK3β (Ser9)(1:1000; CST), rabbit anti-GSK3β (Ser9) (1:1000; CST), rabbit anti-phospho-JNK (Thr183/Tyr185) (1:1000; CST), rabbit anti-JNK (1:1000; CST), rabbit anti-phospho-aPKCζ/λ(Thr410/Thr403) (1:1000; CST), rabbit anti-aPKCζ/λ(1:1000; CST), and rabbit anti-β-tubulin (1:1000; CST). Immunodetection was performed with horseradish peroxidase-conjugated secondary antibodies (1:2000; CST) and chemiluminescence detection reagent Chemi-Lumi one L (Nacalai tesque, Kyoto, Japan) or the ImmunoStar LD (Fujifilm Wako Pure Chemical Corporation Japan, Osaka, Japan). The images were scanned using the Amersham Imager 680 (GE Healthcare UK Ltd., Little Chalfont, Buckinghamshire HP7 9NA, England ).
2.3. Water T Maze Test
Hippocampal-dependent spatial memory was tested using a water T maze [
24
,
25
] according to our previous report [
20
]. The maze consisted of a start box, a left arm, and a right arm, which was filled with water at 23 ± 1 °C up to 1 cm above the surface of the platform. Mice were allowed to swim to the right or left arm. This screening step was repeated three times at 15 s intervals. The platform was placed on the side that the mice reached less often. After the screening step, mice were allowed to explore the maze freely. If mice reached the platform, they were allowed to rest there for 5 s (correct choice). If not, the arm entry was closed with a board and they were forced to swim for 15 s as a deterrent (incorrect choice). This trial step was repeated five times at 4-min intervals. Mice were subjected to this trial step for five days. To evaluate the results of the trial, the percentage of correct responses per day was determined. After two days of rest, to test hippocampal and prefrontal cortex (PFC)-dependent working memory, the platform was moved to the opposite arm. Similarly, mice were allowed to explore the maze freely. The trial step was repeated 15 times at 4-min intervals in a day. To evaluate the results of the trial, the percentage of the correct responses were calculated after every three responses.
2.4. Measurement of Metabolic Parameters
Body weight and the blood glucose levels were recorded after 6 h of fasting. Blood glucose levels were measured using a portable glucose meter (ACCU-CHEK ® Aviva; Roche DC Japan K.K.). The level of plasma insulin at 6 h fasting was determined using an insulin enzyme-linked immunosorbent assay kit (Morinaga, Yokohama, Japan).
2.5. Enzyme-Linked Immunosorbent Assay (ELISA) Quantitation of Aβ
In order to measure the Aβ levels in the hippocampus, hippocampal tissue was isolated on ice and homogenized in a lysis buffer (T-PER
®
Tissue Protein Extraction Reagent; Thermo Fisher Scientific, Waltham, MA, USA) containing a protease inhibitor cocktail (Nacalai Tesque, Kyoto, Japan) and a phosphatase inhibitor cocktail (Nacalai Tesque) with a pellet mixer. After incubation on ice for 15 min, the lysates were centrifuged at 14,200×
g
for 5 min at 4 °C and the supernatants were placed in a fresh tube. Protein concentration was determined using a Bicinchoninic acid (BCA) protein assay kit (Thermo Fisher Scientific, Waltham, MA, USA). The levels of T-PER-extractable Aβ were measured with the Human β Amyloid (1–40) enzyme-linked immunosorbent assay (ELISA) Kit Wako II (#298-64601; Fujifilm Wako Pure Chemical Corp., Osaka, Japan), the Human β Amyloid (1–42) ELISA Kit Wako, High Sensitivity (#296-64401, Fujifilm Wako Pure Chemical Corp.), the Human/Rat/Mouse β Amyloid (1–40) ELISA Kit Wako II (#294-64701; Fujifilm Wako Pure Chemical Corp., Osaka, Japan), and the Human/Rat/Mouse β Amyloid (1–42) ELISA Kit Wako, High Sensitivity (#292-64501, Fujifilm Wako Pure Chemical Corp.) in accordance with the manufacturers’ instructions.
2.6. Statistics
All results are presented as mean ± standard error of the mean (SEM) in the text. Statistical analyses were performed using Prism7 for Mac OS X v.7.0d (GrapPad Software Inc., La Jolla, CA, USA). Data were statistically analyzed using Student’s t -test and two-way analysis of variance (ANOVA). Significance is indicated as * p < 0.05 and ** p < 0.01.
3. Results
3.1. Activation of Specific Ser Residues on Hippocampal Insulin Receptor Substrate 1 (IRS1) Is Associated with T2DM-Induced Memory Impairment
We recently reported that T2DM-related cognitive declines in 45-week-old DIO mice fed a 60% HFD for 42 weeks were accompanied by an increased phosphorylation of hippocampal IRS1 at mSer1097 [ 20 ]. While mice fed a 60% HFD for 17 days and mice or rats fed a 40% HFD for 6–8 weeks exhibited memory impairment accompanied by increased phosphorylation at hSer616/mSer612 or hSer312/mSer307 [ 21 , 22 ], 12-week-old DIO mice fed a 60% HFD for 9 weeks exhibited normal memory function under our experimental conditions ( Figure S1 ), suggesting that changes in neural IRS1 Ser residues are variable on a temporal scale in DIO mice. Therefore, we investigated the phosphorylation levels of hippocampal IRS1 at Ser sites and the activities of downstream factors involved in memory impairment in 35-week-old (middle-aged) DIO mice fed a 60% HFD for 32 weeks ( Figure 1 A,C). At 35 weeks of age, DIO mice displayed significant weight gain, hyperglycemia, and hyperinsulinemia ( Figure 1 B, Figure S2A ), as observed at other time points [ 20 , 21 , 22 , 26 ].
Figure 1.
Changes in specific Ser sites on hippocampal insulin receptor substrate 1 (IRS1) in type 2 diabetes (T2DM)-induced memory impairment. (
A
) Schematic diagram of the experimental procedure. (
B
) Graphs of body weight and blood glucose level in wild-type (WT) and diet-induced obesity (DIO) mice (35 weeks of age, n = 5 mice per group). (
C
) Evaluation of learning memory function in middle-aged WT and DIO mice (n = 14 mice per group) using the water T-maze test. (
D
) Quantitative analysis of T-PER (Tissue Protein Extraction Reagent)-extractable Aβ40 and Aβ42 levels in the hippocampi of middle-aged WT and DIO mice using the human/rat/mouse β amyloid (1–40 and 1–42) enzyme-linked immunosorbent assay (ELISA) (35 weeks of age, n = 5 biologically independent samples per group). (E) Western blot analysis of phosphorylated insulin receptor substrates 1 mouse Ser307 [p-IRS1 (mSer307)], p-IRS1 (mSer612), p-IRS1 (mSer632/635), p-IRS1 (mSer1097), IRS1, and β-tubulin in the hippocampi of middle-aged WT and DIO mice (35 weeks of age, n = 5 biologically independent samples per group). Arrow indicates the p-IRS1 mSer612-corresponding band (lower band) in (
E
). Quantitative analysis of the phosphorylation of IRS1 at mSer307, mSer612, mSer632/635, and mSer1097 normalized to total protein. (
F
) Western blot analysis of phosphorylation levels of Akt Ser473, p70S6K Thr389, AMP-activated protein kinase (AMPK) Thr172, and glycogen synthase kinase 3 beta (GSK3β) Ser9 as well as total protein levels of Akt, p70 S6K, AMPK, GSK3β, and ß-tubulin in the hippocampi of middle-aged WT and DIO mice (35 weeks of age, n = 5 biologically independent samples per group). Quantitative analysis of the phosphorylation of Akt Ser473, p70S6K Thr389, AMPK Thr172, and GSK3β Ser9 normalized to the respective total protein contents. Results are presented as mean ± standard error of the mean (SEM), *
p
< 0.05; **
p
< 0.01.
Furthermore, we examined whether memory impairment in middle-aged DIO mice is linked to increased levels of Aβ42, a pathological feature of AD. Biochemical analysis with specific kits (see Materials and Methods) demonstrated that, compared with age-matched wild-type (WT) mice, there was no change in Aβ40 and Aβ42 levels in the T-PER fractions obtained from the hippocampi of 35-week-old DIO mice ( Figure 1 D).
In contrast to DIO mice at 45 weeks of age, the phosphorylation of IRS1 at mSer307, which increases in insulin resistance, diabetes, and obesity [ 5 ], with phosphorylation at mSer1097 significantly increased in the hippocampus of DIO mice at 35 weeks of age, although there were no significant differences in phosphorylation at mSer612 and mSer632/635 between DIO and age-matched WT mice ( Figure 1 E, Figure S4 A). Consistent with previous studies [ 27 , 28 ], the basal phosphorylation level of p70S6K slightly but significantly increased in the hippocampus of middle-aged DIO mice compared with that in the hippocampus of age-matched WT mice, whereas the basal phosphorylation of Akt and GSK3β and activation of AMPK and atypical protein kinase C ζ/λ (aPKC ζ/λ), downstream factors of insulin signaling, in the hippocampus were comparable between middle-aged WT and DIO mice ( Figure 1 F, Figures S3A, S4B and S5A ). Additionally, the basal phosphorylation of JNK, an inflammation- and stress-related factor, remained unchanged in the hippocampus between the two groups ( Figures S3A and S5A ), although a relationship between the phosphorylation of IRS1 at mSer307 and activation of these factors in yeast cells, culture cells, and muscles has been reported [ 5 ]. These results indicate that T2DM-induced memory decline is provoked by an Aβ-independent mechanism and that the concomitant activation of IRS1 mSer307 and mSer1097 with p70S6K activation in the hippocampus is associated with memory deficits in 35-week-old DIO mice.
3.2. Type 1 Diabetes Mellitus (T1DM)-Induced Memory Deficits Occur Independently of IRS1 Activity
To investigate whether the alteration of IRS1 through Ser phosphorylation is associated with type 1 diabetes mellitus (T1DM)-induced memory deficits, we generated STZ-induced insulin-deficient T1DM mice. Two weeks after STZ injection, STZ mice exhibited weight loss, elevated blood glucose levels (>400 mg/dL), and low insulin levels ( Figure 2 A, Figure S2B ). While there were no significant differences in hippocampus-dependent spatial memory between WT and STZ mice, STZ mice displayed hippocampus- and prefrontal cortex-related memory decline ( Figure 2 B), consistent with the findings reported in previous studies [ 29 , 30 , 31 , 32 ]. However, STZ-induced T1DM had no effect on Aβ40 and Aβ42 levels in the T-PER fractions of the hippocampus ( Figure 2 C).
Figure 2.
No alteration of IRS1 Ser phosphorylation in the hippocampus of T1DM mouse models. (
A
) Graphs of body weight and blood glucose level in wild-type (WT) and streptozotocin (STZ)-induced insulin-deficient type 1 diabetes (T1DM) model mice (10 weeks of age, n = 5 mice per group). (
B
) Evaluation of hippocampus-dependent learning and memory function and hippocampus/prefrontal cortex associated working memory function in WT (10 weeks of age, n = 19 mice per group) and STZ mice (10 weeks of age, n = 18 mice per group) using the water T-maze test and reverse water T-maze test. (
C
) Quantitative analysis of T-PER-extractable Aβ40 and Aβ42 levels in the hippocampi of WT and STZ mice using the human/rat/mouse β amyloid (1–40 and 1–42) ELISA (10 weeks of age, n = 5 biologically independent samples per group). (
D
) In WT and STZ-induced type 1 diabetes mice (10 weeks of age, n = 5 biologically independent samples per group), western blot analysis of phosphorylated insulin receptor substrates 1 mouse Ser307 [p-IRS1 (mSer307)], p-IRS1 (mSer612), p-IRS1 (mSer632/635), p-IRS1 (mSer1097), IRS1, and ß-tubulin was performed. Quantitative analysis of the phosphorylation of IRS1 at mSer307, mSer612, mSer632/635, and mSer1097 normalized to total protein. (
E
) Western blot analysis of phosphorylation levels of Akt Ser473, p70S6K Thr389, AMPK Thr172, and GSK3β Ser9 as well as total protein levels of Akt, p70S6K, AMPK, GSK3β, ß-tubulin in WT and STZ mice (10 weeks of age, n = 5 biologically independent samples per group). Arrows indicate the p-IRS1 mSer612-corresponding band (lower band) and the p-IRS1 mSer632/635-corresponding band (lower band) in (
D
). Quantitative analysis of the phosphorylation of Akt Ser473, p70 S6K Thr389, AMPK Thr172, and GSK3β Ser9 normalized to the respective total protein contents. Results are presented as mean ± SEM, *
p
< 0.05; **
p
< 0.01.
Subsequently, we examined the impact of STZ-induced T1DM on the phosphorylation of IRS1 at Ser residues and downstream components in the hippocampus. In STZ mice that had already developed memory impairment, the phosphorylation levels of hippocampal IRS1 at Ser residues in STZ mice were comparable to those in WT mice (
Figure 2
D,
Figure S4C
). Although the activation of p70S6K and the monotonous activities of Akt, AMPK, aPKC ζ/λ, and JNK were observed in STZ mice as well as in middle-aged DIO mice regardless of the presence or absence of Ser phosphorylation on hippocampal IRS1, the phosphorylation of GSK3β at Ser9 significantly increased in the hippocampus of STZ mice (
Figure 2
E,
Figure S3B, S4D and S5B
). These data indicate that T1DM-induced memory deficits accompanied by increased phosphorylation of GSK3β arises independently of the modification of IRS1 signaling via Ser phosphorylation and independently of Aβ elevation.
3.3. Phosphorylation of IRS1 at Age-Specific Ser Residues with the Activation of Downstream Kinases Is Linked to Age-Related Memory Deficits
Although memory decline associated with physiological aging can occur naturally, in contrast to pathogenic memory deficits, whether the onset processes of age-related memory impairment are related to the mechanisms underlying pathogenic memory deficits in T2DM and AD remains unclear. We examined the modification of IRS1 at Ser residues and the activity of downstream factors in the hippocampi of 21-month-old mice (aged mice). Aged mice displayed memory impairments without an increase in blood glucose and plasma insulin levels, despite an increase in body weight (
Figure 3
A,B,
Figure S2C
). Meanwhile, the Aβ40 and Aβ42 levels in the T-PER fractions of the hippocampus were comparable between young and aged WT mice (
Figure 3
C).
Figure 3.
Age-related memory deficits accompanied by increased phosphorylation of IRS1 Ser sites in the hippocampus. (
A
) The graphs of body weight and blood glucose levels in young (12 weeks of age, n = 7 mice per group) and aged (84 weeks of age, n = 7 mice per group) wild-type (WT) mice. (
B
) Evaluation of learning memory functions in young WT mice (n = 16 mice per group) and aged WT mice (n = 18 mice per group) using the water T-maze test. (
C
) Quantitative analysis of T-PER-extractable Aβ40 and Aβ42 levels in the hippocampi of young (12 weeks of age, n = 6 biologically independent samples) and aged (84 weeks of age, n = 6 biologically independent samples) WT mice using the human/rat/mouse β amyloid (1–40 and 1–42) ELISA. (
D
) Western blot analysis of phosphorylated insulin receptor substrates 1 mouse Ser307 [p-IRS1 (mSer307)], p-IRS1 (mSer612), p-IRS1 (mSer632/635), p-IRS1 (mSer1097), IRS1, and ß-tubulin in the hippocampi of young WT mice (12 weeks of age, n = 6 biologically independent samples) and aged WT mice (84 weeks of age, n = 6 biologically independent samples). Quantitative analysis of the phosphorylation of IRS1 at mSer307, mSer612, mSer632/635, and mSer1097 normalized to total protein. (
E
) Western blot analysis of phosphorylation levels of Akt Ser473, p70S6K Thr389, AMPK Thr172, and GSK3β Ser9 as well as total protein levels of Akt, p70S6K, AMPK, GSK3β, and ß-tubulin in the hippocampi of young WT mice (12 weeks of age, n = 6 biologically independent samples) and aged WT mice (84 weeks of age, n = 6 biologically independent samples). Arrows indicate the p-IRS1 mSer612-corresponding band (lower band) and the p-IRS1 mSer632/635-corresponding band (lower band) in (
D
). Quantitative analysis of the phosphorylation of Akt Ser473, p70S6K Thr389, AMPK Thr172, and GSK3β Ser9 normalized to the respective total protein contents. Results are presented as mean ± SEM, *
p
< 0.05; **
p
< 0.01.
In common with DIO mice, the activation of mSer307, but not of mSer1097, on IRS1 accompanied by p70S6K activation and unchanged AMPK was observed with increased phosphorylation of IRS1 at mSer612 and mSer632/635 in the hippocampi of aged mice ( Figure 3 D, Figure S4E ). Nonetheless, unlike in DIO mice, the basal phosphorylation levels of Akt and GSK3β prominently increased in the hippocampus of aged mice ( Figure 3 E, Figure S4F ); however, the basal activities of aPKC ζ/λ, and JNKs remained unchanged, similar to those in DIO mice ( Figure S3C and S5C ). These results suggest that aging causes the concomitant phosphorylation of hippocampal IRS1 at mSer307, mSer612, and mSer632/635 with the activation of canonical downstream kinases, which may be associated with Aβ-unrelated physiological decline in memory function.
3.4. Increased Phosphorylation of Hippocampal IRS1 at Ser Residues in Young Amyloid Precursor Protein (APP) Knock-In (APP KI NL-G-F ) Mice Occurs Prior to the Onset of Memory Decline
To investigate whether AD-related activation of Ser residues on neural IRS1 emerges before or after the onset of memory decline, we employed a novel AD mouse model, APPKI
NL-G-F
mice carrying a humanized Aβ sequence and three AD mutations, i.e., Swedish, Beyreuther/Iberian, and Arctic mutations, in the endogenous
App
gene [
19
]. First, we measured body weight and glucose metabolism in 12-week-old (young) APPKI
NL-G-F
mice. There were no differences in terms of body weight, blood glucose level, and plasma insulin concentration between WT and APPKI
NL-G-F
mice at 12 weeks of age (
Figure 4
A,
Figure S2B
). Next, we confirmed memory function as well as Aβ40 and Aβ42 levels in the hippocampi of young APPKI
NL-G-F
mice. At 12 weeks of age, APPKI
NL-G-F
mice exhibited normal memory function (
Figure 4
B).
Figure 4.
Activation of multiple Ser residues on hippocampal IRS1 unrelated to memory decline in young amyloid precursor protein (APP) knock-in (APPKI
NL-G-F
) mice. (
A
) The graphs of body weight and blood glucose levels in young wild-type (WT) and APPKI
NL-G-F
mice (12 weeks of age, n = 6 mice per group). (
B
) Evaluation of learning memory function in young WT (n = 5 mice per group) and APP KI
NL-G-F
mice (n = 5 mice per group) using the water T-maze test. (
C
) Quantitative analysis of T-PER-extractable Aβ40 and Aβ42 levels in the hippocampi of young WT and APPKI
NL-G-F
mice using the human/rat/mouse β amyloid (1–40 and 1–42) ELISA (12 weeks of age, n = 5 biologically independent samples per group). (
D
) Quantitative analysis of T-PER-extractable Aβ40 and Aβ42 levels in the hippocampi of young WT and APPKI
NL-G-F
mice using the human β amyloid (1–40 and 1–42) ELISA (12 weeks of age, n = 5 biologically independent samples per group). (
E
) Western blot analysis of phosphorylated insulin receptor substrates 1 mouse Ser307 [p-IRS1 (mSer307)], p-IRS1 (mSer612), p-IRS1 (mSer632/635), p-IRS1 (mSer1097), IRS1, and ß-tubulin in the hippocampi of young WT and APP KI
NL-G-F
mice (12 weeks of age, n = 6 biologically independent samples per group). Arrows indicate the p-IRS1 mSer612-corresponding band (lower band) and p-IRS1 mSer632/635-corresponding band (lower band) in (
E
). Quantitative analysis of the phosphorylation of IRS1 at mSer307, mSer612, mSer632/635, and mSer1097 normalized to the respective total protein contents. (
F
) Western blot analysis of phosphorylation levels of Akt Ser473, p70S6K Thr389, AMPK Thr172, and GSK3β Ser9 as well as total protein levels of Akt, p70S6K, AMPK, GSK3β, and ß-tubulin in the hippocampi of young WT and APPKI
NL-G-F
mice (12 weeks of age, n = 6 biologically independent samples per group). Quantitative analysis of phosphorylation of Akt Ser473, p70S6K Thr389, AMPK Thr172, and GSK3β Ser9 normalized to the respective total protein contents. Results are presented as mean ± SEM, *
p
< 0.05; **
p
< 0.01.
Using monoclonal antibody (BNT77/BC05)-based sandwich ELISA for human/rat/mouse Aβ42, we successfully confirmed that T-PER-extractable Aβ42 level had already increased in young APP KI NL-G-F mice ( Figure 4 C, right). A conspicuous increase in T-PER-extractable Aβ42 level in these mice was detected by human Aβ42 sandwich ELISA using monoclonal antibodies (BAN50/BC05) ( Figure 4 D, right). However, T-PER-extractable Aβ42 levels in both ELISA were comparable to the range of Tris-buffered saline (TBS)-extractable Aβ42 level in the brain and cortex of APPKI NL-G-F mice reported by Saito et al. (2019) and Saito et al. (2014). Similarly, human/rat/mouse Aβ40 and human Aβ40 sandwich ELISA revealed the same range for Aβ40 level in the T-PER fractions of the hippocampi of young APPKI NL-G-F mice (black bar on the left in Figure 4 C,D and Figure 5 C,D). Meanwhile, regardless of age, human/rat/mouse Aβ40 or human Aβ40 sandwich ELISA showed almost the same levels (white bar on the left in Figure 1 D, Figure 2 C, Figure 3 C, Figure 4 C and Figure 5 C) or range (white bar on the left in Figure 4 D and Figure 5 D) of T-PER-extractable Aβ40 in WT mice, respectively.
Figure 5.
Memory decline accompanied by sustained phosphorylation of IRS1 Ser residues in the hippocampus of middle-aged APPKI
NL-G-F
mice. (
A
) The graphs of body weight and blood glucose levels in middle-aged wild-type (WT) and APPKI
NL-G-F
mice (34–36 weeks of age, n = 5 mice per group). (
B
) Evaluation of learning memory function in middle-aged WT (n = 14) and APPKI
NL-G-F
mice (n = 15 mice per group) using the water T-maze test. (
C
) Quantitative analysis of T-PER-extractable Aβ40 and Aβ42 levels in the hippocampi of middle-aged WT and APPKI
NL-G-F
mice using the human/rat/mouse β amyloid (1–40 and 1–42) ELISA (34–36 weeks of age, n = 4 biologically independent samples per group). (
D
) Quantitative analysis of T-PER-extractable Aβ40 and Aβ42 levels in the hippocampi of middle-aged WT and APPKI
NL-G-F
mice using the human β amyloid (1–40 and 1–42) ELISA (34–36 weeks of age, n = 4 biologically independent samples per group). (
E
) Western blot analysis of phosphorylated insulin receptor substrates 1 mouse Ser307 [p-IRS1 (mSer307)], p-IRS1 (mSer612), p-IRS1 (mSer632/635), p-IRS1 (mSer1097), IRS1, and ß-tubulin in the hippocampi of middle-aged WT and APPKI
NL-G-F
mice (34–36 weeks of age, n = 6 biologically independent samples per group). Arrow indicates the p-IRS1 mSer612 -corresponding band (lower band) in (
E
). Quantitative analysis of the phosphorylation of IRS1 at mSer307, mSer612, mSer632/635, and mSer1097 normalized to total protein. (
F
) Western blot analysis of phosphorylation levels of Akt Ser473, p70S6K Thr389, AMPK Thr172, and GSK3β Ser9 as well as total protein levels of Akt, p70S6K, AMPK, GSK3β, and ß-tubulin in the hippocampi of middle-aged WT and APPKI
NL-G-F
mice (34–36 weeks of age, n = 6 biologically independent samples per group). Quantitative analysis of the phosphorylation of Akt Ser473, p70S6K Thr389, AMPK Thr172, and GSK3β Ser9 normalized to the respective total protein contents. Results are presented as mean ± SEM, *
p
< 0.05; **
p
< 0.01.
Subsequently, we investigated the phosphorylation levels of hippocampal IRS1 at Ser residues in young APPKI NL-G-F mice. Importantly, the phosphorylation of hippocampal IRS1 at mSer307, mSer612, and mSer1097, but not at mSer632/635, significantly increased in 12-week-old APPKI NL-G-F mice ( Figure 4 E, Figure S4G ) displaying normal memory function ( Figure 4 B). In parallel to these increases, a concomitant elevation in the basal phosphorylation of AMPK, a metabolic energy sensor, with p70S6K activation and a slight decrease in basal JNK phosphorylation were observed in these mice, along with monotonous Akt, GSK3β, and aPKC ζ/λ activity ( Figure 4 F, Figure S3D, S4H and S5D ). Thus, in young APPKI NL-G-F mice exhibiting normal memory function, the increased phosphorylation of hippocampal IRS1 at multiple Ser sites accompanied by AMPK-related low energy conditions had already occurred in the presence of increased Aβ42 level, suggesting that the elevation of Aβ42 level and/or AMPK activation provokes the activation of Ser sites on IRS1 in brains of patients with AD prior to the onset of memory decline.
3.5. Memory Decline in Middle-Aged APPKI NL-G-F Mice Is Accompanied by the Activation of Specific Ser Sites on IRS1 and Energy Depletion
Next, we examined age-related alterations in the patterns of phosphorylation of IRS1 at Ser sites and its downstream components in the hippocampi of middle-aged APPKI NL-G-F mice at 34–36 weeks of age. Consistently, body weight, blood glucose level, and plasma insulin concentration were comparable between middle-aged WT and APPKI NL-G-F mice ( Figure 5 A, Figure S2A ).
Although the onset of memory deficits was reported by 6 months in APPKI
NL-G-F
mice [
19
], 6-month-old APPKI
NL-G-F
mice did not display memory decline under our experimental conditions (data not shown). However, the water T-maze test demonstrated that middle-aged APPKI
NL-G-F
mice exhibited memory decline after 34 weeks under our experimental conditions (
Figure 5
B). Meanwhile, both human/rat/mouse Aβ42 and human Aβ42 sandwich ELISA demonstrated increased levels of T-PER-extractable Aβ42 in the hippocampi of middle-aged APPKI
NL-G-F
mice (right in
Figure 5
C, D) and young APPKI
NL-G-F
mice, which were comparable to TBS-extractable Aβ42 levels in the brain and cortex of APPKI
NL-G-F
mice [
33
].
While an age-related increase in the phosphorylation of IRS1 at mSer612 and mSer632/635 accompanied by sustained phosphorylation of IRS1 at T2DM-related mSer1097 site and of AMPK was observed in the hippocampi of middle-aged APPKI NL-G-F mice showing memory decline ( Figure 5 E, Figure S4I , Table S1 ), there were no significant differences in phosphorylation levels at mSer307 site and of p70S6K between middle-aged WT and APPKI NL-G-F mice ( Figure 5 E,F) owing to the age-related elevation of these factors ( Figure 3 D,E). Regardless of age, the activity of downstream components, such as Akt, GSK3β, aPKC ζ/λ, and JNKs, remained almost unchanged in the hippocampi of APPKI NL-G-F mice ( Figure 5 F, Figure S3E, S4J and S5E ). Our data suggest that the increased phosphorylation of hippocampal IRS1 at multiple Ser residues and persistent AMPK activation that corresponds to energy depletion accompanied by age-related elevation of Aβ42 levels are associated with the onset of memory decline in these mice.
4. Discussion
The present study demonstrates that memory decline in T1DM and T2DM in middle age occurs in an Aβ-independent manner, which is consistent with the findings of previous studies [ 34 , 35 , 36 ]. Similarly, age-related memory impairments arise with no alteration in Aβ levels.
In middle-aged DIO and aged mice, Aβ-unrelated memory deficits are accompanied by increased basal phosphorylation of hippocampal IRS1 at specific Ser residues, whereas Aβ-unrelated memory impairments develop in STZ mice without the modification of IRS1. Although p70S6K activation accompanied by unchanged AMPK activity in the hippocampus is mutually observed with Aβ-unrelated memory deficits in middle-aged DIO, STZ, and aged mice regardless of the presence or absence of the phosphorylation of IRS1 at Ser residues, different alterations in other downstream components were observed in these mouse models. Furthermore, we found that, in APPKI
NL-G-F
mice, a concomitant increase in the basal phosphorylation of hippocampal IRS1 at multiple Ser sites with the activation of AMPK and elevation of Aβ42 level had already arisen at a young age, before the onset of memory decline, and that memory decline in middle age was accompanied by the persistence of these changes with age-related increase in the phosphorylation of IRS1 at specific Ser sites and in Aβ42 level.
HFD and genetically obese animals exhibit increased phosphorylation at mSer307 and p70S6K-induced phosphorylation at mSer1097 in peripheral tissues [ 37 , 38 ]. In the central nervous system, the involvement of non-activated AMPK with/without phosphorylation of IRS1 at mSer307 accompanied by p70S6K activation or different combinations of alterations in Akt and GSK3β activity (i.e., increased or decreased phosphorylation) in cognitive impairment in 40–45% HFD-fed and STZ mice has been reported [ 21 , 22 , 27 , 28 , 32 , 34 , 39 , 40 ], whereas the monotonous levels of phosphorylation of IRS1 at Ser sites and of downstream kinases including Akt, AMPK, GSK3β, and p70S6K are observed in 45% HFD-induced cognitive deficits [ 41 ]. Consistent with these results, memory decline in middle-aged DIO mice is accompanied by a concomitant increase in the basal phosphorylation of IRS1 at mSer307 and mSer1097 with p70S6K activation and monotonous activity of Akt, GSK3β, and AMPK in the hippocampus. On the other hand, in aged mice, the concomitant activation of Akt and GSK3β with an increase in the basal phosphorylation of hippocampal IRS1 at mSer307, mSer612, and mSer632/635 with p70S6K activation is observed, which is consistent with previous studies showing that the increased phosphorylation of mSer632/635 or mSer1097 on IRS1 is associated with p70S6K [ 5 , 37 , 38 ]. Given that the activation of mSer612 on IRS1 may negatively correlate with intracellular signaling and that the activation of Ser632/635 on IRS1 may occur independently of Akt [ 5 ], it is likely that, in aged mice, the increased phosphorylation of IRS1 at mSer307, mSer612, and mSer632/635 with the activation of multiple downstream factors other than AMPK may arise through reciprocal feedback regulation.
Additionally, HFD- and STZ-induced diabetes increases the phosphorylation of JNK accompanied by the activation of mSer307 on IRS1 in the brain [ 21 , 32 ]. The activity of JNK is elevated in aged mice and transgenic mouse models of AD, although the involvement of phosphorylation of IRS1 at Ser sites in the altered activation of JNK has not been reported [ 16 , 42 ]. Furthermore, the activation of aPKC ζ/λ is associated with the phosphorylation of IRS1 at Ser sites, including mSer1097 [ 5 , 20 ]. However, in all types of mouse models of memory impairment in the present study, the basal phosphorylation levels of JNK and aPKC ζ/λ consistently remained unchanged under our experimental conditions. These discrepancies may be due to the differences in observation time, animal species, and HFD or STZ protocols, such as age, duration of exposure, diet fat content, and drug dosages. Taken together, these results suggest that the reciprocal effects of the phosphorylation of IRS1 at T2DM- or age-related Ser sites and downstream components via feedback loops that may lead to the common alterations in the activity of p70S6K and AMPK are involved in Aβ-unrelated memory decline; however, the modification of IRS1 through Ser sites is not required for the onset of memory deficits in STZ-induced T1DM mice.
Although a link between the phosphorylation of neural IRS1 at mSer307, mSer612, and mSer632/635 and brain insulin resistance has been proposed [ 14 , 16 , 43 ], brain insulin resistance is not yet defined, and the phosphorylation of IRS1 at Ser sites emerges in insulin-dependent and insulin-independent manners [ 5 , 6 ]. Given that diabetes- and obesity-induced memory impairments were accompanied by the phosphorylation of IRS1 at mSer307 [ 5 ], we found that young APPKI NL-G-F mice showing normal metabolism and memory function displayed increased phosphorylation of hippocampal IRS1 at three Ser residues including mSer307, mSer612, and mSer1097, in which the Aβ42 level had already increased before the onset of memory decline. Consistent with previous studies [ 13 , 14 , 15 , 16 ], the increased phosphorylation at mSer612 and mSer 632/635 and persistent activation of mSer1097 are observed in the hippocampus of middle-aged APPKI NL-G-F mice exhibiting memory decline with age-associated increase in the Aβ42 level.
Interestingly, in both young and middle-aged APPKI
NL-G-F
mice, the concomitant phosphorylation of hippocampal IRS1 at mSer612 and mSer1097 with the activation of AMPK is constantly observed regardless of the presence or absence of the activation of mSer307 or mSer 632/635, suggesting that persistent phosphorylation of mSer612 and mSer1097 accompanied by AMPK activation may contribute to memory dysfunction in AD.
Reportedly, the Arctic mutation in APPKI
NL-G-F
mice reduces immunoreactivity in ELISA because the location of this mutation on the Aβ sequences is overlapped with the binding region of monoclonal antibody to Aβ used in human/rat/mouse Aβ sandwich ELISA [
19
]; however, T-PER-extractable Aβ40 and Aβ42 levels were successfully determined by human/rat/mouse Aβ sandwich ELISA using BNT77 (binds to the location of the Arctic mutation) and human Aβ sandwich ELISA using BAN50 (does not bind to the location of the Arctic mutation). We confirmed that the elevation of Aβ42 level is evident in young APPKI
NL-G-F
mice and that the Aβ42 level increased in middle-aged APPKI
NL-G-F
mice. Owing to the elevation of Aβ42 level in the hippocampi of APPKI
NL-G-F
mice from a young age, it is likely that the increased phosphorylation of IRS1 at Ser sites is associated with Aβ42 level but not with memory decline. Consistent with this finding, a previous study showed that the phosphorylation of IRS1 at mSer307/hSer312 and mSer612/hSer616 increased in cultured hippocampal neurons exposed to Aβ oligomers prepared from synthetic Aβ1–42 peptide and in the AβO-injected hippocampi of non-human primates [
16
]. Interestingly, the increased basal phosphorylation of hippocampal IRS1 at multiple Ser sites in APPKI
NL-G-F
mice is accompanied by AMPK activation regardless of the presence or absence of memory decline. Consistent with our findings, recent studies suggest that AMPK activation is implicated in brain aging and development of neurodegenerative diseases, including AD [
44
,
45
]. These results suggest that the elevation of Aβ42 accompanied by AMPK activation induced by energy depletion that occurs from a young age before the onset of memory decline is associated with increased phosphorylation of hippocampal IRS1 at multiple Ser sites and that sustained activation of these factors contributes to the onset of memory decline in middle-aged APPKI
NL-G-F
mice.
In summary, whether the modification of IRS1 through its phosphorylation at Ser sites in the hippocampus has a pathogenic or an adaptive function remains unknown because the phosphorylation of hippocampal IRS1 at mSer307, mSer612, and mSer1097 increased when metformin improves memory deficits in middle-aged DIO mice [ 20 , 46 ]. Studies using mutant mice with IRS1 Ser residues in the brain will help us to understand the roles of Ser sites in memory function and to identify unrecognized downstream pathways.
5. Conclusions
Our findings indicate that the phosphorylation of IRS1 at disease-specific Ser residues in the hippocampus may be a potential marker of Aβ-unrelated memory impairments induced by T2DM and aging. Alternatively, in Aβ-related memory decline in AD, the modification of IRS1 via its phosphorylation at multiple Ser sites accompanied by the activation of AMPK, a sensor of energy metabolism, may be a marker of the response to an early detection of elevated Aβ42 level before the onset of memory decline in AD.
Supplementary Materials
The following are available online at https://www.mdpi.com/2072-6643/11/8/1942/s1 : Figure S1: No difference in memory function between wild-type (WT) and DIO mice at a young age.; Figure S2: Levels of blood insulin in the respective mouse models.; Figure S3: Evaluation of the other signaling factors associated with IRS1 signaling in the hippocampus.; Figures S4 and S5: Full images of Western blots; Table S1: Summary of phosphorylated Ser residues on hippocampal IRS1 in all models.
Author Contributions
W.W., D.T., Y.F., M.M., and C.K. researched data. W.W. and D.T. analyzed data. W.W., D.T., and Y.F. wrote the manuscript. T.S. and T.C.S. provided the APPKI mice and interpreted the data. A.T. designed experiments, analyzed data, and wrote and edited the manuscript. All authors read and approved the final manuscript.
Funding
This work was supported by JSPS KAKENHI (JP26282026, JP17K19951, JP17H02188) (A.T.), the Research Funding for Longevity Science from National Center for Geriatrics and Gerontology, Japan (A.T.), and grants from the Mitsubishi Foundation (A.T.)
Acknowledgments
We thank Kohei Tomita (Laboratory of Experimental Animal, National Center for Geriatrics and Gerontology) for animal care and M. Sawaura and K. Tabata for providing aged wild-type mice (Charles river, Japan).
Conflicts of Interest
The authors declare no conflict of interest.
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Figure 1. Changes in specific Ser sites on hippocampal insulin receptor substrate 1 (IRS1) in type 2 diabetes (T2DM)-induced memory impairment. ( A ) Schematic diagram of the experimental procedure. ( B ) Graphs of body weight and blood glucose level in wild-type (WT) and diet-induced obesity (DIO) mice (35 weeks of age, n = 5 mice per group). ( C ) Evaluation of learning memory function in middle-aged WT and DIO mice (n = 14 mice per group) using the water T-maze test. ( D ) Quantitative analysis of T-PER (Tissue Protein Extraction Reagent)-extractable Aβ40 and Aβ42 levels in the hippocampi of middle-aged WT and DIO mice using the human/rat/mouse β amyloid (1–40 and 1–42) enzyme-linked immunosorbent assay (ELISA) (35 weeks of age, n = 5 biologically independent samples per group). (E) Western blot analysis of phosphorylated insulin receptor substrates 1 mouse Ser307 [p-IRS1 (mSer307)], p-IRS1 (mSer612), p-IRS1 (mSer632/635), p-IRS1 (mSer1097), IRS1, and β-tubulin in the hippocampi of middle-aged WT and DIO mice (35 weeks of age, n = 5 biologically independent samples per group). Arrow indicates the p-IRS1 mSer612-corresponding band (lower band) in ( E ). Quantitative analysis of the phosphorylation of IRS1 at mSer307, mSer612, mSer632/635, and mSer1097 normalized to total protein. ( F ) Western blot analysis of phosphorylation levels of Akt Ser473, p70S6K Thr389, AMP-activated protein kinase (AMPK) Thr172, and glycogen synthase kinase 3 beta (GSK3β) Ser9 as well as total protein levels of Akt, p70 S6K, AMPK, GSK3β, and ß-tubulin in the hippocampi of middle-aged WT and DIO mice (35 weeks of age, n = 5 biologically independent samples per group). Quantitative analysis of the phosphorylation of Akt Ser473, p70S6K Thr389, AMPK Thr172, and GSK3β Ser9 normalized to the respective total protein contents. Results are presented as mean ± standard error of the mean (SEM), * p < 0.05; ** p < 0.01.
Figure 2. No alteration of IRS1 Ser phosphorylation in the hippocampus of T1DM mouse models. ( A ) Graphs of body weight and blood glucose level in wild-type (WT) and streptozotocin (STZ)-induced insulin-deficient type 1 diabetes (T1DM) model mice (10 weeks of age, n = 5 mice per group). ( B ) Evaluation of hippocampus-dependent learning and memory function and hippocampus/prefrontal cortex associated working memory function in WT (10 weeks of age, n = 19 mice per group) and STZ mice (10 weeks of age, n = 18 mice per group) using the water T-maze test and reverse water T-maze test. ( C ) Quantitative analysis of T-PER-extractable Aβ40 and Aβ42 levels in the hippocampi of WT and STZ mice using the human/rat/mouse β amyloid (1–40 and 1–42) ELISA (10 weeks of age, n = 5 biologically independent samples per group). ( D ) In WT and STZ-induced type 1 diabetes mice (10 weeks of age, n = 5 biologically independent samples per group), western blot analysis of phosphorylated insulin receptor substrates 1 mouse Ser307 [p-IRS1 (mSer307)], p-IRS1 (mSer612), p-IRS1 (mSer632/635), p-IRS1 (mSer1097), IRS1, and ß-tubulin was performed. Quantitative analysis of the phosphorylation of IRS1 at mSer307, mSer612, mSer632/635, and mSer1097 normalized to total protein. ( E ) Western blot analysis of phosphorylation levels of Akt Ser473, p70S6K Thr389, AMPK Thr172, and GSK3β Ser9 as well as total protein levels of Akt, p70S6K, AMPK, GSK3β, ß-tubulin in WT and STZ mice (10 weeks of age, n = 5 biologically independent samples per group). Arrows indicate the p-IRS1 mSer612-corresponding band (lower band) and the p-IRS1 mSer632/635-corresponding band (lower band) in ( D ). Quantitative analysis of the phosphorylation of Akt Ser473, p70 S6K Thr389, AMPK Thr172, and GSK3β Ser9 normalized to the respective total protein contents. Results are presented as mean ± SEM, * p < 0.05; ** p < 0.01.
Figure 3. Age-related memory deficits accompanied by increased phosphorylation of IRS1 Ser sites in the hippocampus. ( A ) The graphs of body weight and blood glucose levels in young (12 weeks of age, n = 7 mice per group) and aged (84 weeks of age, n = 7 mice per group) wild-type (WT) mice. ( B ) Evaluation of learning memory functions in young WT mice (n = 16 mice per group) and aged WT mice (n = 18 mice per group) using the water T-maze test. ( C ) Quantitative analysis of T-PER-extractable Aβ40 and Aβ42 levels in the hippocampi of young (12 weeks of age, n = 6 biologically independent samples) and aged (84 weeks of age, n = 6 biologically independent samples) WT mice using the human/rat/mouse β amyloid (1–40 and 1–42) ELISA. ( D ) Western blot analysis of phosphorylated insulin receptor substrates 1 mouse Ser307 [p-IRS1 (mSer307)], p-IRS1 (mSer612), p-IRS1 (mSer632/635), p-IRS1 (mSer1097), IRS1, and ß-tubulin in the hippocampi of young WT mice (12 weeks of age, n = 6 biologically independent samples) and aged WT mice (84 weeks of age, n = 6 biologically independent samples). Quantitative analysis of the phosphorylation of IRS1 at mSer307, mSer612, mSer632/635, and mSer1097 normalized to total protein. ( E ) Western blot analysis of phosphorylation levels of Akt Ser473, p70S6K Thr389, AMPK Thr172, and GSK3β Ser9 as well as total protein levels of Akt, p70S6K, AMPK, GSK3β, and ß-tubulin in the hippocampi of young WT mice (12 weeks of age, n = 6 biologically independent samples) and aged WT mice (84 weeks of age, n = 6 biologically independent samples). Arrows indicate the p-IRS1 mSer612-corresponding band (lower band) and the p-IRS1 mSer632/635-corresponding band (lower band) in ( D ). Quantitative analysis of the phosphorylation of Akt Ser473, p70S6K Thr389, AMPK Thr172, and GSK3β Ser9 normalized to the respective total protein contents. Results are presented as mean ± SEM, * p < 0.05; ** p < 0.01.
Figure 4. Activation of multiple Ser residues on hippocampal IRS1 unrelated to memory decline in young amyloid precursor protein (APP) knock-in (APPKI NL-G-F ) mice. ( A ) The graphs of body weight and blood glucose levels in young wild-type (WT) and APPKI NL-G-F mice (12 weeks of age, n = 6 mice per group). ( B ) Evaluation of learning memory function in young WT (n = 5 mice per group) and APP KI NL-G-F mice (n = 5 mice per group) using the water T-maze test. ( C ) Quantitative analysis of T-PER-extractable Aβ40 and Aβ42 levels in the hippocampi of young WT and APPKI NL-G-F mice using the human/rat/mouse β amyloid (1–40 and 1–42) ELISA (12 weeks of age, n = 5 biologically independent samples per group). ( D ) Quantitative analysis of T-PER-extractable Aβ40 and Aβ42 levels in the hippocampi of young WT and APPKI NL-G-F mice using the human β amyloid (1–40 and 1–42) ELISA (12 weeks of age, n = 5 biologically independent samples per group). ( E ) Western blot analysis of phosphorylated insulin receptor substrates 1 mouse Ser307 [p-IRS1 (mSer307)], p-IRS1 (mSer612), p-IRS1 (mSer632/635), p-IRS1 (mSer1097), IRS1, and ß-tubulin in the hippocampi of young WT and APP KI NL-G-F mice (12 weeks of age, n = 6 biologically independent samples per group). Arrows indicate the p-IRS1 mSer612-corresponding band (lower band) and p-IRS1 mSer632/635-corresponding band (lower band) in ( E ). Quantitative analysis of the phosphorylation of IRS1 at mSer307, mSer612, mSer632/635, and mSer1097 normalized to the respective total protein contents. ( F ) Western blot analysis of phosphorylation levels of Akt Ser473, p70S6K Thr389, AMPK Thr172, and GSK3β Ser9 as well as total protein levels of Akt, p70S6K, AMPK, GSK3β, and ß-tubulin in the hippocampi of young WT and APPKI NL-G-F mice (12 weeks of age, n = 6 biologically independent samples per group). Quantitative analysis of phosphorylation of Akt Ser473, p70S6K Thr389, AMPK Thr172, and GSK3β Ser9 normalized to the respective total protein contents. Results are presented as mean ± SEM, * p < 0.05; ** p < 0.01.
Figure 5. Memory decline accompanied by sustained phosphorylation of IRS1 Ser residues in the hippocampus of middle-aged APPKI NL-G-F mice. ( A ) The graphs of body weight and blood glucose levels in middle-aged wild-type (WT) and APPKI NL-G-F mice (34–36 weeks of age, n = 5 mice per group). ( B ) Evaluation of learning memory function in middle-aged WT (n = 14) and APPKI NL-G-F mice (n = 15 mice per group) using the water T-maze test. ( C ) Quantitative analysis of T-PER-extractable Aβ40 and Aβ42 levels in the hippocampi of middle-aged WT and APPKI NL-G-F mice using the human/rat/mouse β amyloid (1–40 and 1–42) ELISA (34–36 weeks of age, n = 4 biologically independent samples per group). ( D ) Quantitative analysis of T-PER-extractable Aβ40 and Aβ42 levels in the hippocampi of middle-aged WT and APPKI NL-G-F mice using the human β amyloid (1–40 and 1–42) ELISA (34–36 weeks of age, n = 4 biologically independent samples per group). ( E ) Western blot analysis of phosphorylated insulin receptor substrates 1 mouse Ser307 [p-IRS1 (mSer307)], p-IRS1 (mSer612), p-IRS1 (mSer632/635), p-IRS1 (mSer1097), IRS1, and ß-tubulin in the hippocampi of middle-aged WT and APPKI NL-G-F mice (34–36 weeks of age, n = 6 biologically independent samples per group). Arrow indicates the p-IRS1 mSer612 -corresponding band (lower band) in ( E ). Quantitative analysis of the phosphorylation of IRS1 at mSer307, mSer612, mSer632/635, and mSer1097 normalized to total protein. ( F ) Western blot analysis of phosphorylation levels of Akt Ser473, p70S6K Thr389, AMPK Thr172, and GSK3β Ser9 as well as total protein levels of Akt, p70S6K, AMPK, GSK3β, and ß-tubulin in the hippocampi of middle-aged WT and APPKI NL-G-F mice (34–36 weeks of age, n = 6 biologically independent samples per group). Quantitative analysis of the phosphorylation of Akt Ser473, p70S6K Thr389, AMPK Thr172, and GSK3β Ser9 normalized to the respective total protein contents. Results are presented as mean ± SEM, * p < 0.05; ** p < 0.01.
MDPI and ACS Style
Wang, W.; Tanokashira, D.; Fukui, Y.; Maruyama, M.; Kuroiwa, C.; Saito, T.; Saido, T.C.; Taguchi, A. Serine Phosphorylation of IRS1 Correlates with Aβ-Unrelated Memory Deficits and Elevation in Aβ Level Prior to the Onset of Memory Decline in AD. Nutrients 2019, 11, 1942.
https://doi.org/10.3390/nu11081942
AMA Style
Wang W, Tanokashira D, Fukui Y, Maruyama M, Kuroiwa C, Saito T, Saido TC, Taguchi A. Serine Phosphorylation of IRS1 Correlates with Aβ-Unrelated Memory Deficits and Elevation in Aβ Level Prior to the Onset of Memory Decline in AD. Nutrients. 2019; 11(8):1942.
https://doi.org/10.3390/nu11081942
Chicago/Turabian Style
Wang, Wei, Daisuke Tanokashira, Yusuke Fukui, Megumi Maruyama, Chiemi Kuroiwa, Takashi Saito, Takaomi C. Saido, and Akiko Taguchi. 2019. "Serine Phosphorylation of IRS1 Correlates with Aβ-Unrelated Memory Deficits and Elevation in Aβ Level Prior to the Onset of Memory Decline in AD" Nutrients11, no. 8: 1942.
https://doi.org/10.3390/nu11081942
| https://www.mdpi.com/2072-6643/11/8/1942/xml |
Gaines v. New Orleans - Federal Cases - Case Law - VLEX 892899085
0: [object Object]. 1: [object Object]. 2: [object Object]. 3: [object Object]. 4: [object Object]
Gaines v. New Orleans
Court United States Supreme Court Writing for the Court DAVIS Citation 6 Wall. 642,18 L.Ed. 950,73 U.S. 642 Parties GAINES v. NEW ORLEANS Decision Date 01 December 1867
73 U.S. 642
18 L.Ed. 950
6 Wall. 642
GAINES
v.
NEW ORLEANS.
December Term, 1867
Page 643
THIS case came here upon appeal from the Circuit Court of the District of Louisiana.
It was a bill in equity, filed by Mrs. Myra Clark Gaines,
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December 22d, 1856, against certain defendants, in which she sought to recover very valuable real estate, situated in New Orleans, which belonged, as she alleged, to Daniel Clark, her father, who died in New Orleans, in August, 1813, Mrs. Gaines claiming title as universal legatee under a last will of his made in 1813.
The bill alleged,——
1st. That the complainant was the only legitimate child of Clark.
2d. That all the property sought to be recovered belonged to Clark at his decease.
3d. That at his death he left a valid last will and testament in which the complainant was declared his only legitimate child, and made his universal legatee, subject to certain payments.
4th. That this will of 1813, having been lost or destroyed, it was duly recognized and admitted to probate by the Supreme Court of Louisiana in 1856, and ordered to be executed.
5th. That Clark had made a provisional will in 1811, in which he made his mother, Mary Clark, his universal legatee and sole heir, and appointed Richard Relf and Beverly Chew the testamentary executors thereof; which will of 1811 was revoked by the will of 1813, but that Relf & Chew wrongfully obtained the probate of the will of 1811, and illegally administered the estate under it; making sales fraudulently and with notice of the complainant's equities, &c.
6th. That the complainant was a minor until 1827, and ignorant of her parentage and rights in her father's estate until 1834, and that from that time to the present she had persistently claimed this estate, and diligently sought its recovery by all the legal means in her power.
The bill sought a discovery from the defendants, and prayed a delivery of the property, and an account of the rents and profits, and for general relief.
THE ANSWER of the defendants admitted the possession in them of the property claimed in the bill, and that the legal
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title thereof was in Clark, at the time of his death in 1813; but they set up——
That Clark's title passed to them or their grantors by virtue of sales made by Relf & Chew, as testamentary executors of the will of 1811.
That this title passed also under sales made by Relf & Chew, as attorneys of Mary Clark, 'sole heir and legatee' of the will of 1811.
That the estate of Clark was insolvent.
That the accounts of Chew & Relf reporting the sales had been duly approved by the Probate Court of New Orleans; and that this was binding on the complainant.
That an equitable title to two-thirds of the property was in Relf & Chew, andc reditors of Clark, by virtue of certain partnership articles, of June 19th, 1813.
They also pleaded the prescription of five, ten, twenty, and thirty years; and that they are 'purchasers in good faith, without notice, for a valuable consideration;' and that they are purchasers from 'purchasers in good faith, without notice, for a valuable consideration.'
They also relied upon the nullity of the probate of the will of 1813, by the Supreme Court of Louisiana, in 1856, there having been no decree of nullity of the prior will of 1811.
Upon these issues judgment was rendered against the complainant, and from such judgment it was that the present appeal was taken.
The case with two accompanying it constituted the seventh, eighth and ninth appeals to this court of a controversy known as the 'Gaines case.' For more than one-third of a century, in one form and another, it had been the subject of judicial decision in this court, and the records now—complicated in the extreme—reached nearly eight thousand closely printed pages. If this court, when the case was last heard before it, 1 spoke of it as 'one which, when hereafter some distinguished American lawyer shall retire from his
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practice to write the history of his country's jurisprudence, will be registered by him as the most remarkable in the records of its courts,' the present reporter will surely be excused, if, in that haste which a speedy publication of current decisions requires, he shall, from such records as he has described,—and in a matter where as to facts, simply, this high tribunal has been always largely divided on the evidence,—have attained much less than perfect accuracy of detail or even than the truest form of presentation generally. As far as he has himself conceived the case from the huge volumes in which it was imbedded—but deprecating reliance upon his statement in any matter affecting property involved in these issues if, contrary to the hope expressed by this court, further question about property is anywhere to be made—the subject, in its outlines and general effect, seemed thus to present itself:
The close of the last century found residing at New Orleans, then but a small town, a person named Danied Clark. He was a native of Ireland, born at Sligo about the year 1766, but had received an education in England, at Eton and other places there. Before reaching the age of 21 he had come to New Orleans by invitation of an uncle already resident there; a person of some consideration, and to whose property he succeeded in 1799. He is described as having been a man of much personal pride and social ambition, of high intellignece, full of enterprise, and though 'very peculiar in some respects' (and, in at least one, censurable), to have been characterized by numerous chivalric and honorable dispositions. His pecuniary integrity was unquestioned. He became early an actor in the events of his day and region, a leader of party there, and connected either by concert or by opposition with many public men of the time. To him more than to almost any one, as it seemed, was to be attributed the acquisition by our country of the State of Louisiana. He had been consul of the United States there before the acquisition, and in 1806-8, represented the Territory in Congress; its first representative in
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that body. Everywhere his associations were of a marked kind, and with people of social importance. Up to 1808 or 1810 he was engaged in commercial affairs on a considerable scale, and extending from New Orleans to Montreal; being associated at New Orleans with two gentlemen, both long known there as occupying positions of public trust, Messrs. Richard Relf and Beverly Chew, as partners, and in Philadelphia with the late Daniel W. Coxe, a person of distinguished standing in that city. With Mr. Coxe his relations began so far back as 1791. Mr. Clark died in New Orleans August 16th, 1813, at the age of 48, and, as was commonly reputed, a bachelor; but as was testified, engaged to be married to lady of that place, Madame _____, previously married and now divorced. No will but one, dated in 1811, was found after his death. It left his property to his mother, who with her husband had followed Daniel Clark to this country, and was now resident at Germantown, near Philadelphia; but of any wife or child, or children, lawful or illegitimate, it said nothing. That document had been made on the eve of a voyage from New Orleans to Philadelphia, and was in these words:
'IN THE NAME OF GOD, AMEN! I, Daniel Clark, of New Orleans, do make this my last will and testament: Imprimis, I order all my just debts to be paid; second, I leave and bequeath unto my mother, Mary Clark, now of Germantown, in the State of Pennsylvania, all estate, whether real or personal, which I may die possessed of; thirdly, I hereby nominate and appoint my friends, Richard Relf and Beverly Chew, my executors, with power to settle everything relating to my estate.
'DANIEL CLARK.
'NEW ORLEANS, 20th May, 1811.'
A few hours after Clark's death allegations were made by one Chevalier Dusuau De la Croix,—who represented that he had 'strong reasons to believe, and did verily believe, that such a will was executed,' and that he was interested in it,—of a later will, and a petition was presented to the Court of Probate, in New Orleans, setting forth the probable
Page 648
existence of such a will, and praying that each one of the different notaries of the city might appear before the court immediately, 'in order to certify if there does or does not exist in his office any testament or codicial or sealed packet deposited by the said late Daniel Clark.' None such was produced. The will above quoted was therefore proved before Judge Pitou, Judge of Probate, hereafter mentioned, and under it Relf and Chew, the persons named in it as executors—his already mentioned partners in trade—disposed of Clark's estates.
Soon after the time that Clark first found himself at New Orleans, was living there also a native of Clermont, France, named Jerome Des Granges. Des Granges made some pretensions to family importance at home, but in New Orleans was a confectionr; making and vending syrups and liquors also, and having a distillery. He had married in 1794, with the ceremonies of the Roman church, a young person of New Orleans, Zulime de Carriere, not then, as it seemed, above fourteen or fifteen years old, a native of New Orleans, from French parents in Gascony and Bordeaux, and was living with her as his wife: a person whom various testimony proved to have been remarkable for beauty.
With Zulime, Clark became acquainted, and formed an illicit connection in or prior to 1801.
In the spring of the year just named Des Granges sailed for France, his apparent purpose there being the recovery of some property, to which his wife and her sisters, two of whom were Madame Despau and Madame Caillavet, were entitled. On the 26th of March, in the same year, these all gave to him—describing him as 'our brother-in-law'—a power of attorney of the fullest kind to act for them. Des Granges in turn on that same day gives to Marie Zulime Carriere, describing her...
38 practice notes
Succession of Marinoni, 33013 United States Supreme Court of Louisiana November 4, 1935 ...in favor of the good faith of the parties. Succession of Navarro, 24 La.Ann. 298; Gaines v. City of New Orleans, 73 U.S. (6 Wall.) 642, 18 L.Ed. 950 . "'The good faith referred to means an honest and reasonable belief that the marriage was valid and that there existed no legal impediment the......
Daniels v. Isham United States United States State Supreme Court of Idaho April 25, 1925 ...v. Board of Commissioners, 12 Okla. 267, 70 P. 378; Byrne v. Hume, 84 Mich. 185, 47 N.W. 679; Gaines v. New Orleans, 6 Wall. (U.S.) 642, 18 L.Ed. 950 ; Ackley v. Tinker, 26 Kan. 485.) The probate court had jurisdiction to admit the will to probate and to enter the judgment decreeing that Ell......
Parker v. Parker, 2654. United States United States Courts of Appeals. United States Court of Appeals (5th Circuit) April 15, 1915 ...298; Harrington v. Barfield, 30 La.Ann.Part 2, 1297; Gaines v. Hennen, 24 How. 553, 16 L.Ed. 770; Gaines v. New Orleans, 6 Wall. 642, 18 L.Ed. 950 ; Smith Smith, 1 Tex. 621, 46 Am.Dec. 121; Lee v. Smith, 18 Tex. 141; Henderson v. Ryan, 27 Tex. 670, cited. If this separate opinion may be crit......
In Re Bentley's Will. United States Virginia Supreme Court of Virginia June 10, 1940 ...v. Schultz, supra, is cited with approval. See also, Gaines v. Hennen, 65 U.S. 553, 24 How. 553, 16 L.Ed. 770; Gaines v. New Orleans, 73 U.S. 642 , 6 Wall. 642, 18 L.Ed. 950.2 But the appellees insist that the offer to probate the later will is in effect a contest of the earlier will, and th......
38 cases
Succession of Marinoni, 33013 United States Supreme Court of Louisiana November 4, 1935 ...in favor of the good faith of the parties. Succession of Navarro, 24 La.Ann. 298; Gaines v. City of New Orleans, 73 U.S. (6 Wall.) 642, 18 L.Ed. 950 . "'The good faith referred to means an honest and reasonable belief that the marriage was valid and that there existed no legal impediment the......
Daniels v. Isham United States United States State Supreme Court of Idaho April 25, 1925 ...v. Board of Commissioners, 12 Okla. 267, 70 P. 378; Byrne v. Hume, 84 Mich. 185, 47 N.W. 679; Gaines v. New Orleans, 6 Wall. (U.S.) 642, 18 L.Ed. 950 ; Ackley v. Tinker, 26 Kan. 485.) The probate court had jurisdiction to admit the will to probate and to enter the judgment decreeing that Ell......
Parker v. Parker, 2654. United States United States Courts of Appeals. United States Court of Appeals (5th Circuit) April 15, 1915 ...298; Harrington v. Barfield, 30 La.Ann.Part 2, 1297; Gaines v. Hennen, 24 How. 553, 16 L.Ed. 770; Gaines v. New Orleans, 6 Wall. 642, 18 L.Ed. 950 ; Smith Smith, 1 Tex. 621, 46 Am.Dec. 121; Lee v. Smith, 18 Tex. 141; Henderson v. Ryan, 27 Tex. 670, cited. If this separate opinion may be crit......
In Re Bentley's Will. United States Virginia Supreme Court of Virginia June 10, 1940 ...v. Schultz, supra, is cited with approval. See also, Gaines v. Hennen, 65 U.S. 553, 24 How. 553, 16 L.Ed. 770; Gaines v. New Orleans, 73 U.S. 642 , 6 Wall. 642, 18 L.Ed. 950.2 But the appellees insist that the offer to probate the later will is in effect a contest of the earlier will, and th......
| https://case-law.vlex.com/vid/gaines-v-new-orleans-892899085 |
Health, employment, and economic change, 1973-2009: repeated cross sectional study | The BMJ
Health, employment, and economic change, 1973-2009: repeated cross sectional study
Article
Jonathan William Minton , research associate 1 ,
Kate E Pickett , professor of epidemiology 2 ,
Danny Dorling , professor of human geography 3
Author affiliations
1 University of Sheffield, School of Health and Related Research, Sheffield S1 4DA, UK
2 University of York, Department of Health Sciences, Heslington YO20 5DD, UK
3 University of Sheffield, Department of Geography, Sheffield S10 2TN
Correspondence to: Jonathan William Minton [email protected]
Accepted 1 March 2012
Abstract
ObjectiveTo see whether adverse relations between social class, health, and economic activity, observed between 1973 and 1993 and previously identified in a 1996 BMJpaper, were still apparent between 1994 and 2009 despite improvements in the general economic climate and overall population health.
DesignReplication of repeated cross sectional analysis from the original paper, using the same source (the General Household Survey) and occupation coding scheme, but extended from the period 1973-93 to 1973-2009, and including women as well as men.
SubjectsMen and women aged 20-59 years in each annual survey between 1973 and 2009.
Main outcome measuresChange over time in class specific rates of employment, unemployment, and economic inactivity within subgroups of respondents.
ResultsOverall employment rates have decreased for men of working age while increasing for working age women. For men in particular, the gradient of these changes seems to depend on occupational group. Over 37 years, the differences in occupational group specific economic inactivity and employment rates between people reporting and those not reporting a limiting long term illness has increased substantially.
ConclusionBetween 1973 and 2009, the relation between good health and securing and sustaining employment has strengthened for both men and women. For men, this has been due to employment rates decreasing and economic inactivity rates increasing among men with poor health. For women, this has largely been due to a general trend of increased employment and reduced economic inactivity occurring among healthier women but not in women of poorer health. Some evidence suggests that, since 2005, the relation between health, employment, and economic inactivity for women in the top two occupational groups has become more like that for men, with poor health becoming associated with reducing employment rates.
Introduction
This paper looks at how the relation between occupational background, ill health, and economic activity has changed over the period 1973 to 2009, following an approach described in a paper published in the BMJin 1996.1The research in the original paper was done to understand why falls in unemployment following the peaks of recessions in 1986 and 1990 were not accompanied by equal increases in employment. It found that job loss and economic inactivity related to ill health had a social gradient, with adverse employment consequences more likely for people in lower socioeconomic groups. The aim of this paper is to assess the long term consequences of the recessions of the 1980s and 1990s, and to look for early indications of the effect of the recession beginning in 2008.
Methods
The methods follow those described in the original paper. We used data from the General Household Surveys of Great Britain (incorporated as a module within the Integrated Household Survey and renamed the General Lifestyle Survey in 2008).
The General Household Surveys/General Lifestyle Surveys are annual surveys of households in Great Britain, which have been done by the Office for National Statistics (ONS) almost every year since 1971. Before 2005 it used a cross sectional design, and from 2005 onwards longitudinal components were incorporated so that some people were interviewed up to four years in succession. The surveys use a two stage, cluster randomised design. In stage one, postcodes are randomly selected using the postcode address file; in stage two, households within the postcode are selected. The number of households surveyed has varied each year and for most years has been in excess of 10 000. Annual response rates have varied between 67% and 85%, and in 2009 it was 73%.2The ONS has not directly recorded demographic characteristics of non-responders, but differences between responders and non-responders have been indirectly assessed by comparison with the 2001 census.3
The original study used only men, aged between 20 and 59 years and excluding students and people on training schemes. In contrast, this paper will look separately at both men and women. Members of the population were assigned to one of four social classes on the basis of usual occupation, one of three labour market categories, and one of two health states. The social classes are class 1—professional/managerial; class 2—intermediate non-manual; class 3—skilled manual; and class 4—semi-skilled and unskilled manual. The labour market categories comprise three mutually exclusive and exhaustive states: employed, unemployed, and economically inactive. Both employment and unemployment are classed as forms of economic activity; unemployment differs from economic inactivity in that unemployed people remain part of the labour force through actively seeking work, whereas economically inactive people do not. The binary health state indicates whether the respondent reported a limiting long term illness. Although most of the surveys are cross sectional, and so do not allow tracking of the changing health and employment of individuals over time, they have the advantage of being done in a consistent way, using identical or near identical questions and classifications throughout the period.
Results
Figure 1 ⇓shows employment levels for men in each occupational group, along with a dashed vertical line to indicate 1993, the final observation in the original paper. Figure 2 ⇓shows the equivalent figures for women.
Fig 1Employment rate in men of working age
Fig 2Employment rate in women of working age
The general trend apparent by comparing figures 1 ⇑and 2 ⇑is that rates of employment have decreased for men but increased for women. For both men and women, rates of employment have tended to be higher among higher occupational groups, though the distinction seems to be more consistent for men than women. For men, a clear cyclic pattern in employment rates can be seen, corresponding to the recessions of the early 1980s and early 1990s; a clear decline is also evident in 2009. This cyclic pattern is less evident for women and is perhaps masked by the stronger long term trend towards higher employment rates.
Figure 3 ⇓shows employment rates for men, separately for those with and those without limiting long term illness, and for each of the four occupational groups. Figure 4 ⇓shows the equivalent trends for women. Characterised crudely, rates of occupational group specific employment have declined only marginally for men without limiting long term illness and have declined significantly for those with such illness. Conversely, rates of occupational group specific employment have remained broadly constant for women with limiting long term illness and risen substantially for those without limiting illness. For both men and women, the employment deficit associated with limiting long term illness has increased substantially over time. For men in particular, occupational group seems to affect the disparity between those with and without limiting long term illness; “lower” occupational groups are associated with wider and more quickly increasing disparities. Figure 4 ⇓indicates that employment rates have fallen for women with limiting long term illness in the two highest occupational categories since around 2005.
Fig 3Employment rate in men of working age with and without limiting long term illness, by occupational group
Fig 4Employment rate in women of working age with and without limiting long term illness, by occupational group
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Figures 5 ⇓and 6 ⇓show what happened to rates of unemployment in men and women over the same time period. Occupational group specific rates have tended to be higher for men than women and both higher and more responsive to economic conditions for men of lower occupational groups. For all occupational groups and for both sexes, trends have not differed between those with and those without limiting long term illness.
Fig 5Unemployment rate in men of working age with and without limiting long term illness, by occupational group
Fig 6Unemployment rate in women of working age with and without limiting long term illness, by occupational group
Figure 7 ⇓shows rates of occupational group specific economic inactivity for men with and without limiting long term illness. Figure 8 ⇓shows the equivalent trends for women. The trend for men is clear: rates of occupational group specific economic inactivity have remained broadly constant for men without limiting long term illness but have increased substantially for each occupational group for men with limiting illness. The rate of the rise in economic inactivity among men with limiting long term illness is lowest for men in the highest occupational group and highest for those in the lowest occupational group. For women, rates of economic inactivity have decreased over the long term within each occupational group for those without limiting long term illness but have remained at relatively constant levels throughout for those with limiting illness. Mirroring trends seen in figure 4 ⇑, figure 8 ⇓shows increases in inactivity rates for women with limiting long term illness in the highest two occupational groups but not in those without such illness.
Fig 7Economic inactivity rate in men of working age with and without limiting long term illness, by occupational group
Fig 8Economic inactivity rate in women of working age with and without limiting long term illness, by occupational group
The table ⇓shows the Pearson correlation between unemployment, employment, and economic inactivity for men and women in each occupational group and for those with and without limiting long term illness. For men, the presence or absence of a limiting illness seems to affect the relative strength of the occupational group specific correlation between employment and unemployment and between employment and economic inactivity: for those with limiting illness, employment and inactivity are very strongly negatively correlated, and employment and unemployment are only moderately negatively correlated. For those without limiting long term illness, by contrast, employment is strongly negatively correlated with unemployment and only weakly and inconsistently correlated with inactivity. For women, by contrast, employment is strongly negatively correlated with inactivity for both those with and those without limiting illness.
Pearson correlation between employment, unemployment, and economic inactivity for working age men and women, with and without limiting long term illness
Discussion
These analyses have shown a general long term trend towards reduced rates of occupational group specific employment among men of working age and a similar long term trend towards increased employment rates among women of working age. For both men and women, the employment gap between those with and without limiting long term illness has grown. For men this has mainly been due to employment rates being relatively stable for those without limiting long term illness while falling for those with such illness, whereas for women it has mainly resulted from relatively stable levels of employment among those with limiting illness and increased employment among those without such illness. For both men and women, occupational group seems to have a significant moderating effect on the effect of limiting long term illness on employment, unemployment, and inactivity rates, with greater and more rapidly widening deficits for people with limiting illness in lower occupational groups than in higher occupational groups.
Strengths and weaknesses of study
The main strength of this study is the long duration for which the General Household Survey/General Lifestyle Survey has been done, and the consistency with which the questions about health and occupation have been asked. This has allowed patterns in the relation between health and the labour market to be analysed over a time period of more than three decades. As a random sample of the population is selected for the survey each year, the results should remain representative of the UK population despite changes in its demography. As a subjective rather than objective assessment of participants’ health was used, we cannot identify whether objective standards of ill health have changed over time. More specific details on types of health complaint are limited.
Strengths and weaknesses in relation to other studies
The results presented here should be understood in the context of other research looking at different populations and sources of data. The effect of differences in culture and welfare systems is already recognised.456Research has also used cohort studies,78allowing causal relations to be scrutinised in greater depth and providing more specific and objective measurement of and information about health complaints.9Research exists showing, for instance, that men and women have broadly similar rates of poorer health, although men tend to die earlier and more often at younger ages,10that class gradients exist even in countries with more comprehensive and generous welfare systems such as Sweden,1112and that both acute and chronic health conditions have deleterious effects in the labour market.1314Existing research in general supports the conclusions presented here.
Meaning of study: possible explanations and implications for clinicians and policymakers
The substantive implications of being of working age and economically inactive have changed for both men and women over the long time period of this study. Historically, the default expectation for a man of working age has been to be either in or seeking employment. By contrast, this expectation of (formally defined) economic activity for working age women has not always been as strong owing to the historical expectation that the role of “homemaker” should be occupied by the woman of the household. The trends observed in this paper provide evidence of men and women becoming more alike in terms of engagement with the labour market. As this has happened, the effect of being in poor health on a person’s chances of being in employment has increased, widening the employment divide between those with and without limiting long term illness. On aggregate, the pattern of this widening health divide has been different for men and women. For men, it has been due to employment rates falling and economic inactivity rates increasing for those with limiting illness. For women, it has been due to employment rates not increasing and economic inactivity rates not falling among those with limiting long term illness, against a trend of increased employment and reduced economic inactivity among healthier women.
During periods of recession, people in poorer health are more likely to lose their jobs than are those in better health, as well as being more likely to have difficulty finding new jobs. Although their health may have been so poor as to make them eligible for incapacity benefit even when they were working, it was only once they lost their job that this latent ill health problem became realised as a (legitimate) claim for incapacity benefit, as they faced a choice between a lower rate as an unemployed person or a higher rate as an economically inactive person.151617After the replacement of invalidity benefit with incapacity benefit in 1995, the United Kingdom was recognised as having some of the toughest eligibility criteria for sickness based benefits in the developed world.18When incapacity benefit was replaced by employment and support allowance in 2008, these criteria became tougher still, as personal capability assessment was replaced by the even more controversial work capability assessment.19Employment and support allowance and before it the new Pathways to Work programme for new incapacity benefit claimants have represented a change in emphasis from what people with limited health cannot do to what would they could do.20However, even slight disadvantages in terms of health can lead to large disadvantages in terms of employability during recessions, placing people at the back of a longer queue.
These findings have several implications for policy makers. They suggest that people with poor health face an increasing risk of leaving the labour market, and that re-entry may be difficult. Given this, ensuring that working people in poor and worsening health are supported to remain working where they wish to and where it is appropriate to do so seems important. The onus for making “reasonable adjustments” to a workplace, as well as financial liability for making such changes, is on the employer. Financial support for making such changes may make it easier for employers to support workers in poorer health without jeopardising their economic viability. Appropriate support and similar “demand side” interventions may also encourage potential employers to give greater consideration to candidates with poorer health, reducing the employment disadvantage they encounter and balancing the predominantly “supply side” policy changes introduced in recent years to reduce the claimant population for incapacity benefit and employment and support allowance.21“Cutting red tape” and making it easier to initiate redundancy should be expected to further exacerbate the adverse trends identified here.
Given the nature of manual labour, making accommodations to the demands of the work may be more difficult for people in poorer physical health in manual work compared with non-manual work, so poor health may make these kinds of work activity particularly hard. However, differences seem to exist between nations in terms of the extent to which the effect of chronic illness on employment and economic inactivity is class differentiated, suggesting that labour market policies can have a considerable effect on these trends.22Ensuring that sufficient opportunities exist for retraining manual workers with poor health with the skills necessary for non-manual work seems important for ensuring that poor health does not lead to workers falling out of the labour market completely. Given that these results suggest that more than half of male unskilled and semi-skilled manual workers with poor health are economically inactive, an urgent need seems to exist for improvements in this area. Given the highly politicised nature of this area of health management, clinicians have a vital role in ensuring that the health needs of people reporting poor health are recognised and met, and that both the theory and practice of welfare to work initiatives for this patient group are conducive to improving health and wellbeing.
Unanswered questions and further research
Of course, further questions remain—in particular, how the current recession will compare with the previous recessions in the 1930s, 1970s, 1980s, and 1990s. To answer this consistently will require that the General Household Survey/General Lifestyle Survey remains in existence and in a sufficiently similar format to allow comparability with previous editions, allowing this research to be updated again in five or 10 years. Unfortunately, in 2011 the ONS announced that the General Lifestyle Survey will be discontinued after January 2012,23so the 2010 and 2011 releases of the dataset will be the final opportunities for updating this analysis. Even these data could allow further avenues for research, such as research exploring the influence of age on the patterns seen in this paper. In addition to further research using panel surveys along the lines mentioned previously and doing systematic reviews to effectively summarise the existing evidence, exploring such matters using a survey with more than three decades of observations should make a major contribution to our understanding of long term trends in work and public health. By allowing us to take the long view, this research provides evidence that can help to inform our understanding of some of the evidence used and misused in contemporary debates about incapacity benefits and welfare reform.24
What is already known on this topic
People of working age with limiting long term illness have higher rates of economic inactivity and lower rates of employment than do working age people without such illness
What this study adds
The gap in employment opportunities between people with and without limiting long term illness has grown substantially since 1973
Notes
Cite this as: BMJ2012;340:e2316
Footnotes
Contributors: JM had the idea for the research, did the statistical analysis, and wrote the initial draft. DD and KEP contributed to the analysis plan, interpretation of data, and all revisions of the manuscript. JM is the guarantor.
Funding: None.
Competing interests: All authors have completed the Unified Competing Interest form athttp://www.icmje.org/coi_disclosure.pdf(available on request from the corresponding author) and declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.
Ethical approval: Not needed.
Data sharing: Further summary data and the R script developed to analyse the data are available from the corresponding author at [email protected]. The surveys used remain property of the Office for National Statistics.
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| https://www.bmj.com/content/344/bmj.e2316?ijkey=aa6324652b2253c9fa5b0195d5c668740d0900ea&keytype2=tf_ipsecsha |
AbbVie Reports Full-Year and Fourth-Quarter 2022 Financial Results – 1stOncology™: Cancer Intelligence Service
AbbVie Reports Full-Year and Fourth-Quarter 2022 Financial Results
On February 9, 2023 AbbVie (NYSE:ABBV) reported financial results for the fourth quarter and full year ended December 31, 2022 (Press release, AbbVie, FEB 9, 2023, View Source [SID1234626987]).
"2022 was another highly productive year capping a decade of outstanding performance. Since our inception, we have built a diverse portfolio of growth products with significant leadership positions, developed a robust pipeline of innovative assets and created a culture of strong execution," said Richard A. Gonzalez, chairman and chief executive officer, AbbVie. "Looking forward, we have a solid foundation which will allow us to absorb the U.S. Humira loss of exclusivity, return to strong top-line growth in 2025 and drive top-tier financial performance over the long term."
Note: "Operational" comparisons are presented at constant currency rates that reflect comparative local currency net revenues at the prior year’s foreign exchange rates.
1Beginning in the first quarter 2022, AbbVie includes the impact of upfront and milestone payments related to collaborations, licensing agreements and other asset acquisitions in its reported non-GAAP financial measures.
Fourth-Quarter Results
Worldwide net revenues were $15.121 billion, an increase of 1.6 percent on a reported basis, or 3.8 percent on an operational basis.Global net revenues from the immunology portfolio were $7.925 billion, an increase of 17.5 percent on a reported basis, or 19.5 percent on an operational basis.Global Humira net revenues of $5.579 billion increased 4.6 percent on a reported, or 6.0 percent on an operational basis. U.S. Humira net revenues were $5.006 billion, an increase of 9.9 percent. Internationally, Humira net revenues were $573 million, a decrease of 26.5 percent on a reported basis, or 16.9 percent on an operational basis.Global Skyrizi net revenues were $1.576 billion, an increase of 76.1 percent on a reported basis, or 78.9 percent on an operational basis.Global Rinvoq net revenues were $770 million, an increase of 49.0 percent on a reported basis, or 55.4 percent on an operational basis.Global net revenues from the hematologic oncology portfolio were $1.631 billion, a decrease of 12.9 percent on a reported basis, or 11.2 percent on an operational basis.Global Imbruvica net revenues were $1.115 billion, a decrease of 19.5 percent, with U.S. net revenues of $841 million and international profit sharing of $274 million.Global Venclexta net revenues were $516 million, an increase of 5.7 percent on a reported basis, or 12.2 percent on an operational basis.Global net revenues from the neuroscience portfolio were $1.710 billion, an increase of 3.4 percent on a reported basis, or 5.1 percent on an operational basis.Global Botox Therapeutic net revenues were $728 million, an increase of 8.5 percent on a reported basis, or 10.7 percent on an operational basis.Global Vraylar net revenues were $565 million, an increase of 15.5 percent.Global Ubrelvy net revenues were $197 million, an increase of 7.7 percent.Global net revenues from the aesthetics portfolio were $1.287 billion, a decrease of 8.5 percent on a reported basis, or 4.2 percent on an operational basis.Global Botox Cosmetic net revenues were $642 million, an increase of 2.6 percent on a reported basis, or 7.1 percent on an operational basis.Global Juvederm net revenues were $322 million, a decrease of 25.4 percent on a reported basis, or 19.0 percent on an operational basis.On a GAAP basis, the gross margin ratio in the fourth quarter was 72.4 percent. The adjusted gross margin ratio was 86.0 percent.On a GAAP basis, selling, general and administrative (SG&A) expense was 22.6 percent of net revenues. The adjusted SG&A expense was 20.8 percent of net revenues.On a GAAP basis, research and development (R&D) expense was 11.8 percent of net revenues. The adjusted R&D expense was 11.5 percent of net revenues, reflecting funding actions supporting all stages of our pipeline.Acquired IPR&D and milestones expense was 1.6 percent of net revenues.On a GAAP basis, the operating margin in the fourth quarter was 36.4 percent. The adjusted operating margin was 52.1 percent.Net interest expense was $476 million.On a GAAP basis, the tax rate in the quarter was 16.6 percent. The adjusted tax rate was 13.4 percent.Diluted EPS in the fourth quarter was $1.38 on a GAAP basis. Adjusted diluted EPS, excluding specified items, was $3.60. These results include an unfavorable impact of $0.13 per share related to acquired IPR&D and milestones expense.
Note: "Operational" comparisons are presented at constant currency rates that reflect comparative local currency net revenues at the prior year’s foreign exchange rates.
Recent Events
AbbVie announced the European Commission (EC) approved Skyrizi (risankizumab, 600 mg intravenous induction and 360 mg subcutaneous maintenance therapy) as the first specific interleukin-23 (IL-23) inhibitor for the treatment of adults with moderately to severely active Crohn’s disease (CD) who have had inadequate response, lost response or were intolerant to conventional or biologic therapy. The approval is supported by results from three Phase 3 studies in which Skyrizi demonstrated significant improvement in clinical remission and endoscopic response, compared to placebo, as both induction and maintenance therapy. This approval marks the third indication for Skyrizi in the European Union (EU). Skyrizi is part of a collaboration between Boehringer Ingelheim and AbbVie, with AbbVie leading development and commercialization globally.
At the American College of Rheumatology’s (ACR) annual meeting, AbbVie shared 36 abstracts that underscore AbbVie’s commitment to advancing research to help more people living with rheumatic diseases. Analyses presented showcased data from the clinical trial programs evaluating Rinvoq (upadacitinib) for the treatment of rheumatoid arthritis (RA), psoriatic arthritis (PsA) and axial spondyloarthritis (AS) as well as data evaluating Skyrizi for the treatment of psoriasis (PsO) and PsA.
AbbVie announced that the U.S. Food and Drug Administration (FDA) accepted, for priority review, the Biologics License Application (BLA) for epcoritamab, an investigational subcutaneous bispecific antibody for the treatment of adult patients with relapsed/refractory (r/r) large B-cell lymphoma (LBCL). Additionally, AbbVie announced the European Medicines Agency (EMA) validated AbbVie’s Marketing Authorization Application (MAA) for epcoritamab for the treatment of adult patients with r/r diffuse LBCL. Both applications are supported by data from the EPCORE NHL-1 Phase 2 trial evaluating the safety and preliminary efficacy of subcutaneous epcoritamab in adult patients with relapsed, progressive or refractory CD20+ mature B-cell non-Hodgkin’s lymphoma (NHL). Epcoritamab is being co-developed by Genmab and AbbVie.
AbbVie announced that the FDA approved Vraylar (cariprazine) as an adjunctive therapy to antidepressants for the treatment of major depressive disorder (MDD) in adults. The approval marks the fourth indication for Vraylar, which is now the first and only dopamine and serotonin partial agonist FDA-approved for the most common forms of depression – as an adjunctive treatment for MDD and the treatment of depressive episodes associated with bipolar I disorder. The approval is supported by clinical data demonstrating the efficacy and well-established tolerability of Vraylar as an adjunctive treatment for MDD with an antidepressant therapy. Vraylar is being co-developed by AbbVie and Gedeon Richter Plc.
At the European Headache Federation Congress (EHC) 2022, AbbVie shared 15 abstracts which underscore its commitment to people living with migraine. Presentations highlighted late-breaking data from the Chronic Migraine Epidemiology and Outcomes – International (CaMEO-I) study, evaluating the frequency and burden of neck pain with headache among people with and without migraine, as well as results from the Phase 3 PROGRESS trial evaluating Qulipta (atogepant) for the preventive treatment of chronic migraine (CM) in patients living in Europe.AbbVie announced new results from its exploratory NOVA phase 2 dose-ranging study evaluating the efficacy and safety of AGN-151607, a novel investigational neurotoxin for the prevention of postoperative atrial fibrillation (POAF) in cardiac surgery patients, at the American Heart Association Scientific Sessions meeting. The study’s primary endpoint was not met for the modified intent-to-treat (mITT) population; however, the data showed relative risk reduction in specific study populations such as coronary artery bypass graft (CABG) patients and patients aged 65 years and older, as well as overall lower rates of rehospitalization within 30 days compared to placebo. Adverse Events (AEs) were numerically similar across all treatment groups.
AbbVie and HotSpot Therapeutics, Inc., a biotechnology company pioneering the discovery and development of small molecule allosteric therapies for the treatment of cancer and autoimmune diseases, announced an exclusive worldwide collaboration and option to license agreement for HotSpot’s discovery-stage interferon regulatory factor 5 (IRF5) inhibitor program for the potential treatment of autoimmune diseases.
AbbVie and Immunome, a clinical-stage biopharmaceutical company that utilizes its human memory B cell platform to discover and develop first-in-class antibody therapeutics, announced a worldwide collaboration and option agreement directed to the discovery of up to 10 novel antibody-target pairs arising from three specified tumor types using Immunome’s Discovery Engine.
AbbVie and Anima Biotech, announced a collaboration to discover and develop mRNA biology modulators for three targets across Immunology and Oncology. Anima will use its mRNA Lightning platform to discover novel mRNA biology modulators against the collaboration targets providing AbbVie exclusive rights to license and further develop and commercialize the programs.Full-Year 2023 Outlook
AbbVie is issuing its adjusted diluted EPS guidance for the full-year 2023 of $10.70 to $11.10. The company’s 2023 adjusted diluted EPS guidance excludes any impact from acquired IPR&D and milestones that may be incurred during 2023, as both cannot be reliably forecasted.
| https://www.1stoncology.com/blog/abbvie-reports-full-yearfourth-quarter-2022-financial-results1234626987/ |
Legal Developments: Third Quarter, 2008; International Bank of Azerbaijan
Legal Developments: Third Quarter, 2008
Order Issued under International Banking Act
International Bank of Azerbaijan Baku, Azerbaijan Order Approving Establishment of a Representative Office
International Bank of Azerbaijan ("Bank"), Baku, Azerbaijan, a foreign bank within the meaning of the International Banking Act ("IBA"), has applied under section 10(a) of the IBA
1
to establish a representative office in New York, New York. The Foreign Bank Supervision Enhancement Act of 1991, which amended the IBA, provides that a foreign bank must obtain the approval of the Board to establish a representative office in the United States.
Notice of the application, affording interested persons an opportunity to submit comments, has been published in a newspaper of general circulation in New York, New York (
New York Daily News
, August 13, 2007). The time for filing comments has expired, and all comments received have been considered.
Bank, with total consolidated assets of approximately $3.2 billion,
2
is the largest commercial bank in Azerbaijan
and provides wholesale and retail banking services through a network of domestic branches as well as several foreign offices and subsidiaries.
3
The proposed representative office is intended to act as a liaison between Bank's head office in Azerbaijan, other U.S. financial institutions, and its existing and prospective customers in Azerbaijan and the United States. The office would engage in representative functions in connection with the activities of Bank, solicit new business, provide information to customers concerning their accounts, promote business investment in and trading opportunities with
Azerbaijan, conduct research, and receive applications for extensions of credit and other banking services on behalf of Bank.
In acting on a foreign bank's application under the IBA and Regulation K to establish a representative office, the Board shall take into account whether the foreign bank engages directly in the business of banking outside of the United States and has furnished to the Board the information it needs to assess the application adequately.
4
The Board shall also take into account whether the foreign bank is subject to comprehensive supervision on a consolidated basis by its home-country supervisor.
5
Under Regulation K, a representative-office application may be approved if the Board determines that the applicant bank is subject to a supervisory framework that is consistent with the activities of the proposed representative office, taking into account the nature of such activities.
6
This is a lesser standard than the comprehensive, consolidated supervision standard applicable to applications to establish branch or agency offices of a foreign bank. The Board considers the lesser standard sufficient for approval of representative office applications because representative offices may not engage in banking activities.
7
The Board also considers additional standards set forth in the IBA and Regulation K.
8
As noted above, Bank engages directly in the business of banking outside the United States. Bank also has provided the Board with information necessary to assess the application through submissions that address the relevant issues.
In connection with this application, Bank has provided certain commitments that limit the activities of the representative office. It has committed that the representative office will engage only in certain specified activities and will not make credit decisions, solicit or accept deposits, process or initiate transactions on behalf of Bank, or engage in activities related to securities trading, foreign exchange, or money transmission.
As noted above, Bank engages directly in the business of banking outside the United States. Bank also has provided the Board with information necessary to assess the application through submissions that address the relevant issues.
With respect to supervision by home-country authorities, the Board has considered the following information. Bank is supervised by the National Bank of Azerbaijan ("NBA"), which is responsible for the regulation and supervision of financial institutions operating in Azerbaijan and is in the
process of enhancing its supervisory framework. The NBA issues rules and implements regulations concerning accounting requirements, asset quality, management, operations, capital adequacy, loan classification, and loan-loss-reserve requirements. In addition, the NBA has authority to order
corrective measures, impose sanctions, and assume management of a financial institution or liquidate it.
The NBA supervises and regulates Bank in Azerbaijan through a combination of on-site examinations and off-site monitoring. On-site examinations are conducted annually and cover capital adequacy, asset quality, profitability, liquidity, and compliance with the law. If necessary, the NBA can also conduct special on-site examinations. The NBA conducts off-site monitoring of Bank through the review of required biannual reports. An external audit is also part of the supervisory process and must be conducted at least annually.
Based on all the facts of record, including the commitments provided by Bank limiting the activities of the proposed office, it has been determined that Bank is subject to a supervisory framework that is consistent with the activities of the proposed representative office, taking into account the nature of such activities.
The additional standards set forth in section 7 of the IBA and Regulation K have also been taken into account.
9
The NBA has no objection to the establishment of the proposed representative office.
With respect to the financial and managerial resources of Bank, taking into consideration its record of operations in its home country, its overall financial resources, and its standing with its home-country supervisor, financial and managerial factors are consistent with approval. Bank
appears to have the experience and capacity to support the proposed representative office and has established controls and procedures for the proposed representative office to ensure compliance with U.S. law.
Although Azerbaijan is not a member of the Financial Action Task Force, it participates in international fora that address the prevention of money laundering.
10
Money laundering is a criminal offense in Azerbaijan, and banks are required to establish internal policies and procedures for the detection and prevention of money laundering.
11
Legislation and regulations require banks to adopt know-your-customer policies and maintain records.
12
Bank has established anti-money-laundering policies and procedures, which include the implementation of know-your-customer policies, suspicious activity reporting procedures, and related training programs and manuals. Bank's internal and external auditors review compliance with requirements to prevent money laundering.
With respect to access to information on Bank's operations, the restrictions on disclosure in relevant jurisdictions in which Bank operates have been reviewed and relevant government authorities have been communicated with regarding access to information. Bank has committed to
make available to the Board such information on the operations of Bank and any of its affiliates as the Board deems necessary to determine and enforce compliance with the IBA, the Bank Holding Company Act of 1956, as amended, and other applicable federal law. To the extent that the provision of such information to the Board may be prohibited by law or otherwise, Bank has committed to cooperate with the Board to obtain any necessary consents or waivers that might be required from third parties for disclosure of such information. In addition, subject to certain conditions, the NBA may share information on Bank's operations with other supervisors, including the Board. In light of these commitments and other facts of record, and subject to the condition described below, it has been determined that Bank has provided adequate assurances of access to any necessary information that the Board may request.
Based on the foregoing and all the facts of record, and subject to the commitments made by Bank and to the terms and conditions set forth in this order, Bank's application to establish the representative office is hereby approved by the Director of the Division of Banking Supervision and Regulation, with the concurrence of the General Counsel, pursuant to authority delegated by the Board.
13
Should any restrictions on access to information on the operations or activities of Bank or any of its affiliates subsequently interfere with the Board's ability to obtain information to determine and enforce compliance by Bank or its affiliates with applicable federal statutes, the Board may require or recommend termination of any of Bank's direct and indirect activities in the United States. Approval of this application also is specifically conditioned on compliance by Bank with the conditions imposed in this order and the commitments made to the Board in connection with this application.
14
For purposes of this action, these commitments and conditions are deemed to be conditions imposed in writing by the Board in connection with its finding and decision and may be enforced in proceedings under 12 U.S.C. §1818 against Bank and its affiliates.
By order, approved pursuant to authority delegated by the Board, effective July 31, 2008.
Robert deV. Frierson Deputy Secretary of the Board
1. 12 U.S.C. § 3107(a).
2. Unless otherwise indicated, data are as of December 31, 2007.
3. Bank is majority owned by the government of Azerbaijan through its Ministry of Finance and operates as a commercial bank in addition to promoting trade by and with Azeri companies. No other shareholder owns more than 5 percent of the shares of Bank.
4. 12 U.S.C. § 3107(a)(2).
5.
Id
.
6. 12 CFR 211.24(d)(2).
7. A representative office may engage in representational and administrative functions in connection with the banking activities of the foreign bank, including soliciting new business for the foreign bank; conducting research; acting as a liaison between the foreign bank's head office and customers in the United States; performing preliminary and servicing steps in connection with lending; and performing back-office functions. A representative office may not contract for any deposit or deposit-like liability, lend money, or engage in any other banking activity (12 CFR 211.24(d)(1)).
8.
See
12 U.S.C. § 3105(d)(3)-(4); 12 CFR 211.24(c)(2). These standards include (1) whether the bank's home-country supervisor has consented to the establishment of the office; the financial and managerial resources of the bank; (2) whether the bank has procedures to combat money laundering, whether there is a legal regime in place in the home country to address money laundering, and whether the home country is participating in multilateral efforts to combat money
laundering; (3) whether the appropriate supervisors in the home country may share information on the bank's operations with the Board; and (4) whether the bank and its U.S. affiliates are in
compliance with U.S. law; the needs of the community; and the bank's record of operation.
9.
See supra
note 8.
10. Azerbaijan is a party to the 1988 UN Convention Against the Illicit Traffic of Narcotics and Psychotropic Substances, the UN International Convention Against Transnational Organized Crime, the UN International Convention for the Suppression of the Financing of Terrorism, the 2004 UN Convention Against Corruption, and the Council of Europe Convention on Laundering, Search, Seizure, and Confiscation of Proceeds from Crime. Azerbaijan is also a member of the Council of Europe's Select Committee of Experts on the Evaluation of Anti-Money Laundering Measures.
11. Azerbaijan has taken steps to strengthen its anti-money-laundering policies and procedures; the Board believes that factors related to anti-money laundering are consistent with approval of the application to establish a representative office.
12. Bank's internal guidelines require that it report suspicious transactions.
13.
See
12 CFR 265.7(d)(12).
14. The Board's authority to approve the establishment of the proposed representative office parallels the continuing authority of the state of New York to license offices of a foreign bank. The Board's approval of this application does not supplant the authority of the state of New York or its agent, the New York State Banking Department, to license the proposed office of Bank in accordance with any terms or conditions that it may impose.
| https://www.federalreserve.gov/Pubs/Bulletin/2008/legal/q308/order7.htm |
Citrulline Malate Enhances Athletic Anaerobic Performance and Relieves Muscle Soreness | Request PDF
Request PDF | Citrulline Malate Enhances Athletic Anaerobic Performance and Relieves Muscle Soreness | The purpose of the present study was to determine the effects of a single dose of citrulline malate (CM) on the performance of flat barbell bench... | Find, read and cite all the research you need on ResearchGate
Citrulline Malate Enhances Athletic Anaerobic Performance and Relieves Muscle Soreness
April 2010
The Journal of Strength and Conditioning Research 24(5):1215-22
DOI: 10.1519/JSC.0b013e3181cb28e0
Authors:
Joaquín Pérez-Guisado
University of Limerick
Abstract
The purpose of the present study was to determine the effects of a single dose of citrulline malate (CM) on the performance of flat barbell bench presses as an anaerobic exercise and in terms of decreasing muscle soreness after exercise. Forty-one men performed 2 consecutive pectoral training session protocols (16 sets). The study was performed as a randomized, double-blind, 2-period crossover design. Eight grams of CM was used in 1 of the 2 training sessions, and a placebo was used in the other. The subjects' resistance was tested using the repetitions to fatigue test, at 80% of their predetermined 1 repetition maximum (RM), in the 8 sets of flat barbell bench presses during the pectoral training session (S1-4 and S1'-4'). The p-value was 0.05. The number of repetitions showed a significant increase from placebo treatment to CM treatment from the third set evaluated (p <0.0001). This increase was positively correlated with the number of sets, achieving 52.92% more repetitions and the 100% of response in the last set (S4'). A significant decrease of 40% in muscle soreness at 24 hours and 48 hours after the pectoral training session and a higher percentage response than 90% was achieved with CM supplementation. The only side effect reported was a feeling of stomach discomfort in 14.63% of the subjects. We conclude that the use of CM might be useful to increase athletic performance in high-intensity anaerobic exercises with short rest times and to relieve postexercise muscle soreness. Thus, athletes undergoing intensive preparation involving a high level of training or in competitive events might profit from CM.
... Bei einer Einnahme von 8 g L-Citrullin-Malat konnte eine Erhöhung der Arbeitskapazität um 19% festgestellt werden, gemessen an den ausgeführten Wiederholungen bis zum Versagen bei einem Langhantel-Flachbankdrücken mit 80% 1-RM
[98]
. Eine weitere Studie konnte ebenfalls einen Anstieg der ausgeführten Wiederholung von 10% bis 53% dokumentieren. ...
... Eine weitere Studie konnte ebenfalls einen Anstieg der ausgeführten Wiederholung von 10% bis 53% dokumentieren. Trainings-induzierter Muskelkater war gegenüber einem Placebo nach 24 Stunden um 39,7% und nach 48 Stunden um 41,7% reduziert
[98]
. ...
... Die -in Form von verbesserter genereller Leistungsfähigkeit, erhöhter Sauerstoffaufnahme, verlängerter Zeit bis Erschöpfung sowie verringerter wahrgenommener Erschöpfung -messbaren Effekte auf die Ausdauerkapazität können hierbei insbesondere im Rahmen eines Ausdauer-basierten Fitnesstrainings eine Leistungssteigerung ermöglichen [95,96,97] . Ebenso kann L-Citrullin bei einem Fitnesstraining mit Gewichten eine Erhöhung der, sich an den ausgeführten Wiederholungen bemessenden Arbeitskapazität bewirken und somit zu einem Kraftanstieg beitragen
[98]
. Zudem kann L-Citrullin nach einer Belastung zu einer verbesserten Regeneration Trainings-induzierter Muskelschmerzen -durch Verringerung dieser -beitragen [98] . ...
The use and dosage of pre-workout supplements amongst recreational athletes
Article
Full-text available
Feb 2019
Jan Philipp Leber
Simon Gavanda
Judith von Andrian-Werburg
Stephan Geisler
Consumption of pre-workout supplements (PWS) has increased substantially in recent years. However, dosages of ingredients vary between manufacturers. Therefore, the aim of this study was to analyze ingredients from various products and to survey past and present (4 weeks) consumption behavior. Analysis of ingredients was performed in 30 products according to manufacturer's specifications. Subsequently, online questionnaire was used to assess reasons for taking, timing and dosing of PWS in 39 recreational athletes (4 females; 35 males; 25.15 ± 3.67 years). Most prevalent ingredients in PWS were caffeine, beta-alanine, L-citrulline, L-arginine, L-tyrosine, taurine and creatine. Average dosing per serving were 254mg caffeine (125-410 mg), 2513 mg beta-alanine (500-4000 mg), L-citrulline 3506 mg (500-8000 mg), L-arginine 2726 mg (500-8000 mg), L-tyrosine 1227 mg (150-3000 mg), taurine 1211 mg (90-2500 mg) and creatine 3031 mg (1000-5000 mg). Average values were in (63%) or below (36%) the recommended ergogenic dosage. Major motives for PWS use were improved concentration, increased blood flow and delayed onset of fatigue. Most subjects consumed PWS 1-3 times per month. In most cases consumption took place 15-30 min before training. Manufacturers' recommendations for consumption were generally followed. A large number of subjects (82%) reported minor side effects from PWS consumption (e. g. paresthesia, insomnia, headache). Based on current research only caffeine, L-citrulline, L-arginine and taurine show relevant direct performance-enhancing effects, while the benefit of beta-alanine, L-tyrosine and creatine in PWS seems highly questionable. Dosages of ingredients were safe, but often too low to increase performance.
... Contrasting with L-arginine, L-citrulline bypasses hepatic metabolism, maintaining bioavailability, and converted to Larginine via kidneys (13). Moreover, for L-citrulline to have an ergogenic effect on resistance training, it must be paired with malate, intermediate of the tricarboxylic acid cycle, which augments the amount of adenosine triphosphate production (ATP) and may impact acid-base balance by stimulating systemic alkalosis (5,
24)
. Mechanistically, the combination of L-citrulline and malate has potential to increase exercise performance. ...
... In addition, no significant performance differences were found between trials during the 50RP test for any variables examined. The physiological mechanisms behind our findings include enhanced circulating NO increasing contractile properties through an increase in cellular calcium handling, skeletal muscle glucose uptake, and an increase in ATP production (4,8,
24)
. Through the conversion of L-citrulline, NO has shown to improve muscle mechanical and metabolic capability while improving glucose oxidation (4,24). ...
... The physiological mechanisms behind our findings include enhanced circulating NO increasing contractile properties through an increase in cellular calcium handling, skeletal muscle glucose uptake, and an increase in ATP production (4,8,24). Through the conversion of L-citrulline, NO has shown to improve muscle mechanical and metabolic capability while improving glucose oxidation (4,
24)
. Because the ATP-PCr system is the main form of energy that produced these results, such mechanisms are likely in play. ...
Acute Citrulline-Malate Supplementation Increases Total Work in Short Lower-Body Isokinetic Tasks for Recreationally Active Females During Menstruation
Article
Full-text available
Jul 2021
Joshua L. Gills
Blake Spliker
Jordan Glenn
Michelle Gray
Gills, JL, Spliker, B, Glenn, JM, Szymanski, D, Romer, B, Lu, H-C, and Gray, M. Acute citrulline-malate supplementation increases total work in short lower-body isokinetic tasks for recreationally active females during menstruation. J Strength Cond Res XX(X): 000-000, 2021-Citrulline-Malate (CM) exhibits acute ergogenic benefits through nitric oxide production (NO) and augmentation of vasodilatory properties. Nitric oxide is upregulated by estrogen and may influence CM's ergogenic efficacy in women. Therefore, the objective of this study was to evaluate the acute effects of CM supplementation on lower-body isokinetic performance in recreationally active women. Nineteen women (23.5 ± 3.1 years; 164.8 ± 7.0 cm; 61.9 ± 27.4 kg; 28.8 ± 8.1% body fat) completed 2 randomized, double-blind, crossover trials consuming CM (8 g CM + 12 g dextrose) or placebo (12 g dextrose). For testing trials, subjects were in the menstruating portion of the follicular phase of their menstrual cycle. Subjects performed a 5-repetition isokinetic leg extension protocol (5RP) followed by a 50-repetition isokinetic leg extension protocol (50RP), 60 minutes after supplement consumption. Repeated measures analysis of variance analysis showed that CM significantly increased total work completed, relative total work, and total work during maximum repetition compared with placebo (p < 0.05); but no significant performance differences existed between trials for peak torque production (p = 0.14) for the 5RP. No significant differences were identified between trials for peak torque production (p = 0.69) or total work (p = 0.33) completed during the 50RP. CM increased total work completed during the 5RP, but provided no ergogenic benefit during the 50RP in recreationally active menstruating women. Citrulline-Malate amplifies power-based resistance exercise performance in women during the follicular phase of the menstrual cycle, potentially because of depressed estrogen levels. Additional research is needed to identify timing efficacy of CM to increase sport performance during each phase of the menstrual cycle.
... Nevertheless, several studies have investigated the ergogenic potential of CitMal supplementation on both aerobic and anaerobic exercise performance (Gonzalez & Trexler, 2020). Due to its potential to delay fatigue during highintensity exercise, studies have specifically investigated the acute effects of CitMal supplementation on strength, power, and resistance training performance (Chappell et al., 2018a(Chappell et al., , 2018bCunniffe et al., 2016;Cutrufello et al., 2015;da Silva et al., 2017;Farney et al., 2017;Glenn et al., 2015Glenn et al., , 2016Gonzalez et al., 2017;Martínez-Sánchez et al., 2017;
Pérez-Guisado & Jakeman, 2010;
Trexler et al., 2019a;Wax et al., 2015aWax et al., , 2015b. Although these studies have offered mixed findings, some have shown that acute CitMal supplementation may increase performance during highintensity strength and power tasks. ...
... The majority of the research pertaining to strength training has investigated the acute effect of CitMal supplementation on repetitions to failure during single-joint and/or multijoint exercise protocols. Here, several of the studies have demonstrated that subjects who consume a single dose of CitMal (6-8 g) experience less fatigue to the working muscles compared with a placebo groupallowing them to perform more repetitions to failure
(Pérez-Guisado & Jakeman, 2010;
Wax et al., 2015aWax et al., , 2015b. However, not all studies have shown such favorable results (Chappell et al., 2018a(Chappell et al., , 2018bda Silva et al., 2017;Gonzalez et al., 2017). ...
... Participants performed 3-10 (5 ± 3) sets to voluntary failure, on average, which resulted in 51 ± 23 total repetitions for each exercise. The dosage of CitMal supplementation ranged from 6 g (da Silva et al., 2017) to 8 g (Chappell et al., 2018a(Chappell et al., , 2018bGlenn et al., 2015;Gonzalez et al., 2017;
Pérez-Guisado & Jakeman, 2010;
Wax et al., 2015aWax et al., , 2015b and was ingested 40 min (Gonzalez et al., 2017) or 60 min preexercise (Chappell et al., 2018a(Chappell et al., , 2018bda Silva et al., 2017;Glenn et al., 2015;Pérez-Guisado & Jakeman, 2010;Wax et al., 2015aWax et al., , 2015b. To control for diet, all studies instructed participants to duplicate the nutritional intake prior to each experimental trial. ...
Acute Effect of Citrulline Malate on Repetition Performance During Strength Training: A Systematic Review and Meta-Analysis
Article
Full-text available
Thomas Bjørnsen
Adam Gonzalez
Citrulline malate (CitMal) is a dietary supplement that is suggested to enhance strength training performance. However, there is conflicting evidence on this matter. Thus, the purpose of this meta-analysis was to determine whether supplementing with CitMal prior to strength training could increase the total number of repetitions performed before reaching voluntary muscular failure. A systematic search was conducted wherein the inclusion criteria were double-blind, placebo-controlled studies in healthy participants that examined the effect of CitMal on repetitions to failure during upper body and lower body resistance exercises. The Hedges’s g standardized mean differences (SMD) between the placebo and CitMal trials were calculated and used in a random effect model. Two separate subanalyses were performed for upper body and lower body exercises. Eight studies, including 137 participants who consisted of strength-trained men ( n = 101) and women ( n = 26) in addition to untrained men ( n = 9), fulfilled the inclusion criteria. Across the studies, 14 single-joint and multijoint exercises were performed with an average of 51 ± 23 total repetitions during 5 ± 3 sets per exercise at ∼70% of one-repetition maximum. Supplementing with 6–8 g of CitMal 40–60 min before exercise increased repetitions by 3 ± 5 (6.4 ± 7.9%) compared with placebo ( p = .022) with a small SMD (0.196). The subanalysis for the lower body resulted in a tendency for an effect of the supplement (8.1 ± 8.4%, SMD: 0.27, p = .051) with no significant effect for the upper body (5.7 ± 8.4%, SMD: 0.16, p = .131). The current analysis observed a small ergogenic effect of CitMal compared with placebo. Acute CitMal supplementation may, therefore, delay fatigue and enhance muscle endurance during high-intensity strength training.
... The potential ergogenic effects of CIT have been attributed to three main mechanisms: First, L-citrulline supplementation seems to increase L-arginine plasma levels [4][5][6] under rest and physical exercise conditions. Considering that L-arginine is the main substrate for nitric oxide synthesis (ON), an important blood flow modulator 7 , it has been suggested that CIT supplementation can indirectly increase ON synthesis
8
and thus increase blood flow to the active muscles. As a result, CIT supplementation could increase the release of nutrients and/or the removal of metabolic residues 9,10 (e.g. ...
... Considering that urea is the main vehicle for eliminating ammonia -a promoter of muscle fatigue through anaerobic glycolysis and resulting lactic acid production 13 -it has been suggested that supplementation with CIT can improve ammonia homeostasis 14 and, consequently, muscle function. Finally, malate is an intermediate of the Krebs cycle and its greater availability after supplementation with CIT seems to increase ATP production through anaplastic Krebs cycle reactions 2 , resulting in decreased muscle fatigue and increased muscle performance 2,
8,
15 . ...
... The objective of this study was to investigate the CIT supplementation effects on aerobic and muscular resistance in young adult individuals. Based on the physiological properties and supposed ergogenic effects of CIT
8,
15,20 , the hypothesis was tested that CIT supplementation could increase the time until exhaustion and the number of maximum repetitions, as well as reduce the heart rate (HR) and the effort subjective perception (PSE) in the respective tests. ...
Effects of Citrulline Malate Supplementation on Aerobic and Muscular Endurance in Young Adults Men
Article
Full-text available
Éderson Candellório
Paulo Sperandio
Andreo Fernando Aguiar
The aim of this study was to evaluate the effects of citrulline malate (CIT) supplementation on aerobic and muscular endurance in young adult males. Eighteen young adult men (age: 21.5 ± 2.7 years) were randomized into two groups (Citrulline malate - CIT and Placebo - PLA; N = 9/group ) and received the respective supplements for 7 days. The CIT group was supplemented with 6 g CIT + 6 g dextrose (total: 12 g), while the PLA group received the same amount (12 g) of dextrose. At the pre- and post-supplementation, the following variables were analyzed: aerobic (maximal treadmill test, Tmax) and muscle (repetitions maximum test, Rmax) endurance tests, as well as mean and maximum heart rate (HR) in Tmax and ratings of perceived exertion (PSE) in Rmax. No significant (P > 0.05) differences were found between CIT and PLA groups in time until exhaustion in Tmax, total repetitions in Rmax, maximal HR and PSE from pre- to post-supplementation. The mean HR was statistically lower (P < 0.05) in the CIT group compared to the PLA in the Tmax. In conclusion, supplementation of CIT (6 g / day) does not improve aerobic and muscular endurance, as well as maximal HR or PSE in healthy young adults, despite reducing the mean HR during the maximal incremental test. Keywords: Endurance Training. Dietary Supplements. Physical Functional Performance. Citrulline. Nitric Oxide. ResumoO objetivo deste estudo foi avaliar os efeitos da suplementação de citrulina malato (CIT) sobre a resistência aeróbica e muscular em homens adultos jovens. Em um desenho experimental randomizado, duplo-cego e controlado com placebo, dezoito homens adultos jovens (idade: 21,5 ± 2,7 anos) foram randomizados em dois grupos (Citrulina malato – CIT e Placebo – PLA; N = 9/grupo) e receberam os respectivos suplementos por um período de 7 dias. O grupo CIT foi suplementado com 6 g de CIT + 6 g de dextrose (total: 12 g), enquanto o grupo PLA recebeu a mesma quantidade (12 g) de dextrose. Nos momentos pré e pós suplementação as seguintes variáveis foram analisadas: resistência aeróbia (teste incremental máximo em esteira rolante, Tmáx) e muscular (teste de repetições máximas, Rmáx), bem como a frequência cardíaca (FC) média e máxima no Tmáx e a análise da percepção subjetiva de esforço (PSE) no Rmáx. Nenhuma diferença significante (P > 0,05) foi encontrada entre os grupos CIT e PLA no tempo até a exaustão no Tmáx, total de repetições no Rmáx, FC máxima e PSE do momento pré para o pós suplementação. A FC média foi estatisticamente (P < 0,05) menor no grupo CIT comparado ao PLA no Tmáx. Em conclusão, a suplementação de CIT (6 g/dia) não melhora a resistência aeróbica e muscular, bem como a FC máxima ou PSE em adultos jovens saudáveis, apesar de reduzir a FC média durante o teste incremental máximo. Palavras-chave: Treino Aeróbico. Suplementos Nutricionais. Desempenho Físico Funcional. Citrulina. Óxido Nítrico.
... Citrulline malate is typically provided as an acute 8 g (g) dose in a 1:1 or 2:1 ratio which would yield approximately 4.0 to 5.3 g of L-citrulline and 3.7 to 4.0 g of malate. Some studies have shown that 8 g of citrulline malate could delay fatigue, improve power output, and increase the work performed during resistance exercise [8][9][10]
[11]
[12][13]. However, others have failed to demonstrate an ergogenic benefit following 8 g of citrulline malate [14][15][16][17][18][19]. ...
... Studies from Wax and colleagues have shown that 8 g of citrulline malate could improve the repetitions performed during a protocol consisting of five sets of leg presses, hack squats, and leg extensions at 60% 1RM [13] and during a protocol consisting of three sets of bodyweight chin-ups, reverse chin-ups, and push-ups [12]. An acute 8 g dose of citrulline malate was also reported to improve repetitions of failure during eight sets of bench press at 80% 1RM
[11]
and during six sets of bench press and leg press exercises at 80% 1RM [10]. Therefore, the current state of evidence is mixed, yet a recent meta-analysis [20] showed how citrulline malate could significantly increase repetitions to failure during high-intensity strength training. ...
Acute Effect of L-Citrulline Supplementation on Resistance Exercise Performance and Muscle Oxygenation in Recreationally Resistance Trained Men and Women
Article
Full-text available
Katie M. Sell
Adam Gonzalez
L-citrulline serves as a nitric oxide precursor with the potential to increase blood flow and improve resistance exercise performance, yet more research is needed to examine its ergogenic potential. To examine the effect of L-citrulline supplementation on resistance exercise performance, muscle oxygenation, and the subjective perception of effort, energy, focus, fatigue, and muscle pump, eighteen resistance-trained men (n = 11) and women (n = 7) (21.4 ± 1.8 years; 172.3 ± 7.5 cm; 76.9 ± 10.8 kg) were randomly assigned for supplementation with 8 g of L-citrulline (CIT) or a placebo (PL) in a cross-over fashion one hour prior to testing. Participants completed an isometric mid-thigh pull test (IMTP), a ballistic bench press protocol [two sets of two repetitions at 75% 1-repetition maximum (1 RM) with maximum ballistic intent], and a strength-endurance bench press protocol [five repetition-maximum sets at 75% 1RM]. Barbell velocity and power were measured via a linear position transducer during the ballistic protocol, while the repetitions completed, volume load and muscle oxygenation were quantified during the strength-endurance protocol. Subjective measures were assessed at the baseline and immediately pre- and post-exercise. Repeated measures of the analysis of variance and Bayesian equivalents revealed no significant interactions, providing evidence favoring the null hypothesis (BF10 < 1) for IMTP (PL 497.5 ± 133.6 vs. CIT 492.5 ± 129.4 N), barbell velocity, and power, and repetitions completed (PL 36.7 ± 7.2 vs. CIT 36.9 ± 8.1 repetitions). There were also no significant interactions for muscle oxygenation parameters or subjective measures except perceived fatigue. Women reported greater fatigue across all time points compared to men (~1.88 au, p = 0.045, BF10 = 0.2). The results indicate that a single 8 g dose of L-citrulline did not enhance isometric force production, muscle endurance, or muscle oxygenation parameters during the protocol implemented in this study.
... L-citrulline is sometimes combined with malate, and at oral doses of 6-8g administered 60 min before exercise, has been shown to acutely improve muscular endurance (i.e., repetitions to failure) and reduce perceived exertion and subjective muscle soreness in men
[7]
[8][9] and in women 10 , albeit with some inconsistent findings [11][12][13] . As a result, Lcitrulline has been the topic of several recent reviews in an attempt to develop a consensus of the literature [4][5][6][14][15][16] . ...
... Lastly, fewer adverse events occurred under the 3DPump condition. Previous investigations commonly examined 8g of citrulline to stimulate vasodilatory and performance effects within the muscle
[7]
[8][9]13 . Notably both conditions in this study had a similar effect on appendicular girth pre to post workout along with subjective ratings of a muscle pump despite a lower citrulline dose in the 3D PUMP condition. ...
A Randomized, Single-Blind, Crossover Study to Evaluate the Efficacy of a Novel Dietary Supplement Blend with L-Citrulline on Biomarkers of Hydration, Muscle Size, Affect, Inflammation, and Muscular Endurance: Original Research
Article
Full-text available
Introduction: Citrulline is a non-essential amino acid that has previously been shown to improve athletic performance, reduce fatigue, and increase blood flow. The purpose of this study was to examine the efficacy of a novel dietary supplement blend (3D PUMP BREAKTHROUGH®, 3DPump) vs. citrulline alone on changes in muscle volume, fluid shifts, markers of hydration, inflammation, recovery, affect, and muscular endurance. Methods: Twenty-eight recreationally active subjects (6 women, 22 men) participated in a randomized, positive-controlled, single-blind, crossover study which involved 4 testing visits (2 workout visits each with a 24-hr follow-up visit). Participants ingested 3DPump (containing 3g L-citrulline, 1.2g glycerol, 165mg Amla fruit extract) or 8g of L-citrulline alone 45min before an aerobic and resistance training workout. Assessments of body fluid shifts (via BIA), markers of hydration (urine and serum osmolality, USG, hemoglobin), and appendicular girth were taken before and after exercise while markers of damage and inflammation (neutrophils, CK, ESR, MCP-1, CRP) were taken before and 24 hours after exercise, muscular endurance (reps to failure) was assessed during resistance exercises, and subjective measures of affect and recovery were taken before, after and 24 hours after exercise. Mixed factorial ANOVAs with dependent t-tests were used to compare treatments. Results: A significant interaction occurred for right thigh circumference; however post hoc testing indicated both groups increased similarly in post workout girth (p<0.05). A significant interaction occurred for ECF/TBW indicating post workout was greater than pre workout in 3DPump only (p=0.002). An interaction trend (p≤0.010) occurred for SBP and DBP indicating that 3DPump was uniquely able to significantly lower blood pressure (SBP and DBP) post workout compared to baseline and 24 hours after exercise (p<0.001). Conclusions: 3DPump, which contains 3g L-citrulline was able to provide similar effects in muscular endurance, muscle pump and other subjective feelings of affect, hydration, damage and inflammation markers, and body fluid shifts as an 8g dose of L-citrulline alone. 3DPump may have unique benefits on improving post exercise vascular tone and ECF/TBW.
... However, the relationship between improved athletic performance and increased NO production in response to Cit supplementation is unclear [30]. Furthermore, previous studies that reported improved athletic performance with Cit supplementation used it in combination with malates and other components [30,[49]
[50]
[51][52]. Most studies have reported that supplementation of Cit and malate is done in combination due to their synergistic coupling at the intramuscular level [52][53][54]. ...
... According to a review study, taking a single acute dose of 8 g of CitMal 1 h prior to exercise in resistance-trained men and women may improve dynamic muscle endurance and strength performance [53]. In a study involving resistance-trained men, the iteration of failure was improved in all sets of barbell bench presses (except for the first two sets) after ingestion of 8 g of CitMal 1 h before exercise
[50]
. Similar results were observed in a study of resistance-trained females, with improved performance responses during six sets of plate-loaded leg press and bench press exercises at 80% 1RM [132]. ...
Dietary Arginine and Citrulline Supplements for Cardiovascular Health and Athletic Performance: A Narrative Review
Article
Full-text available
Hun-Young Park
Jisoo Seo
Kiwon Lim
The global market for nutritional supplements (NS) is growing rapidly, and the use of L-arginine (Arg), L-citrulline (Cit), and citrulline malate (CitMal) supplements has been shown to enhance cardiovascular health and athletic performance. Over the past decade, Arg, Cit, and CitMal supplements have received considerable attention from researchers in the field of exercise nutrition, who have investigated their potential effects on hemodynamic function, endothelial function, aerobic and anaerobic capacity, strength, power, and endurance. Previous studies were reviewed to determine the potential impact of Arg, Cit, and CitMal supplements on cardiovascular health and exercise performance. By synthesizing the existing literature, the study aimed to provide insight into the possible uses and limitations of these supplements for these purposes. The results showed that both recreational and trained athletes did not see improved physical performance or increased nitric oxide (NO) synthesis with 0.075 g or 6 g doses of Arg supplement per body weight. However, 2.4 to 6 g of Cit per day for 7 to 16 days of various NSs had a positive impact, increasing NO synthesis, enhancing athletic performance indicators, and reducing feelings of exertion. The effects of an 8 g acute dose of CitMal supplement were inconsistent, and more research is needed to determine its impact on muscle endurance performance. Based on the positive effects reported in previous studies, further testing is warranted in various populations that may benefit from nutritional supplements, including aerobic and anaerobic athletes, resistance-trained individuals, elderly people, and clinical populations, to determine the impact of different doses, timing of ingestion, and long-term and acute effects of Arg, Cit, and CitMal supplements on cardiovascular health and athletic performance.
... The association of CM supplementation (3 g/day) for six weeks, associated with a programmed protocol of physical activity adapted to elders, resulted in a general tendency to improve in terms of adaptation to exercise and optimal recovery. Several authors, using higher doses of CM (8 g/day) showed a clear improvement in strength
[39,
40]. However, these data were not reproduced in a study with a similar design carried out on women [41]. ...
... This disparity leads us to hypothesise that lowering the dose to 6 g/day may be the reason why Cutrufello et al. [41] did not find the performance benefits cited in other studies with male volunteers using higher doses (8 g/day). We did not observe significant increases either, only slight increases (a tendency), but the dose used was the lower (3 g/day) compared to other studies
[39]
[40][41]. Glen et al. [42] carried out a study only with young (23 ± 3 years) trained female volunteers, who were supplemented with 8 g/day of CM and performed a submaximal bench press test until exhaustion. These authors observed similar results to those obtained in groups of men. ...
L-Citrulline Supplementation and Exercise in the Management of Sarcopenia
Article
Full-text available
Sarcopenia is a process associated to aging. Persistent inflammation and oxidative stress in muscle favour muscle wasting and decreased ability to perform physical activity. Controlled exercise can optimize blood flux and moderate the production of reactive oxygen species. Therefore, supplements that can work as a vasodilators and control oxidative stress, might be beneficial for active elders. In this context, we have tested citrulline supplementation in a group of 44 participants aged from 60–73 years that followed a physical activity program adapted to their age and capacities. Volunteers were divided in two groups: placebo (n = 22) and citrullline supplemented (n = 22). Different physical tests and blood extractions were performed at the beginning and at the end of intervention (six weeks). Strength and endurance showed a tendency to increase in the citrulline supplemented group, with no significant differences respect to placebo. However, walking speed in the citrulline supplemented group improved significantly compared to placebo. Markers of muscle damage as well as circulating levels of testosterone, cortisol and vitamin D showed no significant changes, but a tendency to improve at the end of intervention in the supplemented group compared to placebo. Additional studies are necessary to confirm the effect of citrulline supplementation in sarcopenia delay.
... This could be important for either subsequent performance when recovery between bouts is limited (i.e., track and field) and/ or overall quality and quantity of chronic training. In a large study of forty-one men, ingestion of 8 g CM 1 h before a resistance training bout led to decreases in muscle soreness at both 24 h (-40%) and 48 h (-41%), respectively, compared to a placebo
(Perez-Guisado et al. 2010
). However, there was no subsequent performance bout to substantiate whether the reduction in soreness translates to improved performance. ...
... However, there was no subsequent performance bout to substantiate whether the reduction in soreness translates to improved performance. In a more thorough study (da Silva et al. 2017), CM supplementation (6 g, 1 h before exercise) failed to improve muscle soreness when more reporting points (24, 48, and 72 h) were used compared to
Perez-Guisado et al. (2010)
. Importantly, da Silva et al. (2017) also reported no improvement in subsequent performance for neither leg press exercise, nor hack squat to exhaustion. ...
A critical review of citrulline malate supplementation and exercise performance
Lars Mcnaughton
Craig A. Bridge
As a nitric oxide (NO) enhancer, citrulline malate (CM) has recently been touted as a potential ergogenic aid to both resistance and high-intensity exercise performance, as well as the recovery of muscular performance. The mechanism has been associated with enhanced blood flow to active musculature, however, it might be more far-reaching as either ammonia homeostasis could be improved, or ATP production could be increased via greater availability of malate. Moreover, CM might improve muscle recovery via increased nutrient delivery and/or removal of waste products. To date, a single acute 8 g dose of CM on either resistance exercise performance or cycling has been supplemented, which has produced equivocal results. This makes the effectiveness of CM to improve exercise performance difficult to determine. Reasons for the disparity in conclusions seem to be due to methodological discrepancies such as the testing protocols and the associated test-retest reliability, dosing strategy (i.e. amount and timing), and the recent discovery of quality control issues with some manufacturers stated (i.e. citrulline:malate ratios). Further exploration of the optimal dose is therefore required including quantification of the bioavailability of NO, citrulline, and malate following ingestion of a range of CM doses. Similarly, further well-controlled studies using highly repeatable exercise protocols with a large aerobic component are required to assess the mechanisms associated with this supplement appropriately. Until such studies are completed, the efficacy of CM supplementation to improve exercise performance remains ambiguous.
... CM is a pharmaceutical compound (Stimol ® Biocodex, Gentilly, France), authorized for treating asthenia, with the recommended dose being 1 g thrice daily
[72]
. Higher rates of ATP production during CM supplementation have been demonstrated in active human skeletal muscle using magnetic resonance spectroscopy [73], this result is thought to be driven by malate's role in mitochondrial oxidative metabolism [74]. ...
... Accordingly, oral administration of CM in healthy rats, 1 g/kg thrice daily for 48 h, led to an improved muscular efficiency, enhancing specific muscle force production by 23%, associated with a significant fall in phosphocreatine (PCr) (28%) as well as in oxidative (32%) costs of contraction [78]. Additionally, Perez-Guisado and Jakeman
[72]
showed a fall of 40% in muscle soreness 24 and 48 h after a pectoral training session and a higher percentage response, over 90%, was reached using just one 8 g dose of supplementary CM. Moreover, other authors described less fatigue in working muscles, enabling them to carry out a larger number of repetitions on exercise performance during lower-body dynamic resistance exercise under CM supplementation (8 g) [79]. ...
L-Citrulline: A Non-Essential Amino Acid with Important Roles in Human Health
L-Arginine (Arg) has been widely used due to its functional properties as a substrate for nitric oxide (NO) generation. However, L-citrulline (CIT), whose main natural source is watermelon, is a non-essential amino acid but which has important health potential. This review provides a comprehensive approach to different studies of the endogenous synthesis of CIT, metabolism, pharmacokinetics, and pharmacodynamics as well as its ergogenic effect in exercise performance. The novel aspect of this paper focuses on the different effects of CIT, citrulline malate and CIT from natural sources such as watermelon on several topics, including cardiovascular diseases, diabetes, erectile dysfunction, cancer, and exercise performance. CIT from watermelon could be a natural food-sourced substitute for pharmacological products and therefore the consumption of this fruit is promoted.
... In a recent meta-analysis, it has been reported that the acute ingestion of citrulline malate, in a range of 6-8 g one hour before exercise, could increase athletes' capacity for greater training volume and lower neuromuscular-metabolic fatigue during high-intensity activities [12]. The latter could be attributed to enhanced oxygen uptake, muscles' aerobic metabolism, the delivery of nutrients to the muscles [72], muscles' buffer capacity
[73]
, and post-exercise perceived effort and muscle soreness [74]. BCAAs, probably through the enhancement of muscle metabolism and protection against muscle damage, also positively affect anaerobic performance [11]. ...
The Effect of Acute Pre-Workout Supplement Ingestion on Basketball-Specific Performance of Well-Trained Athletes
May 2023
Athanasios Douligeris
Spyridon Methenitis
A pre-workout supplement’s (PWS; 200 mg caffeine, 3.3 g creatine monohydrate, 3.2 g β-alanine, 6 g citrulline malate and 5 g branched chained amino acid (BCAA) per dose) acute effects on the alactic (jumping, sprinting, agility), lactic (Running-Based Anaerobic Sprint Test, RAST) and aerobic performance (Yo-Yo Intermittent Recovery Test Level 1, Yo-Yo IRL1 VO2max) of well-trained basketball players was investigated in this double-blind placebo-controlled study. Thirty players (age 18–31 years, height 166–195 cm, weight 70.2–116.7 kg, body fat 10.6–26.4%) were allocated to pre-workout (PWS, n = 15) or placebo (PL, n = 15) groups. Half of the participants in each group performed the evaluations without PWS or PL, while the rest consumed PWS or PL 30 min before the assessments (1st trial) and vice versa (2nd trial). Significant improvements in counter-movement jump (CMJ) (PWS: 4.3 ± 2.1%; PL: 1.2 ± 1.0%), agility (PWS: −2.9 ± 1.8%; PL: 1.8 ± 1.7%), RAST average (PWS: 18.3 ± 9.1%; PL: −2.2 ± 2.0%), minimum power (PWS: 13.7 ± 8.9%; PL: −7.5 ± 5.9%), and fatigue index (PWS: −25.0 ± 0.9%; PL: −4.6 ± 0.6%) were observed in the PWS group vs. the PL group (p < 0.05). No differences were found regarding sprinting, aerobic performance, and blood lactate concentrations. Thus, although players’ alactic and lactic anaerobic performance could be improved, peak power, sprinting and aerobic performance are not.
... L-citrulline is an amino acid involved in the urea cycle and may promote the excretion of ammonia and faster recovery of creatine phosphate after exercise. Intracellular accumulation of ammonia promotes glycolysis by inhibiting aerobic pyruvate utilization
[37,
38] and subsequent lactate formation, which can contribute to fatigue [39,40]. Lactate is the most measurable metabolite, as its level is one of the predictors of the onset of overtraining [41]. ...
Molecular Profiling of Athletes Performing High-Intensity Exercises in Extreme Environments
A. L. Kaysheva
The aim of this study was to determine the influence of high-intensity training under extreme conditions (T = 40 °C) on the metabolism and immunological reactions of athletes. Male triathletes (n = 11) with a high level of sports training performed load testing to failure (17 ± 2.7 min) and maximum oxygen consumption (64.1 ± 6.4 mL/min/kg). Blood plasma samples were collected before and immediately after exercise. Mass spectrometric metabolomic analysis identified 30 metabolites and 6 hormones in the plasma, of which 21 and 4 changed after exercise, respectively. Changes in the intermediate products of tricarboxylic and amino acids were observed (FC > 1.5) after exercise. The obtained data can be associated with the effect of physical activity on metabolism in athletes. Therefore, constant monitoring of the biochemical parameters of athletes can help coaches identify individual shortcomings in a timely manner and track changes, especially as the volume of training increases. In addition, it was revealed that the immunological reaction (manifestation of a hyperactive reaction to food components) is personalized in nature. Therefore, it is important for coaches and sports doctors to analyze and control the eating behavior of athletes to identify food intolerances or food allergies in a timely manner and develop an individual elimination diet.
... Glenn et al. [63] reported that a single 8 g dose of CitMal significantly increased total repetitions to failure performed during both the bench press and leg press exercises over six sets for each exercise at 80% 1RM as well as decreased post-session rating of perceived exertion (RPE) in resistance-trained females. Pérez-Guisado & Jakeman
[64]
also reported that a single 8 g dose of CitMal significantly increased repetitions to failure during eight sets of bench press to failure at 80% 1RM in resistance-trained males. Expanding on these findings, a single 8 g dose of CitMal has also been observed to enhance repetitions to failure in a high-volume lower body resistance exercise protocol consisting of five sets of leg press, hack squat, and leg extension to failure at 60% 1RM in advanced male weightlifters [65]. ...
Supplementation with Nitric Oxide Precursors for Strength Performance: A Review of the Current Literature
Nitric-oxide-stimulating dietary supplements are widely available and marketed to strength athletes and weightlifters seeking to increase muscle performance and augment training adaptations. These supplements contain ingredients classified as nitric oxide (NO) precursors (i.e., “NO boosters”). Endogenous NO is generated via a nitric oxide synthase (NOS)-dependent pathway and a NOS-independent pathway that rely on precursors including L-arginine and nitrates, with L-citrulline serving as an effective precursor of L-arginine. Nitric oxide plays a critical role in endothelial function, promoting relaxation of vascular smooth muscle and subsequent dilation which may favorably impact blood flow and augment mechanisms contributing to skeletal muscle performance, hypertrophy, and strength adaptations. The aim of this review is to describe the NO production pathways and summarize the current literature on the effects of supplementation with NO precursors for strength and power performance. The information will allow for an informed decision when considering the use of L-arginine, L-citrulline, and nitrates to improve muscular function by increasing NO bioavailability.
... For example, ORN is used in dietary supplements as an agent to improve liver function (Müting et al. 1992), as a sleep enhancer (Horiuchi et al. 2013;Miyake et al. 2014), or as a precursor to polyamine production and subsequent collagen formation for bone healing (Meesters et al. 2020;Wijnands et al. 2012). CIT has been claimed to aid in recovery from fatigue or exercise (Bendahan et al. 2002;
Perez-Guisado et al. 2010)
and to reduce swelling (Morita et al. 2012). In recent years, some human studies of CIT supplementation have been reported about protein metabolism under malnutrition (Jourdan et al 2015;Bouillane et al. 2019) and high-intensity interval training (Marcangeli et al 2022). ...
Subchronic tolerance trials of graded oral supplementation with ornithine hydrochloride or citrulline in healthy adults
Full-text available
Dec 2022
AMINO ACIDS
Naoki Miura
Koji Morishita
Takamasa Yasuda
Hideki Matsumoto
Ornithine and citrulline are amino acids used in dietary supplements and nutritional products consumed by healthy consumers, but the safe supplementation levels of these compounds are unknown. The objective of this study was to conduct two 4-week clinical trials to evaluate the safety and tolerability of graded dosages of oral ornithine (as hydrochloride) and citrulline. Healthy male adults ( n = 60, age 41.4 ± 1.5 years) completed graded dosages of either ornithine hydrochloride (3.2, 6, 9.2, and 12 g/day) or citrulline (6, 12, 18, and 24 g/day) supplement for 4 weeks with 2-week wash-out periods in between. Primary outcomes included vitals, a broad spectrum of circulating biochemical analytes, body weight, sleep quality, and mental self-assessment. In the ornithine hydrochloride supplementation group, minor increase in plasma aspartic acid and glutamic acid concentrations was observed at the highest intake dosages. In the citrulline supplementation group, minor changes in laboratory data for serum lactate dehydrogenase and plasma amino acid concentration of lysine, methionine, threonine, aspartic acid, glutamic acid, glutamine and ornithine, arginine, and citrulline itself were measured. No other changes in measured parameters were observed, and study subjects tolerated 4-week-long oral supplementation of ornithine hydrochloride or citrulline without treatment-related adverse events. A clinical, no-observed-adverse-effect-level (NOAEL) of ornithine hydrochloride and citrulline supplementation in healthy adult males was determined to be 12 g/day and 24 g/day (4 weeks), respectively.
... An increase in the availability of plasma arginine has also been linked to availability of substrate for NO synthesis and to the activity of polymorphonuclear neutrophils. Another current study by Perez-Guisado and Jakeman confirmed that a single 8-g dose L-citrulline with malate increased working capacity by almost 19%, as measured by the number of repetitions completed until exhaustion in a bench-press fitness test at 80% of one-repetition-maximum [16,
22]
. ...
Dietary supplements for improving nitric-oxide synthesis
Article
Full-text available
Oct 2022
Aysha Kiani
Nitric oxide (NO) is an essential component of the human body, involved in blood vessel dilation, stimulation of hormone release, signaling and regulation of neurotransmission. Nitric oxide is synthesized by nitric-oxide-synthase-dependent and -independent pathways. Nitric oxide supplementation improves cardiac health, enhances performance during exercise, reduces high blood pressure during pregnancy, reduces erectile dysfunction and improves healing processes and respiratory response. Nitric-oxide-associated benefits are mostly apparent in untrained or moderately trained individuals. L-arginine and L-citrulline supplementation contributes to nitric oxide levels because L-arginine is directly involved in NO synthesis, whereas L-citrulline acts as an L-arginine precursor that is further converted to NO by a reaction catalyzed by NO synthase. L-arginine supplements increase respiratory response and enhance performance during exercise, while L-citrulline with malate and other molecules increase working capacity. Various studies involving beetroot juice have reported a significant increase in plasma nitrite levels, regarded as markers of NO, after intake of beetroot juice. Although NO supplementation may have mild to moderate side-effects, using smaller or divided doses could avoid some of these side-effects. Since nitric oxide supplementation may worsen certain health conditions and may interfere with certain medicines, it should only be taken under medical supervision.
... Specifically, EAA+ contained additional amino acids and natural botanical compounds, including: 1.20 g of citrulline, 805 mg of glutamine, 689 mg of Schisandra chinensis, 200 mg of Lycium barbarum, and 50.0 mg of ferulic acid. Citrulline has been reported to improve nitric oxidemediated vasodilation [35], enhance muscle recovery following RE in men
[36]
, and protect skeletal muscle cells from catabolic stimuli [37] whereas glutamine, which may influence protein synthesis by modulating mammalian target of rapamycin complex 1 (mTORC1) activity in cell culture [38], has been reported to enhance muscle recovery following RE in men [39]. The inclusion of the natural botanical compounds was based on preclinical evidence that Schisandra chinensis and compounds of the Lycium family have been reported to promote myoblast differentiation and mTORC1-mediated protein synthesis, as well as inhibit ubiquitin-proteasome-mediated protein degradation in rodent [40] and skeletal muscle cell models [41]. ...
Essential Amino Acid Ingestion Facilitates Leucine Retention and Attenuates Myofibrillar Protein Breakdown following Bodyweight Resistance Exercise in Young Adults in a Home-Based Setting
Article
Full-text available
Aug 2022
Marcus Waskiw-Ford
Nathan Hodson
Hugo JW Fung
Daniel R Moore
Home-based resistance exercise (RE) has become increasingly prevalent, but its effects on protein metabolism are understudied. We tested the effect of an essential amino acid formulation (EAA+: 9 g EAAs, 3 g leucine) and branched-chain amino acids (BCAAs: 6 g BCAAs, 3 g leucine), relative to a carbohydrate (CHO) placebo, on exogenous leucine retention and myofibrillar protein breakdown following dynamic bodyweight RE in a home-based setting. Twelve recreationally active adults (nine male, three female) participated in a double-blind, placebo-controlled, crossover study with four trial conditions: (i) RE and EAA+ (EX-EAA+); (ii) RE and BCAAs (EX-BCAA); (iii) RE and CHO placebo (EX-CHO); and (iv) rest and CHO placebo (REST-CHO). Total exogenous leucine oxidation and retention (estimates of whole-body anabolism) and urinary 3-methylhistidine:creatinine ratio (3MH:Cr; estimate of muscle catabolism) were assessed over 5 h post-supplement. Total exogenous leucine oxidation and retention in EX-EAA+ and EX-BCAA did not significantly differ (p = 0.116) but were greater than EX-CHO (p < 0.01). There was a main effect of condition on urinary 3MH:Cr (p = 0.034), with post hoc analysis revealing a trend (p = 0.096) for reduced urinary 3MH:Cr with EX-EAA+ (32%) compared to EX-CHO. By direct comparison, urinary 3MH:Cr was significantly lower (23%) in EX-EAA+ than EX-BCAA (p = 0.026). In summary, the ingestion of EAA+ or BCAA provided leucine that was ~60% retained for protein synthesis following home-based bodyweight RE, but EAA+ most effectively attenuated myofibrillar protein breakdown.
... However, a study by Jones (2016) reported that insufficient evidence was available to link increased exercise performance to the increased NO production in response to L-Cit supplementation [20]. Furthermore, several studies claiming that L-Cit supplementation improved exercise performance in recreationally active individuals and well-trained athletes did not use standalone L-Cit [42]
[43]
[44][45]; instead, they combined it with malate and other components [20]. Most of the available literature has combined L-Cit with malate because of its synergistic combination at the intramuscular level [45][46][47]. ...
The Effects of Consuming Amino Acids L-Arginine, L-Citrulline (and Their Combination) as a Beverage or Powder, on Athletic and Physical Performance: A Systematic Review
Article
Full-text available
Aug 2022
Siphamandla Nyawose
Rowena Naidoo
Nenad Naumovski
Andrew J Mckune
Consumption of amino acids L-arginine (L-Arg) and L-citrulline (L-Cit) are purported to increase nitric oxide (NO) production and improve physical performance. Clinical trials have shown relatively more favorable outcomes than not after supplementing with L-Cit and combined L-Arg and L-Cit. However, in most studies, other active ingredients such as malate were included in the supplement. Therefore, the aim of this study was to determine the efficacy of consuming standalone L-Arg, L-Cit, and their combination (in the form of powder or beverage) on blood NO level and physical performance markers. A systematic review was undertaken following PRISMA 2020 guidelines (PROSPERO: CRD42021287530). Four electronic databases (PubMed, Ebscohost, Science Direct, and Google scholar) were used. An acute dose of 0.075 g/kg of L-Arg or 6 g L-Arg had no significant increase in NO biomarkers and physical performance markers (p > 0.05). Consumption of 2.4 to 6 g/day of L-Cit over 7 to 16 days significantly increased NO level and physical performance markers (p < 0.05). Combined L-Arg and L-Cit supplementation significantly increased circulating NO, improved performance, and reduced feelings of exertion (p < 0.05). Standalone L-Cit and combined L-Arg with L-Cit consumed over several days effectively increases circulating NO and improves physical performance and feelings of exertion in recreationally active and well-trained athletes.
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... A 2019 review of the ingredient profiles of the top 100 selling MIPS on a commercial supplement website found that 86% of products contained caffeine, with an average dose of 254 mg per serving [7]. Investigations of other common ingredients in MIPS, such as citrulline [8,
9]
, beta-alanine [10,11], and taurine [12,13] suggest potential ergogenic effects, which when combined in a product formulation could theoretically provide additional benefits over caffeine alone. However, due to the common conclusion that caffeine is the primary cause for any observed exercise performance improvement with MIPS ingestion, less attention has been given to formulations that do not include caffeine. ...
The influence of caffeinated and non-caffeinated multi-ingredient pre-workout supplements on resistance exercise performance and subjective outcomes
Article
Full-text available
Apr 2022
Sports Nutr Rev J
Matthew Stratton
Madelin Siedler
Patrick S. Harty
Grant M. Tinsley
Background:
There is substantial consumer and practitioner interest in an emerging supplement class known as multi-ingredient pre-workout supplements (MIPS), largely due to their prevalence in resistance training communities as well as research findings demonstrating the ergogenic impact of caffeine on muscular performance. However, limited research has examined the potential efficacy of non-caffeinated MIPS, despite their growing popularity among those who are caffeine-sensitive or who train later in the day.
Methods:
Twenty-four resistance-trained college-aged males (n = 12) and females (n = 12) completed three visits in which they ingested either a caffeinated MIPS (C), an otherwise identical non-caffeinated MIPS (NC), or placebo in a double-blind, counterbalanced, crossover fashion. Squat isometric peak force (PFiso), rate of force development (RFD), and isokinetic performance were assessed. Upper and lower body maximal muscular strength and endurance were evaluated using the bench press and leg press, respectively. Visual analog scales for energy, focus, and fatigue were completed five times throughout the testing protocol. The effects of supplementation and biological sex on all variables were examined using linear mixed effects models.
Results:
Significantly greater PFiso was observed in both C (b: 0.36 transformed units [0.09, 0.62]) and NC (b: 0.32 transformed units [95% CI: 0.05, 0.58]) conditions, relative to placebo. Early RFD (RFD50) may have been higher with supplementation, particularly in females, with no effects for late RFD (RFD200) or peak RFD. In addition, increases in subjective energy after supplement ingestion were noted for C, but not NC. No effects of supplementation on traditional resistance exercise performance or isokinetic squat performance were observed, other than a lower leg press one-repetition maximum for males in the NC condition.
Conclusions:
These data indicate that acute ingestion of either a caffeinated or non-caffeinated pre-workout formulation improved maximal force production during an isometric squat test but did not provide additional benefit to leg press, bench press, or isokinetic squat performance over placebo, within the context of a laboratory environment. The consumption of a caffeinated, but not non-caffeinated, MIPS increased subjective ratings of energy over placebo when assessed as part of a testing battery.
... Sitrülin malat (SM) son zamanlarda vücut geliştiricileri arasında popüler bir takviye haline gelmiştir; fakat sağlıklı insanlarda SM takviyesi ilgili çok az bilimsel araştırma yapılmıştır. SM'ın performansı üç mekanizma ile iyileştirdiği varsayılır: 1) sitrulin, üre siklüsünün önemli bir parçasıdır ve amonyak temizlenmesine katılabilir, 2) malat, laktik asit birikimini azaltabilecek bir trikarboksilik asit döngüsü ara maddesidir ve 3) sitrülin, arjinine dönüşebilir; fakat, sitrülinin bu mekanizma ile ergojenik etki yarattığı belli değildir
(55)
. 15 günlük SM desteğinin, egzersiz sırasında ATP üretimini %34 oranında artırdığı, egzersiz sonrası fosfokreatin geri kazanım oranını %20 artırdığı ve yorgunluk algılamalarını azalttığı gösterilmiştir. ...
Güncel Verilerle Vücut Geliştirme Sporcularında Beslenme (Nutrition in Bodybuilding Athletes with Current Data)
Article
Full-text available
Apr 2022
Nur Sinem Türkmen
Çağla Pınarlı
Vücut geliştirme sporunun popülaritesi gün geçtikçe artmaktadır fakat buna karşılık literatüre bakıldığında kanıta dayalı beslenme önerilerinin sayısının oldukça az olduğu görülmektedir. Bu çalışmada literatürde geçen, vücut ge- liştirme sporcuları için verilen kanıta dayalı güncel beslenme önerileri derlenmiştir. Vücut geliştirme sporuyla ilgilenen bireylerde enerji ihtiyacının doğru hesaplanması, vücut ağırlığında azalma sağlamak için temel hedef olmalıdır. Vücut geliştirme sporcularında kas kaybını önlemek için haftalık en fazla %1’lik vücut ağırlığında azalma önerilmektedir. Vücut geliştirme sporcusu için gerekli enerji hesaplaması yapıldıktan sonra, vücut ağırlığında kilogram başına en az 2.3 g/kg/gün protein alımı önerilmektedir. Aynı zamanda her öğünün 0.4-0.5 g/kg protein içermesi önerilmektedir. Günlük enerji gereksiniminin %15-30’unun yağlardan, %20’sinin proteinlerden ve geri kalanın ise karbonhidratlardan gelecek şekilde beslenme programı düzenlenmelidir. Vücut geliştirme sporcuları için ideal öğün sayısında ise özellikle dayanıklılık egzersizleri süresince günlük 3 ile 6 öğün tercih edilmelidir. Yapılan araştırma sonuçlarına göre öğün saatleri ve sıklığının vücut ağırlığında azalma veya yağsız kütleyi korumak için belirgin bir pozitif etkisinin olmadığı görülmüştür. Müsabakalardan birkaç gün önce uygulanan dehidrasyon programı, elektrolit imbalansına sebep olabileceğinden dikkatli olunması gerekmektedir. Müsabakalara hazırlanılan son dönemlerde karbonhidrat alımındaki artışın olumlu etkileri olabilir, bu sebeple karbonhidrat yüklemesi sporcuya uygun olarak yapılmalıdır. Vücut geliştirme sporcularında supleman kullanımıyla ilgili de farklı tartışmalar bulunmaktadır. Kreatin monohidrat, kafein ve beta alanin alımının müsabakalara hazırlanma süresince olumlu etkileri olduğu görülmüştür. Diğer suplemanlarla ilgili daha fazla çalışmaya ihtiyaç olduğu, güncel literatür verileri dahilinde düşünülmektedir. Son olarak, estetik bir spor çeşidi olan vücut geliştirme sporcularında yeme bozuklukları ve vücut algısı bozukluklarının sık görüldüğü unutulmamalıdır.
... The participants did not present any disease, and they did not drink alcohol, smoke or consume other drugs or stimulant substances during the study period which could alter the hormone response. Likewise, to eliminate the probable interference of other nutritional aids with the different outcomes measured in this research, a 2-week washout period was included [39]
[40]
[41]. ...
Long-Term Combined Effects of Citrulline and Nitrate-Rich Beetroot Extract Supplementation on Recovery Status in Trained Male Triathletes: A Randomized, Double-Blind, Placebo-Controlled Trial
Article
Full-text available
Jan 2022
Julio Calleja Gonzalez
José Burgos
Aitor Viribay
Juan Mielgo-Ayuso
Simple Summary: Recovery is one of the main elements in achieving adequate athletic performance. Various supplements have been used for this purpose. Citrulline (CIT) and Nitrate-Rich Beetroot Extract (BR) are so-called nitric oxide precursor supplements that have shown an ergogenic effect on sports performance when used on a short-term, individual basis. These supplements appear to have other pathways that may promote athletic performance. The purpose of this study was to assess the effect of a co-supplementation for 9 weeks of 3 g/day of CIT plus 2.1 g/day of BR (300 mg/day of nitrates) on recovery by exercise-induced muscle damage markers (EIMD), anabolic/cat-abolic hormones and distance covered in the Cooper test (CP). Thirty-two male triathletes were randomized into 4 groups of 8 in this double-blind, placebo-controlled trial: placebo group, CIT group, BR group and CIT-BR group. Blood samples and CP were collected at baseline and after 9 weeks. The main conclusions were the combination of 3 g/day of CIT plus 2.1 g/day of BR (300 mg/day of NO3 −) supplementation for 9 weeks did not present any benefit for EIMD. However, CIT-BR improved recovery status by preventing an increase in cortisol and showing an increase in Tes-tosterone/Cortisol ratio and distance covered in the CP. Abstract: Citrulline (CIT) and nitrate-rich beetroot extract (BR) are widely studied ergogenic aids. Nevertheless, both supplements have been studied in short-term trials and separately. To the best of the authors' knowledge, the effects of combining CIT and BR supplementation on recovery status observed by distance covered in the Cooper test, exercise-induced muscle damage (EIMD) and an-abolic/catabolic hormone status have not been investigated to date. Therefore, the main purpose of this research was to assess the effect of the long-term (9 weeks) mixture of 3 g/day of CIT plus 2.1 g/day of BR (300 mg/day of nitrates (NO3 −)) supplementation on recovery by distance covered in the Cooper test, EIMD markers (urea, creatinine, AST, ALT, GGT, LDH and CK) and Citation: Burgos, J.; Viribay, A.; Calleja-González, J.; Fernández-Lázaro, D.; Olasagasti-Ibargoien, J.; Seco-Calvo, J.; Mielgo-Ayuso, J. Publisher's Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons At-tribution (CC BY) license (http://crea-tivecommons.org/licenses/by/4.0/). Biology 2022, 11, 75 2 of 17 anabolic/catabolic hormones (testosterone, cortisol and testosterone/cortisol ratio (T/C)) in male trained triathletes. Thirty-two triathletes were randomized into four different groups of eight triath-letes in this double-blind, placebo-controlled trial: placebo group (PLG), CIT group (CITG; 3 g/day of CIT), BR group (BRG; 2.1 g/day of BR (300 mg/day of NO3 −)) and CIT-BR group (CIT-BRG; 3 g/day of CIT plus 2.1 g/day of BR (300 mg/day of NO3 −)). Distance covered in the Cooper test and blood samples were collected from all participants at baseline (T1) and after 9 weeks of supplementation (T2). There were no significant differences in the interaction between group and time in EIMD markers (urea, creatinine, AST, ALT, GGT, LDH and CK) (p > 0.05). However, significant differences were observed in the group-by-time interaction in distance covered in the Cooper test (p = 0.002; η 2 p = 0.418), cortisol (p = 0.044; η 2 p = 0.247) and T/C (p = 0.005; η²p = 0.359). Concretely, significant differences were observed in distance covered in the Cooper test percentage of change (p = 0.002; η²p = 0.418) between CIT-BRG and PLG and CITG, in cortisol percentage change (p = 0.049; η 2 p = 0.257) and in T/C percentage change (p = 0.018; η 2 p = 0.297) between CIT-BRG and PLG. In conclusion, the combination of 3 g/day of CIT plus 2.1 g/day of BR (300 mg/day of NO3 −) supplementation for 9 weeks did not present any benefit for EIMD. However, CIT + BR improved recovery status by preventing an increase in cortisol and showing an increase in distance covered in the Cooper test and T/C.
... The participants did not present any disease, and they did not drink alcohol, smoke or consume other drugs or stimulant substances during the study period which could alter the hormone response. Likewise, to eliminate the probable interference of other nutritional aids with the different outcomes measured in this research, a 2-week washout period was included [39]
[40]
[41]. ...
Long-Term Combined Effects of Citrulline and Nitrate-Rich Beetroot Extract Supplementation on Recovery Status in Trained Male Triathletes: A Randomized, Double-Blind, Placebo-Controlled Trial
Article
Full-text available
Jan 2022
Julio Calleja-González
Carlo Reggiani
José Burgos
Aitor Viribay
Simple Summary: Recovery is one of the main elements in achieving adequate athletic performance. Various supplements have been used for this purpose. Citrulline (CIT) and Nitrate-Rich Beetroot Extract (BR) are so-called nitric oxide precursor supplements that have shown an ergogenic effect on sports performance when used on a short-term, individual basis. These supplements appear to have other pathways that may promote athletic performance. The purpose of this study was to assess the effect of a co-supplementation for 9 weeks of 3 g/day of CIT plus 2.1 g/day of BR (300 mg/day of nitrates) on recovery by exercise-induced muscle damage markers (EIMD), anabolic/cat-abolic hormones and distance covered in the Cooper test (CP). Thirty-two male triathletes were randomized into 4 groups of 8 in this double-blind, placebo-controlled trial: placebo group, CIT group, BR group and CIT-BR group. Blood samples and CP were collected at baseline and after 9 weeks. The main conclusions were the combination of 3 g/day of CIT plus 2.1 g/day of BR (300 mg/day of NO3 −) supplementation for 9 weeks did not present any benefit for EIMD. However, CIT-BR improved recovery status by preventing an increase in cortisol and showing an increase in Tes-tosterone/Cortisol ratio and distance covered in the CP. Abstract: Citrulline (CIT) and nitrate-rich beetroot extract (BR) are widely studied ergogenic aids. Nevertheless, both supplements have been studied in short-term trials and separately. To the best of the authors' knowledge, the effects of combining CIT and BR supplementation on recovery status observed by distance covered in the Cooper test, exercise-induced muscle damage (EIMD) and an-abolic/catabolic hormone status have not been investigated to date. Therefore, the main purpose of this research was to assess the effect of the long-term (9 weeks) mixture of 3 g/day of CIT plus 2.1 g/day of BR (300 mg/day of nitrates (NO3 −)) supplementation on recovery by distance covered in the Cooper test, EIMD markers (urea, creatinine, AST, ALT, GGT, LDH and CK) and Citation: Burgos, J.; Viribay, A.; Calleja-González, J.; Fernández-Lázaro, D.; Olasagasti-Ibargoien, J.; Seco-Calvo, J.; Mielgo-Ayuso, J. Publisher's Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons At-tribution (CC BY) license (http://crea-tivecommons.org/licenses/by/4.0/). Biology 2022, 11, 75 2 of 17 anabolic/catabolic hormones (testosterone, cortisol and testosterone/cortisol ratio (T/C)) in male trained triathletes. Thirty-two triathletes were randomized into four different groups of eight triath-letes in this double-blind, placebo-controlled trial: placebo group (PLG), CIT group (CITG; 3 g/day of CIT), BR group (BRG; 2.1 g/day of BR (300 mg/day of NO3 −)) and CIT-BR group (CIT-BRG; 3 g/day of CIT plus 2.1 g/day of BR (300 mg/day of NO3 −)). Distance covered in the Cooper test and blood samples were collected from all participants at baseline (T1) and after 9 weeks of supplementation (T2). There were no significant differences in the interaction between group and time in EIMD markers (urea, creatinine, AST, ALT, GGT, LDH and CK) (p > 0.05). However, significant differences were observed in the group-by-time interaction in distance covered in the Cooper test (p = 0.002; η 2 p = 0.418), cortisol (p = 0.044; η 2 p = 0.247) and T/C (p = 0.005; η²p = 0.359). Concretely, significant differences were observed in distance covered in the Cooper test percentage of change (p = 0.002; η²p = 0.418) between CIT-BRG and PLG and CITG, in cortisol percentage change (p = 0.049; η 2 p = 0.257) and in T/C percentage change (p = 0.018; η 2 p = 0.297) between CIT-BRG and PLG. In conclusion, the combination of 3 g/day of CIT plus 2.1 g/day of BR (300 mg/day of NO3 −) supplementation for 9 weeks did not present any benefit for EIMD. However, CIT + BR improved recovery status by preventing an increase in cortisol and showing an increase in distance covered in the Cooper test and T/C.
... A number of different agents have been suggested to improve or augment performance and mitochondrial function in athletes. These include, but are not limited to supplementary glucose, various amino acids [6][7][8] (i.e., L-arginine [9], beta-alanine [10,11], citrulline (in the form of citrulline-malate [12,13] or citrulline alone [12,
14,
15], glutamine [3,16], taurine [17] among other amino acids [18] and/ or a combination of branched-chain amino acids, particularly including L-Leucine [19]. Additional ergogenic and anaplerotic agents have been investigated, including [20][21][22], pyruvate [23][24][25], citrate [26][27][28], or malate [29] alone, creatine [22,30,31] (often in the form of pyruvate-creatine or creatine citrate [32,33], carnitine [34,35], various vitamins [36,37], co-factors [38], and antioxidants [39,40], among many others, particularly plant derived extracts or natural products (for example green tea [41], Cordyceps sinensis and yohimbine [42]) or complex derivatives thereof concocted into fortified beverages with supplementary carbohydrates [28,43] or protein isolates [44]. ...
"Increasing Exercise Work Capacity via Nutritional Intervention by Administration of Mitochondrial Augmentation Therapy (MAT) Associated Nutrients"
Article
Dec 2019
Frank Merante
... On the other hand, and regarding endurance-strength capacity, Perez-Guisado showed a significant increase in the number of bench press repetitions performed and a reduction in fatigue at 24 and 48 h after ingestion of 8 g of CIT one hour before training
[62]
. Along the same lines, Wax et al. [17] obtained satisfactory results by performing a similar protocol increasing upper-body resistance performance in trained college-age males. ...
Combined Effects of Citrulline Plus Nitrate-Rich Beetroot Extract Co-Supplementation on Maximal and Endurance-Strength and Aerobic Power in Trained Male Triathletes: A Randomized Double-Blind, Placebo-Controlled Trial
Article
Full-text available
Dec 2021
José Burgos
Aitor Viribay
Diego Fernández Lázaro
Juan Mielgo-Ayuso
Citrulline (CIT) and nitrate-rich beetroot extract (BR) are ergogenic aids and nitric oxide
(NO) precursors. In addition, both supplements seem to have other actions at the level of muscle metabolism that can benefit strength and aerobic power performance. Both supplements have been studied in numerous investigations in isolation. However, scientific evidence combining both supplements is scarce, and to the best of the authors’ knowledge, there is no current study of endurance athletes. Therefore, the main purpose of this study was to determine the effect of 9 weeks of CIT plus BR supplementation on maximal and endurance-strength performance and aerobic power in male triathletes. This study was a randomized double-blind, placebo-controlled trial where participants (n = 32) were randomized into four different groups: placebo group (PLG; n = 8), CIT plus BR group (CIT- BRG; 3 g/kg/day of CIT plus 3 mg/kg/day of nitrates (NO3 −); n = 8), CIT group (CITG; 3 g/kg/day; n = 8) and BR group (BRG; 3 mg/kg/day of NO3−; n = 8). Before (T1) and
after 9 weeks (T2), four physical condition tests were carried out in order to assess sport performance: the horizontal jump test (HJUMP), handgrip dynamometer test, 1-min abdominal tests (1-MAT) and finally, the Cooper test. Although, no significant interactions (time × supplementation groups) were found for the strength tests (p > 0.05), the CIT- BRG supplementation presented a trend on HJUMP and 1-MAT tests confirmed by significant increase between two study moments in CIT-BRG. Likewise, CIT-BRG presented significant interactions in the aerobic power test confirmed by this group’s improve estimated VO2max during the study with respect to the other study groups (p = 0.002; η 2p = 0.418). In summary, supplementing with 3 g/day of CIT and 2.1 g/day of BR (300 mg/day of
NO3 −) for 9 weeks could increase maximal and endurance strength. Furthermore, when compared to CIT or BR supplementation alone, this combination improved performance in tests related to aerobic power.
... [8,9,41] Furthermore, the addition of malate to dietary L-citrulline was chosen in this study, since previous studies observed higher levels of NO metabolites with the addition of malate. [11,
42]
Dosages of 8 g Lcitrulline malate and 3 g L-arginine hydrochloride were used in this study, because previous studies consider these dosages to be safe for healthy individuals and without adverse events. [31,33,34] It was observed in literature, that single doses of >15 g of Larginine cause gastrointestinal side effects (i.e., diarrhea and vomiting). ...
Contrast-enhanced ultrasound for determining muscular perfusion after oral intake of L-citrulline, L-arginine, and galloylated epicatechines: A study protocol
Article
Full-text available
Oct 2020
MEDICINE
Julian Doll
Franziska Bürkle
Arndt Neide
Christian Alexander Fischer
Introduction:
The market for dietary supplements in the sports sector has been growing rapidly for several years, though there is still lacking evidence regarding their claimed benefits. One group is that of nitric oxide increasing supplements, so-called "NO-boosters," which are claimed to improve the supply of oxygen and nutrients to the muscle by enhancing vasodilation.The aim of this study was to investigate 3 of these supplements in healthy male athletes for their muscle perfusion-enhancing potential using contrast-enhanced ultrasound (CEUS).
Methods:
This placebo-controlled, double-blind, randomized cross-over trial will be carried out at the Center for Orthopedics, Trauma Surgery and Spinal Cord Injury of the University Hospital Heidelberg. Three commercial NO enhancing products including 300 mg of the specific green tea extract VASO6 and a combination of 8 g L-citrulline malate and 3 g L-arginine hydrochloride will be examined for their potential to increase muscular perfusion in 30-male athletes between 18 and 40 years and will be compared with a placebo. On each of the 3 appointments CEUS of the dominant biceps muscle will be performed at rest and after a standardized resistance training. Every athlete receives each of the 3 supplements once after a wash-out period of at least 1 week. Perfusion will be quantified via VueBox quantification software. The results of CEUS perfusion measurements will be compared intra- and interindividually and correlated with clinical parameters.
Discussion:
The results of this study may help to establish CEUS as a suitable imaging modality for the evaluation of potentially vasodilatory drugs in the field of sports. Other supplements could also be evaluated in this way to verify the content of their advertising claims.
Trial registration:
German Clinical Trials Register (DRKS), ID: DRKS00016972, registered on 25.03.2019.
View
... L-citrulline supplementation acts as a source of energy during exercise and is involved in removal of excess metabolites from the body (2). Pérez-Guisado and Jakeman
(3)
reported that supplementation of 8 g of citrulline malate can reduce muscle soreness at 24 and 48 h following anaerobic exercise. An in vivo study by Meneguello et al. (4) investigated supplementation of mice with a single dose of supplement containing 0.26 g/kg body weight L-citrulline, 0.4 g/kg body weight L-arginine, and 0.2 g/kg body weight L-ornithine lowered blood ammonia accumulation after exercise and prolonged the time until exhaustion in swimming exercises. ...
Supplementation of 100% Flesh Watermelon [Citrullus lanatus (Thunb.) Matsum. and Nakai] Juice Improves Swimming Performance in Rats
Article
Full-text available
Mar 2019
Rasdin Ridwan
Hairil Rashmizal Abdul Razak
Mohd ilham Adenan
Wan Mazlina Md Saad
Nutritional intervention of fruit juice supplementation is able to maximize exercise performance. Watermelon [Citrullus lanatus (Thunb.) Matsum. and Nakai] contains high L-citrulline content and consumption of watermelon juice may promote ergogenic effects. The aim of the present study was to investigate the role of 100% flesh watermelon juice and 100% rind watermelon juice supplementation for 14 days on swimming performance in rats. Twenty four male Sprague-Dawley rats were randomly divided into four groups: Cx group of rats supplemented with filtered tap water (negative control), L-cit group of rats supplemented with L-citrulline (positive control), FR group of rats supplemented with 100% flesh watermelon juice, and RR group of rats supplemented with 100% rind watermelon juice. Each group was supplemented for 14 days ad libitum prior to swimming exercise protocol. The rats were performed swimming exercise for 3 days and swimming time until exhaustion was measured. Plasma samples were collected to measure lactate concentration, ammonia concentration, and nitric oxide production. Rats supplemented with 100% flesh watermelon juice demonstrated significantly prolonged of swimming time until exhaustion, reduction of lactate and ammonia concentrations, and increased of nitric oxide production compared to Cx and L-cit groups (P<0.05). These findings postulate that supplementation with 100% flesh watermelon juice improves endurance in swimming performance.
... • Sekundäre Pflanzenstoffe (S. 28) o Theobromin (S. 28) o Catuaba Extrakt (S. 29) o Maca Extrakt (S. 31) o Grüntee Extrakt, entkoffeiniert (S. 32) o Ingwer Extrakt (S. 33) o Magnolia Extrakt (S. 35) o Piperin (S. 37) • Sonstiges/Beschreibung (S. 38) -Produkt 2: Proteinriegel (S. 39) • Inhaltsstoffe (S. 40) o Süßkartoffel-Pulver (S. 40) • Die wichtigsten Nährstoffe im Überblick (S. 41) o Eiklar-Pulver (S. 47) o Allulose (S. 48) o Datteln (S. 48) o Honig (S. 49) o Propolis (S. 51) o Gelee Royal (S. 52) o Flohsamenschalen (S.
53)
o Bromelain (S. 54) o Curcuminoide (S. 54) o Piperin (S. 56) o Stevia E960 (S. 56) -Zusammenfassung (S. 58 10,11 Ein häufig behaupteter Zusammenhang zwischen tierischen Produkten (insbesondere Fleisch) und Zivilisationskrankheiten ist, in gesundem Maß, wissenschaftlich nicht haltbar. 12,13,14 Veganer und Vegetarier sollten sich hingegen um ihre Gesundheit bemühen, da eine Mangelsituation häufiger vorkommt als vermutet. ...
Konzept für nachhaltige evidenz-basierte Sportnahrungsprodukte (full-text)
Article
Full-text available
Jul 2020
Tristan Nolting
Die hier vorgestellten Produkte mit Schwerpunkt Nachhaltigkeit und Evidenz-basierten Inhaltsstoffen (Energy-Drink & Protein-Riegel) erhalten im Verbrauchermarkt aufsteigendes Interesse. Dies liegt unter anderem daran, dass Nahrungsmittel mit gesundheits- und leistungsfördernden Eigenschaften benötigt werden, um der steigenden Anzahl an Krankheiten präventiv entgegenzuwirken. Besonders wichtig ist die adäquate Zufuhr von Proteinen und sekundären Pflanzenstoffe, um langfristig gesund zu bleiben. Im Gegensatz zu anderen bereits bestehenden Unternehmen liegt der Fokus dieses Konzepts auf der wissenschaftlichen Bestätigung zur Wirksamkeit der einzelnen Inhaltsstoffe. Damit soll dem Käufer ein optimales Preis-Leistungsverhältnis, auch in Bezug auf den Geschmack, geboten werden. Zusätzlich steht der Ressourcen-schonende Umgang mit Rohstoffen und Verpackungsmaterialien im Vordergrund, sodass zukunftsfähiges Handeln ermöglicht wird. Gerade in einer Zeit von hohen menschengemachten Umweltbelastungen, wie beispielsweise durch Plastikaufkommen in den Meeren, ist eine moralische Firmenpolitik notwendiger denn je.
... Kelelahan otot adalah penurunan performa otot akibat aktivitas fisik. Hal ini menyebabkan kapasitas kekuatan maksimal otot berkurang
(Perez & Jakeman, 2010)
. Selain mengurangi kapasitas kekuatan maksimal, akumulasi dari sisa metabolit akibat dari aktivitas fisik menyebabkan sensasi terbakar dan nyeri pada otot yang akan semakin bertambah seiring waktu dan mencapai puncaknya pada 1-2 hari setelah latihan (Sirait et al., 2015). ...
Efektivitas stretching, passive activity dan VO2max dalam mencegah terjadinya delayed onset muscle soreness
Article
Full-text available
Apr 2020
Andika Triansyah
Mimi Haetami
Tujuan dalam penelitian ini adalah: (1) Untuk mengetahui apakah ada perbedaan efektivitas active isolated stretching dan passive activity dalam mencegah terjadinya delayed onset muscle soreness setelah olahraga intensitas tinggi; (2) Untuk mengetahui apakah ada perbedaan efektivitas antara VO2Max tinggi dan VO2Max rendah dalam mencegah terjadinya delayed onset muscle soreness setelah olahraga intensitas tinggi; (3) Untuk mengetahui apakah ada interaksi antara active isolated stretching dan passive activity dengan VO2Max dalam mencegah terjadinya delayed onset muscle soreness setelah olahraga intensitas tinggi. Metode yang digunakan dalam penelitian ini adalah eksperimen. Bentuk penelitian menggunakan rancangan faktorial 2x2. Teknik pengambilan sampel yang digunakan dalam penelitian ini menggunakan menggunakan rumus dari Issac & Michael, sehingga didapat sampel sebanyak 40 orang. Berdasarkan hasil penelitian dan pembahasan yang penulis lakukan pada penelitian ini, dapat disimpulkan bahwa: (1) tidak ada perbedaan efektivitas Active Isolated Stretching dan passive activity dalam mencegah terjadinya Delayed Onset Muscle Soreness setelah olahraga intensitas tinggi. (2) Tidak ada perbedaan efektivitas antara VO2Max tinggi dan VO2Max rendah dalam mencegah terjadinya Delayed Onset Muscle Soreness setelah olahraga intensitas tinggi. (3) Tidak ada interaksi antara Active Isolated Stretching, Passive Activity dengan VO2Max dalam mencegah terjadinya Delayed Onset Muscle Soreness setelah olahraga intensitas tinggi. Effectiveness stretching, passive activity and VO2max prevent the delayed onset muscle soreness. Abstract The objectives of this study are: (1) To determine whether there are differences in the effectiveness of active isolated stretching and passive activity in preventing delayed onset of muscle soreness after high-intensity exercise; (2) To find out whether there is a difference in effectiveness between high VO2Max and low VO2Max in preventing delayed onset of muscle soreness after high-intensity exercise; (3) To determine whether there is an interaction between active isolated stretching and passive activity with VO2Max in preventing delayed onset of muscle soreness after high-intensity exercise. The method used in this research is an experiment. The analysis uses a 2x2 factorial design. Based on the results of research and discussion that the authors do in this study, it can be concluded that:(1) there is no difference in the effectiveness of Active Isolated Stretching and passive activity in preventing Delayed Onset Muscle Soreness after high-intensity exercise. (2) There is no difference in efficacy between high VO2Max and low VO2Max in preventing Delayed Onset Muscle Soreness after high-intensity exercise. (3) There is no interaction between Active Isolated Stretching, Passive Activity with VO2Max in preventing Delayed Onset Muscle Soreness after high-intensity exercise.
... Regarding performance outcomes, a recent systematic review and metaanalysis by Trexler et al. (126) found a significant, yet small, favorable effect of citrulline-based supplements on acute performance of high-intensity strength and power tasks in comparison with a placebo. Specific to resistance training, several studies have reported that acute ingestion of CitMal allows individuals to complete more repetitions-to-failure over a series of sets of single-joint and/ or multijoint exercises (48,
97,
131,132). For example, resistance-trained males were able to complete a significantly greater number of repetitions during 5 sets of leg press, hack squat, and leg extension to failure at 60% one repetition maximum (1RM) (132). ...
Emerging Nutritional Supplements for Strength and Hypertrophy: An Update of the Current Literature
Article
Full-text available
Apr 2020
Adam Gonzalez
David Church
Jeremy R Townsend
Reza Bagheri
Several dietary supplements have been proposed as a means of improving muscle strength and hypertrophy when combined with resistance training. However, few have received sufficient attention from sports scientists to produce robust evidence for being well recommended. A growing body of literature has emerged for several dietary ingredients with the potential to promote muscular adaptations. Therefore, the aim of this review is to provide an evidence-based review of the efficacy of emerging nutritional supplements to allow athletes, coaches, and practitioners to make an informed decision when considering their use as a means of improving muscle strength and hypertrophy.
... In this study a combination of orally administered L-citrulline and L-arginine were selected due to the fact, that some studies described a more effective and rapid increase of plasma L-arginine and augmented NO-dependent response (8,9,41). Furthermore, the addition of malate to dietary L-citrulline was chosen in this study, since previous studies observed higher levels of NO metabolites than malate (11,
42)
. Dosages of 8 g L-citrulline malate and 3 g L-arginine were used in this study, because previous studies consider these dosages to be safe for healthy individuals and without adverse events (31,33,34 ...
Assessment of muscular perfusion after oral intake of pre-workout nitric-oxide stimulating supplements by Contrast-Enhanced Ultrasound (CEUS). Study protocol for a placebo-controlled, randomized cross-over trial in healthy young males
Preprint
Full-text available
Mar 2020
Julian Doll
Franziska Bürkle
Arndt Neide
Christian Alexander Fischer
Background The market for dietary supplements in the sports sector has been growing rapidly for several years, though there is still lacking evidence regarding their claimed benefits. One group is that of nitric oxide increasing supplements, so-called "NO-boosters", which are claimed to improve the supply of oxygen and nutrients to the muscle by enhancing vasodilation. The aim of this study was to investigate three of these supplements in healthy male athletes for their muscle perfusion-enhancing potential using contrast-enhanced ultrasound (CEUS).
Methods This placebo-controlled, double-blind, randomized cross-over trial will be carried out at the Center for Orthopedics, Trauma Surgery and Spinal Cord Injury of the University Hospital Heidelberg. Three commercial NO enhancing products including 300 mg of the specific green tea extract VASO6™ and a combination of 8 g L-citrulline malate and 3 g L-arginine hydrochloride will be examined for their potential to increase muscular perfusion in 30 male athletes between 18 and 40 years and will be compared with a placebo. On each of the three appointments CEUS of the dominant biceps muscle will be performed at rest and after a standardized resistance training. Every athlete receives each of the three supplements once after a wash-out period of at least one week. Perfusion will be quantified via VueBox® quantification software. The results of CEUS perfusion measurements will be compared intra- and interindividually and correlated with clinical parameters.
Discussion The results of this study may help to establish CEUS as a suitable imaging modality for the evaluation of potentially vasodilatory drugs in the field of sports. Other supplements could also be evaluated in this way to verify the content of their advertising claims.
Trial registration German Clinical Trials Register (DRKS), ID: DRKS00016972, registered on 25.03.2019.
Effects of branched chain amino acids, l-citrulline, and alpha-glycerylphosphorylcholine supplementation on exercise performance in trained cyclists: a randomized crossover trial
Article
May 2023
Sports Nutr Rev J
Renee Nicole Harrington
Background:
Nutrition plays a key role in training and athletic performance and dietary supplements can make a small, but potentially valuable, contribution to achieving peak athletic performance. This study is the first to investigate the effects of supplementation from the combination of BCAAs, L-citrulline, and A-GPC on exercise performance.
Methods:
In this randomized, double-blind, crossover study 30 male trained cyclists (age: 43.7 ± 8.5 years) completed a 20 km cycling time trial (TT) test and a high intensity endurance cycling (HIEC) test following a 7-day supplementation period with either a supplement containing 8 g BCAAs, 6 g L-citrulline, and 300 mg A-GPC or a placebo (15 g maltodextrin). For each trial, mean values for time to completion, peak and average power output, OMNI rating of perceived exertion, and visual analogue scale (VAS) responses on perceived exertion were computed for the 20 km TT test. Mean values for time to fatigue and VAS responses on perceived exertion were computed for the HIEC test. Procedures for dietary intake and exercise patterns were implemented to achieve consistency throughout the study period.
Results:
There was a significant increase (p = .003) in peak power in the 20 km TT (354.27 ± 87.88 and 321.67 ± 63.65, for supplement and placebo trials, respectively) and a significant increase (p = .001) in time to fatigue in the HIEC test (0:19:49 ± 0:11:13 min and 0:14:33 ± 0:09:59 min, for supplement and placebo trials, respectively) with the test supplement compared to the placebo. With the test supplement, there was an average increase in TT peak power of 11% and an average increase in time to fatigue of 36.2% in the HIEC test compared to the placebo. There was no significant improvement in time to completion, average power, OMNI rating of perceived exertion, or VAS responses on perceived exertion in the TT test and no significant improvement in VAS measures of perceived exertion in the HIEC test.
Conclusions:
The combination of BCAAs, L-citrulline, and A-GPC used in this study improves cycling performance and may be useful for individuals seeking to improve athletic performance, particularly in disciplines requiring lower body muscular strength and endurance.
Effects of citrulline on endurance performance in young healthy adults: a systematic review and meta-analysis
Article
May 2023
Sports Nutr Rev J
Callum S. Harnden
JOSEPH Agu
TOM Gascoyne
Background
Citrulline is a popular dietary supplement, primarily thought to exert ergogenic effects on exercise performance through the enhancement of nitric oxide (NO) synthesis and ammonia buffering. However, recent findings surrounding citrulline’s effect on endurance performance have been inconsistent. A systematic review and meta-analysis of the relevant literature have yet to be undertaken.
Aim
To determine if acute ingestion of citrulline has an ergogenic effect on endurance performance in young healthy adults.
Methods
A systematic search of three databases was undertaken to find peer-reviewed randomized controlled trials (RCTs) published in English investigating the effects of citrulline supplementation on endurance performance in young healthy adults. Two independent investigators completed a three-phased screening procedure against pre-determined eligibility criteria. Included studies evaluated loading or bolus dosage regimes of citrulline in participants aged 18 or over that were at least recreationally active. Outcome measures focused on time-to-completion (TTC) or time-to-exhaustion (TTE) in continuous submaximal intensity exercise. Cochrane’s Risk of Bias 2 (RoB 2) tool was used to assess the risk of bias in individual studies. Meta-analysis was conducted using a fixed-effects model to pool the weighted estimate of standardized mean differences (SMD) across studies. A chi-squared test assessed heterogeneity between studies. This review was conducted and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.
Results
Nine studies (n = 158 participants) met the eligibility criteria; five reported TTE outcomes (I² = 0%, χ² = 0.37, df = 4, P = 0.99) and four reported TTC outcomes (I² = 0%, χ² = 0.46, df = 3, P = 0.93), both with a low between-study heterogeneity. The results of the meta-analyses showed no significant difference in the endurance performance measures, TTE (pooled SMD = 0.03 [−0.27, 0.33]) and TTC (pooled SMD = −0.07 [−0.50, 0.15]), after acute ingestion of citrulline supplementation or a control in young healthy adults.
Discussion
The current evidence suggests no significant benefit of citrulline supplementation for endurance performance. However, the small evidence base requires further research to fully evaluate this topic. Recommendations include a focus on female populations; higher continuous doses of citrulline over seven days; and TTC outcome measures over longer distances to simulate competition.
The Effects of Protein and Supplements on Sarcopenia in Human Clinical Studies: How Older Adults Should Consume Protein and Supplements
Article
Oct 2022
Young Jin Jang
Sarcopenia is a condition in which muscle mass, strength, and performance decrease with age. It is associated with chronic diseases such as diabetes, cardiovascular disease, and hypertension, and contributes to an increase in mortality. Because managing sarcopenia is critical for maintaining good health and quality of life for the elderly, the condition has sparked concern among many researchers. To counteract sarcopenia, intake of protein is an important factor, while a lack of either protein or vitamin D is a major cause of sarcopenia. In addition, essential amino acids, leucine, βhydroxy β-methylbutyrate (HMB), creatine, and citrulline are used as supplements for muscle health and are suggested as alternatives for controlling sarcopenia. There are many studies on such proteins and supplements, but it is necessary to actually organize the types, amounts, and methods by which proteins and supplements should be consumed to inhibit sarcopenia. In this study, the efficacy of proteins and supplements for controlling sarcopenia according to human clinical studies is summarized to provide suggestions about how the elderly may consume proteins, amino acids, and other supplements.
Citrulline as a Marker of Villous Abnormality and Implications for Diet and Nutrition: Implications for Malabsorption and Nutrition
Chapter
Oct 2022
Alka Singh
Pooja
Govind Makharia
Citrulline is a non-protein amino acid, which is synthesized from glutamine in the small intestinal enterocytes. It is involved in three important metabolic pathways, including the de novo synthesis of arginine in the kidney, intrahepatic transformation of ammonia to urea, and nitric oxide synthesis. Since citrulline is synthesized mainly by enterocytes, the blood levels of citrulline reflect the overall enterocyte mass. A reduction in the levels of citrulline reflects small intestinal enterocyte injury. Plasma concentration of citrulline has been considered to be a noninvasive marker of villous abnormalities and small intestinal length in short bowel syndrome. Plasma citrulline has also been explored to predict and assess the severity of rejection after small intestinal transplantation. Many inborn errors of metabolism such as deficiency of argininosuccinate synthase can lead to hyper-citrullinemia and neurological dysfunctions. Since citrulline is a source of arginine and nitric oxide, its supplementation has been used in many cardiovascular conditions, sarcopenia, and erectile dysfunction. In this chapter, we have comprehensively discussed the synthesis and metabolism of citrulline as well as its diagnostic and therapeutic importance in human health.
Effect of citrulline malate supplementation on muscle function and bioenergetics during short-term repeated bouts of fatiguing exercise
Article
Oct 2022
J SPORT SCI
Laura Meimoun
Emilie Pecchi
Christophe Vilmen
Benoit Giannesini
Citrulline malate (CM) has been shown to improve muscle performance in healthy participants during a single exercise session. Yet, within the framework of exercises repeated at close time interval, the consequences of CM ingestion on mechanical performance are controversial and the bioenergetics side remains undocumented. The aim of this double-blind placebo-controlled study was to evaluate in vivo the effect of short-term (7 doses in 48 h) oral administration of CM upon gastrocnemius muscle function and bioenergetics using non-invasive multimodal NMR techniques in healthy rats. The experimental protocol consisted of two 6-min bouts of fatiguing exercise spaced by an 8-min recovery period. CM treatment did not affect the basal bioenergetics status and increased the half-fatigue time during the first exercise bout. With exercise repetition, it prevented PCr cost alteration and decreased both the glycolytic ATP production and the contractile ATP cost in working muscle, but these changes were not associated to any improvement in mechanical performance. In addition, CM did not influence the replenishment of high-energy phosphorylated compounds during the post-exercise recovery periods. Therefore, short-term CM administration enhances muscle bioenergetics throughout fatiguing bouts of exercise repeated at close time interval but this enhancement does not benefit to mechanical performance.
A comprehensive review on the watermelon phytochemical profile and their bioactive and therapeutic effects
Article
Full-text available
Aug 2022
Muhammad Nadeem
Maham Navida
Kashif Ameer
Ahmad Din
Watermelon (Citrullus lanatus ) is commonly consumed by humans and widely available around the world. It has impressive nutritional properties, a rich phytochemical profile, and various claimed medicinal and health benefits. The major carotenoids in watermelon include lycopene, β-carotene, phytofluene, phytoene, lutein, and neurosporene. Lycopene (approximately 6,888 μg/152 g) is the major bioactive component in the fruit and it reportedly promotes several therapeutic effects, such as anti-cancer and anti-inflammatory activities etc. in humans and animals. Watermelon is also a good source of the amino acid citrulline, which is involved in production of arginine. Pre- and postharvest factors, including fruit sampling area, application of fertilizer, climatic factors, and genetic variability, are known to affect its bioactive compounds and nutrient concentrations. This review summarizes our current understanding of the watermelon phytochemical profile and the factors affecting its bioactivities and therapeutic effects.
Citrulline as a Marker of Villous Abnormality and Implications for Diet and Nutrition: Implications for Malabsorption and Nutrition
Chapter
Jan 2022
Alka Singh
Pooja
Govind Makharia
Nutritional Integrative Approaches for the Management of Sarcopenia
Article
Full-text available
Jan 2022
Rajwant Kaur
Saahil Arora
Manish Goswami
ABSTRACTSarcopenia is a societal health issue owing to population density shifts and characterized by musclemass and muscle function loss due to age. Despite many efforts to develop treatment strategies forsarcopenia, exceptionally restricted therapies are still available for clinical use. Mostpharmacological drugs studied too far have been hormonal and targeting myostatin signaling.Alternatively, dietary supplements help to improve sarcopenia and recover muscular function. Asubstantial body of scientific and clinical data supports a positive outlook for the use of naturaltherapy and chemicals to manage or treat diseases. It is possible to take nutritional supplements insuch a way that will provide sufficient vital nutrients for human requirements. The purpose of thisstudy is to provide an overview of current information about the nutritional characteristics, helpfuland nutritious substances, and their application in the management and treatment of sarcopenia.
KEYWORDS: Sarcopenia, muscle mass, ageing, giant muscle, musculoskeletal system
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Acute and Chronic Citrulline Malate Supplementation on Muscle Contractile Properties and Fatigue Rate of the Quadriceps
Article
Sep 2021
Alyssa N. Fick
Robert Kowalsky
Matthew S. Stone
Tyler M Farney
This study compared the acute and chronic impact of citrulline malate (CM) supplementation on muscle contractile properties and fatigue rate of the quadriceps. Eighteen recreationally trained males consumed both a placebo (PL) and CM treatment for two separate dosing periods. The first experimental testing session for each dosing period was considered the baseline day, the second session the acute day, and the third session the chronic day, which followed seven consecutive days of supplementation. All testing sessions included exercising on a cycle ergometer at 50%–60% of their max power output for 30 min followed by performing the Thorstensson test on an isokinetic dynamometer. A two-way (Supplement × Time) analysis of variance with repeated measures resulted in no significant interactions ( p > .05) (PL: baseline day, acute day, chronic day vs. CM: baseline day, acute day, chronic day) for peak power (in watts) (469 ± 81, 490 ± 97, 502 ± 99 vs. 464 ± 85, 480 ± 103, 501 ± 81); peak torque (in newton meters) (150 ± 26, 157 ± 32, 161 ± 31 vs. 149 ± 27, 156 ± 33, 161 ± 26); fatigue rate (in percentage) (57 ± 9, 57 ± 10, 58 ± 9 vs. 57 ± 10, 56 ± 9, 58 ± 9); and heart rate (in beats per minute) (156 ± 17, 146 ± 13, 146 ± 9 vs. 155 ± 11, 146 ± 11, 146 ± 9). The results of this study suggest that neither acute nor chronic supplementation of CM had an effect on recovery or fatigue rate of the quadriceps.
Amino Acids and Their Metabolites for Improving Human Exercising Performance
Chapter
Jul 2021
ADV EXP MED BIOL
Erin Posey
Fuller W Bazer
Guoyao Wu
Achieving adequate nutrition for exercising humans is especially important for improving both muscle mass and metabolic health. One of the most common misunderstandings in the fitness industry is that the human body has requirements for dietary whole protein and that exercising individuals must consume only whole protein to meet their physiological needs. This view, however, is incorrect. Instead, humans at rest or during exercise have requirements for dietary amino acids (AAs), and dietary protein is a source of AAs in the body. The requirements for AAs must be met each day to avoid a negative nitrogen balance in individuals with moderate or intense physical activity. By properly meeting increased requirements for AAs through increased intake of high-quality protein (the source of AAs) plus supplemental AAs, athletes can improve their overall athletic performance. AAs or metabolites that are of special importance for exercising individuals include arginine, branched-chain AAs, creatine, glycine, taurine, and glutamine. The AAs play vital roles as both substrates for protein synthesis and molecules for regulating blood flow and nutrient metabolism. The functional roles of AAs include the maintenance of cell and tissue integrity; stimulation of mechanistic target of rapamycin and AMP-activated protein kinase cell signaling pathways; energy sources for the small intestine, cells of the immune system, and skeletal muscle; antioxidant and anti-inflammatory reactions; production of neurotransmitters; modulation of acid–base balance in the body. All of those roles are crucial for the overall goal of improving exercise performance. Therefore, adequate intakes of proteinogenic AAs and their functional metabolites, especially those noted in this review, are essential for optimal human health (including optimum muscle mass and function) and should be a primary goal of exercising individuals.
Effects of Citrulline Malate Supplementation on Muscle Strength in Resistance-Trained Adults: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Article
Jun 2021
Juliano Casonatto
Andreo Fernando Aguiar
Although the ergogenic mechanisms of supplementation with citrulline malate are well known, unclear findings regarding variables of muscle strength have been recorded. Such misleading findings in the literature illustrate the need for well-conducted meta-analysis research to elucidate the possible ergogenic impact, which could have major practical consequences for athletes and recreational practitioners seeking to optimize gains in muscle strength. The objective of this systematic review was to summarize the existing literature that evaluated the effects of citrulline malate supplementation on muscle strength outcomes from resistance exercise in resistance-trained individuals. A systematic electronic search in Medline and Scientific Electronic Library Online (SciELO) was completed in August 2020 identifying randomized controlled trials investigating the effect of citrulline malate supplementation on muscle strength in resistance-trained adults. A subsequent meta-analysis was performed. The meta-analysis involved four studies and 138 assessments (69 in citrulline-malate and 69 in placebo groups). We did not observe an overall effect favoring citrulline-malate supplementation (SMD95% = 0.13 [−0.21; 0.46]). Considering the lower (SMD95% = 0.06 [−0.47; 0.60]) and upper (SMD95% = 0.17 [−0.26; 0.60]) limbs, a non-significant overall effect was identified. The mean effects were similar for “limbs” (upper vs lower) [p = 0.763]. Accordingly, our findings suggest that citrulline malate supplementation does not improve muscle strength in healthy and resistance-trained individuals (PROSPERO registration number: CRD42020159338).
Pre-workout Supplementation: The Good, The Bad, and The Ugly
Article
Jun 2021
Strength Condit
Ronald Snarr
Approximately half of the United States adult population consumes some form of dietary supplementation, with that proportion rising in physically active adults and athletes (23). One of the most commonly consumed supplements is a “pre-workout”. Pre-workouts can be categorized as any supplement ingested prior to an exercise session or sporting event with the intent of increasing mental focus, endurance, blood flow, strength, power, aerobic and anaerobic capacity, or overall perceived increase in energy level.
Pre-workouts come in a variety of forms ranging from single- (e.g., caffeine) to multi-ingredients (MIPS); stimulant versus stimulant-free; and powdered, pill, or liquid form (e.g., energy drinks). While countless formulas exist, Table 1 highlights and breaks down the individual ingredients most often found in these products and how each has been demonstrated to affect the body. Despite conflicting evidence of effectiveness, pre-workouts continue to gain popularity in both recreational and athletic populations due to the anecdotal claims of increased performance, reduced recovery time, and increased perceived energy. However, along with the increased usage of these products, there is an ever-growing cause for concern pertaining to not only their effectiveness, but also safety. Therefore, this article will discuss the most common individual ingredients typically found within pre-workouts and describe “the good, the bad, and the ugly” associated with its usage.
Efek Akut Pemberian Asam Amino Citrulin Alami Terhadap Kekuatan Otot
Article
Full-text available
Dec 2020
Anies Setiowati
Sri Sumartiningsih
Tujuan penelitian untuk menganalisa efek akut asam amino sitrulin alami terhadap kekuatan otot. Metode penelitian dengan desain -post test controlled group design. Sampel penelitian adalah mahasiwa IKOR FIK dibagi secara acak menjadi 2 kelompok yaitu kelompok kontrol dan kelompok sitrulin. Perlakuan pada kelompok sitrulin berupa pemberian jus semangka 428 ml (600-700 g daging buah semangka) kandungan sitrulin sebesar 1 mg. sedang pada kelompok control diberikan placebo yaitu air sirup. Jus semangka ataupun air sirup diberikan 60 menit sebelum dilakukan tes kekuatan otot yaitu kekuatan otot tungkai, punggung, bahu dan genggam tangan dengan menggunakan Dynamometer. Data dianalisis diuji T-test dengan SPSS. Hasil penelitian: rerata kekuatan otot total diperoleh dari hasil penjumalahan kekuatan otot punggung, tungkai, bahu, genggam tangan. Retata kekuatan otot total kelompok kontrol 362,98±87,26 kg, kelompok perlakuan critrulline alami (semangka) 378,46±128,23, p=0,782. Tidak terdapat perbedaan efek akut asam amino sitrulin alami terhadap kekuatan otot
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Effects of a L-citrulline supplementation on nitric oxide and blood lactate in young women after a maximum exercise session
Article
Full-text available
Nov 2020
Atefeh Fereidooni
Parvaneh Nazarali
Fahimeh Kazemi
Introduction: The consumption of sports supplements and their effects on the performance of athletes needs to be evaluated. The purpose of this study was to determine the effects of L-citrulline supplementation on nitric oxide (NO) and blood lactate in young women after a maximal exercise session.
Methods & Materials: The research method was quasi-experimental with double blind design. After filling out the health questionnaire, 24 voluntary inactive young women with body mass index less than 25 kg/m2 were randomly divided into two groups (n=12) and placebo (n=12). Subjects visited the laboratory twice; in the first session, the first blood samples were taken immediately after the exercise protocol. After 5 minutes of warm-up, the subjects were performed the Bruce treadmill test protocol to time to exhaustion. Then the supplement group consumed 6 grams daily L-citrulline powder and placebo (starch powder) for one week. The second session was performed one week later in the same conditions as the first session. Immediately after the test, time to exhaustion was recorded, blood samples collected and lactate and NO plasma levels measured. Analysis of variance with repeated measures with significant level P<0.05 was used for analyzing data.
Findings: The results showed that there was no significant difference between time to exhaustion, plasma levels of lactate and NO of two groups (placebo and supplement) in two sessions.
Discussion & Conclusions: It seems that acute supplementation of L-citrulline has no effect on nitric NO and blood lactate in young women after a maximal exercise session.
Arginine and citrulline as nutraceuticals: efficacy and safety in diseases
Chapter
Jan 2021
Navin Kaore
Navinchandra M Kaore
L-citrulline and L-arginine are naturally occurring amino acids that are conditionally essential in periods of stress (sepsis, intestinal pathology). Previously considered to be only intermediates in the urea acid cycle, they are now found to be effective precursors of nitric oxide that are exploited in therapeutics. Its their supplementation is likely to be used in conditions like such as erectile dysfunction, male infertility, sickle cell anemia, short bowel syndrome (to restore nitrogen balance), hyperlipidemia, cancer chemotherapy, hyperoxic lung damage, uric acid cycle disorders, and intrauterine growth restriction. Other emerging uses are include immunonutrition, immunomodulation, cystic fibrosis, Alzheimer’s disease, multiinfarct dementia, T-cell dysfunction, as an antioxidant in conditions like sepsis, and for athletic training. Overall, citrulline (Cit) is a more effective precursor of arginine than arginine itself. Its role as a biomarker in intestinal pathology and diagnosis of early rheumatoid arthritis is of considerable interest. These nutraceuticals should be further explored in large-scale clinical trials in these areas. Another area of interest regarding Cit is the detection of an antibody to citrullinated peptides that serve as predictors for diseases, thus serving as biomarkers in various diseases. Cit has been used as a biomarker for diseases such as rheumatoid arthritis, intestinal pathology, and short bowel syndrome short bowel syndrome as biomarkers. It will either be proved or disproved as a biomarker in the future for other conditions such as parenteral nutrition in HIV patients, congenital anomalies, acute rejections in transplantations, intrauterine growth restriction, critically ill patients, acute kidney failure, and nitrosative stress (NO/NOS) and reactive nitrogen species (RNS) in conditions such as anticholinesterase poisoning and, kainic acid-induced neurotoxicity because oxidative stress increases RNS and reactive oxygen species reactive oxygen species (when the rate of adenosine triphosphate demand exceeds production), causing lipid peroxidation and DNA damage. Further studies are required in this regards.
Effects of acute citrulline malate supplementation on NO, lactate, sport performance and some markers of muscle damage in healthy trained men
Article
Full-text available
May 2020
Ahmadreza Eshaghian
Ali Asghar Ravasi
Abbas Ali Gaeini
Citrulline malate (CM) is an increasingly common dietary supplement that is thought to enhance exercise performance by increasing nitric oxide production. The aim of this study was to investigate the effect of short term use of CM supplement on NO, blood lactate, sport performance, LDH and CK in 8 healthy trained men. In a semi-experimental study, a group of 8 people randomly selected and after attending in the first session to measure anthropometry characteristics and basic performance factors, participated in three sessions of placebo (8g dexterose) and then three sessions of supplement (8g CM). Placebo or supplement was taken 60 minute before intervention sessions. Blood samples were taken in three phase, before the 4th session and after 2nd and 3rd sessions. Then blood factors were measured by laboratory kits. Exercise performance factors were measured by pushup, cooper and rast tests. At the end, data were analyzed by repeated measure test as well as the follow-up Bonfroni test, at a significance level of 0/05.
Results showed that acute CM supplementation compared to placebo, significantly reduced CK response to exercise (ϼ=0/041), increased NO response to exercise (ϼ=0/006), increased average anaerobic power (ϼ=0/037) and increased muscular endurance (ϼ=0/005). Nevertheless, acute CM supplementation compared to placebo, didn't have a significant effect on LDH and lactate response to exercise (ϼ=1), maximal anaerobic power (ϼ=0/13) and aerobic endurance (ϼ=0/08).
Acute CM supplementation may improve anaerobic performance, muscle performance, vasodilation and decrease muscle damage.
Acute citrulline-malate ingestion does not enhance performance in judo athletes
Article
Full-text available
Jan 2021
Julio Cezar
Arthur Azevedo
Rodrigo Freire De Almeida
Lucas Guimarães-Ferreira
Background. Judo is a combat sport that involves grappling and throwing techniques, and multiple high-intensity efforts. Citrul-line Malate (CM) is a nutritional supplement used to enhance physical performance, albeit not all studies have corroborated its ergogenic properties during high-intensity exercise. Problem and aim. To the best of our knowledge, the effects of CM on judo performance has not been investigated. To fill this gap the aim of the current study was to investigate the effects of acute CM ingestion on performance in judo athletes. Methods. Using a randomized crossover and double-blinded design, 10 judo athletes ingested 8g of CM (2:1 proportion) or placebo 60 minutes prior to the execution of three bouts of the Special Judo Fitness Test (SJFT). The number of throws, the SJFT index, blood lactate concentration before and after each bout and rating of perceived exertion (RPE) after each bout were assessed. Results. Acute CM ingestion did not result in an increase of throws during three sets of the SJFT, nor in the SJFT index and RPE. The blood lactate concentration was higher in the CM condition only after the second SJFT bout, with no differences at any other time points. Conclusions. Acute CM ingestion by judo athletes did not improve performance in the SJFT.
The effect of six weeks’ watermelon juice on nitric oxide and exercise performance in elite female taekwondo
Article
Full-text available
Dec 2020
Parvin Aghabeigi Amin
Mohammad Azizi
Worya Tahmasebi
| https://www.researchgate.net/publication/43131299_Citrulline_Malate_Enhances_Athletic_Anaerobic_Performance_and_Relieves_Muscle_Soreness?ref=arjmahadevan.com |
United Nations (Anti-terrorism Measures) Regulations - Singapore Statutes Online
Singapore Statutes Online is provided by the Legislation Division of the Singapore Attorney-General's Chambers
United Nations (Anti-terrorism Measures) Regulations
Status:
Not current version
(version history — see timeline)
United Nations Act
(Chapter 339, Section 2(1))
United Nations (Anti-terrorism Measures) Regulations
Rg 1
G.N. No. S 561/2001
REVISED EDITION 2003
(31st January 2003)
[13th November 2001]
Citation
1. These Regulations may be cited as the United Nations (Anti-Terrorism Measures) Regulations.
Object
2. The object of these Regulations is to assist in giving effect to Resolution 1373 (2001) and Resolution 1390 (2002) of the Security Council of the United Nations.
Application
3. These Regulations shall not apply to any financial institution or class of financial institutions to the extent that the financial institution or class of financial institutions is or may be subject to the directions of the Monetary Authority of Singapore under section 27A of the Monetary Authority of Singapore Act (Cap. 186).
Definitions
4. —(1) In these Regulations — “arms and related material” means any type of weapon, ammunition, military vehicle or military or paramilitary equipment, and includes their spare parts; “funds” includes cheques, bank deposits and other financial resources; “property” means real or personal property, moveable or immovable, including a lease of immovable property as well as a right or interest in such property; “Singapore ship” means a ship registered under Part II of the Merchant Shipping Act (Cap. 179); “terrorist” means any person who — ( a ) commits, or attempts to commit, any terrorist act; or ( b ) participates in or facilitates the commission of any terrorist act, and includes any person set out in the Schedule; “terrorist act” means the use or threat of action — ( a ) where the action — (i) involves serious violence against a person; (ii) involves serious damage to property; (iii) endangers a person’s life; (iv) creates a serious risk to the health or the safety of the public or a section of the public; (v) involves the use of firearms or explosives; (vi) involves releasing into the environment or any part thereof, or distributing or otherwise exposing the public or any part thereof to — (A) any dangerous, hazardous, radioactive or harmful substance; (B) any toxic chemical; or (C) any microbial or other biological agent, or toxin; (vii) is designed to disrupt any public computer system or the provision of services directly related to communications infrastructure, banking and financial services, public utilities, public transportation or public key infrastructure; (viii) is designed to disrupt the provision of essential emergency services such as the police, civil defence and medical services; or (ix) involves prejudice to public security or national defence; and ( b ) where the use or threat is intended or reasonably regarded as intending to — (i) influence the Government or any other government; or (ii) intimidate the public or a section of the public. (2) For the purposes of paragraph (1) — ( a ) “action” includes action outside Singapore; and ( b ) a reference to the public includes a reference to the public of a country or territory other than Singapore. (3) In these Regulations, unless the context otherwise requires, any reference to “terrorist act” shall include any act referred to in regulation 8(2) or (3).
Prohibition against provision or collection of funds for terrorists
5. No person in Singapore and no citizen of Singapore outside Singapore shall — ( a ) provide funds to any person by any means, directly or indirectly; or ( b ) collect funds for any person by any means, directly or indirectly, if he knows or has reasonable grounds to believe that the funds will be used to commit any terrorist act or facilitate the commission of any terrorist act.
Prohibition against dealing with property of terrorists
6. No person in Singapore and no citizen of Singapore outside Singapore shall — ( a ) deal, directly or indirectly, in any property that is owned or controlled by or on behalf of any terrorist or any entity owned or controlled by any terrorist, including funds derived or generated from property owned or controlled, directly or indirectly, by any terrorist or any entity owned or controlled by any terrorist; ( b ) enter into or facilitate, directly or indirectly, any financial transaction related to a dealing in property referred to in paragraph ( a ); or ( c ) provide any financial services or any other related services in respect of any property referred to in paragraph ( a ), to or for the benefit of, or on the direction or order of, any terrorist or any entity owned or controlled by any terrorist.
Prohibition against provision of resources and services for benefit of terrorists
7. —(1) No person in Singapore and no citizen of Singapore outside Singapore shall — ( a ) make available any funds or other financial assets or economic resources; or ( b ) make available any financial or other related services, for the benefit of any prohibited person. (2) In paragraph (1), “prohibited person” means — ( a ) any terrorist; ( b ) any entity owned or controlled by any terrorist; or ( c ) any person or entity acting on behalf of or at the direction of any person referred to in sub-paragraph ( a ) or ( b ).
Prohibition against sale, supply, etc., of arms and related material to terrorists
7A. No person in Singapore and no citizen of Singapore outside Singapore shall, directly or indirectly, export, sell, supply or ship any arms and related material, wherever situated, to any terrorist.
Prohibition against carriage of arms and related material by Singapore ships and aircraft for terrorists
7B. No owner or master of a Singapore ship and no operator of an aircraft registered in Singapore shall, directly or indirectly, carry or cause or permit to be carried any arms and related material, wherever situated, for any terrorist.
Prohibition against provision of technical advice, assistance, etc., related to military activities of terrorists
7C. No person in Singapore and no citizen of Singapore outside Singapore shall, directly or indirectly, provide any terrorist with technical advice, assistance or training related to military activities.
Prohibition against false threats of terrorist acts
8. —(1) No person in Singapore and no citizen of Singapore outside Singapore shall communicate or make available by any means any information which he knows or believes to be false to another person with the intention of inducing in him or any other person a false belief that a terrorist act has been, is being or will be carried out. (2) No person in Singapore and no citizen of Singapore outside Singapore shall place any article or substance in any place whatsoever with the intention of inducing in some other person a false belief that — ( a ) the article or substance is likely to explode or ignite and thereby cause personal injury or damage to property; or ( b ) the article contains or the substance consists of — (i) any dangerous, hazardous, radioactive or harmful substance; (ii) any toxic chemical; or (iii) any microbial or other biological agent, or toxin, that is likely to cause death, disease or personal injury or damage to property. (3) No person in Singapore and no citizen of Singapore outside Singapore shall despatch any article or substance by post, rail or any other means whatever of sending things from one place to another with the intention of inducing in some other person a false belief that — ( a ) the article or substance is likely to explode or ignite and thereby cause personal injury or damage to property; or ( b ) the article contains or the substance consists of — (i) any dangerous, hazardous, radioactive or harmful substance; (ii) any toxic chemical; or (iii) any microbial or other biological agent, or toxin, that is likely to cause death, disease or personal injury or damage to property. (4) For the purposes of paragraphs (1), (2) and (3), a reference to a person inducing in any other person a false belief does not require the first-mentioned person to have any particular person in mind as the person in whom he intends to induce the false belief.
General prohibition
9. No person in Singapore and no citizen of Singapore outside Singapore shall knowingly do anything that causes, assists or promotes, or is intended to cause, assist or promote, any act or thing prohibited by regulation 5, 6, 7, 7A, 7B, 7C or 8.
Duty to provide information
10. Every person in Singapore and any citizen of Singapore outside Singapore who — ( a ) has possession, custody or control of any property belonging to any terrorist or any entity owned or controlled by any terrorist; or ( b ) has information about any transaction or proposed transaction in respect of any property belonging to any terrorist or any entity owned or controlled by any terrorist, shall immediately inform the Commissioner of Police or such other person as the Minister may designate of that fact or information and provide such further information relating to the property, or transaction or proposed transaction, as the Commissioner or designated person may require.
Offences
11. Any person in Singapore or any citizen of Singapore outside Singapore who contravenes regulation 5, 6, 7, 7A, 7B, 7C, 8, 9 or 10 shall be guilty of an offence.
Exemption
12. The Minister or a person designated by the Minister may, if he considers that it is appropriate to do so in the circumstances of the case and is consistent with the intention of the Security Council of the United Nations under Resolutions 1373 and 1390, by notice in writing exempt, subject to such conditions as he may specify — ( a ) any person or class of persons; or ( b ) any activity or class of activities, from the operation of any or all provisions of these Regulations.
| https://sso.agc.gov.sg/SL/UNA2001-RG1/Historical/20040507?ValidDate=20040507 |
Exodus 25:40 (YLT) - Adam Clarke
And see thou and do `them' by their pattern which thou art shewn in the mount.
Exodus 25:40 ( Young's Literal Translation )
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Exodus 25:40
And look that thou make, etc. -This verse should be understood as an order toMosesafter the tabernacle, etc., had been described to him; as if he had said: "When thou comest to make all the things that I have already described to thee, with the other matters of which I shall afterwards treat, see that thou make every thing according to the pattern which thou didst see in the mount." The Septuagint have it, · according to the Type-form or fashion, which was shown thee. It appears to me that St. Paul had this command particularly in view when he gave that to his son Timothy which we find in the second epistle,II Timothy 1:13: ̔ ̔ , ̔ ' . "Hold fast the Form of sound words which thou hast heard of me." The tabernacle was a type of the Church ofGod; that Church is built upon the foundation of the prophets and apostles,Jesus Christbeing the chief cornerstone,Ephesians 2:20-22: the doctrines, therefore, delivered by the prophets, Jesus Christ, and his apostles, are essential to the constitution of this church. As God, therefore, gave the plan or form according to which the tabernacle must be constructed, so he gives the doctrines according to which the Christian Church is to be modeled; and apostles, and subordinate builders, are to have and hold fast that Form of sound words, and construct this heavenly building according to that form or pattern which has come through the express revelation of God.
In different parts of this work we have had occasion to remark that the heathens borrowed their best things from Divine revelation, both as it refers to what was pure in their doctrines, and significant in their religious rites. Indeed, they seem in many cases to have studied the closest imitation possible, consistent with the adaptation of all to their preposterous and idolatrous worship. They had their Iao or Jove, in imitation of the true Jehovah; and from different attributes of the Divine Nature they formed an innumerable group of gods and goddesses. They had also their temples in imitation of the temple of God; and in these they had their holy and more holy places, in imitation of the courts of the Lord' s house. The heathen temples consisted of several parts or divisions:
1.The area or porch;
2.The or temple, similar to the nave of our churches;
3.The adytum or holy place, called also penetrale and sacrarium; and,
4.The or the inner temple, the most secret recess, where they had their mysteria, and which answered to the holy of holies in the tabernacle.
And as there is no evidence whatever that there was any temple among the heathens prior to the tabernacle, it is reasonable to conclude that it served as a model for all that they afterwards built. They had even their portable temples, to imitate the tabernacle; and the shrines for Diana, mentionedActs 19:24, were of this kind. They had even their arks or sacred coffers, where they kept their most holy things, and the mysterious emblems of their religion; together with candlesticks or lamps, to illuminate their temples, which had few windows, to imitate the golden candlestick in the Mosaic tabernacle. They had even their processions, in imitation of the carrying about of the ark in the wilderness, accompanied by such ceremonies as sufficiently show, to an unprejudiced mind, that they borrowed them from this sacred original. Dr. Dodd has a good note on this subject, which I shall take the liberty to extract.
Speaking of the ark, he says, "We meet with imitations of this Divinely instituted emblem among several heathen nations. Thus Tacitus, De Moribus Germanorum, cap. 40, informs us that the inhabitants of the north of Germany, our Saxon ancestors, in general worshipped Herthum or Hertham, i.e., the mother earth: Hertham being plainly derived from arets , earth, and am , mother: and they believed her to interpose in the affairs of men, and to visit nations: that to her, in a sacred grove in a certain island of the ocean, a vehicle covered with a vestment was consecrated, and allowed to be touched by the priests only, (compareII Samuel 6:6,II Samuel 6:7;I Chronicles 13:9,I Chronicles 13:10), who perceived when the goddess entered into her secret place, penetrale, and with profound veneration attended her vehicle, which was drawn by cows; seeI Samuel 6:7-10. While the goddess was on her progress, days of rejoicing were kept in every place which she vouchsafed to visit; they engaged in no war, they handled no weapons;peaceand quietness were then only known, only relished, till the same priest reconducted the goddess to her temple. Then the vehicle and vestment, and, if you can believe it, the goddess herself, were washed in a sacred lake."
Apuleius, De Aur. Asin., lib. ii., describing a solemn idolatrous procession, after the Egyptian mode, says, "A chest, or ark, was carried by another, containing their secret things, entirely concealing the mysteries of religion."
And Plutarch, in his treatise De Iside, etc., describing the rites of Osiris, says, "On the tenth day of the month, at night, they go down to the sea; and the stolists, together with the priest, carry forth the sacred chest, in which is a small boat or vessel of gold."
Pausanius likewise testifies, lib. vii., c. 19, that the ancient Trojans had a sacred ark, wherein was the image of Bacchus, made by Vulcan, which had been given to Dardanus by Jupiter. As the ark was deposited in the holy of holies, so the heathens had in the inmost part of their temples an adytum or penetrale, to which none had access but the priests. And it is remarkable that, among the Mexicans, Vitzliputzli, their supreme god, was represented under a human shape, sitting on a throne, supported by an azure globe which they called heaven; four poles or sticks came out from two sides of this globe, at the end of which serpents' heads were carved, the whole making a litter which the priests carried on their shoulders whenever the idol was shown in public - Religious Ceremonies, vol. iii., p. 146.
Calmet remarks that the ancients used to dedicate candlesticks in the temples of their gods, bearing a great number of lamps.
And Athenaeus, lib. xv., c. 19, 20, mentions one that supported three hundred and sixty-five lamps, which Dionysius the younger, king of Syracuse, dedicated in the Prytaneum at Athens. As the Egyptians, according to the testimony of Clemens Alexandrinus, Strom., lib. i., were the first who used lamps in their temples, they probably borrowed the use from the golden candlestick in the tabernacle and temple.
From the solemn and very particular charge, Look that thou make them after their pattern, which was showed thee in the mount, it appears plainly that God showed Moses a model of the tabernacle and all its furniture; and to receive instructions relative to this was one part of his employment while on the mount forty days with God. As God designed that this building, and all that belonged to it, should be patterns or representations of good things to come, it was indispensably necessary that Moses should receive a model and specification of the whole, according to which he might direct the different artificers in their constructing the work.
1.We may observe that the whole tabernacle and its furniture resembled a dwelling-house and its furniture.
2. That this tabernacle was the house of God, not merely for the performance of his worship, but for his residence.
3.That God had promised to dwell among this people, and this was the habitation which he appointed for his glory.
4.That the tabernacle, as well as the temple, was a type of the incarnation of Jesus Christ. SeeJohn 1:14, andJohn 2:19,John 2:21.
5.That as the glory of God was manifested between the cherubim, above the mercy-seat, in this tabernacle, so God was in Christ, and in him dwelt all the fullness of the Godhead bodily.
6.As in the tabernacle were found bread, light, etc., probably all these were emblematical of the ample provision made in Christ for the direction, support, and salvation of the soul of man. Of these, and many other things in the law and the prophets, we shall know more when mortality is swallowed up of life.
| https://www.bibletools.org/index.cfm/fuseaction/Bible.show/sVerseID/2236/eVerseID/2236/RTD/clarke/version/ylt |
National guard stretching to perform new missions. - Free Online Library
Free Online Library: National guard stretching to perform new missions. by " National Defense" ; Aerospace and defense industries Business
National guard stretching to perform new missions.
MLA style: "National guard stretching to perform new missions.." The Free Library . 2003 National Defense Industrial Association 29 May. 2023 https://www.thefreelibrary.com/National+guard+stretching+to+perform+new+missions.-a0108195839
Chicago style: The Free Library . S.v. National guard stretching to perform new missions.." Retrieved May 29 2023 from https://www.thefreelibrary.com/National+guard+stretching+to+perform+new+missions.-a0108195839
APA style: National guard stretching to perform new missions.. (n.d.) >The Free Library. (2014). Retrieved May 29 2023 from https://www.thefreelibrary.com/National+guard+stretching+to+perform+new+missions.-a0108195839
The National Guard--the oldest component of the U.S. armed
services--is being reconfigured in an effort to fulfill new assignments
in the war against terrorism.
Until now, the nearly 400-year-old Guard may have been best known
for providing relief during local or statewide emergencies, such as
hurricanes, fires or civil disorders. Most of its members serve
part-time, usually one weekend a month and two weeks each summer.
Now, however, in addition to these domestic assignments, they are
being asked, with increasing frequency, to fight in overseas combat
operations, such as Afghanistan and Iraq, and to protect against
terrorist attacks within the United States.
In fact, the Army in July alerted two Guard brigades to prepare to
relieve battle-weary Marine and Army troops in Iraq. If mobilized, the
brigades would deploy this winter, possibly for as long as a year or
more.
Fulfilling such missions requites changes in organization and
equipment for the Guard, said Lt. Gen. H Steven Blum, chief of the
National Guard Bureau, headquartered in Arlington, Va.
"There'll be some rice bowls that will be--if nor
smashed--then unsettled," he told National Defense. "But the
National Guard cannot remain the way it is."
Blum, formerly chief of staff of the U.S. Northern Command, took
over the bureau in April. A month later, he told a conference of state
and territorial adjutants general that each of the Guard units under
their command would be required to consolidate its three top
headquarters into one joint operation.
Currently, each of the 50 states, three territories and the
District of Columbia has three Guard headquarters--one for the
state's overall Guard organization, another for its Army Guard unit
and a third for its Air Guard, for a total of 162 offices. By October 1,
108 of these will no longer exist, he said.
The multiple headquarters are "just too excessive," Blum
said. "And it is nut in keeping with the way that the Defense
Department needs to go to deal with emerging realities and the way we
will fight in the future."
Increasingly, U.S. armed services "fight jointly,"
pooling units from different services as needed to perform specific
missions, Blum said. The Guard needs to do the same, he said. "We
need to train and operate on a daily basis in a joint environment."
Blum is urging the states to include members of other military
reserve components within their borders, such as those from the Navy,
Marine and Coast Guard, in their new joint headquarters. He said he
plans to do that at the Guard Bureau in Arlington.
"This will give the best and brightest in all of our Guard and
reserve units a chance to serve in a joint headquarters that they
wouldn't ordinarily have," Blum said. "It will give the
states, for the first time ever, a chance to harness ,all of the reserve
resources that the Pentagon has residing within their borders."
These changes are as important as two other milestones in Guard
history, Blum said. One was the Militia Act of 1903--known as the Dick
Act--that established federal guidelines for organizing, training and
equipping the Guard. The other was the creation of tire Air Guard in
1947.
Despite their significance, however, Blum cannot order the states
to make the changes. He can only recommend. As chief of the Bureau, he
does not command the 466,000 members of the Army and Air Force Guards.
Instead, Blum is the senior uniformed officer responsible for
developing ,and coordinating all policies, programs and plans for the
Guard. He is the principal advisor on National Guard affairs to the Army
and Air Force secretaries, chiefs of staff and NorthCom. He also serves
as the official channel of communication of the Army; Air Force and
NorthCom with the governors and adjutants general.
During peacetime, Guard units are commanded by state and
territorial governors, through their adjutants general. Each governor
can call out the Guard to respond in domestic emergencies within their
borders.
In May, for example, nearly 200 Guardsmen were deployed after
tornadoes hit Missouri, Kansas and Tennessee and flooding ravaged parts
of Alabama.
The president can activate Guard units to participate in federal
missions. In fact, the Guard has fought in every U.S. war since 1607,
when the English colony at Jamestown, Va., organized a militia. During
World War II, the Guard contributed 19 divisions, doubling the size of
the regular Army. Guard units also served in Korea, Vietnam and Desert
Storm.
After the active-duty services were downsized at the end of the
Cold War, the Guard became even more active. In the past i3 years, its
units have been mobilized eight times, Thomas F. Hall, assistant
secretary of defense for reserve affairs, told a breakfast gathering of
reporters.
At most recent count, 147,000 Guard troops were deployed in 44
different countries, including Iraq, Afghanistan, Bosnia and Kosovo. In
fact, Blum--a career, fulltime Guard officer--commanded the
Multinational Division (North) in Bosnia. Other examples, cited in Guard
press statements, included these:
In Afghanistan, members of the Virginia's 20th Special Forces
Group captured more than 20 Taliban and al Qaida fighters. They also
took or destroyed more than 30 caches of weapons mad munitions.
In Iraq, .50 caliber machine-gun teams from the Texas Air
Guard's 204th Security Forces Squadron maintained the perimeter at
a forward-operating airfield. Other teams from the squadron were
deployed with an anti-terrorist joint task force on the Horn of Africa.
The Guard also is playing a major role in homeland security. Just
minutes after hijacked airliners crashed into the World Trade Center in
2001, two F-15 combat aircraft from the 102nd Fighter Wing of the
Massachusetts Air Guard began patrolling the skies over New York City.
Four F-16 jets from the 147th Fighter Wing of the Texas Air Guard
joined Air Force One, carrying the president, and escorted it from
Florida, to Louisiana, to Nebraska and finally to Washington, D.C.
The 10 fighter wings of the 1st Air Force--primarily an Air Guard
unit--began combat patrols over the United States. Previously, they had
guarded against intruders trying to enter U.S. air space. Now, they were
watching for suspicious activity within U.S. airways.
On the ground, nearly 9,000 Guard troops, dressed in camouflage
uniforms and bearing M-16 rifles, were deployed to guard 444 airports
across the nation. Others protected ports, bridges and other important
structures.
The District of Columbia Guard stationed troops on Capitol Hill,
the first time that armed military units had been assigned there since
the May Day demonstrations of 1971.
To help state and local authorities respond to incidents that
involve possible weapons of mass destruction, Congress in 1999
established a system of full-time Civil Support Teams in the Guard. Each
of these teams is made up of 22 troopers who are specially trained and
equipped to help civil authorities cope with WMD incidents. (related
story p. 38)
At the order of their state governors, CSTs deploy to possible WMD
sites to help identify suspicious substances, assess the situation and
advise on an appropriate response.
Congress has authorized a total of 55 CSTs--at least one for each
state and territory. Because of its large population, California has two
teams, one based in the Los Angeles area and the other in greater San
Francisco.
Thus far, however, only 32 of the CSTs have been set up. The Senate
Appropriations Committee in July passed a 2004 defense spending bill
that included $22 million to field 12 additional teams, which would
result in a total of 44 units by the end of that fiscal year. The
version passed by the House of Representatives does not contain a
similar measure. At press time, it was not clear whether the Senate bill
would prevail, but observers note that, until now, the teams have had
considerable political support. In fact, pressure is growing for
Congress to fund all 55.
"The ongoing threat of terrorist activities and the recent
military action in Iraq make the presence of at least one Civil Support
Team in every state all the more imperative," said Sen. Russ
Feingold, DWis.
While waiting for Congress to act, some states have set up
so-called "light" Civil Support Teams, without federal funding
and made up of part-time Guard members. Feingold said that his home
state, Wisconsin, is one of the stares with a light CST. Because of the
lack of a fulltime team in Wisconsin, the CST from neighboring Minnesota
had to be called in to help protect Major League Baseball's 2002
All-Star Game in Milwaukee, he said.
There's no doubt that the CSTs "have proven their
worth," Blum said. "They are universally accepted as a
necessary asset. I don't know of a single governor who would give
up one."
The teams also are staying busy, Blum said. "There's not
been a single day that I can recall without a CST response somewhere in
the country." In fact, during the year following the 9/11 attacks,
CSTs performed nearly 800 missions, Blum told a Senate hearing.
New York's team was on duty within hours of the attacks upon
the World Trade Center, sampling the air to ensure than no biological or
chemical contaminants were present. "The Los Angeles team provided
security for the 2003 Academy Awards, two World Series, a Super Bowl and
last year's Winter Olympics in Salt Lake City.
After the space shuttle Columbia disintegrated in the skies over
Texas in February, teams from Texas, New Mexico, Oklahoma, Arkansas and
Louisiana helped collect, test, photograph and catalogue potentially
hazardous debris along the route.
Should a major WMD incident occur, the lead federal agency--usually
the Federal Emergency Preparedness Agency--can request the assistance of
the Joint Task Force Civil Support.
JTF-CS, headquartered at Fort Monroe, in Hampton, Va., is a part of
NorthCom, which was established in 2002 to defined the domestic United
States. NorthCom is developing a close relationship with the Guard, Blum
said.
The task three, commanded by a Guard major general, consists of
about 160 military and civilian personnel, whose mission is to provide
command-and-control capability for military forces helping to manage the
consequences of a nuclear, biological or chemical event.
In addition, the head of NorthCom, Air Force Gen. Ralph E.
Eberhardt, has asked the Guard to develop larger units "roughly
analogous to the Marines' CBIRF (Chemical Biological Incident
Response Force)," Blum said.
CBIRF, based at the Naval Surface Warfare Center in Indian Head,
Md., just outside the nation's capital, is much larger than the
average CST. It has about 350 Marines and sailors trained to extract,
decontaminate and treat mass casualties in a chemical, biological or
nuclear incident.
CBIRF is intended to respond quickly to such incidents anywhere in
the world, but its primary focus is protecting federal agencies and U.S.
military forces in Washington, D.C., around the country and throughout
the world.
The Guard units are bring designed to protect targets within each
state, Blum said. The first 10 teams are scheduled to stand up by
October.
To make it easier to respond to the frequent pace of deployments at
home and abroad, the Guard has embarked upon a wide-ranging program to
modernize its structure, weapons and equipment, Blum explained.
In September 2002, then-Army Secretary Thomas E. White introduced
the Army National Guard Restructuring Initiative. The plan is to convert
the Guard's existing right divisions and 18 separate
brigades--which constitute about 40 percent of the Army's fighting
force--into mole agile and effective units tentatively called
"multi-functional divisions" and "mobile light
brigades." The first unit could begin conversion as soon as 2005,
Blum said.
A key component of this reorganization will be the transformation
of the Pennsylvania Guard's 56th Brigade into a Stryker Brigade
Combat Team--one of six in the entire Army--by 2008. The Stryker units
are intended to become rapid-deployment forces that can be deployed
anywhere in the world within 96 hours.
Such changes ultimately will result in a 30-percent reduction in
the number of tracked vehicles, including its oldest Abrams tanks and
Bradley Fighting Vehicles, Guard officials said.
The Guard also is working to modernize its helicopter units, which
represent almost half of those available to the Army. Hundreds of Black
Hawk, Chinook and Apache choppers have been transferred from the
active-duty Army to Guard units.
But the Guard has not received enough aviation equipment to perform
its expanding missions, Lt. Gen. Roger Schultz, director of the Army
Guard, told the Senate hearing. Tool kits, test equipment and parts
needed to support the helicopters often were not included in the
transfers, he said. Furthermore, he said, the Guard has not received
enough helicopters.
The Air Guard, meanwhile, is updating its fixed-wing aircraft, its
director, Lt. Gen. Daniel James III, and the Senate hearing. In
Afghanistan, he noted, Guard pilots flew Block 25/30/32 F-16s, equipped
with Litening II precision-targeting pods, enabling them to provide
close air support to Special Forces engaging Taliban and al Qaida units
on the ground.
The Guard's A-10 Warthogs also are receiving upgrades,
including a new cockpit designed to ease the pilot's workload,
precision-guided munitions and the Joint Tactical Radio System, James
said.
The Senate Appropriations Committee, in a report accompanying its
2004 defense-spending bill, noted that the Guard needs to improve its
fleet of C-130 cargo aircraft, many of which are decades old. The Guard
relies upon them to provide 49 percent of the nation's tactical
airlift and 9 percent of its strategic airlift.
Concern, meanwhile, is growing about the impact of frequent
deployments upon Guard personnel. A Guard member's chances of being
mobilized once--for a period of six months to a year, and perhaps
longer--is about 65 percent, Hall said. The chances of being mobilized
twice are about 4 percent, and three times, 1 percent, he said.
Those numbers, however, don't tell the whole story, he said.
"What we are doing is mobilizing the same group of people a number
of times. If you are a military policeman, air traffic controller,
mortuary affairs, civil affairs, you are getting mobilized perhaps all
or the time or too many times."
Defense Secretary Donald H. Rumsfeld has ordered the Guard and
reserves this summer to come up with a plan to reduce the rate of
mobilizations. One possibility, officials said, is to increase the
number of these specialists in the active-duty forces. Whatever solution
is chosen, the plan is likely to be implemented in fiscal year 2005,
Hall said. Added Blum:
"We do not want to lose the national treasure of the National
Guard and the citizen soldier. We have to be very careful that we
don't go beyond the elasticity that this soldier will
tolerate."
Article Details
Author:
Kennedy, Harold
Publication:
National Defense
Geographic Code:
1USA
Date:
Sep 1, 2003
Words:
2431
| https://www.thefreelibrary.com/National+guard+stretching+to+perform+new+missions.-a0108195839 |
Moharam, M. G. & Gaylord, T. K. Rigorous coupled-wave analysis of planar-grating diffraction. J. Opt. Soc. Am. 71, 811-818
Download Citation | Moharam, M. G. & Gaylord, T. K. Rigorous coupled-wave analysis of planar-grating diffraction. J. Opt. Soc. Am. 71, 811-818 | A rigorous coupled-wave approach is used to analyze diffraction by general planar gratings bounded by two different media. The grating fringes may... | Find, read and cite all the research you need on ResearchGate
Moharam, M. G. & Gaylord, T. K. Rigorous coupled-wave analysis of planar-grating diffraction. J. Opt. Soc. Am. 71, 811-818
July 1981
Journal of the Optical Society of America 71(7)
DOI: 10.1364/JOSA.71.000811
Authors:
M. G. Moharam
T. K. Gaylord
Abstract
A rigorous coupled-wave approach is used to analyze diffraction by general planar gratings bounded by two different media. The grating fringes may have any orientation (slanted or unslanted) with respect to the grating surfaces. The analysis is based on a state-variables representation and results in a unifying, easily computer-implementable matrix formulation of the general planar-grating diffraction problem. Accurate diffraction characteristics are presented for the first time to the authors’ knowledge for general slanted gratings. This present rigorous formulation is compared with rigorous modal theory, approximate two-wave modal theory, approximate multiwave coupled-wave theory, and approximate two-wave coupled-wave theory. Typical errors in the diffraction characteristics introduced by these various approximate theories are evaluated for transmission, slanted, and reflection gratings. Inclusion of higher-order waves in a theory is important for obtaining accurate predictions when forward-diffracted orders are dominant (transmission-grating behavior). Conversely, when backward-diffracted orders dominate (reflection-grating behavior), second derivatives of the field amplitudes and boundary diffraction need to be included to produce accurate results.
... So, no chiral dopant to the 2 nd layer, and that brings negligible error to the efficienc mance. The rigorous coupled wave analysis (RCWA) method [42,
43]
is used to simu three-layer multi-twist grating structure, and several interchangeably optimizat rithms are used to optimize its parameters. Moreover, they reported the fabrica cess and materials in detail. ...
... Based on the idea of broadband PGs above, in 2020, Tao Zhan et al. [11] pr three-layer multi-twist polarization lens (or Pancharatnam-Berry lens, PBL). Co The rigorous coupled wave analysis (RCWA) method [42,
43]
is used to simulate their three-layer multi-twist grating structure, and several interchangeably optimization algorithms are used to optimize its parameters. Moreover, they reported the fabrication process and materials in detail. ...
... The results ( Figure 6) showed that the diffraction efficiency of the three-layer twist PG at 50 • in simulation and experiment is 87.2% and 84.1%, respectively, in this work, much higher than that of dual-twist PG (75.7%) [35]. The rigorous coupled wave analysis (RCWA) method [42,
43]
is used to simulate their three-layer multi-twist grating structure, and several interchangeably optimization algorithms are used to optimize its parameters. Moreover, they reported the fabrication process and materials in detail. ...
Twisting Structures in Liquid Crystal Polarization Gratings and Lenses
Feb 2021
Shiyuan Zhang
Wan Chen
Yang Yu
Jin Chen
Recently, diverse twisting structures have been discovered to be a potential approach to design liquid crystal polarization gratings and lenses (LCPGs and LCPLs) with a high diffraction efficiency, broad bandwidth, wide view, and large diffraction angle. In this review, we divide these twisting structures into two main types, namely, multi-layer twisting structures with phase compensation and twisting structures forming Bragg diffraction. We found that multi-layer twisting structure LCPGs and LCPLs presented a broader bandwidth and a wider view angle by phase compensation. While for transmissive or reflective Bragg LCPGs, a large diffraction angle with high diffraction efficiency could be achieved. Based on the theoretical analysis in the review, potential research directions on novel twisting structures were prospected.
... M3D effects can be calculated rigorously using electromagnetic (EM) simulators. [3][4][5]
[6]
[7][8] However, these simulators are highly time consuming, especially for optical proximity correction (OPC) applications. *Address all correspondence to Hiroyoshi Tanabe, [email protected] ...
... Rigorous coupled-wave analysis
6
and the 3D waveguide model 7 solve Maxwell's equation in momentum (or frequency) space, and the solution is far-field diffraction amplitudes. These models solve coupled wave equations in momentum space, and all relations between the incident momentum and the outgoing momentum are calculated simultaneously. ...
Evaluation of convolutional neural network for fast extreme ultraviolet lithography simulation using imec 3 nm node mask patterns
Jun 2023
Akira Jinguji
Hiroyoshi Tanabe
Atsushi Takahashi
... The diffraction efficiency was calculated from the angular-resolved transmission. By comparing the angular resolved diffraction efficiency with a rigorous solution of the coupled wave theory (RCWT)
[39]
, the layer thickness d and the refractive index contrast ∆n were derived: The diffraction efficiency η for a probe wavelength λ and the probe angle ϑ p is given by: ...
... The diffraction efficiency was calculated from the angular-resolved transmission. By comparing the angular resolved diffraction efficiency with a rigorous solution of the coupled wave theory (RCWT)
[39]
, the layer thickness d and the refractive index contrast Δn were derived: The diffraction efficiency η for a probe wavelength λ and the probe angle ϑp is given by: ...
The Interplay of Processing-Related Influences on the Formation of Volume Holographic Gratings in a Free-Surface Epoxy-Based Recording Material
Tina Sabel-Grau
Understanding the formation processes of holographic gratings in polymers as a function of material composition and processing is important for the development of new materials for holography and its associated applications. Among the processing-related factors that affect grating formation in volume holographic recording material, pre-exposure, prebaking and dark storage, as well as the associated variations in layer thickness and composition, are usually underestimated. This study highlights the influence and interaction of these factors and shows that they should not be neglected. This is of particular importance for samples with a free surface. Here, one such epoxy-based free-surface material is investigated. To determine the influence of prebaking on the holographic grating formation, as well as on the achieved refractive index contrast, angular resolved analysis of volume holographic phase gratings is applied through point-by-point scanning of the local material response. Grating characteristics are determined by comparison with simulations based on rigorous coupled wave theory. Thus, the optimal dose for prebaking can be determined, as well as the optimal exposure time, depending on the dose. The influence of dark storage on the material response is investigated over a period of 12 weeks and shows a strong dependence on the deposited energy density.
... When the characteristic size of the nanostructure is smaller than or equivalent to the wavelength of incident light, the vector diffraction theory becomes the theoretical basis for the study of subwavelength structures, of which the main analysis methods of vector diffraction theory include the modal theory, finite element method, finite difference time domain method, strictly coupled wave theory, boundary element method, and frequency domain finite difference method. The strictly coupled wave theory, first proposed by Moharam in 1981
[23]
, expands the solution of the light wave electromagnetic field into a series of spatial harmonics according to the plane wave components, each of which is the function of the groove depth of the grating. The expressions of these spatial harmonics are determined by solving the coupled wave differential equations of the plane waves in the grating region, and then the electromagnetic field of the grating modulated light waves is obtained. ...
Design and Preparation of Anti-Reflection Nanoarray Structure on the Surface of Space Solar Cell Glass Cover
Jun 2023
Guanglu Zhang
Jindong Huang
Luoshu Wang
Juncheng Liu
Space solar cell glass covers require high radiation resistance and wide-spectrum high light transmittance. The existing research on the preparation of thin films or special optical structures on the surface of solar cells rarely involves systematic research and the precise control of the high transmittance structural parameters of specific spectral bands by glass covers. Nanoarray structures were designed and constructed on high-purity quartz glass covers, achieving high anti-reflection within the 350–1100 nm range, the high energy part of the solar spectrum on Mars, regardless of the preparation of antireflective film and its radiation resistance. First, G-Solver software package was used to establish a nanoarray structure model according to the equivalent medium theory, and the effects of structural parameters such as the grating period, grating depth, and duty cycle on the glass cover transmittance were investigated. The results show that when the grating period is 50–200 nm, the transmittance ranges from 97.8% to 99.9%. When the grating period further increases from 300 nm, the lowest point of the transmittance spectrum moves to the longwave direction, and the transmittance from 350 nm to the lowest transmittance point significantly reduces. The optimal grating depth is 500 nm for a 300 nm grating period, the transmittance at 350 nm reaches 88.91%, and the average transmittance is 98.23%. When the period is 300 nm and the depth is 500 nm, the optimal duty cycle is 0.67, the transmittance at 350 nm reaches 96.52%, and the average transmittance is 99.23%. Nanoarray structures were constructed on the glass covers with nanoimprint and plasma etching, then modified with atomic layer deposition (ALD) to adjust their depth and duty cycle. The influence rules of the grating period, depth, and duty cycle on the cover transmittance from the experimental results are basically consistent with those from the simulation calculation. The nanoarray structure increases the average transmittance within 350–1100 nm of the glass cover by an average of 2.02% and the peak transmittance by 2.66%. The research results and experimental methods of this study have application value and promotion prospects for improving the photoelectric conversion efficiency of space solar cells and ground solar cells.
... Coupled wave theory
[6,
7] and modal theory [8,9] are widely used because of their high calculation accuracy and easy programming. From the viewpoint of the calculation principle, the coupled wave theory and modal theory are essentially the same, except that the modal theory needs to expand the relative dielectric constant according to Fourier series, and then carry out one-step modal processing. ...
Influence of cutting parameters on system vibration and optical performance of diamond turned optics
Guilin Zhuang
Hanzhong Liu
Wenjun Zong
In this paper the influence of vibration on reflectivity is systematically analyzed. A three-dimensional topography model of a machined surface considering vibration is established first. Based on the three-dimensional morphology model, the reflectivity of a diamond turned surface is calculated by a rigorous coupled wave method. The influences of cutting parameters on the diffraction effect of a diamond turned surface are discussed. The predicted and experimental results reveal that as the vibration intensifies with an increase in cutting depth and feed rate, the peak–valley (PV) roughness of the machined surface increases, which yields an increasing diffraction effect, i.e., resulting in a decrease in reflectivity. When the spindle speed is low, the tool and workpiece have a small sliding velocity, causing a great deal of friction, which amplifies the deformation of the workpiece surface. In this case, the PV value of the machined surface roughness is large, leading to a greater diffraction effect and bad reflectivity. With the increment of spindle rotation speed, the friction is relieved quickly, but the vibration is intensified, which produces increasing reflectivity. When the spindle speed is set to about 1200r/min, the reflectivity reaches the maximum value. When the spindle speed is larger than 1200r/min, the increase of vibration is dominant, resulting in a gradual increase in PV surface roughness and a decrease in reflectivity.
... The diffraction efficiency of PG mainly refers to the diffraction efficiency of Volume Bragg gratings. Therefore, the calculation of diffraction efficiency can be analyzed and computed using rigorous coupled-wave analysis (RCWA)
[16]
, scalar coupled-wave theory [17], matrix-based methods, and multiple-beam interference theory [18]. The rigorous coupled-wave theory can obtain accurate theoretical diffraction efficiency, but the equation must be solved using numerical methods, which can be quite complex. ...
Design of a Prism-Grating Wide Spectral Range Transmittance Imaging Spectrometer
Article
May 2023
SENSORS-BASEL
Xu Zhang
Bo Li
Xue Jiang
Guanyu Lin
As spectroscopic detection technology rapidly advances, back-illuminated InGaAs detectors with a wider spectral range have emerged. Compared to traditional detectors such as HgCdTe, CCD, and CMOS, InGaAs detectors offer a working range of 400–1800 nm and exhibit a quantum efficiency of over 60% in both the visible and near-infrared bands. This is leading to the demand for innovative designs of imaging spectrometers with wider spectral ranges. However, the widening of the spectral range has led to the presence of significant axial chromatic aberration and secondary spectrum in imaging spectrometers. Additionally, there is difficulty in aligning the system optical axis perpendicular to the detector image plane, resulting in increased challenges during post-installation adjustment. Based on chromatic aberration correction theory, this paper presents the design of a wide spectral range transmission prism-grating imaging spectrometer with a working range of 400–1750 nm using Code V. The spectral range of this spectrometer covers both the visible and near-infrared regions, which is beyond the capability of traditional PG spectrometers. In the past, the working spectral range of transmission-type PG imaging spectrometers has been limited to 400–1000 nm. This study’s proposed chromatic aberration correction process involves selecting optical glass materials that match the design requirements and correcting the axial chromatic aberration and secondary spectrum, ensuring that the system axis is perpendicular to the detector plane and easy to adjust during installation. The results show that the spectrometer has a spectral resolution of 5 nm, a root-mean-square spot diagram less than 8 μm over the full field of view, and an optical transfer function MTF greater than 0.6 at a Nyquist frequency of 30 lp/mm. The system size is less than 90 mm. Spherical lenses are employed in the system design to reduce manufacturing costs and complexity while meeting the requirements of wide spectral range, miniaturization, and easy installation.
... Apart from such microscopic theory, the rigorous treatment of the EOT analysis is, in general, performed using the rigorous numerical technique. In our case, due to the structural periodicity, our in-house software package is effectively used with the implemented Fourier Modal Method (also traditionally called the rigorous coupled-wave analysis, RCWA)
[22,
23]. ...
Fiber Optic Sensor of Ammonia Gas Using Plasmonic Extraordinary Optical Transmission
Apr 2023
SENSORS-BASEL
Ladislav Kalvoda
Jaroslava Jakoubková
Milan Burda
Jaromír Kopeček
While standard surface plasmon resonance (bio) sensing, relaying on propagating surface plasmon polariton sensitivity on homogeneous metal/dielectric boundaries, represents nowadays a routine sensing technique, other alternatives, such as inverse designs with nanostructured plasmonic periodic hole arrays, have been far less studied, especially in the context of gas sensing applications. Here, we present a specific application of such a plasmonic nanostructured array for ammonia gas sensing, based on a combination of fiber optics, extraordinary optical transmission (EOT) effect, and chemo-optical transducer selectively sensitive to ammonia gas. The nanostructured array of holes is drilled in a thin plasmonic gold layer by means of focused ion beam technique. The structure is covered by chemo-optical transducer layer showing selective spectral sensitivity towards gaseous ammonia. Metallic complex of 5-(4′-dialkylamino-phenylimino)-quinoline-8-one dye soaked in polydimethylsiloxane (PDMS) matrix is used in place of the transducer. Spectral transmission of the resulting structure and its changes under exposition to ammonia gas of various concentrations is then interrogated by fiber optics tools. The observed VIS-NIR EOT spectra are juxtaposed to the predictions performed by the rigorous Fourier modal method (FMM), providing useful theoretical feedback to the experimental data, and ammonia gas sensing mechanism of the whole EOT system and its parameters are discussed.
... This assumes that the perturbation c < c m (so there is no coupling into higher diffraction orders) and only a single pair of coupled waves. More rigorous models able to exactly account for such effects (e.g., coupling into higher diffraction orders or multiple superimposed gratings) have been reported [20,
25]
. Equation (4) demonstrates that the fraction of energy coupled into the output field by a volumehologram grating is determined by the angles of the two plane waves, the magnitude of the sound-speed perturbation, the frequency, and the thickness of the hologram. ...
Binary Volume Acoustic Holograms
Bradley E. Treeby
In recent years, high-resolution additive manufacturing has enabled a diverse range of low-cost methods for ultrasonic wave-front shaping. Acoustic holograms, in particular, allow for the generation of arbitrary diffraction-limited acoustic fields at megahertz frequencies from single-element transducers. These are phase plates that function as direct acoustic analogs to thin optical holograms. In this work, it is shown that, by using multiple polymer three-dimensional (3D) printing, two-material (binary) acoustic analogs to “thick” or volume optical holograms can also be generated. First, an analytic approach for designing a volume hologram that diffracts a set of input fields onto a desired set of output fields is briefly summarized. Next, a greedy-optimization approach based on random downhill binary search able to account for the constraints imposed by the chosen fabrication method is introduced. Finally, an experimental test case designed to diffract the field generated by a 2.54-cm planar lead zirconate titanate (PZT) transducer onto eight distinct patterns dependent on the direction of the incident field is used to validate the approach and the design method. Field scans of the eight target fields demonstrate that acoustic analogs of optical volume holograms can be generated using multipolymer printing and that these allow the multiplexing of distinct fields onto different incident field directions.
... This research employed the rigorous coupled-wave analysis (RCWA) function [40,
50]
and the Monte Carlo simulation to calculate the reflectance curve under a MATLAB 2022b environment, utilizing parallel computing and graphic processing toolboxes. In addition, 151 diffraction orders were applied to ensure that all results from the studied surfaces achieved convergence, which will be further discussed in Section 3.1. ...
Sensing Mechanisms of Rough Plasmonic Surfaces for Protein Binding of Surface Plasmon Resonance Detection
SENSORS-BASEL
Treesukon Treebupachatsakul
Siratchakrit Shinnakerdchoke
Suejit Pechprasarn
Surface plasmon resonance (SPR) has been utilized in various optical applications, including biosensors. The SPR-based sensor is a gold standard for protein kinetic measurement due to its ultrasensitivity on the plasmonic metal surface. However, a slight change in the surface morphology, such as roughness or pattern, can significantly impact its performance. This study proposes a theoretical framework to explain sensing mechanisms and quantify sensing performance parameters of angular surface plasmon resonance detection for binding kinetic sensing at different levels of surface roughness. The theoretical investigation utilized two models, a protein layer coating on a rough plasmonic surface with and without sidewall coatings. The two models enable us to separate and quantify the enhancement factors due to the localized surface plasmon polaritons at sharp edges of the rough surfaces and the increased surface area for protein binding due to roughness. The Gaussian random surface technique was employed to create rough metal surfaces. Reflectance spectra and quantitative performance parameters were simulated and quantified using rigorous coupled-wave analysis and Monte Carlo simulation. These parameters include sensitivity, plasmonic dip position, intensity contrast, full width at half maximum, plasmonic angle, and figure of merit. Roughness can significantly impact the intensity measurement of binding kinetics, positively or negatively, depending on the roughness levels. Due to the increased scattering loss, a tradeoff between sensitivity and increased roughness leads to a widened plasmonic reflectance dip. Some roughness profiles can give a negative and enhanced sensitivity without broadening the SPR spectra. We also discuss how the improved sensitivity of rough surfaces is predominantly due to the localized surface wave, not the increased density of the binding domain.
... In the field of photonics, a variety of established computational methods exist that can be applied on a wide range of different problems. Some of the most commonly used approaches are the finite element method (FEM), finite integral technique (FIT), finite difference time domain (FDTD) method, volume integral method (VIM), surface integral method (SIM), and fourier modal method (FMM)
[1]
[2][3][4][5][6][7][8]. ...
The influence of structural disorder on plasmonic metasurfaces and their colors – a coupled point dipole approach
Ediz Herkert
Florian Sterl
Steffen Both
Harald Giessen
The optical properties of plasmonic metasurfaces are determined not only by the shape and size of the constituting nanostructures, but also by their spatial arrangement. The fast progress in nanofabrication has facilitated the emergence of many advanced metasurface designs that enable controlling the propagation of light on the nanoscale. While simple metasurface designs can be derived from theoretical considerations, it is inevitable to employ computational approaches for complex manipulations of incident light. However, most of the currently available full-wave simulation approaches such as the finite element method (FEM) or finite difference time domain method come with drawbacks that limit the applicability to certain usually simplified or less complex geometries. Within this tutorial, different approaches are outlined for modeling light propagation in complex metasurfaces. We focus on an approach that approximates the nanostructure ensemble as a coupled set of point dipoles and determine their far-field response via the reciprocity theorem. This coupled point dipole approximation (CPDA) model is used to examine randomly distributed, oriented, and scaled nanostructure ensembles. A disorder formalism to introduce the randomness is developed that allows one to progressively perturb periodic arrangements of identical nanostructures and thereby investigate the effects of disorder and correlation. Several disorder metrics are provided that allow one to quantify the disorder, and the relation with the far-field scattering properties is discussed. Spatially and angle resolved hyperspectral datasets are computed for various disordered metasurfaces to assess the capabilities of the CPDA model for different polarization states and incidence angles, among others. The hyperspectral datasets are converted into sRGB color space to deduce the appearances in the image and F ourier planes. Very good agreement of the simulation results with M ie theory, FEM results, and experiments is observed, and possible reasons for the present differences are discussed. The presented CPDA model establishes a highly efficient approach that provides the possibility to rapidly compute the hyperspectral scattering characteristics of metasurfaces with more than 10,000 structures with moderate computational resources, such as state-of-the-art desktop computers with sufficient memory; 16 GB allow for the simulations in this paper, whereas scaling to up to more memory by the factor of N ² allows for the simulation of N times more dipoles. For that reason, the CPDA is a suitable approach for tailoring the bidirectional reflectance distribution function of metasurfaces under consideration of structural perturbations and experimental parameters.
... The dependence of the DE on the angle of incidence and wavelength was estimated within the framework of rigorous diffraction theory by solving a system of Maxwell equations with appropriate boundary conditions using rigorous coupled-wave analysis (RCWA)
[14]
. We have taken into account that when evaluating by the RCWA method, the modulus of the negative angle of incidence on the microstructure |ψN| and the positive angle of incidence ψP (see Figure 1a) lead to the same decrease in DE. ...
Highly Efficient Double-Layer Diffraction Microstructures Based on New Plastics and Molded Glasses
Rigorous coupled wave analysis (RCWA) is conducted on in situ spectroscopic ellipsometry data to understand profile evolution during film deposition inside nanotrenches. Lithographically patterned SiO 2 nanotrenches are used as test structures. The nanotrenches are 170 nm wide at the top with a taper angle of 4.5° and are 300 nm in depth. Atomic layer deposition of ZnO is used as a model process where the thickness (cycles) of the film is varied from 0 (0 cycles) to 46 nm (300 cycles). The analysis predicts transient behavior in deposition affecting film conformality and changes to the trench taper angle. In the process, the aspect ratio varies from 2.05 at the start of the process to 6.67 at the end. The model predicts changes in the refractive index of the ZnO film as a function of thickness. The real and imaginary parts of the refractive index at a wavelength of 350 nm change from 1.81 to 2.37 and 0.25 to 0.87, respectively. Scanning electron microscopy cross sections confirm thickness at the top and bottom of the trench to within 13% of those predicted by RCWA. The experimentally measured conformality degrades as film deposition proceeds from 97.3% at 100 cycles to 91.1% at 300 cycles. These results demonstrate the potential of using RCWA for continuous and in situ monitoring of growth inside 3D nanostructures.
| https://www.researchgate.net/publication/239664514_Moharam_M_G_Gaylord_T_K_Rigorous_coupled-wave_analysis_of_planar-grating_diffraction_J_Opt_Soc_Am_71_811-818 |
(PDF) Simulating Humans-Computer Graphics Animation and Control
PDF | People are all around us. They inhabit our home, workplace, entertainment, and environment. Their presence and actions are noted or ignored,... | Find, read and cite all the research you need on ResearchGate
Simulating Humans-Computer Graphics Animation and Control
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Abstract and Figures
People are all around us. They inhabit our home, workplace, entertainment, and environment. Their presence and actions are noted or ignored, enjoyed or disdained, analyzed or prescribed. The very ubiquitousness of other people in our lives poses a tantalizing challenge to the computational modeler: people are at once the most common object of interest and yet the most structurally complex. Their everyday movements are amazingly uid yet demanding to reproduce, with actions driven not just mechanically by muscles and bones but also cognitively by beliefs and intentions. Our motor systems manage to learn how to make us move without leaving us the burden or pleasure of knowing how we did it. Likewise we learn how to describe the actions and behaviors of others without consciously struggling with the processes of perception, recognition, and language.
Is it the Motion or the Posture? …
Spherical Trajectory of the Shoulder. the intervertebral disc size, the joint limits 3 rotations with 2 limits per rotation, and the joint rest initial position. In Section 4.2.3 we will see how spine movement is realized. 2.4 Shoulder Complex 5 It is well known that the movement of the humerus the upper arm is not a matter of simple articulation as most computer graphics models would have it. The movement is caused by articulations of several joints glenohumeral joint, claviscapular joint and sternoclavicular joint. Collectively, they are called the shoulder complex EP87, ET899. In Jack, the shoulder complex is simpliied with two joints one connecting the sternum to the clavicle and the other connecting the clavicle to the humerus GQO + 899. We call the former joint the clavicle joint and the latter the shoulder joint. This simpliication implies that the rotational center of the humerus lies on a spatial sphere when the upper arm moves. It turns out that it is very close to empirical data collected with a 6-D sensor attached to the external midpoint b e t ween the dorsal and ventral side of the right upper arm Mau91. The z-axis of the sensor was along the longitudinal axis of the upper arm with the positive z axis direction pointing proximally, and the negative y-axis pointing into the upper arm. The sensor was placed 10 inches from the shoulder the extremal point of the humerus. From the experimental data the trajectory of the shoulder can be easily computed. We tted the trajectory by the sphere which yields minimum average residual error. The result is quite satisfactory: the radius of the sphere is 6.05cm, and the average error the distance from the trajectory point to the sphere is 0.16cm. Figure 2.1. Notice that the radius of the …
A Neutral Human Figure. …
Sample Display F rom SASS. …
Torques Computed by Static Analysis. The strength bar display can be used to show strengths of any n umber of joint s i n a b o d y c hain. It give s a v ery clear view of the simultaneous eeects of the body connguration on several muscle group strengths. It also shows the safe and forbidden regions of each joint in a body chain. This display method does not depend on a particular strength model: it only shows whatever data is currently available for the gure. …
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... Generating realistic and controllable human motion is still an open research question despite decades of efforts in this domain [6,
7]
. In this work, we tackle the task of actionconditioned generation of realistic human motion sequences of varying length, with or without observation of past motion. ...
... Human motion forecasting. Predicting future human poses given a past motion is a topic of interest in human motion analysis [6,
7]
. The first successful methods were based on statistical models [12,24], with most recent work relying on deep learning based methods [27,36]. ...
PoseGPT: Quantization-based 3D Human Motion Generation and Forecasting
Preprint
Full-text available
Oct 2022
Thomas Lucas
Fabien Baradel
Philippe Weinzaepfel
Grégory Rogez
We address the problem of action-conditioned generation of human motion sequences. Existing work falls into two categories: forecast models conditioned on observed past motions, or generative models conditioned on action labels and duration only. In contrast, we generate motion conditioned on observations of arbitrary length, including none. To solve this generalized problem, we propose PoseGPT, an auto-regressive transformer-based approach which internally compresses human motion into quantized latent sequences. An auto-encoder first maps human motion to latent index sequences in a discrete space, and vice-versa. Inspired by the Generative Pretrained Transformer (GPT), we propose to train a GPT-like model for next-index prediction in that space; this allows PoseGPT to output distributions on possible futures, with or without conditioning on past motion. The discrete and compressed nature of the latent space allows the GPT-like model to focus on long-range signal, as it removes low-level redundancy in the input signal. Predicting discrete indices also alleviates the common pitfall of predicting averaged poses, a typical failure case when regressing continuous values, as the average of discrete targets is not a target itself. Our experimental results show that our proposed approach achieves state-of-the-art results on HumanAct12, a standard but small scale dataset, as well as on BABEL, a recent large scale MoCap dataset, and on GRAB, a human-object interactions dataset.
... Human motion generation has been an active area of research for many years
[5]
. Early work in this field focused on unconditional motion generation [18,30,40], with some studies attempting to predict future motion based on an initial pose or starting motion sequence [8,32]. ...
AMD Autoregressive Motion Diffusion
Preprint
May 2023
Bo Han
Hao Peng
Minjing Dong
Yuheng Li
Human motion generation aims to produce plausible human motion sequences according to various conditional inputs, such as text or audio. Despite the feasibility of existing methods in generating motion based on short prompts and simple motion patterns, they encounter difficulties when dealing with long prompts or complex motions. The challenges are two-fold: 1) the scarcity of human motion-captured data for long prompts and complex motions. 2) the high diversity of human motions in the temporal domain and the substantial divergence of distributions from conditional modalities, leading to a many-to-many mapping problem when generating motion with complex and long texts. In this work, we address these gaps by 1) elaborating the first dataset pairing long textual descriptions and 3D complex motions (HumanLong3D), and 2) proposing an autoregressive motion diffusion model (AMD). Specifically, AMD integrates the text prompt at the current timestep with the text prompt and action sequences at the previous timestep as conditional information to predict the current action sequences in an iterative manner. Furthermore, we present its generalization for X-to-Motion with "No Modality Left Behind", enabling for the first time the generation of high-definition and high-fidelity human motions based on user-defined modality input.
... Recent publications have presented a variety of techniques for creating animations of human motion. Promising approaches include techniques for manipulating keyframed or motion capture data [29,28,4,25], control systems for dynamic simulations [11,18], and other procedural or hybrid approaches
[1,
3,15,19,5,21]. Each method has its own strengths and weaknesses, making the visual comparison of results essential, especially for the evaluation of such subjective qualities as "natu-ralness" and "realism." ...
Do Geometric Models Affect Judgments of Human Motion?
Preprint
Full-text available
Feb 2023
Jessica K. Hodgins
James F. O'Brien
Jack Tumblin
Human figures have been animated using a wide variety of geometric models including stick figures, polygonal models, and NURBS-based models with muscles, flexible skin, or clothing. This paper reports on experiments designed to ascertain whether a viewer's perception of motion characteristics is affected by the geometric model used for rendering. Subjects were shown a series of paired motion sequences and asked if the two motions in each pair were "the same" or "different." The two motion sequences in each pair used the same geometric model. For each trial, the pairs of motion sequences were grouped into two sets where one set was rendered with a stick figure model and the other set was rendered with a polygonal model. Sensitivity measures for each trial indicate that for these sequences subjects were better able to discriminate motion variations with the polygonal model than with the stick figure model.
... Human motion synthesis. Research on human motion synthesis has a long history
[8]
. One of the most active research fields is human motion prediction, which aims at predicting the future motion sequence based on past observed motion. ...
T2M-GPT: Generating Human Motion from Textual Descriptions with discrete Representations
Preprint
Full-text available
Jan 2023
Jianrong Zhang
Yangsong Zhang
Xiaodong Cun
Xi Shen
In this work, we investigate a simple and must-known conditional generative framework based on Vector Quantised-Variational AutoEncoder (VQ-VAE) and Generative Pre-trained Transformer (GPT) for human motion generation from textural descriptions. We show that a simple CNN-based VQ-VAE with commonly used training recipes (EMA and Code Reset) allows us to obtain high-quality discrete representations. For GPT, we incorporate a simple corruption strategy during the training to alleviate training-testing discrepancy. Despite its simplicity, our T2M-GPT shows better performance than competitive approaches, including recent diffusion-based approaches. For example, on HumanML3D, which is currently the largest dataset, we achieve comparable performance on the consistency between text and generated motion (R-Precision), but with FID 0.116 largely outperforming MotionDiffuse of 0.630. Additionally, we conduct analyses on HumanML3D and observe that the dataset size is a limitation of our approach. Our work suggests that VQ-VAE still remains a competitive approach for human motion generation.
... C Reating physically accurate, controllable, and adaptable character motions that can mimic real-world humans is challenging, interesting, and important [1], [2],
[3]
, [4]. In particular, there is a great interest in developing techniques and algorithms that can run at real-time frame-rates while being robust and interactive. ...
Watch Your Step: Real-Time Adaptive Character Stepping
Preprint
Full-text available
Oct 2022
Ben Kenwright
An effective 3D stepping control algorithm that is computationally fast, robust, and easy to implement is extremely important and valuable to character animation research. In this paper, we present a novel technique for generating dynamic, interactive, and controllable biped stepping motions. Our approach uses a low-dimensional physics-based model to create balanced humanoid avatars that can handle a wide variety of interactive situations, such as terrain height shifting and push exertions, while remaining upright and balanced. We accomplish this by combining the popular inverted-pendulum model with an ankle-feedback torque and variable leg-length mechanism to create a controllable solution that can adapt to unforeseen circumstances in real-time without key-framed data, any offline pre-processing, or on-line optimizations joint torque computations. We explain and address oversimplifications and limitations with the basic IP model and the reasons for extending the model by means of additional control mechanisms. We demonstrate a simple and fast approach for extending the IP model based on an ankle-torque and variable leg lengths approximation without hindering the extremely attractive properties (i.e., computational speed, robustness, and simplicity) that make the IP model so ideal for generating upright responsive balancing biped movements. Finally, while our technique focuses on lower body motions, it can, nevertheless, handle both small and large push forces even during terrain height variations. Moreover, our model effectively creates human-like motions that synthesize low-level upright stepping movements, and can be combined with additional controller techniques to produce whole body autonomous agents.
... Au niveau du choix d'un avatar en interface pour raconter les histoires, de nombreuses études ont été réalisées dans les années 2000 en ce qui concerne les effets de la personnification de l'interface hommes/machine. Les résultats semblent relativement mitigés dans la mesure où ils sont peu consensuels (Bates, 1994 ;Blumberg, 1994 ;Elliott, 1994 ;Lashkari, Metral, & Maes, 1994 ;Sheth, 1994 ;Laurel, 1990 ;Rickel & Johnson, 1996 ;Thórisson, 2002 ;Vilhjálmsson & Cassell, 1998 ;
Webber, Phillips, & Badler, 1993)
. ...
Capacités inférentielles en compréhension orale chez l'enfant. Le langage non littéral au coeur de l'expérimentation d'un protocole pédagogique à l'école primaire
Thesis
Dec 2019
Alexandrine Carra
Cette thèse prend son origine dans la problématique nationale de lutte contre l'illettrisme. Elle vise plus précisément à tester et à proposer une démarche d'enseignement dont l'objectif serait de mettre en place une démarche de prévention précoce de l'illettrisme dans le cadre des apprentissages scolaires en considérant la compréhension orale comme un des prérequis fondamentaux à l'apprentissage de la lecture. Nous proposons une recherche qui s'inscrit dans la cadre de l'approche pragmatique du développement du langage et qui revêt un double objectif : recueillir des données expérimentales relatives aux capacités inférentielles des jeunes enfants et élaborer un dispositif de formation initiale et continue des enseignants du premier degré pour l'enseignement de la compréhension orale.La problématique qui sous-tend ce travail de recherche questionne la faisabilité et l'efficacité d'un apprentissage explicite et contextualisé des procédures de compréhension du langage implicite à l'oral dès la maternelle. Pour y répondre, nous avons élaboré et testé dans le cadre de la classe, l'efficacité d'un protocole pédagogique visant l'enseignement de la compréhension orale à des élèves de Grande Section de Maternelle et à des élèves de Cours Préparatoire. Les compétences visées plus spécifiquement ici pour les élèves sont le processus inférentiel et l'autonomie cognitive dans la mise en œuvre de la procédure de compréhension. Le protocole pédagogique testé est composé d'un outil informatisé d'évaluation des capacités inférentielles en situation de communication (IMPLICIMAGE), d'un album contextualisant des énoncés non littéraux créé spécifiquement pour cette recherche et d'une séquence pédagogique composée de douze séances d'enseignement. La population est composée de 162 élèves.L'analyse des résultats de cette expérience montre que la séquence pédagogique proposée aux élèves des groupes expérimentaux leur a permis de progresser significativement dans leurs capacités à réaliser des inférences logiques, sémantiques et pragmatiques. L'efficacité du protocole pédagogique permet d'aboutir à la proposition d'une plateforme numérique de formation des enseignants pour l'enseignement de la compréhension orale à l'école primaire : IMPLICIBOX.
View
Show abstract
TEACH: Temporal Action Composition for 3D Humans
Conference Paper
Sep 2022
Nikos Athanasiou
Mathis Petrovich
Michael J Black
Gül Varol
A texture-driven model for male baldness
Conference Paper
Oct 2022
Dennis Balreira
Luiz Henrique de Figueiredo
Marcio Volkweis
Marcelo Walter
Regularized Deep Signed Distance Fields for Reactive Motion Generation
Conference Paper
Oct 2022
Puze Liu
Kuo Zhang
Davide Tateo
Georgia Chalvatzaki
GOAL: Generating 4D Whole-Body Motion for Hand-Object Grasping
Conference Paper
Jun 2022
Omid Taheri
Vasileios Choutas
Michael J Black
Dimitrios Tzionas
An Adaptive and Efficient System for Computing the 3-D Reachable Workspace
Conference Paper
Full-text available
Aug 1990
Tarek K. Alameldin
Norman Badler
Tarek Sobh
In this paper, we present an efficient system for computing the 3-D reachable workspace for redundant manipulators with joint limits. In our system, we have decomposed the 3-D reachable workspace problem into two major subproblems: workspace point generation and surface computation. We describe different algorithms that are used to build these modules. Finally, we discuss the advantages offered by our system.
Recommendations
Discover more about: Animation
Chapter
| https://www.researchgate.net/publication/228853685_Simulating_Humans-Computer_Graphics_Animation_and_Control |
Long-Term Safety of PRC-063 in Adolescents and Adults With ADHD - Full Text View - ClinicalTrials.gov
Long-Term Safety of PRC-063 in Adolescents and Adults With ADHD
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government.
Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02168127 Recruitment Status :
Completed First Posted : June 20, 2014 Last Update Posted : July 8, 2015
Sponsor:
Rhodes Pharmaceuticals, L.P.
Collaborator:
Purdue Pharma LP
Information provided by (Responsible Party):
Rhodes Pharmaceuticals, L.P.
Study Details
Study Description
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Brief Summary:
The purpose of this six month, open-label study is to evaluate the long-term safety and efficacy of PRC-063 in adults and adolescents with ADHD.
Condition or disease Intervention/treatment Phase ADHD Drug: Drug: PRC-063 Drug: PRC-063 Phase 3
Detailed Description:
This is an open label, multicenter, phase 3 study to evaluate the safety and efficacy of PRC-063 (methylphenidate hydrochloride controlled-release capsules 25, 35, 45, 55, 70, 85 or 100 mg/day) in the treatment of Attention-Deficit/Hyperactivity Disorder (ADHD) in adolescent subjects aged ≥12 to <18 years of age and adult subjects aged ≥18 years of age. In order to participate, subjects must have completed Purdue Pharma Study 063-009 or Purdue Pharma Study 063-010. This study will be conducted at approximately 50 centers across the United States and Canada. After giving written informed consent (as well as informed assent for subjects <18 years of age), subjects will be screened to ascertain their suitability for the study according to the inclusion and exclusion criteria. There will be seven monthly efficacy and safety visits during which subjects will be assessed on active, open-label PRC-063. The starting dose will be at the discretion of the Investigator. Dose-adjustment visits may occur weekly to optimize the subject's dose via titration. For adolescent subjects, the maximum dose will be 85 mg/day. For adult subjects, the maximum dose will be 100 mg/day.
Study Design
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Layout table for study information Study Type : Interventional
(Clinical Trial) Actual Enrollment : 360 participants Allocation: N/A Intervention Model: Single Group Assignment Masking: None (Open Label) Primary Purpose: Treatment Official Title: A Six-month, Open-label, Multi-center Study of the Safety and Efficacy of PRC-063 in Adults and Adolescents With ADHD Study Start Date : May 2014 Actual Primary Completion Date : May 2015 Actual Study Completion Date : June 2015
Resource links provided by the National Library of Medicine
Drug Information available for: Methylphenidate Methylphenidate hydrochloride
U.S. FDA Resources
Arms and Interventions
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Arm Intervention/treatment Experimental: Active drug group PRC-063 - Active methylphenidate hydrochloride extended-release capsules drug group Drug: Drug: PRC-063 Methylphenidate Hydrochloride Extended-Release Capsules Other Name: Methylphenidate Drug: PRC-063 Methylphenidate Hydrochloride Extended-Release Capsules Other Name: Methylphenidate
Outcome Measures
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Primary Outcome Measures
:
occurrence of treatment-emergent adverse events [ Time Frame: Within 6 months ]
Secondary Outcome Measures
:
Clinician-administered ADHD-5-Rating Scale [ Time Frame: Within 6 months ]
Eligibility Criteria
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Information from the National Library of Medicine
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
Layout table for eligibility information Ages Eligible for Study: 12 Years and older (Child, Adult, Older Adult) Sexes Eligible for Study: All Accepts Healthy Volunteers: No
Criteria
Inclusion Criteria: Subjects must satisfy the following criteria to be enrolled in the study as an adolescent:
• Male or non-pregnant, non-nursing female at least 12 years of age and less than 18 years of age.
Subjects must satisfy the following criteria to be enrolled in the study as an adult:
• Male or non-pregnant, non-nursing female at least 18 years of age and meeting the local, legal definition of adult.
All subjects must also satisfy the following criteria to be enrolled in the study:
Confirmation of ADHD diagnosis made at Visit 1 of Study 063-009 or 063-010 (inattentive, hyperactive/impulsive or combined-type, as defined by the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition based on clinician assessment using multiple informants and a structured interview).
Female subjects must be one of the following:
Surgically sterile prior to screening
Postmenopausal
if of childbearing potential, abstinent or willing to use a reliable method of contraception, such as oral contraceptive, two barrier methods, a barrier method plus a spermicidal agent.
Female subjects of Child-Bearing Potential (FOCP) must have a negative serum β-hCG pregnancy test, as assessed at Visit 6 of Study 063-009 or 063-010 (data will not be available at the time of entry).
If the subject is an adult, mentally and physically competent to sign an informed consent document indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study. If the subject is an adolescent, mentally and physically competent to sign an informed assent document, in the case of the subject, and an informed consent document, in the case of the parent/guardian, indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study.
Able and willing to comply with the study procedures for the entire length of the study.
Exclusion Criteria:
• Having met any exclusion criteria for Study 063-009 or 063-010.
Having been diagnosed during Study 063-009 or 063-010 with strokes, epilepsy, migraine headaches (greater than 1 instance every two months), glaucoma, thyrotoxicosis, tachyarrhythmias or severe angina pectoris or have serious or unstable medical illness. Subjects with controlled or stable asthma or diabetes will be permitted.
Elevated blood pressure, defined as any values above 89 diastolic or 139 systolic, as assessed at Visit 6 of Study 063-009 or 063-010.
Clinically significant ECG abnormalities, as assessed at Visit 6 of Study 063-009 or 063-010 (data will not be available at the time of entry).
Currently receiving guanethidine, pressor agents, MAO inhibitors, coumarin anticoagulants, anticonvulsants (e.g. phenobarbital, phenytoin, primidone), phenylbutazone, tricyclic antidepressants (e.g. imipramine, desipramine), selective serotonin reuptake inhibitors (SSRIs) or herbal remedies (unless on a stable dose for 4 weeks).
If the Investigator judges that continued treatment with PRC-063 is not in the subject's best interest.
Subjects who are currently considered a suicide risk by the investigator.
Having been diagnosed during Study 063-009 or 063-010 with schizophrenia, schizoaffective disorder, primary affective disorder, schizotypal personality, major depression, bipolar disorder, generalized anxiety, borderline personality disorder, antisocial personality or another unstable psychiatric condition requiring treatment.
Having been diagnosed during Study 063-009 or 063-010 with physiological dependence (excluding nicotine) on narcotic analgesics or other psychoactive drugs (including barbiturates, opiates, cocaine, cannabinoids, amphetamines and benzodiazepines).
Excessive consumption of alcohol occurring during Study 063-009 or 063-010 (consumes alcohol in quantities greater than 15 drinks per week on average; 1 drink is defined as 360 mL/12 oz. of beer, 120 mL/4 oz. of wine, or 30 mL/1 oz. of hard liquor).
Currently (or within 30 days before the planned start of treatment) receiving an investigational drug or using an experimental medical device, other than PRC-063.
Homeless.
| https://clinicaltrials.gov/ct2/show/NCT02168127 |
232f3ced493d3ebe99bce99fd4486f38e33babee957e86760f395a02becdd462_optim.pdf
Aroma Diffuser 400 ml - Extra stil - Lange werking - Luchtbevochtiger - Vernevelaar -... | bol.com
User Manual for AROMA models including: DT-1522, Essential Oil Humidifier, DT-1522 Essential Oil Humidifier
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Aroma Diffuser User Manual - Bol.com
In the event of the unit being knocked over or tipped during use, please follow the steps below to avoid damage to the unit.
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Aroma Diffuser 400 ml - Extra stil - Lange werking - Luchtbevochtiger - Vernevelaar -... | bol.com
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Aroma Diffuser User Manual
Use Manual
This Aroma Diffuser uses Ultrasonic Technology to atomize the water and essentail oil in the water tank, and produces a cool, humid and fragrant mist.
d2
LIGHT Button
Drainage Outlet Water Tank Main Body
Waterline
Arma Diffuser
Cover MIST Button
Water Outlet DC Socket Air Intake Aroma Diffuser
User Manual
1. Position the Aroma Diuser upright, pull upwards
to remove cover. (Fig. 1) 2. Connect AC adaptor power cord into the DC input
jack at the base of the Aoma Diuse. lt is suggested to route cable via track provided. (Fig. 2)
4'/
T
/ I """"""<l
3. Pour water and essential oil into Aroma Diffuser. DO NOT fill above the "MAX" marking 400ml. DO NOT
use boiling water. DO NOTH when power is on
Fig 1
Fig 2
It is recommended to add 2-3 drops of essential oil
for each 1OOml of water. (Fig. 3)
4. Set the cover back on the base. Spout is adjustable to guide aroma into desidirection. Aroma Diffu must NOT be operated without the cover. (Fig. 4
A
9
JI
5. Plug diuser into power outlet.
r:-------
6. To turn on mist, press "MIST" and choose operation ... J
time required ( Timing: 1H/3H/6H/ON). Mist level is adjustable by hard-pressing "MIST' until the Aroma
Fig 3
Fig 4
Diffuser beeps (One beep for high and two beeps for
low). To switch off, continue pressingIST" through the cycle until it is off. (1 hour->3 hour->6 hour
. _A L
K A L
ON Continuous ->0. (Fig. 5) 7. Press "LIGHT" turn on LED light. Brightness is
/ I\ / I\
ustable through the following cycle. (Bright -> Dim->OFig. 6) 8. It is recommended to dain wate fom tank and
"' _J Fig 5
'y"' Fig 6
keep dry when not in use
9. Diffuser will automatically shut o when there is
insuicient water.
Aroma Diffuser
ATTENTION
Use Manual
· The amount and intensity of mist will vary depending on water type, temperture and air currents
· Automatically powers off when water uns out · Only use 100% natural essential oils. Using oils that contain chemical ingedients,
flavors or impurities may cause damage to the product.
ACCIDENTAL LEAKAGE
In the event of the unit being knocked over or tipped during use, please follow the steps below to avoid damage to the unit 1. Unplug the unit and remove cover. 2. Pour out any maining water from the water tank. 3. Tip the unit to drain wate and then ai dy it for at least 24 hou
\ rs
J
"'"""'
/ u
"- -
Water Outlet Aroma Diffuser
User Manual
After using 5-6 tines, or 3-5 days, please clean the product as follow 1. Unplug the unit and remove cover. 2. Pou out any emaining water from the tank 3. Use a small amount of dish soap to clean. Gently wipe with a soft cloth. Use a dy
towel to dry the diffuser afte it is clean 4. NEVER use other acids or enzymes to clean the unit as they could eact with the
essential oil residue and cause harmful vapors to be released or cause a malfunction
Ai Outlet
b d
Aroma Diffuser
Use Manual
Please read below to avoid any malfunction to the unit: · lf you a not a technician do not ty to dismantle the diffuser to repair it. Contact the
seller if repair is necessary · Do not turn power on when the tank is empty · Do not touch the atomization plate · Clean regularly as per Maintenance instructions to avoid malfunction · Always unplug before maintenance. · For hygiene reasons, after use, pour out the remaining wateom the tank
and wipe with a clean dry cloth · Only use the measuring cup to add water into the tank, do not fill water directly
from the sink. · Do not let mist come in direct contact with fumitlre, clothing, walls, etc · Keep out of direct sunlight. · Always keep on a hard, stable at surface. Do not pla on a towel, carpet or any
othe unstable surface · Keep away from electronic equipment, such as TV and Audio equipment · Wait 60 minutes between uses to avoid damage to the atomization piece · Do not use spakling wateOnly use tap water or mineral water. · Never move product when it is woking · Do not touch any part of the product with wet hands · Keep away from pets and small childen · If the power cois smoking or burning, unplug immediately!
Aroma Diffuser
User Manual
Please refe to the table below in the event of the product operating abnormally
If product doesn't work well, please refer to the following points before requesting repaiS
Will not switch on or switch off
· Is there enough water in the tank? -- Please add water to the tank.
· Is the power cod connected propety? Please disconnect, check bles and re-connect carefully
No mist or abnomal mist
i
· Not enough water? or too much water? -- Please add suitable amount of water in the tank, water must never be filled over 400ML (MAX) line
· Dior dust in the air intake on the underside of the base? -- There is a fan on the underside of the base that is requied to blow the mist out. If it gets clogged with dust or dirt it will p·event mist fom coming out.
· Cover not set on the base properly? -- Remove the cover and set it back on the base right above the buttons
· Low temperatue or high humidity? -- Under these conditions, the mist may condense quickly into water droplets
Aroma D1ffl.ser
SPECIFICATIONS
Dimensions Weight(excluding adapto Power: Input/Output Length of cod Power Working Mode Tank Capacity LED light Material Accessory Working frequency
Use Manual
(0)168.5 x (H)215MM Approx 470G AC100-240V 50/60Hz DC24V 650mA Approx 170CM Approx 13W 1 H/3H/6H/ON 400ML 3PCS PP/ABS/PC AC Adapter and User manual 2.4MHz
Aroma Diuser
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| https://manuals.plus/m/232f3ced493d3ebe99bce99fd4486f38e33babee957e86760f395a02becdd462_doc |
Federal Cases, Volume 14
281
Case No. 7,686.
KEMP v. KENNEDY.
[Pet C. C. 30.] 1
Circuit Court, D. New Jersey.
Oct Term, 1808. 2
TREASON—JURISDICTION OF STATE COURTS—MARRIED WOMEN—FORFEITURE.
1. The jurisdiction of state courts as to treason, is not limited.
2. Courts of limited jurisdiction, must act within the scope of their authority; and it must appear, on the face of their proceedings, that they did so exercise their authority, or all they do will be coram non judice and void. The legislature which creates such courts, may alter or qualify this principle, and when this is 282done, the law creating the exception, is alone to be regarded.
[Cited in Lincoln v. Tower, Case No. 8,355; U. S. v. New Bedford Bridge, Id. 15,867; Waring v. Clarke, 5 How. (46 U. S.) 500.]
[Cited in Wyman v. Campbell, 6 Ala. 219; Silver v. County of Schyulkill, 32 Pa. St. 357.]
3. A feme covert, who, in April, 1776, joined the enemy in company with her husband, committed no offence under the act of the legislature of New Jersey, passed 11th December, 1778, relating to forfeited estates; and voluntarily remaining with the enemy, after the enacting of that law, without aiding them, by council or otherwise, was not an offence against its provisions.
4. If a court, authorised to try and decide on such offences, declares an act to be treason, which by the laws constituting the court is not such, it is error, and its judgment may be reversed by a superior tribunal; but this is not an usurpation of power.
5. The owners of estates, wrongfully forfeited under the act of 11th December, 1778, have no remedy, by ejectment, to recover the property forfeited; but could only proceed by writ of error according to the statute.
6. Quere, if an alien plaintiff can recover in ejectment.
The lessor of the plaintiff, deduced a regular title to the land in question to herself. She was the wife of John T. Kemp, formerly of New York; and it appeared that he and his wife, continued to reside in that province, from a period anterior to 1773, until the evacuation of the city by the British in 1783; when they removed to Great Britain, where the lessor of the plaintiff has always continued to reside. It did not appear that they ever took part with the Americans, in the Revolutionary war, but adhered to their former allegiance. John T. Kemp died in 1792. The title of the defendant, was founded upon an inquisition and judgment rendered in August, 1779, by the inferior court of common pleas for the county of Hunterdon, pronouncing Kemp and his wife to be traitors, within the laws of the state of New Jersey. The land was regularly sold and conveyed, by the commissioners of forfeited lands, to the defendant. The inquisition upon which the judgment was founded finds “that J. T. Kemp and Grace his wife, and C. M'Iver, of the city of New York, are offenders in manner as described in the act of 11th December, 1778,” and that they, the said J. T. Kemp and Grace his wife, “did go to the enemy, and took refuge with them some time in April, 1776, and still remain with them.” The important parts of the different acts of the state upon this subject, are as follows: The first act, passed on the 4th October, 1776, declares what persons do owe allegiance to the government of New Jersey, and “that every such person, who after the publication of the law, should levy war against the state, within the same, or be adherent to the king of Great Britain, or other enemies of the state, within the same, or to the enemies of the United States, giving them aid and comfort, or giving them advice or intelligence, or furnishing them with provisions or warlike stores; and thereof shall be provably attainted, of open deed by people of his or her condition; shall be adjudged guilty of high treason, and be punished accordingly, saving the corruption of the blood.” The next act, passed on the 20th September, 1777, declares what shall be the punishment of treason. The act of the 18th of April, 1778, declares, that the commissioners of forfeited property, shall return to some justice of the peace of their respective counties, the name and place of the late abode of each person, whose personal property they had seized; 3on the ground of their being traitors, and obtain a precept for summoning a jury of freeholders of the county, to enquire whether such person is an offender, within the treason law. After notice of the time and place of the meeting of the jurors, the said jurors, in presence of the justice, are to make an inquisition, stating the acts of treason committed by the offenders according to a certain prescribed form. This inquisition is to be returned by the justice, to the next inferior court of common pleas for that county; which is directed to make proclamation, calling upon the person against whom the inquisition is found, or who may be interested, to appear and traverse the same; which if done on the terms prescribed, a trial was to be awarded. If no person appeared, a second proclamation with notice is directed to be given, and another opportunity is offered to the party to appear and traverse. If he then fail, final judgment is to be rendered in favour of the state, and his personal property is then to be sold by the commissioners. The act of 11th December, 1778 (Patt. Laws N. J. p. 40), declares, in the 2d section, that every person an inhabitant of this state, who between the 19th April, 1775, and the 4th October, 1776, aided and assisted the enemy, by joining their armies, or who voluntarily went to, took refuge, or continued with, or endeavoured to continue with the enemy, and aided them by counsel or otherwise, and who had not returned and taken the oath of abjuration and allegiance to the state; to be guilty of high treason; and on conviction by inquisition and final judgment, his whole estate real and personal, is declared to be forfeited, but his person is not to be affected. By the 3d section, the inhabitants of any other of the United States, seized, or possessed of, or entitled, to real or personal property, in the state; convicted in like manner, by inquisition and final judgment, 283of similar acts of treason, are also declared to be guilty of high treason, and their said estates are declared to be forfeited and vested in the state, without further proceedings to be had. The law then goes on to prescribe the form of the proceedings in taking, returning and trying questions, and entering judgment thereon; which are to be the same as under the act of the 18th of April, with some slight alterations in form, not of sufficient importance to be mentioned. The law then directs, how the forfeited estates are to be sold by the commissioners, and the proceeds are to be appropriated to the payment of the debts of the attainted persons. The 11th section declares, that if any process or proceeding, by virtue of which any such sale as aforesaid may be made as aforesaid, shall hereafter be reversed or made void for error, or any other cause whatsoever; such reversal shall not affect or injure, or be of force, or in any otherwise operate, against any bona fide purchaser under this act, but against the state only; and in such case the plaintiff in error, or person injured by the sale, shall apply to the legislature, to be indemnified out of the treasury, to the amount of the purchase money received for the estate.
Messrs. Stockton and Edward Tilghman, for lessor of plaintiff, contended: that the only act to be considered, was that of 11th December, 1778, all the others applying to inhabitants of New Jersey. The question is; is Mrs. Kemp an object of the 3d section of the law, and are the proceedings against her of any validity in point of law? She is not an object of the law, because it is not stated, that she or her husband were inhabitants of another state, or that they were seized, possessed of, or entitled to any estate real or personal in this state, or that they voluntarily went to, or remained with the enemy, or that they aided them by counsel or otherwise. Stating them to be of New Jersey, is not sufficient to give jurisdiction. [Bingham v. Cabot] 3 Dall. [3 U. S.] 382; [Wood v. Wagnon] 2 Cranch [6 U. S.] 1.Indeed, they could not be inhabitants of the United States in April, 1776, when it is found they went to the enemy; because, at that time the states were not united, and they had a right to take their part Respublica v. Chapman, 1 Dall. [1 U. S.] 53.Although the form of the inquisition is prescribed in the law, and the word “inhabitant” is not inserted in it, still the inquest is to set forth the nature of the offence, and it was of the nature of the offence, to state that they were inhabitants of another state, owned property, and voluntarily joined the enemy. 2 Hawk. P. C. 355; §§ 112, 113; Id. 320; § 57; 2 Burrows, 127. But independent of these objections, the plaintiff being at the time a feme covert, she could not be an object of the law. It was her duty to accompany her husband, and at the time she did so, she violated no law of the state. The word “her” to be found in the different laws may be satisfied by applying it to a single woman; the word “inhabitant” is inapplicable to a feme covert, who, being with her husband, is not an inhabitant 1 Bl. Comm. 442. A feme covert cannot be guilty of larceny, or even of burglary, in company with her husband, or even of misprision of treason, for receiving her husband he being a traitor. 1 Hawk. P. c. 3; 1 Hale, P. C. 47; Mass. Term R. 347. If these objections, or any of them, are well founded, then the judgment is not merely erroneous, but it is void; because the jurisdiction of the court being special, and limited to certain specified cases of trial, it should appear upon the face of the proceedings, that, this was one of those cases or else all is coram non judice and void. 2 Wilson, 382; 6 Mod. 224; 9 Mod. 95; 2 Hawk. P. C. p. 94, § 21; 4 Burrows, 2281, 2244; 1 Burrows, 148; 1 Esp. 178; Cowp. 26, 29; Plow. 390; 3 Co. Inst. 231; 12 Mod. 355; 1 Lev. 160; 2 Black. 1145.
Messrs. Leake and Williamson, for defendant, contended: as to the objection, that Mrs. Kemp was a feme covert, the general words of the law furnish a complete answer. The words are, “every person”—“any inhabitant,” and throughout the laws, speak of “him or her,” “his or her.” This is agreeable to the common law doctrine. A feme covert, guilty of treason, murder or robbery, though in company with her husband, is punishable as a feme sole; and she is even guilty of larceny, committed out of his presence, though by his command. If she consent to his treason, she is guilty of misprision. 1 Hawk. P. C. pp. 11, 12, § 11; 4 Bl. Comm. 29; 1 Hale, P. C. 44, 45, 47, 48; 1 Cruise, Dig. 172. Besides, it does not follow from the finding, that Mrs. Kemp went to the enemy in company with her husband. As to the other objections, they contended: 1st, that this is not the case of a special and limited jurisdiction. The court which gave this judgment, has, in civil cases, a jurisdiction over all persons, and to any amount, except that they cannot try ejectments, or suits for land. Their jurisdiction, in cases of treason, is general under the laws which have been read. But, secondly; the 11th section furnishes a complete bar to this suit. If the plaintiff, having an election to proceed by writ of error or original action, can get out of the provisions of this section, by choosing the latter; the intention of the legislature would be entirely defeated. Besides, if she can recover in this action, it is possible she may get her land back, although the whole proceeds may have been expended in paying her debts; which could not be the case, if she should be compelled to apply to the legislature.
WASHINGTON, Circuit Justice
(charging jury). There are two questions which I shall submit to your consideration. First, is the
284
judgment in this case erroneous, for all or any of the reasons assigned by the plaintiff's counsel? Secondly, if erroneous, can advantage be taken of such errors, in this action?
First The objections all go to the form of the inquisition, except that which refers to the incapacity of the lessor of the plaintiff, being a married woman, at the time the acts of treason are charged to have been committed. The objections to the form of the inquisition are, that Kemp and his wife are not found to be inhabitants of any one of the United States; or that they owned any real or personal property in the state of New Jersey; or that they voluntarily went to, or remained with, the enemy; or that they aided the enemy by counsel, or in any other manner.
The rules laid down by the plaintiff's counsel are, upon the general principles of law, certainly correct. Courts of limited jurisdiction must not only act within the scope of their authority, but it must appear upon the face of their proceedings that they did so; and if this does not appear, all that they do is coram non judice, and void. But it is competent to the legislature to alter or qualify this principle, as it may think proper; and where the observance of the general principle is thus dispensed with, in a particular case, the law creating the exception is alone to be regarded. It is true, that, in this case, the person contemplated by the third section is an inhabitant of another state, owning property in this; and this would have been a necessary description of Kemp and his wife, if the fourth section, which gives the form of the inquisition, had not dispensed with this necessity. In that part of the prescribed form which mentions the party accused, he is stated to be of——, or late of——; and in no part of it, is he stated to own property in the state. In stating the offence, a blank is left in the form; and the jury are required to set forth the time and nature of the offence. It is not true, that the description of the person, is of the nature of the offence; and therefore the omission to set forth, that these persons were inhabitants of some other state, and owned property here; could not, upon a writ of error, have been alleged as ground of reversal.
The other objections are more serious—the going and remaining with the enemy, are essentially parts of the offence, and it should have been stated that this was done voluntarily, for, otherwise, no offence was committed within the law. The going to the enemy, in April 1776, in company with her husband, if this appeared, might not be an offence in the plaintiff; because, as, at that time, it violated no law of the state, she acted lawfully under his control, which was not then subordinate to any superior duty; and therefore it could be fairly said, that, in 1770, that she still remains with the enemy; which is a distinct offence under the previous law of December 1778; but still it was no offence unless she continued voluntarily; and as this is not found, this objection is certainly well founded. The fourth objection is too clear to admit of doubt The voluntarily remaining with the enemy was no offence under this law, unless the parties aided the enemy by counsel, or otherwise; which not being stated, it does not appear that they were legally convicted. For mere errors, there is no doubt but that this judgment might have been reversed, but then:
Secondly. Can they be taken advantage of in this suit? Can the plaintiff step over the judgment, as if it had never passed, and recover the land which was sold under judgment? It is contended by the plaintiff, that the inquisition is the act of a tribunal, vested only with a limited authority, to inquire into certain specified offences, and that their acts in relation to offences, not of this description, are utterly void. It is more correct to inquire, whether the inferior courts of common pleas possessed this limited jurisdiction? because, if there be error, it is not in the inquisition but in the judgment. We cannot get at the inquisition, but through the judgment, It is this which is “erroneous,” or “void,” if either term be properly applicable to the case. The question then is, is the judgment of the court of common pleas of Hunterdon, void upon the ground, that it was a court of special and limited jurisdiction? What is the constitution of that court? It seems to be agreed, on all hands, that it is a court of record, possessing, in civil cases, a general jurisdiction to any amount; and over all cases of tort or contract wherever the cause of action arose, the defendant residing or being served with process within the county. An exception from this general jurisdiction exists, in respect to suits for real property.
What is its jurisdiction in cases of treason?
The first law, that of the 4th of October, 1776, is purely a treason law, which vests in no particular tribunal a jurisdiction to try persons charged with this offence. The act of the 20th of September, 1777, fixes the punishment of treason. That of the 18th of April, 1778, points out the mode of trial, and, instead of proceeding by way of indictment, as at common law, the inquisition taken before a justice of the peace, is to be returned to the inferior court of common pleas for the county; where the trial, if any, is to take place, and final judgment is to be rendered. This law then, prescribes the mode of trial of an offence before defined, and points out the court where the trial is to take place. Every case of treason, arising under the former laws, is to be tried in this court, and in the prescribed form. In all such cases, the jurisdiction is general.
We come then to the act of the 11th of December, 1778, which makes some slight alteration in the form of proceedings, and
285
extends the doctrine of treason to persons and to acts not before comprehended in former laws. An act, not criminal by virtue of any pre-existing law, is now declared to amount to treason. The jurisdiction of the court, however, remains as formerly, and cannot be said to be limited and restricted by extending the crime of treason to acts not before deemed criminal. There is, surely, a striking difference between a special delegation of power to try particular cases, and multiplying the offences which the same tribunal was before authorized to try. In the exercise of their power to decide what acts constitute treason under this law, the court has certainly erred, by declaring that to be treason, which, in point of law, is not treason. This is an error in judgment sufficient to have authorized a superior tribunal to reverse it. But it does not amount to the usurpation of a power to judge and to decide, not granted by the legislature. The power to judge in the case is general—the correctness of the judgment is another matter. The circuit courts of the United States, are vested with the power of trying criminal offences against the laws of the United States. We know what it is that constitutes treason, murder, perjury, and the like. Suppose, that the crime of treason were not denned by the constitution, and that congress should declare certain acts to amount to treason, murder, or perjury, which before were not offences against the law. Should the court, in any particular case, determine that to amount to treason, &c. which, under the new law, is not strictly within the definition, would the judgment be void? I think it certainly would not.
But, if this were the case of a judgment rendered by a court of limited jurisdiction, I should feel strongly inclined to think, that, upon a just and legal construction of the eleventh section, the lessor of the plaintiff is bar red of her remedy against the purchaser. In that case, the only argument of any consequence must be founded on the words in that section, “or made void.” It might be said, and has been strongly insisted upon, that this expression necessarily relates to a valid and subsisting judgment; because that which is already void, and never had an existence, cannot be made void. There are certainly very strong reasons for condemning this construction, as being too literal and rigid. If the legislature had used the word “declared,” instead of “made,” the construction contended for by the plaintiff's counsel could not have been supported; because, whether the remedy pursued by the injured party were by writ of error, motion to quash, or ejectment to recover the land, the ground of success must have been, that the judgment should be declared to be void. Now there seems to be strong reasons for believing, that the legislature intended, in all cases, to protect the purchaser, and to substitute the state in his place. One reason is, that it could never have been intended to permit the party to escape from the provisions of this section, and thus to leave the other party unprotected by the mere form in which he might elect to proceed. If he had brought a writ of error, which was dearly one of his remedies, no doubt can exist but that he would have been within the provisions of this section, and the purchaser would have been safe under it. But he would never pursue this remedy, if, in another form, he could stride over the judgment, and recover in a collateral suit. Another reason is, that the forfeited property was, by this law, made liable to pay the debts of the attainted person to its full amount; and it would therefore be most unreasonable that, after the proceeds had been thus applied, the party should also recover his property from a bona fide purchaser, for whose indemnity no provision whatever is made. If the arguments used by the plaintiff be true, to the extent in which they were expressed, I can imagine very few cases indeed, where the injured party would find it necessary to proceed by way of writ of error, and, consequently, this beneficial provision, so intended at least, for the purchaser, would be nearly inoperative. Upon the whole, I think the verdict ought to be for the defendant.
Verdict for the defendant.
NOTE.—One point, made by the defendant, was, that the plaintiff and the lessor of the plaintiff, being stated to be British subjects, the plaintiff was exposed to the objection of alienage. Washington, Circuit Justice, observed, that he recollected no case where an alien plaintiff had recovered in ejectment. He referred to the case of
Dawson v. Godfrey [4 Cranch (8 U. S.) 321],
where the supreme court decided against the plaintiff, on the ground of alienage. But in this case, the title did not accrue till 1786, after the treaty of peace. However, the court being against the plaintiff upon the merits, no further notice was taken of this objection.
[From this judgment the plaintiff took the case to the supreme court on writ of error. The judgment was affirmed in an opinion by Chief Justice Marshall. 6 Cranch (9 U. S.) 173. The judgment rendered by the court of common pleas, while erroneous, yet was held not to be disregarded, because it was rendered by a duly-constituted court, in the form prescribed by law, and by persons authorized to find the facts. The act of 11th December, 1778, makes no alteration in the tribunal before which the offence of treason is to be tried. “The courts of the United States are all of limited jurisdiction, and their proceedings are erroneous, if the jurisdiction be not shown upon them.” Judgments rendered in such cases may be reversed, but cannot be treated as absolute nullities.]
1[Reported by Richard Peters, Jr., Esq.]
2[Affirmed in 5 Cranch (9 U. S.) 173.]
3The act of the 5th June, 1779, contained an offer of pardon, to those who had offended against the treason law, on certain conditions; which if not complied with, certain commissioners were to take possession of all their personal property in the state, which is declared to be forfeited on conviction.
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Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Trials Knowledge Area of Prous Science Intergrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: 249553, 2-Methoxyestradiol; Abatacept, Adalimumab, Adefovir dipivoxil, Agalsidase beta, Albinterferon alfa-2b, Aliskiren fumarate, Alovudine, Amdoxovir, Amlodipine besylate/atorvastatin calcium, Amrubicin hydrochloride, Anakinra, AQ-13, Aripiprazole, AS-1404, Asoprisnil, Atacicept, Atrasentan; Belimumab, Bevacizumab, Bortezomib, Bosentan, Botulinum toxin type B, Brivaracetam; Catumaxomab, Cediranib, Cetuximab, cG250, Ciclesonide, Cinacalcet hydrochloride, Curcumin, Cypher; Darbepoetin alfa, Denosumab, Dihydrexidine; Eicosapentaenoic acid/docosahexaenoic acid, Entecavir, Erlotinib hydrochloride, Escitalopram oxalate, Etoricoxib, Everolimus, Ezetimibe; Febuxostat, Fenspiride hydrochloride, Fondaparinux sodium; Gefitinib, Ghrelin (human), GSK-1562902A; HSV-tk/GCV; Iclaprim, Imatinib mesylate, Imexon, Indacaterol, Insulinotropin, ISIS-112989; L-Alanosine, Lapatinib ditosylate, Laropiprant; Methoxy polyethylene glycol-epoetin-beta, Mipomersen sodium, Motexafin gadolinium; Natalizumab, Nimotuzumab; OSC, Ozarelix; PACAP-38, Paclitaxel nanoparticles, Parathyroid Hormone-Related Protein-(1-36), Pasireotide, Pegfilgrastim, Peginterferon alfa-2a, Peginterferon alfa-2b, Pemetrexed disodium, Pertuzumab, Picoplatin, Pimecrolimus, Pitavastatin calcium, Plitidepsin; Ranelic acid distrontium salt, Ranolazine, Recombinant human relaxin H2, Regadenoson, RFB4(dsFv)-PE38, RO-3300074, Rosuvastatin calcium; SIR-Spheres, Solifenacin succinate, Sorafenib, Sunitinib malate; Tadalafil, Talabostat, Taribavirin hydrochloride, Taxus, Temsirolimus, Teriparatide, Tiotropium bromide, Tipifarnib, Tirapazamine, Tocilizumab; UCN-01, Ularitide, Uracil, Ustekinumab; V-260, Vandetanib, Vatalanib succinate, Vernakalant hydrochloride, Vorinostat ; YM-155; Zileuton, Zoledronic acid monohydrate.
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PMID:Gateways to clinical trials. 1820 Mar 33
Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Trials Knowledge Area of Prouse Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: 101M, 3F8; Abatacept, ABT-263, Adalimumab, AG-7352, Agatolimod sodium, Alfimeprase, Aliskiren fumarate, Alvimopan hydrate, Aminolevulinic acid hexyl ester, Ammonium tetrathiomolybdate, Anakinra, Aripiprazole, AS-1404, AT-9283, Atomoxetine hydrochloride, AVE-1642, AVE-9633, Axitinib, AZD-0530; Becocalcidiol, Belotecan hydrochloride, Bevacizumab, BG-9928, BIBF-1120, BMS-275183, Bortezomib, Bosentan; Catumaxomab, Cetuximab, CHR-2797, Ciclesonide, Clevidipine, Cypher, Cytarabine/daunorubicin; Darifenacin hydrobromide, Darunavir, Denosumab, Desvenlafaxine succinate, Disufenton sodium, Duloxetine hydrochloride, Dutasteride; Eculizumab, Efalizumab, Eicosapentaenoic acid/docosahexaenoic acid, Eplerenone, Epratuzumab, Erlotinib hydrochloride, Escitalopram oxalate, Ethynylcytidine, Etravirine, Everolimus, Ezetimibe; Fulvestrant; Garenoxacin mesilate, Gefitinib, Gestodene; HI-164, Hydralazine hydrochloride/isosorbide dinitrate; Icatibant acetate, ICX-RHY, Idraparinux sodium, Indacaterol, Ispronicline, Ivabradine hydrochloride, Ixabepilone; KB-2115, KW-2449; L-791515, Lapatinib ditosylate, LGD-4665, Licofelone, Liposomal doxorubicin, Lisdexamfetamine mesilate, Lumiracoxib; Methoxy polyethylene glycol-epoetin-beta, Miglustat, Mipomersen sodium, Mitumprotimut-T, MK-0822A, MK-0974; Nelarabine; Obatoclax mesylate, Olmesartan medoxomil, Olmesartan medoxomil/hydrochlorothiazide; Paliperidone, Palonosetron hydrochloride, Panitumumab, Pegfilgrastim, Peginterferon alfa-2a, Pemetrexed disodium, Perospirone hydrochloride, Pertuzumab, Pimecrolimus, Pitrakinra, Pixantrone maleate, Posaconazole, Pregabalin; Quercetin; RALGA, Raltegravir potassium, Ranelic acid distrontium salt, rhHistone 1.3, Rimonabant, Rivaroxaban, Rosuvastatin calcium, RTS,S/SBAS2; Satraplatin, SNDX-275, Sodium butyrate, Solifenacin succinate, Sorafenib, SU-14813, Sunitinib malate; Tadalafil, Tafenoquine succinate, Tamatinib fosdium, Taxus, Telbivudine, Telmisartan/hydrochlorothiazide, Temsirolimus, Tiotropium bromide, Tipranavir, Tocilizumab, Trabectedin, Tramadol hydrochloride/acetaminophen; Ulipristal acetate, Uracil, Ursodeoxycholyltaurine; Valdecoxib, Vardenafil hydrochloride hydrate, Varenicline tartrate, Vildagliptin, Vinflunine, Vitespen, Vorinostat ; ZK-EPO, Zoledronic acid monohydrate.
...
PMID:Gateways to clinical trials. 1838 98
Nonselective inhibitors of human histone deacetylases (HDAC) are known to have antitumor activity in mice in vivo, and several of them are under clinical investigation. The first of these,
Vorinostat (SAHA), has been approved for treatment of cutaneous T-cell lymphoma. Questions remain concerning which HDAC isotype(s) are the best to target for anticancer activity and whether increased efficacy and safety will result with an isotype-selective HDAC inhibitor. We have developed an isotype-selective HDAC inhibitor, MGCD0103, which potently targets human HDAC1 but also has inhibitory activity against HDAC2, HDAC3, and HDAC11 in vitro. In intact cells, MGCD0103 inhibited only a fraction of the total HDAC activity and showed long-lasting inhibitory activity even upon drug removal. MGCD0103 induced hyperacetylation of histones, selectively induced apoptosis, and caused cell cycle blockade in various human cancer cell lines in a dose-dependent manner. MGCD0103 exhibited potent and selective antiproliferative activities against a broad spectrum of human cancer cell lines in vitro, and HDAC inhibitory activity was required for these effects. In vivo, MGCD0103 significantly inhibited growth of human tumor xenografts in nude mice in a dose-dependent manner and the antitumor activity correlated with induction of histone acetylation in tumors. Our findings suggest that the isotype-selective HDAC inhibition by MGCD0103 is sufficient for antitumor activity in vivo and that further clinical investigation is warranted.
...
PMID:MGCD0103, a novel isotype-selective histone deacetylase inhibitor, has broad spectrum antitumor activity in vitro and in vivo. 1841 90
Vorinostat ( Zolinza ) is a histone deacetylase inhibitor that has demonstrated activity in patients with advanced solid tumors in phase I trials. A multicenter, open-label phase II trial of oral vorinostat 200, 300 or 400 mg bid for 14 days followed by a 7-day rest until disease progression or intolerable toxicity was conducted. Patients with measurable, relapsed or refractory breast or non-small cell lung cancer who had received > or = 1 prior therapy or colorectal cancer who had received > or = 2 prior therapies were eligible. The response rate, safety and tolerability were evaluated. Sixteen patients (median age, 62 years; median 5.5 prior therapies) were enrolled. Six patients received 400 mg bid, six received 300 mg bid and four received 200 mg bid (14 days/3 weeks). Dose-limiting toxicities (DLTs) at the 400 or 300 mg bid levels were anorexia, asthenia, nausea, thrombocytopenia, vomiting, and weight loss. No DLTs were observed at the 200 mg bid level. Disease stabilization was observed in eight patients, but there were no confirmed responses. The median TTP was 33.5 days. Eleven patients discontinued due to clinical adverse experiences (AEs). The most common drug-related AEs were anorexia (81%), fatigue (62%), nausea (62%), diarrhea (56%), vomiting (56%), thrombocytopenia (50%) and weight loss (50%). Drug-related AEs > or = grade 3 included thrombocytopenia (50%), anemia (12%), asthenia (12%) and nausea (12%). Vorinostat in a daily oral schedule for 14 days/3 weeks was tolerable at 200 mg bid only, and no responses were observed in this study. Most patients, however, had limited drug exposure which did not allow a reliable efficacy analysis.
...
PMID:Early phase II trial of oral vorinostat in relapsed or refractory breast, colorectal, or non-small cell lung cancer. 1842 18
Target specificity and off-target liabilities are routinely monitored during the early phases of drug discovery for most kinase projects. Typically these criteria are evaluated using a profiling panel comprised of a diverse collection of in vitro kinase assays and relates compound structure to potency and selectivity. The success of these efforts has led to the design of similar panels for phosphatase, protease, and epigenetic targets. Here the implementation of an epigenetic profiling panel, comprised of eleven histone deacetylases (HDACs) and one histone acetyltransferase (HAT), was used to evaluate chemical modulators of these enzymes. HDAC inhibitors (HDACi) such as sodium butyrate and trichostatin A demonstrate diverse biological effects which have led to broad speculation about their therapeutic potential in multiple disease states. Some HDACi have demonstrated tumor suppression in vivo and recently Zolinza was the first HDACi approved by the FDA for the treatment of cutaneous T-cell lymphoma. While HDACi have demonstrated therapeutic utility, many of the first generation compounds are pan-inhibitors. Thus, use of an HDAC profiling panel will be essential in achieving isoform specificity of the next generation of inhibitors. To this end, twenty-one compounds, twelve of which are known to have activities against the HDACs, were tested to evaluate the utility of the epigenetic panel. Additionally, these compounds were tested against a larger 72 member enzyme panel comprised of kinase, phosphatase and protease activities. This effort represents the first time these compounds have been profiled with such a broad range of biochemical activities.
...
PMID:The use of diversity profiling to characterize chemical modulators of the histone deacetylases. 1845 94
Vorinostat is a histone deacetylase inhibitor that induces differentiation, growth arrest, and/or apoptosis of malignant cells both in vitro and in vivo and has shown clinical responses in approximately 30% of patients with advanced mycosis fungoides and Sézary syndrome cutaneous T-cell lymphoma (CTCL). The purpose of this study was to identify biomarkers predictive of vorinostat response in CTCL using preclinical model systems and to assess these biomarkers in clinical samples. The signal transducer and activator of transcription (STAT) signaling pathway was evaluated. The data indicate that persistent activation of STAT1, STAT3, and STAT5 correlate with resistance to vorinostat in lymphoma cell lines. Simultaneous treatment with a pan-Janus-activated kinase inhibitor resulted in synergistic antiproliferative effect and down-regulation of the expression of several antiapoptotic genes. Immunohistochemical analysis of STAT1 and phosphorylated tyrosine STAT3 (pSTAT3) in skin biopsies obtained from CTCL patients enrolled in the vorinostat phase IIb trial showed that nuclear accumulation of STAT1 and high levels of nuclear pSTAT3 in malignant T cells correlate with a lack of clinical response. These results suggest that deregulation of STAT activity plays a role in vorinostat resistance in CTCL, and strategies that block this pathway may improve vorinostat response. Furthermore, these findings may be of prognostic value in predicting the response of CTCL patients to vorinostat.
...
PMID:Constitutive activation of signal transducers and activators of transcription predicts vorinostat resistance in cutaneous T-cell lymphoma. 1848 62
Histone deacetylase (HDAC) inhibitors have garnered significant attention as cancer drugs. These therapeutic agents have recently been clinically validated with the market approval of vorinostat (SAHA, Zolinza ) for treatment of cutaneous T-cell lymphoma. Like vorinostat, most of the small-molecule HDAC inhibitors in clinical development are hydroxamic acids, whose inhibitory activity stems from their ability to coordinate the catalytic Zn2+ in the active site of HDACs. We sought to identify novel, nonhydroxamate-based HDAC inhibitors with potentially distinct pharmaceutical properties via an ultra-high throughput small molecule biochemical screen against the HDAC activity in a HeLa cell nuclear extract. An alpha-mercaptoketone series was identified and chemically optimized. The lead compound, KD5170, exhibits HDAC inhibitory activity with an IC50 of 0.045 micromol/L in the screening biochemical assay and an EC50 of 0.025 micromol/L in HeLa cell-based assays that monitor histone H3 acetylation. KD5170 also exhibits broad spectrum classes I and II HDAC inhibition in assays using purified recombinant human isoforms. KD5170 shows significant antiproliferative activity against a variety of human tumor cell lines, including the NCI-60 panel. Significant tumor growth inhibition was observed after p.o. dosing in human HCT-116 (colorectal cancer), NCI-H460 (non-small cell lung carcinoma), and PC-3 (prostate cancer) s.c. xenografts in nude mice. In addition, a significant increase in antitumor activity and time to end-point occurred when KD5170 was combined with docetaxel in xenografts of the PC-3 prostate cancer cell line. The biological and pharmaceutical profile of KD5170 supports its continued preclinical and clinical development as a broad spectrum anticancer agent.
...
PMID:KD5170, a novel mercaptoketone-based histone deacetylase inhibitor that exhibits broad spectrum antitumor activity in vitro and in vivo. 1848 95
Histone deacetylase inhibitors (HDACIs) are emerging as a new class of therapeutic agents with potent antitumor activities in a broad spectrum of human cancers. In this study, the in vitro plasma stability, permeability, solubility, and lipophilicity (log D) of two mercaptoacetamide-based HDACIs (coded as W2 and S2) were evaluated and compared to Vorinostat (SAHA). The results demonstrated that the compounds manifested high solubility in HCl (pH 1.2) but lower in PBS (pH 7.4) than SAHA. Moreover, mercaptoacetamide-based HDACIs exhibited higher lipophilicity values compared to SAHA. The permeability of these compounds was evaluated using the Caco-2 cell monolayer as a model of the intestinal mucosa. The Caco-2 studies revealed that the compounds S2 and W2 are highly permeable with apparent permeability coefficients (P(app)) in the apical to basolateral direction of 7.33 x 10(-6) and 15.0 x 10(-6)cm/s, respectively. The in vitro stability was determined in human, mouse, porcine and rat plasma. Data showed that the compound W2 is more stable in human and rat plasma and the S2 is more stable in all plasma species than SAHA. Taken together, these results indicate that the mercaptoacetamide-based HDACIs possess favorable solubility, lipophilicity, permeability and plasma stability features.
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PMID:In vitro plasma stability, permeability and solubility of mercaptoacetamide histone deacetylase inhibitors. 1856 36
Histone deacetylases (HDACs) remove the acetyl groups of lysine residues of histone tails leading to chromatin compaction and transcriptional repression. In addition, HDACs can also influence transcription-independent events such as mitosis or deoxyribonucleic acid (DNA) repair and deacetylate nonhistone proteins involved in cell proliferation and death, altering their function. Histone deacetylase inhibitors (HDACi) constitute a promising treatment for cancer therapy due to their low toxicity. HDACi have been shown to induce differentiation, cell-cycle arrest, and apoptosis and to inhibit migration, invasion, and angiogenesis in many cancer cell lines. In addition, these compounds inhibit tumor growth in animal models and show antitumor activity in patients. HDACi alone and in combination with a variety of anticancer drugs are being tested in clinical trials, showing significant anticancer activity both in hematological and solid tumors. SAHA (vorinostat, Zolinza ) was the first HDACi approved by the US Food and Drug Administration to enter the clinical oncology market for treating cutaneous T-cell lymphoma (CTCL) and is being tested for other malignancies.
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PMID:Histone deacetylase inhibitors: mechanism of action and therapeutic use in cancer. 1862 67
Suberoylanilide hydroxamic acid (SAHA, vorinostat, Zolinza ) and trichostatin A (TSA) are inhibitors of the Zn(II)-dependent class I and class II histone deacetylases (HDACs), which are enzymes that operate in concert with histone acetyltransferases (HATs) to regulate the acetylation status of the epsilon-amino group of lysine residues of nucleosomal histones in chromatin. An increased level of histone acetylation resulting from the SAHA or TSA inhibition of Zn(II)-dependent HDACs relaxes the chromatin structure and upregulates transcription. The links made in the 1990s between the inhibition of HDAC activity and the suppression of tumor growth have brought the design of HDAC inhibitors (HDACi) to the forefront of oncology research. SAHA has anticancer activity against hematologic and solid tumors and has been approved by the FDA for the treatment of cutaneous T-cell lymphoma. The increased molecular-level understanding of class I and class IIa HDACs from X-ray crystallography highlights differences in the residues distal to the active site and in the cavity size, which has implications for HDACi substrate specificity and enzyme mechanism. Results from HDAC-focussed activity-based protein profiling experiments may lead to the design of molecules that are class-specific HDACi.
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PMID:Zn(II)-dependent histone deacetylase inhibitors: suberoylanilide hydroxamic acid and trichostatin A. 1872 19
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CAS:25857-64-1 - FACTA Search
The kinetics of benzaldehyde formation during the oxidation of benzylamine by pig plasma benzylamine oxidase have been studied at different pH values. It has been shown that the first step of the reaction catalyzed by this enzyme is the formation of a Schiff base between the amino group of the substrate and the aldehyde group of the enzyme. Present kinetic studies are consistent with this mechanism and demonstrate the existence of two steps which are alternatively rate-limiting one below pH 6.0, the other above this pH value. The rate-limiting step above pH 6.0 requires the participation of OH-. A mechanism of reaction has been proposed in which the release of products follows the sequence: hydrogen peroxide, aldehyde , ammonia.
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PMID:Pig plasma benzylamine oxidase: some considerations on the mechanism of the reaction. 1 26
Stopped-flow experiments in which sheep liver cytoplasmic aldehyde dehydrogenase (EC 1.2.1.3) was rapidly mixed with NAD(+) and aldehyde showed a burst of NADH formation, followed by a slower steady-state turnover. The kinetic data obtained when the relative concentrations and orders of mixing of NAD(+) and propionaldehyde with the enzyme were varied were fitted to the following mechanism: [Formula: see text] where the release of NADH is slow. By monitoring the quenching of protein fluorescence on the binding of NAD(+), estimates of 2x10(5) litre.mol(-1).s(-1) and 2s(-1) were obtained for k(+1) and k(-1) respectively. Although k(+3) could be determined from the dependence of the burst rate constant on the concentration of propionaldehyde to be 11s(-1), k(+2) and k(-2) could not be determined uniquely, but could be related by the equation: (k(-2)+k(+3))/k(+2) =50x10(-6)mol.litre(-1). No significant isotope effect was observed when [1-(2)H]propionaldehyde was used as substrate. The burst rate constant was pH-dependent, with the greatest rate constants occurring at high pH. Similar data were obtained by using acetaldehyde, where for this substrate (k(-2)+k(+3))/k(+2)=2.3x10 (-3)mol.litre(-1) and k(+3) is 23s(-1). When [1,2,2,2-(2)H]acetaldehyde was used, no isotope effect was observed on k(+3), but there was a significant effect on k(+2) and k(-2). A burst of NADH production has also been observed with furfuraldehyde, trans-4-(NN-dimethylamino)cinnamaldehyde, formaldehyde, benzaldehyde , 4-(imidazol-2-ylazo) benzaldehyde , p-methoxybenzaldehyde and p-methylbenzaldehyde as substrates, but not with p-nitrobenzaldehyde.
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PMID:Pre-steady-state kinetic studies on cytoplasmic sheep liver aldehyde dehydrogenase. 2 12
Procedures for the purification of an aldehyde dehydrogenase from extracts of the obligate methylotroph, Methylomonas methylovora are described. The purified enzyme is homogeneous as judged from polyacrylamide gel electrophoresis. In the presence of an artificial electron acceptor (phenazine methosulfate), the purified enzyme catalyzes the oxidation of straight chain aldehydes (C1--C10 tested), aromatic aldehydes ( benzaldehyde , salicylaldehyde), glyoxylate, and glyceraldehyde. Biological electron acceptors such as NAD+, NADP+, FAD, FMN, pyridoxal phosphate, and cytochrome c cannot act as electron carriers. The activity of the enzyme is inhibited by sulfhydryl agents [p-chloromercuribenzoate, N-ethylmaleimide and 5,5-dithiobis (2-nitrobenzoic acid)], cuprous chloride, and ferrour nitrate. The molecular weight of the enzyme as estimated by gel filtration is approximately 45000 and the subunit size determined by sodium dodecyl sulfate-gel electrophoresis is approximately 23000. The purified enzyme is light brown and has an absorption peak at 410 nm. Reduction of enzyme with sodium dithionite or aldehyde substrate resulted in the appearance of peaks at 523 nm and 552nm. These results suggest that the enzyme is a hemoprotein. There was no evidence that flavins were present as prosthetic group. The amino acid composition of the enzyme is also presented.
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PMID:Microbial oxidation of methane and methanol: purification and properties of a heme-containing aldehyde dehydrogenase from Methylomonas methylovora. 4 58
The transient-state kinetics of enzymic reduction of acetaldehyde and benzaldehyde by NADH, catalyzed by horse liver alcohol dehydrogenase, have been examined under single-turnover conditions, obtained by carrying out reactions either with limiting amounts of enzyme in the presence of 20 mM pyrazole or with limiting amounts of substrate. Analysis of the variation with substrate, coenzyme, and enzyme concentrations of amplitudes and time constants for the exponential transients observed at 328 nm and 300 nm shows that the kinetics of enzymic aldehyde reduction are qualitatively and quantitatively consistent with the relationships derived in the preceding paper for an ordered ternary-complex mechanism involving identical and independent catalytic sites. It is concluded that there is no evidence whatsoever for the kinetic significance of a half-of-the-sites reactivity or any other kind of subunit interaction in the liver alcohol dehydrogenase system. The biphasic transients observed at 328 nm for the reduction of aromatic aldehydes such as benzaldehyde are a normal kinetic characteristic of the ordered ternary-complex mechanism, being attributable to accumulation of the ternary enzyme-NAD-product complex when product dissociation from this complex is slow in comparison to its formation by ternary-complex interconversion.
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PMID:Kinetic transients in the reduction of aldehydes catalysed by liver alcohol dehydrogenase. 18 64
The effect of pH on steady state kinetic parameters for the yeast alcohol dehydrogenase-catalyzed reduction of aldehydes and oxidation of alcohols has been studied. The oxidation of p-CH3 benzyl alcohol-1,1-h2 and -1,1-d2 by NAD+ was found to be characterized by large deuterium isotope effects (kH/kD = 4.1 plus or minus 0.1) between pH 7.5 and 9.5, indicating a rate-limiting hydride trahsfer step in this pH range; a plot of kCAT versus pH could be fit to a theoretical titration curve, pK = 8.25, where kCAT increases with increasing pH. The Michaelis constnat for p-CH3 benzyl alcohol was independent of pH. The reduction of p-CH3 benzaldehyde by NADH and reduced nicotinamide adenine dinucleotide with deuterium in the 4-A position (NADD) cound not be studied below pH 8.5 due to substrate inhibition; however, between pH 8.5 and 9.5, kCAT was found to decrease with increasing pH and to be characterized by significant isotope effects (kH/kD = 3.3 plus or minus 0.3). In the case of acetaldehyde reduction by NADH and NADD, isotope effects were found to be small and exxentially invariant (kH/kD = 2.O plus or minus 0.4) between pH 7.2 and 9.5, suggesting a partially rate-limiting hydride transger step for this substrate; a plot of kCAT/K'b (where K'b is the Michaelis constant for acetaldehyde) versus pH could be fit to a titration curve, pK = 8.25. The titration curve for acetaldehyde reduction has the same pK but is opposite in direction to that observed for p-CH3 benzyl alcohol oxidation. The data presented in this paper indicate a dependence on different enzyme forms for aldehyde reduction and alcohol oxidation and are consistent with a single active site side chain, pK = 8.25, which functions in acid-base catalysis of the hydride transfer step.
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PMID:Acid-base catalysis in the yeast alcohol dehydrogenase reaction. 23 17
A spectrophotometric method for the analysis of fenclorac and its metabolite, 3-chloro-4-cyclohexylbenzeneglycolic acid, in human serum was developed. The parent compound represented at least 90% of the total species present in blood; the metabolite was present to the extent of about 10%, primarily in the elimination phase. The basic procedure consists of extraction of both compounds from serum, further extraction to remove interfering substances, alkaline conversion of fenclorac to the alpha-hydroxy acid metabolite, oxidation of this metabolite to the corresponding benzaldehyde derivative, and spectrophotometric measurement of the absorbance of the aldehyde at 252 nm. A comparison of serum concentrations obtained by this method with concentrations calculated from 14C-data following oral administration of 1-14C-fenclorac to eight normal adult volunteers indicated a 90% correlation between methodologies over a range of 1.4-25.5 microgram of fenclorac/ml of serum.
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Closed patch tests with balsam of Peru gave rise to nine immediate reactions among 121 patients with different dermatoses and to 10 reactions among 57 patients with chronic urticaria. Among compounds of balsam of Peru, cinnamic aldehyde , cinnamic acid benzoic acid and benzaldehyde also gave the same reactions. The reactions could not passively be transferred with serum from patients. They were abolished by antihistamine given before testing, and by pretreatment with compound 48/80. Balsam of Peru and cinnamic aldehyde did not provoke new symptoms when given orally to patients.
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PMID:Immediate reactions to patch tests with balsam of Peru. 58 84
The reaction of 2-aminopyrimidine with benzaldehyde in all applied methods yielded instead of benzal-2-aminopyrimidine (1) regardless of the procedure used, N.N'-benzilidene-bis-2-aminopyrimidine (2). The expected product benzal-2-aminopyrimidine has not been formed in any case. For this reason the synthesis of aminoalkanesulfonic acids has not been carried out by the use of Schiff bases as starting material. Reaction of aldehyde bisulfite adducts and corresponding amine, was used instead. In the syntheses where 2-aminopyridine was used as the amine part, the corresponding aminoalkanesulfonic acids were formed (3--5), while 2-aminopyrimidine under the same condition gave several reaction products (6--10). All compounds obtained were tested for their growth inhibitory activity on the seeds of cress (Lepidium sativum L.).
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PMID:Aminoalkane sulfonic acids. Synthesis of some mitodepressive heterocyclic aminoalkane sulfonic acids. 72 57
In the scope of our research about the antimicrobial activity of amin- aldehyde -condensates a number of benzylidene-amines (azomethins of benzyldehyde) was synthesized by condensation of primary amines with benzaldehyde . Structures and physical constants are shown in table 1 and 2. The antimicrobial activity of these benzylidene-amines is demonstrated by the results of the disk-test (table 3), of the minimal inhibition concentration test (MIC, table 4) and the suspension test (table 5) following the method of the DGHM. The different hydrophilic behaviour was equalized by using the standard solution described earlier with 3% dioxane. The results show, that the germistatic activity of the benzylideneamines resembles or exceeds in some cases that of benzaldehyde (table 4). Some compounds show good fungistatic activity versus Trichophyton mentagrophytes (table 3). The bactericidal power versus Klebsiella pneumoniae, Pseudomonas aeruginosa and Proteus vulgaris is remarkable and quiet stronger than that of the benzaldehyde .
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PMID:[Investigations on the antimicrobial activity of amin-aldehyde-condensates. 5. Communication: azomethins of benzaldehyde (author's transl)]. 73 66
The Desulfovibrio gigas aldehyde -oxido-reductase contains molybdenum and iron-sulfur clusters. Mössbauer spectroscopy was used to characterize the iron-sulfur clusters. Spectra of the enzyme in its oxidized, partially reduced and benzaldehyde -reacted states were recorded at different temperatures and applied magnetic fields. All the iron atoms in D. gigas aldehyde oxido-reductase are organized as [2Fe-2S] clusters. In the oxidized enzyme, the clusters are diamagnetic and exhibit a single quadrupole doublet with parameters (delta EQ = 0.62 +/- 0.02 mm/s and delta = 0.27 +/- 0.01 mm/s) typical for the [2Fe-2S]2+ state. Mössbauer spectra of the reduced clusters also show the characteristics of a [2Fe-2S]1+ cluster and can be explained by a spin-coupling model proposed for the [2Fe-2S] cluster where a high-spin ferrous ion (S = 2) is antiferromagnetically coupled to a high-spin ferric ion (S = 5/2) to form a S = 1/2 system. Two ferrous sites with different delta EQ values (3.42 mm/s and 2.93 mm/s at 85 K) are observed for the reduced enzyme, indicating the presence of two types of [2Fe-2S] clusters in the D. gigas enzyme. Taking this observation together with the re-evaluated value of iron content (3.5 +/- 0.1 Fe/molecule), it is concluded that, similar to other Mo-hydroxylases, the D. gigas aldehyde oxido-reductase also contains two spectroscopically distinguishable [2Fe-2S] clusters.
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PMID:Mössbauer study of the native, reduced and substrate-reacted Desulfovibrio gigas aldehyde oxido-reductase. 131 79
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| http://www.nactem.ac.uk/facta/cgi-bin/facta3.cgi?query=CAS%3A25857-64-1%7C111111%7C0%7C0%7C242880%7C0%7C10 |
The subsoil architecture of the Lagoon and Gulf of Venice (Italy) by very high resolution seismic surveys in shallows | Earth-prints
DC Field Value Language
dc.contributor.authorall Brancolini, Giuliano en
dc.contributor.authorall Tosi, Luigi en
dc.contributor.authorall Baradello, Luca en
dc.contributor.authorall Donda, Federica en
dc.contributor.authorall Zecchin, Massimo en
dc.contributor.editorall Campostrini, P en
dc.date.accessioned 2014-12-13T00:27:53Z en
dc.date.available 2014-12-13T00:27:53Z en
dc.date.issued 2007 en
dc.identifier.uri http://hdl.handle.net/2122/9176 en
dc.description.abstract
The Project “Application of innovative of very high resolution seismic methodologies in shallow waters aimed at the study of the subsoil of the Venice Lagoon” allowed the characterization of the Late Pleistocene and Holocene depositional sequences with a detail, that has never been reached in the past.
A boat, particularly suitable for very high resolution seismic survey in shallow water (less than 1 m deep) has been fully equipped and tested. It allowed to carried out surveys of specific areas of the Lagoon that have never been investigated in the past. Moreover a seismo-stratigraphic model of the lagoon and gulf of Venice subsoil has been performed. The seismic acquisition system allowed to investigate the subsoil down to 30-40 m deep.
The new data provided significant geological features related to the Late Pleistocene and Holocene evolution of the investigated areas: the southern lagoon, the Lido and Chioggia inlets and part of the shelf of the Gulf of Venice.
en
dc.language.iso English en
dc.relation.ispartof SCIENTIFIC RESEARCH AND SAFEGUARDING OF VENICE 2007: CORILA Research Programme 2004 - 2006, 2006 Results en
dc.subject very high resolution seismic en
dc.subject Venice Lagoon en
dc.subject Holocene en
dc.subject Late Pleistocene en
dc.subject ebb tidal delta en
dc.subject Lido barrier island en
dc.subject channel-levee systems en
dc.subject Active lagoon channel en
dc.title The subsoil architecture of the Lagoon and Gulf of Venice (Italy) by very high resolution seismic surveys in shallows en
dc.type Conference paper en
dc.description.status Published en
dc.identifier.URL http://verbi.corila.it/ en
dc.subject.INGV 04. Solid Earth::04.04. Geology::04.04.10. Stratigraphy en
dc.description.ConferenceLocation Venice, Italy en
dc.relation.references
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Tosi L.,1994b. I sedimenti tardo-quaternari dell’area litorale veneziana: analisi delle caratteristiche fisico-meccaniche. Geologia Tecnica ed Ambientale, 2: 47-60.
Tosi L., 1994c. L'evoluzione paleoambientale tardo quaternaria del litorale veneziano". Il Quaternario - Italian Journal of Quaternary Sciences, Vol. 7, fasc. 2, 589-596.
Tosi L., Brancolini G., Baradello L., Donda F., Rizzetto F., 2006. Very high resolution seismic surveys in the lagoon and gulf of Venice shallow waters. Proceedings of the 5th European Congress on Regional Geoscientific Cartography and Information Systems, Barcellona, June 13th to 16th, 2006, vol. 2, 156-158.
Tosi L., Rizzetto F., Bonardi M., Donnici S., Serandrei Barbero R., Toffoletto F., 2007a. Note illustrative della Carta Geologica d’Italia alla scala 1:50.000. Foglio 128 - Venezia. APAT, Dip. Difesa del Suolo, Servizio Geologico d’Italia, Casa Editrice SystemCart, Roma, 164 pp.
Tosi L., Rizzetto F., Bonardi M., Donnici S., Serandrei Barbero R., Toffoletto F., 2007b. Note illustrative della Carta Geologica d’Italia alla scala 1:50.000. Foglio 148-149 - Chioggia-Malamocco. APAT, Dip. Difesa del Suolo, Servizio Geologico d’Italia, Casa Editrice SystemCart, Roma, 162 pp.
Umgiesser, G., Ferrarin, C. De Pascalis, F. and Amos, C. 2005. Modelling sand transport in a canal system, northern Venice Lagoon. In Campostrini, P., editor, Scientific research and safeguarding of Venice (Co.Ri.La. Research Program 2001-2003), La Garangola, Padova, Italy, 383-390.
Zecchin M., Brancolini G., Donda F., Tosi L., Rizzetto F., Baradello L., 2006a. Sedimentary features and seismic stratigraphy of the Late Pleistocene and Holocene deposits in the Venice Lagoon. Proceedings of Adria 2006 - International Geological Congress on the Adriatic Area, Urbino, June 19th-20th, 2006, 120-121.
Zecchin M., Brancolini G., Donda F., Rizzetto F. Tosi L., 2006b. Sequence stratigraphy of Holocene deposits in the Venice Area, based on high-resolution seismic profiles. In: Thirty years of Sequence Stratigraphy: Applications, Limits and Prospects - 2 October 2006 - Bari – Italy, 81-82
Zecchin M., Brancolini G., Donda F., Rizzetto F. Tosi L., 2006c. High-resolution seismic stratigraphy in the Venice area. GEOSed proceeding, Modena 25-29 Settembre 2006 (ed. Lugli S.), 116.
Zecchin, M., Baradello, L., Brancolini, G., Donda, F., Rizzetto, F., Tosi, L., 2008. Sequence stratigraphy of Holocene deposits in the offshore of Venice based on very high-resolution seismic profiles. GeoActa, Special Publication, 1, 89-96.
en
dc.description.obiettivoSpecifico 7A. Geofisica di esplorazione en
dc.description.fulltext open en
dc.contributor.author Brancolini, Giuliano en
dc.contributor.author Tosi, Luigi en
dc.contributor.author Baradello, Luca en
dc.contributor.author Donda, Federica en
dc.contributor.author Zecchin, Massimo en
dc.contributor.editor Campostrini, P en
item.fulltext With Fulltext -
item.openairetype Conference paper -
item.cerifentitytype Publications -
item.grantfulltext open -
item.openairecristype http://purl.org/coar/resource_type/c_18cf -
item.languageiso639-1 en -
crisitem.author.dept Osservatorio Geofisico Sperimentale, Trieste, Italy -
crisitem.classification.parent 04. Solid Earth -
Appears in Collections: Conference materials
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Publications - Global Disability Innovation Hub
The GDI Hub brings together academic excellence, innovative practice and co-creation; harnessing the power of technology for good.
Type
Editorial
Themes
Culture and Participation
COVID-19 as social disability: the opportunity of social empathy for empowerment
Ikenna D Ebueny, Emma M Smith,Catherine Holloway, Rune Jensen, Lucía D'Arino, Malcolm MacLachlan
Social empathy is ‘the ability to more deeply understand people by perceiving or experiencing their life situations and as a result gain insight into structural inequalities and disparities’. Social empathy comprises three elements: individual empathy, contextual understanding and social responsibility. COVID-19 has created a population-wide experience of exclusion that is only usually experienced by subgroups of the general population. Notably, persons with disability, in their everyday lives, commonly experience many of the phenomena that have only recently been experienced by members of the general population. COVID-19 has conferred new experiential knowledgeon all of us. We have a rare opportunity to understand and better the lives of persons with disabilities for whom some aspects of the COVID- 19 experience are enduring. This allows us greater understanding of the importance of implementing in full a social and human rights model of disability, as outlined in the UNCRPD.
BMJ Global Health; 2020
Abstract
COVID-19 as social disability: the opportunity of social empathy for empowerment
COVID-19 has conferred new experiential knowledge on society and a rare opportunity to better understand the social model of disability and to improve the lives of persons with disabilities.
The COVID-19 experience may offer contextual knowledge of the prepandemic lives of persons with disabilities and foster greater social awareness, responsibility and opportunities for change towards a more inclusive society.
Information, family and social relationships, health protection and healthcare, education, transport and employment should be accessible for all groups of the population. The means must be developed and deployed to ensure equity – the deployment of resources so that people with different types of needs have the same opportunities for living good lives in inclusive communities.
We have learnt from COVID-19 that inclusive healthcare and universal access should be the new normal, that its provision as a social good is both unifying and empowering for society as a whole.
Cite
COVID-19 as social disability: the opportunity of social empathy for empowerment
Ebuenyi ID, Smith EM, Holloway C , et alCOVID-19 as social disability: the opportunity of social empathy for empowerment BMJ Global Health2020;5:e003039.
COVID-19 as social disability: the opportunity of social empathy for empowerment
Type
Editorial
Themes
Assistive & Accessible Technology
Research Group
Social Justice
Developing inclusive and resilient systems: COVID-19 and assistive technology
Emma M. Smith, Malcolm MacLachlan, Ikenna D. Ebuenyi,Catherine Holloway&Victoria Austin
While the inadequacies of our existing assistive technology systems, policies, and services have been highlighted by the acute and rapidly changing nature of the COVID-19 pandemic, these failures are also present and important during non-crisis times. Each of these actions, taken together, will not only address needs for more robust and resilient systems for future crises, but also the day-to-day needs of all assistive technology users. We have a responsibility as a global community, and within our respective countries, to address these inadequacies now to ensure an inclusive future.
Disability & Society; 2020
Abstract
Developing inclusive and resilient systems: COVID-19 and assistive technology
Assistive technology is a critical component of maintaining health, wellbeing, and the realization of rights for persons with disabilities. Assistive technologies, and their associated services, are also paramount to ensuring individuals with functional limitations have access to important health and social service information, particularly during a pandemic where they may be at higher risk than the general population. Social isolation and physical distancing have further marginalized many within this population. We have an opportunity to learn from the COVID-19response to develop more inclusive and resilient systems that will serve people with disabilities more effectively in the future. In this Current Issues piece, we present a starting point for discussion, based on our experiences working to promote access to assistive technologies through inclusive and sustainable systems and policies.
Developing inclusive and resilient systems: COVID-19 and assistive technology
Emma M. Smith, Malcolm MacLachlan, Ikenna D. Ebuenyi, Catherine Holloway & Victoria Austin (2021) Developing inclusive and resilient systems: COVID-19 and assistive technology, Disability & Society, 36:1, 151-154, DOI:10.1080/09687599.2020.1829558
Developing inclusive and resilient systems: COVID-19 and assistive technology
Type
Editorial
Research Group
Social Justice
Assistive Technology (AT), for What?
Vicki Austin, Catherine Holloway
This year (2022) has seen the publication of the World’s first Global Report on Assistive Technology (GReAT) [1]. This completes almost a decade of work to ensure assistive technology (AT) access is a core development issue. The lack of access to assistive products (APs), such as wheelchairs, hearing aids, and eyeglasses, as well as less well-referenced products such as incontinence pads, mobile phone applications, or walking sticks, affects as many as 2.5 billion people globally. Furthermore, the provision of APs would reap a 1:9 return on investment [2]. This could result in a family in need netting (or living without) over GBP 100,000 in their lifetime [2] or more, if we count dynamic overspills in the economy such as employment of assistive technology services and manufacturing of devices [3].
Societies; 2021
Abstract
Assistive Technology (AT), for What?
Amartya Sen’s seminal Tanner lecture: Equality of What?began a contestation on social justice and human wellbeing that saw a new human development paradigm emerge—the capability approach (CA)—which has been influential ever since. Following interviews with leading global assistive technology (AT) stakeholders, and users, this paper takes inspiration from Sen’s core question and posits, AT for what?arguing that AT should be understood as a mechanism to achieve the things that AT users’ value. Significantly, our research found no commonly agreed operational global framework for (disability) justice within which leading AT stakeholders were operating. Instead, actors were loosely aligned through funding priorities and the CRPD. We suggest that this raises the possibility for (welcome and needed) incoming actors to diverge from efficiently designed collective action, due to perverse incentives enabled by unanchored interventions. The Global Report on Assistive Technology (GReAT) helps, greatly! However, we find there are still vital gaps in coordination; as technology advances, and AT proliferates, no longer can the device-plus-service approach suffice. Rather, those of us interested in human flourishing might explore locating AT access within an operational global framework for disability justice, which recognizes AT as a mechanism to achieve broader aims, linked to people’s capabilities to choose what they can do and be.
Assistive Technology (AT), for What?
Austin, V.; Holloway, C. Assistive Technology (AT), for What? Societies2022, 12, 169.https://doi.org/10.3390/soc120...
Assistive Technology (AT), for What?
Type
Article
Themes
Assistive & Accessible Technology
These tools help visually impaired scientists read data and journals
Alla Katsnelson
This article was featured in Nature and discusses tools that help visually impaired scientists read data and Journals. Innovation Manager, Daniel Hajas, was interviewed as part of this piece and highlights the need for an ecosystem approach, and access to data / visualisations for blind members of the research and science community.
Nature; 2023
Type
Editorial
Themes
Assistive & Accessible Technology
Research Group
Disability Interactions
The Digital and Assistive Technologies for Ageing initiative: learning from the GATE initiative
Chapal Khasnabis,Catherine Holloway, Malcolm MacLachlan
We are now in an era of assistive care and assistive living—whereby many people, of all ages, in good health, and those who are more frail, or with cognitive or functional impairments, are using a broad range of technologies to assist and enhance their daily living. Assistive living 1is becoming an important part of population health and rehabilitation, which can help to maximise an individual's abilities, regardless of age or functional capacity. This encouraging shift in ethos has been strengthened by the response to the COVID-19 pandemic, in which a plethora of digital and remote technologies have been used.
The Lancet; 2020
The Digital and Assistive Technologies for Ageing initiative: learning from the GATE initiative
Type
Editorial
Themes
Assistive & Accessible Technology
Culture and Participation
Research Group
Social Justice
Critical Junctures in Assistive Technology and Disability Inclusion
Dr Maria Kett,Catherine Holloway,Vicki Austin,Dr Maria Kett
It is clear from the events of the last 18 months that while technology has a huge potential for transforming the way we live and work, the entire ecosystem—from manufacturing to the supply chain—is vulnerable to the vagaries of that ecosystem, as well as having the potential to exacerbate new and existing inequalities [1]. Nowhere has this been more apparent than in the lives of people with disabilities, who make up around 15% of the world’s population and already face barriers to accessing education, employment, healthcare and other services [2]. Some of these barriers are a result of unequal access and opportunities. However, there is a growing movement to better understand how assistive technology systems and services can be designed to enable more robust and equitable access for all. As part of this growing movement, the Paralympic Games in Tokyo this autumn saw the launch of a new global campaign to transform the lives of the world’s 1.2 bn persons with disabilities: the ‘WeThe15’ campaign reached more than 4.5 billion people through its marketing and stands ready to be the biggest of its kind in history. Next year, the World Health Organization (WHO) and the United Nations Children’s Fund (UNICEF), AT scale and GDI Hub will publish the first World Report on Access to Assistive Technology, which will include research from the £20 million, UK Aid funded, GDI Hub-led, programme, AT2030. Ahead of that, in this Special Issue, we focus on how some events and situations—as diverse as the coronavirus pandemic and the Paralympics—can act as ‘critical junctures’ that can enable a rethink of the status quo to facilitate and promote change.
Sustainability; 2021
Critical Junctures in Assistive Technology and Disability Inclusion
Kett, M.; Holloway, C.; Austin, V. Critical Junctures in Assistive Technology and Disability Inclusion. Sustainability2021, 13, 12744.https://doi.org/10.3390/su1322...
Critical Junctures in Assistive Technology and Disability Inclusion
Type
Editorial
Themes
Assistive & Accessible Technology
Research Group
Disability Interactions
Introduction to the companion papers to the global report on assistive technology
Johan Borg, Wei Zhang, Emma M. Smith,Cathy Holloway
GReAT, but do we care?
If accessible, assistive technology would be life changing for a billion people across the world today – and two billion people in 2050 (WHO,2018). It would make the difference between independence and dependence, inclusion and exclusion, life and death. It holds the potential to improve and transform health, education, livelihood and social participation; fundamental human rights everyone is entitled to. And if we are lucky to grow old, the chances are that we all would use assistive technology by then. But do we care?
Assistive Technology, The Official Journal of RESNA; 2021
Introduction to the companion papers to the global report on assistive technology
Johan Borg, Wei Zhang, Emma M. Smith & Cathy Holloway (2021) Introduction to the companion papers to the global report on assistive technology, Assistive Technology, 33:sup1, 1-2, DOI:10.1080/10400435.2021.2003658
Introduction to the companion papers to the global report on assistive technology
Type
Toolkit
Innovate Now Toolkit
As an entrepreneur, learning how to solve problems by creating and experimenting with different strategies is a core pillar of the entrepreneurial mindset you need to succeed. However, there’s rarely a single correct way to solve problems as an entrepreneur, so you need to learn how to create and compare different solutions.
The open entrepreneurship toolkit is a set of learning materials that can help you and your team do just that. Covering the domains of user, product, market and business development, the set of cards have been designed to be used by two or more group members to actively experiment with different solutions.
Innovate Now
Type
PhD
Themes
Assistive & Accessible Technology
Research Group
Disability Interactions
Specifying a Hybrid, Multiple Material CAD System for Next Generation Prosthetic Design
Troy Bodkin
Doctoral Thesis. This work is one of four multidisciplinary research studies conducted by members of this research cluster, focusing on the area of Computer Aided Design (CAD) for improving the interface with Additive Manufacture (AM) to solve some of the challenges presented with improving prosthetic socket design, with an aim to improve and streamline the process to enable the involvement of clinicians and patients in the design process.
Loughborough University
Abstract
Specifying a Hybrid, Multiple Material CAD System for Next Generation Prosthetic Design
For many years, the biggest issue that causes discomfort and hygiene issues for patients with lower limb amputations have been the interface between body and prosthetic, the socket. Often made of an inflexible, solid polymer that does not allow the residual limb to breathe or perspire and with no consideration for the changes in size and shape of the human body caused by changes in temperature or environment, inflammation, irritation and discomfort often cause reduced usage or outright rejection of the prosthetic by the patient in their day to day lives. To address these issues and move towards a future of improved quality of life for patients who suffer amputations, Loughborough University formed the Next Generation Prosthetics research cluster. This work is one of four multidisciplinary research studies conducted by members of this research cluster, focusing on the area of Computer Aided Design (CAD) for improving the interface with Additive Manufacture (AM) to solve some of the challenges presented with improving prosthetic socket design, with an aim to improve and streamline the process to enable the involvement of clinicians and patients in the design process. The research presented in this thesis is based on three primary studies. The first study involved the conception of a CAD criteria, deciding what features are needed to represent the various properties the future socket outlined by the research cluster needs. These criteria were then used for testing three CAD systems, one each from the Parametric, Non Uniform Rational Basis Spline (NURBS) and Polygon archetypes respectively. The result of these tests led to the creation of a hybrid control workflow, used as the basis for finding improvements. The second study explored emerging CAD solutions, various new systems or plug-ins that had opportunities to improve the control model. These solutions were tested individually in areas where they could improve the workflow, and the successful solutions were added to the hybrid workflow to improve and reduce the workflow further. The final study involved taking the knowledge gained from the literature and the first two studies in order to theorise how an ideal CAD system for producing future prosthetic sockets would work, with considerations for user interface issues as well as background CAD applications. The third study was then used to inform the final deliverable of this research, a software design specification that defines how the system would work. This specification was written as a challenge to the CAD community, hoping to inform and aid future advancements in CAD software. As a final stage of research validation, a number of members of the CAD community were contacted and interviewed about their feelings of the work produced and their feedback was taken in order to inform future research in this area.
Cite
Specifying a Hybrid, Multiple Material CAD System for Next Generation Prosthetic Design
Bodkin, Troy L. (2017): Specifying a hybrid, multiple material CAD system for next-generation prosthetic design. Loughborough University. Thesis.https://hdl.handle.net/2134/25...;
Specifying a Hybrid, Multiple Material CAD System for Next Generation Prosthetic Design
Type
PhD
Themes
Assistive & Accessible Technology
Research Group
Disability Interactions
YouTransfer, YouDesign: A Participatory Approach to Design Assistive Technology for Wheelchair Transfers
Giulia Barbareschi
Doctoral Thesis. This thesis makes two contributions to facilitate wheelchair users’ engagement in the participatory design process for ATs, while being mindful of the burden of participation. The first contribution is a framework that provides a modular structure guiding the participatory design process from initial problem identification and analysis to facilitating collaborations between wheelchair users and designers. The framework identifies four factors determining the need and adoption process for ATs: (i) People focuses on the target population, (ii) Person includes personal characteristics, (iii) Activity refers to the challenges associated with the task, and (iv) Context encompasses the effect of the environment in which the activity takes place. The second contribution constitutes a rich picture of personal and external elements influencing real world wheelchair transfers that emerged from four studies carried out to investigate the effect of the framework factors on the design process for ATs.
UCL (University College London)
Abstract
YouTransfer, YouDesign: A Participatory Approach to Design Assistive Technology for Wheelchair Transfers
Transferring independently to and from their wheelchair is an essential routine task for many wheelchair users but it can be physically demanding and can lead to falls and upper limb injuries that reduce the person’s independence. New assistive technologies (ATs) that facilitate the performance of wheelchair transfers have the potential to allow wheelchair users to gain further independence. To ensure that users’ needs are addressed by ATs, the active involvement of wheelchair users in the process of design and development is critical. However, participation can be burdensome for many wheelchair users as design processes where users are directly involved often require prolonged engagement. This thesis makes two contributions to facilitate wheelchair users’ engagement in the participatory design process for ATs, while being mindful of the burden of participation. The first contribution is a framework that provides a modular structure guiding the participatory design process from initial problem identification and analysis to facilitating collaborations between wheelchair users and designers. The framework identifies four factors determining the need and adoption process for ATs: (i) People focuses on the target population, (ii) Person includes personal characteristics, (iii) Activity refers to the challenges associated with the task, and (iv) Context encompasses the effect of the environment in which the activity takes place. The second contribution constitutes a rich picture of personal and external elements influencing real world wheelchair transfers that emerged from four studies carried out to investigate the effect of the framework factors on the design process for ATs. A related outcome based on these contributions is a framing document to share knowledge between wheelchair users and designers to provide focus and promote an equal collaboration among participants.
Cite
YouTransfer, YouDesign: A Participatory Approach to Design Assistive Technology for Wheelchair Transfers
Barbareschi, Giulia. “YouTransfer, YouDesign : a Participatory Approach to Design Assistive Technology for Wheelchair Transfers / Giulia Barbareschi.” Thesis (Ph.D.)--University College London, 2018., 2018. Print.
YouTransfer, YouDesign: A Participatory Approach to Design Assistive Technology for Wheelchair Transfers
Type
PhD
Themes
Assistive & Accessible Technology
Research Group
Disability Interactions
Understanding wrist splint user needs and personalisation through codesign
Charlotte Pyatt
A Doctoral Thesis. Submitted in partial fulfilment of the requirements for the award of the degree of Doctor of Philosophy at Loughborough University.
Loughborough University
Abstract
Understanding wrist splint user needs and personalisation through codesign
Wrist splints are a common treatment for rheumatoid arthritis, however their effectiveness is compromised by patients not wearing splints as often as prescribed. Previous research has identified a number of reasons for non-compliance, but typically lacks insights that could lead to improved splint design.
This thesis investigates the motivators for patients to wear and not wear their wrist splints and, the impact of personalisation of splint appearance on patient wear. The work is based on the premise that digital design and manufacturing processes, such as Computer-Aided Design (CAD) and 3D Printing, can produce bespoke splints on demand.
The research begins with a literature review across the core areas of: splinting, additive manufacture, product appearance and personalisation. This literature review identifies gaps in knowledge from which research questions are established for the work.
The research employs a qualitative, generative design research approach and, follows a codesign framework employing telling, making and enacting tools. The thesis is made up of three studies. The first study is a sensitisation study and uses design probes to prepare the participants for the research and begin exploring the problem space. The second is a comprehensive study into participants splint wear behaviour and uses context mapping and scenario picture card tools to investigate the motivators for participants to wear and not wear wrist splints, along with positive and negative outcomes or wearing/not wearing splints. The final study uses a personalisation toolkit to elicit patient needs for a future wrist splint design and investigate self-reported expectations regarding compliance of patients who used the toolkit.
The research finds that patient compliance is affected by practical and aesthetic limitations of current splints. It identifies 4 motivating factors to wear a splint and 10 motivating factors to not wear a splint. Additionally, it identifies 6 positive outcomes of wearing splints, 6 negative outcomes of wearing splints, 3 positive outcomes of not wearing splints and 3 negative outcomes of not wearing splints. Requirements for an improved splint design are established and form the basis of the design for a prototype personalisation toolkit. Testing of this toolkit reveals that patients are keen to own more than one splint and personalise splints to match the scenario in which it is to be worn. Patients reported that they expected to be more compliant with a personalised splint when compared to their current splint.
Cite
Understanding wrist splint user needs and personalisation through codesign
Pyatt, Charlotte (2018): Understanding wrist splint user needs and personalisation through codesign. Loughborough University. Thesis.https://doi.org/10.26174/thesi...;
Understanding wrist splint user needs and personalisation through codesign
Type
PhD
Themes
Assistive & Accessible Technology
Shared Control for Wheelchair Interfaces
Dr Chinemelu Ejiamatu Muoma Ezeh
Doctoral Thesis. Independent mobility is fundamental to the quality of life of people with impairment. Most people with severe mobility impairments, whether congenital, e.g., from cerebral palsy, or acquired, e.g., from spinal cord injury, are prescribed a wheelchair. A small yet significant number of people are unable to use a typical powered wheelchair controlled with a joystick. Instead, some of these people require alternative interfaces such as a head- array or Sip/Puff switch to drive their powered wheelchairs. However, these alternative interfaces do not work for everyone and often cause frustration, fatigue and collisions. This thesis develops a novel technique to help improve the usability of some of these alternative interfaces, in particular, the head-array and Sip/Puff switch.
UCL (University College London)
Shared Control for Wheelchair Interfaces
Independent mobility is fundamental to the quality of life of people with impairment. Most people with severe mobility impairments, whether congenital, e.g., from cerebral palsy, or acquired, e.g., from spinal cord injury, are prescribed a wheelchair. A small yet significant number of people are unable to use a typical powered wheelchair controlled with a joystick. Instead, some of these people require alternative interfaces such as a head- array or Sip/Puff switch to drive their powered wheelchairs. However, these alternative interfaces do not work for everyone and often cause frustration, fatigue and collisions. This thesis develops a novel technique to help improve the usability of some of these alternative interfaces, in particular, the head-array and Sip/Puff switch. Control is shared between a powered wheelchair user, using an alternative interface and a pow- ered wheelchair fitted with sensors. This shared control then produces a resulting motion that is close to what the user desires to do but a motion that is also safe. A path planning algorithm on the wheelchair is implemented using techniques in mo- bile robotics. Afterwards, the output of the path planning algorithm and the user’s com- mand are both modelled as random variables. These random variables are then blended in a joint probability distribution where the final velocity to the wheelchair is the one that maximises the joint probability distribution. The performance of the probabilistic approach to blending the user’s inputs with the output of a path planner, is benchmarked against the most common form of shared control called linear blending. The benchmarking consists of several experiments with end users both in a simulated world and in the real-world. The thesis concludes that probabilistic shared control provides safer motion compared with the traditional shared control for difficult tasks and hard-to-use interfaces.
Ezeh, Chinemelu Ejiamatu Muoma. Shared Control for Wheelchair Interfaces. UCL (University College London), 2018. Print.
Type
PhD
Themes
Assistive & Accessible Technology
Research Group
Disability Interactions
Materials For Facial Prostheses In Resource Limited Countries
Sophia Esther Liiba Tetteh
A Doctoral Thesis. Submitted in partial fulfilment of the requirements for the award of the degree of Doctor of Philosophy of Loughborough University
Loughborough University
Abstract
Materials For Facial Prostheses In Resource Limited Countries
Facial prostheses are artificial devices that replace a missing body part in the facial and neck regions of the body. Defects or deformities in these regions can lead to functional deficiencies; social and psychological effects in addition to cosmetic defects. Restoration or rehabilitation in resource limited countries is usually provided by charities and organisations volunteering assistance overseas, with some training of local staff in the fabrication of these prostheses. Furthermore, these countries typically lack technical knowhow and trained personnel. In industrialised nations maxillofacial prosthetics has developed into a sophisticated medical speciality requiring highly skilled staff and expensive facilities. In resource limited countries surgical procedures may be an option for rehabilitation of these deformities/defects however, they tend to be unavailable or unaffordable and donated prostheses are not suitable. Hence, this research explores, from first principles, the appropriate and affordable local provision of maxillofacial prostheses in resource constrained regions. The investigation provides knowledge on identifying requirements for resource limited areas, resulting in the creation of a guideline constituting priorities, requirements and specifications. It further explores the viability of potentially cheaper, locally available candidate materials via weathering and antimicrobial methods in ascertaining material longevity.
Materials For Facial Prostheses In Resource Limited Countries
Tetteh, Sophia (2019): Materials for facial prostheses in resource-limited countries. Loughborough University. Thesis.https://doi.org/10.26174/thesi...;
Type
PhD
Themes
Assistive & Accessible Technology
Research Group
Disability Interactions
Exploring Thermal Discomfort Amongst Lower-Limb Prosthesis Wearers
Rhys James Williams
Thesis: Firstly, the research provides a methodological contribution showing how to conduct mixed-methods research to obtain rich insights into complex prosthesis phenomena. Secondly, the research highlights the need to appreciate psychological and contextual factors when researching prosthesis wearer thermal comfort. The research contributions are also converted into an implication for prosthesis design. The concept of 'regaining control' to psychologically mitigate thermal discomfort could be incorporated into technologies by using 'on-demand' thermal discomfort relief, rather than 'always-on' solutions, as have been created in the past.
UCL, ProQuest Dissertations Publishing
Abstract
Exploring Thermal Discomfort Amongst Lower-Limb Prosthesis Wearers
Amongst lower-limb prosthesis wearers, thermal discomfort is a common problem with an estimated prevalence of more than 50%. Overheating does not just create discomfort to the user, but it has been linked to excessive sweating, skin damage caused by a moist environment and friction. Due to impermeable prosthetic components and a warm moist environment, minor skin damage can result in skin infections that can lead to prosthesis cessation, increased social anxiety, isolation and depression. Despite the seriousness of thermal discomfort, few studies explore the issue, with research predominantly constrained to controlled laboratory scenarios, with only one out of laboratory study. In this thesis, studies investigate how thermal discomfort arises and what are the consequences of thermal discomfort for lower-limb prosthesis wearers. Research studies are designed around the principles of presenting lived experiences of the phenomenon and conducting research in the context of participants' real-life activities. A design exploration chapter investigates modifying liner materials and design to create a passive solution to thermal discomfort. However, this approach was found to be ineffective and unfeasible. Study 1 presents a qualitative study which investigates the user experience of a prosthesis, thermal discomfort and related consequences. Study 2 explores limb temperature of male amputees inside and outside the laboratory, with the latter also collecting perceived thermal comfort (PTC) data. Finally, Study 3 investigates thermal discomfort in the real-world and tracks limb temperature, ambient conditions, activities, and experience sampling of PTC. While there were no apparent relationships presented in sensor data, qualitative data revealed that in situations where prosthesis wearers perceived a lack of control, thermal discomfort seemed to be worse. When combined, the studies create two knowledge contributions. Firstly, the research provides a methodological contribution showing how to conduct mixed-methods research to obtain rich insights into complex prosthesis phenomena. Secondly, the research highlights the need to appreciate psychological and contextual factors when researching prosthesis wearer thermal comfort. The research contributions are also converted into an implication for prosthesis design. The concept of 'regaining control' to psychologically mitigate thermal discomfort could be incorporated into technologies by using 'on-demand' thermal discomfort relief, rather than 'always-on' solutions, as have been created in the past.
Exploring Thermal Discomfort Amongst Lower-Limb Prosthesis Wearers
Williams, Rhys James. “Exploring Thermal Discomfort Amongst Lower-Limb Prosthesis Wearers.” ProQuest Dissertations Publishing, 2020. Print.
Type
PhD
Themes
Assistive & Accessible Technology
Research Group
Disability Interactions
Design rules for additively-manufactured wrist splints
Sarah Kelly
A Doctoral Thesis. Submitted in partial fulfilment of the requirements for the award of the degree of Doctor of Philosophy of Loughborough University.
Loughborough University
Design rules for additively-manufactured wrist splints
Additive Manufacturing (AM) often known by the term three-dimensional printing (3DP) has been acknowledged as a potential manufacturing revolution. AM has many advantages over conventional manufacturing techniques; AM techniques manufacture through the addition of material - rather than traditional machining or moulding methods. AM negates the need for tooling, enabling cost-effective low-volume production in high-wage economies and the design & production of geometries that cannot be made by other means. In addition, the removal of tooling and the potential to grow components and products layer-by-layer means that we can produce more from less in terms of more efficient use of raw materials and energy or by making multifunctional components and products. The proposed Centre for Doctoral Training (CDT) in Additive Manufacturing and 3D Printing has the vision of training the next generation of leaders, scientists and engineers in this diverse and multi-disciplinary field. As AM is so new current training programmes are not aligned with the potential for manufacturing and generally concentrate on the teaching of Rapid Prototyping principles, and whilst this can be useful background knowledge, the skills and requirements of using this concept for manufacturing are very different. This CDT will be training cohorts of students in all of the basic aspects of AM, from design and materials through to processes and the implementation of these systems for manufacturing high value goods and services. The CDT will also offer specialist training on aspects at the forefront of AM research, for example metallic, medical and multi-functional AM considerations. This means that the cohorts graduating from the CDT will have the background knowledge to proliferate throughout industry and the specialist knowledge to become leaders in their fields, broadening out the reach and appeal of AM as a manufacturing technology and embedding this disruptive technology in company thinking. In order to give the cohorts the best view of AM, these students will be taken on study tours in Europe and the USA, the two main research powerhouses of AM, to learn from their international colleagues and see businesses that use AM on a daily basis. One of the aims of the CDT in AM is to educate and attract students from complementary basic science, whether this be chemistry, physics or biology. This is because AM is a fast moving area. The benefits of having a CDT in AM and coupling with students who have a more fundamental science base are essential to ensure innovation & timeliness to maintain the UK's leading position. AM is a disruptive technology to a number of industrial sectors, yet the CDTs industrial supporters, who represent a breadth of industrial end-users, welcome this disruption as the potential business benefits are significant. Growing on this industry foresight, the CDT will work in key markets with our supporters to ensure that AM is positioned to provide a real and lasting contribution & impact to UK manufacturing and provide economic stability and growth. This contribution will provide societal benefits to UK citizens through the generation of wealth and employment from high value manufacturing activities in the UK.
Design rules for additively-manufactured wrist splints
Kelly, Sarah (2020): Design rules for additively-manufactured wrist splints. Loughborough University. Thesis.https://doi.org/10.26174/thesi...;
Design rules for additively-manufactured wrist splints
Type
PhD
Themes
Assistive & Accessible Technology
Emotionally driven Prostheses: Exploring the Effects on Users’ Lives and Societies’ Attitudes in the UK and Greece
Anna Vlachaki
The literature shows that research into the aesthetic aspects of prostheses is limited. Although there are suggestions that prostheses with high levels of emotionally-driven design may improve users’ well-being, they are based only on theoretical findings. Therefore, in this thesis the effects of emotionally-driven prostheses on users’ lives and society’s attitudes were explored, with respect to culture and more specifically, the theories of individualism/ collectivism. In order to investigate the effects of culture, the research was conducted in two countries with different cultures; the UK (individualistic) and Greece (collectivistic). The thesis began with a literature review across three core areas: user, product and environment, and revealed the importance of investigating an additional area; that of prosthetists. The research employed a qualitative approach and consisted of four studies.
Loughborough University
Abstract
Emotionally driven Prostheses: Exploring the Effects on Users’ Lives and Societies’ Attitudes in the UK and Greece
The literature shows that research into the aesthetic aspects of prostheses is limited. Although there are suggestions that prostheses with high levels of emotionally-driven design may improve users’ well-being, they are based only on theoretical findings. Therefore, in this thesis, the effects of emotionally-driven prostheses on users’ lives and society’s attitudes were explored, with respect to culture and more specifically, the theories of individualism/ collectivism. In order to investigate the effects of culture, the research was conducted in two countries with different cultures; the UK (individualistic) and Greece (collectivistic). The thesis began with a literature review across three core areas: user, product and environment, and revealed the importance of investigating an additional area; that of prosthetists. The research employed a qualitative approach and consisted of four studies. Study I was an online questionnaire to explore users’ preferences towards prostheses, with respect to their culture. Study II consisted of semi-structured interviews and informational probes to comprehend the role of prostheses on users’ lives, with respect to prosthetic appearance. In Study III, the aim was to investigate prosthetists’ attitudes towards the needs of prosthetic users by conducting semi-structured interviews. Finally, Study IV was an online questionnaire to explore non-users’ attitudes towards the design of prostheses. The research showed that the use of prostheses for the completion of users’ body was not an adequate factor to improve their well-being, and a shift on users’ desires towards emotionally-driven prostheses has occurred. From the variables that were tested, sex, age, cause and area of limb-loss may affect people’s attitudes towards the design of prostheses. Furthermore, the results showed that prostheses with high emotionally-driven design evoked emotions, in both users and non-users, with higher levels of pleasantness and arousal than the emotions that were elicited by the prostheses of lower emotionally-driven designs and thus, they may trigger a greater behavioural reaction. This suggested that emotionally-driven prostheses may eliminate users’ stigmatisation by increasing their self-confidence and altering society’s attitudes. However, attention needs to be paid in collectivistic countries, as emotionally-driven prostheses may enhance users’ stigmatisation.
Emotionally driven Prostheses: Exploring the Effects on Users’ Lives and Societies’ Attitudes in the UK and Greece
Vlachaki, Anna (2020): Emotionally-driven prostheses: exploring the effects on users’ lives and societies’ attitudes in the UK and Greece. Loughborough University. Thesis.https://doi.org/10.26174/thesi...;
Type
Working Paper
Themes
Culture and Participation
Research Group
Disability Interactions
Barriers to Access and Retain Formal Employment for Persons with Disabilities in Bangladesh and Kenya
Nusrat Jahan andCatherine Holloway
This working paper was developed to support the development of challenge statements for a GDI Hub innovation challenge fund call related to improving access to and retention of employment for persons with disabilities in Kenya and Bangladesh and is written by GDI Hub's Nusrat Jahan andProfessor Catherine Holloway.
The issue of disability and employment has taken centre stage on the global arena in part because it is recognised across several areas of the United Nations Sustainable Development Goals, in which confrontation of extreme poverty in its many manifestations is the number one goal [2]. The World Health Organization (2011) reports about 15 percent of the world’s population has a disability [1]. In developing countries, 80 to 90 percent of people with disabilities of working age are unemployed.
Abstract
Barriers to Access and Retain Formal Employment for Persons with Disabilities in Bangladesh and Kenya
Globally persons with disabilities have lower employment rates compared to the general population due to systemic barriers particularly in the formal sector. In developing countries, 80 percent to 90 percent of people with disabilities of working age are unemployed. There has been limited research in low-income and middle-income countries focused on the barriers to access and retain formal employment for persons with disabilities. The aim of this paper, based on desk research, is to analyse the barriers to access and retain formal employment of persons with disabilities which are framed in three categories according to where the barriers primarily manifest: 1. In the workplace among employers and co-workers without disabilities, 2. Among persons with disabilities seeking or engaged in formal employment and 3. In the wider social, physical and policy environment. Although the study mainly focuses on Kenya and Bangladesh other countries’ literature on access to and retention of employment of persons with disabilities were reviewed where relevant. In the current context where the global pandemic is breaking barriers to remote working one part of the solution will be to empower persons with disabilities with appropriate access to Information and Communication Technology, assistive devices and services, digital skills, creating more accessible and inclusive digital platforms for persons with disabilities which also hold the potential to improve working conditions and productivity for the whole workforce as well as enhancing resilience to potential future shocks.
Barriers to Access and Retain Formal Employment for Persons with Disabilities in Bangladesh and Kenya
Jahan & Holloway, 2020, Barriers to Access and Retain Formal Employment for Persons with Disabilities in Bangladesh and Kenya, GDI Hub Working Paper Series Issue 01
Barriers to Access and Retain Formal Employment for Persons with Disabilities in Bangladesh and Kenya
Type
Editorial
Themes
Assistive & Accessible Technology
A right to the frivolous? Renegotiating a wellbeing agenda for AT research
Giulia Barbareschi& Tom Shakespeare
Assistive products (APs) are broadly defined as “ any product (including devices, equipment, instruments, and software), either specially designed and produced or generally available, whose primary purpose is to maintain or improve an individual’s functioning and independence and thereby promote their wellbeing” (Khasnabis et al.,2015). Although the concept of wellbeing is extremely slippery and researchers have yet to agree on a single definition for it, as individuals we instinctively develop mental models about what does, and does not, promote our happiness and wellbeing. Considerations about values, wellbeing and happiness are extremely personal and are shaped by a variety of factors ranging from our age and socio-cultural background to our life experiences (Schwartz & Bardi,2001).
RESNA
Abstract
A right to the frivolous? Renegotiating a wellbeing agenda for AT research
Assistive products (APs) are broadly defined as “ any product (including devices, equipment, instruments, and software), either specially designed and produced or generally available, whose primary purpose is to maintain or improve an individual’s functioning and independence and thereby promote their wellbeing” (Khasnabis et al.,2015). Although the concept of wellbeing is extremely slippery and researchers have yet to agree on a single definition for it, as individuals we instinctively develop mental models about what does, and does not, promote our happiness and wellbeing. Considerations about values, wellbeing and happiness are extremely personal and are shaped by a variety of factors ranging from our age and socio-cultural background to our life experiences (Schwartz & Bardi,2001).
However, when it comes to assistive technology (AT) research, our focus seems to be primarily geared toward values and activities in the domains of education, employment, transport or health, often framed according to an outcome driven perspective that is heavily influenced by what is seen as useful (often what is measurable), vs what is frivolous (less tangible social or emotional aspects).
This disparity parallels the priorities of the disability rights movement and disability studies research that have helped to shape the research agenda around disability and AT. Often influenced by labor movement politics, or feminism, there appears to have been more concern with public and practical aspects of social life as opposed to the more private and sensitive ones (Shakespeare,2014). The focus on the public utilitarian function of AT becomes even more evident when we consider AT research carried out in the Global South. In this context the success of an intervention is usually assessed using measures of outcome and impact which can be somehow linked to economic improvement (Alkire,2016).
In this editorial, we are not suggesting that enabling people with disabilities to gain a good education, obtain a fulfilling job or be able to vote are not important goals for the APs we develop and research. But are those the only worthwhile goals? Should we not also enquire whether existing and future APs could help people with disabilities to develop meaningful friendships, enjoy fulfilling sex lives with their partners of choice, cook sociable dinners, or engage in their favorite hobbies? Although sporadic publications focus on the role of APs in the context of personal relationships, sexuality, or fun and play for people with disabilities do exist, these are rare, and often framed around utilitarian goals. For example, research around AT and play is largely focused on children and often examined in connection to learning outcomes. Similarly, sex and sexuality are often explored solely in connection to dysfunction, abuse or sexual health (Shakespeare & Richardson,2018).
These unbalanced narratives show how the AT research agenda is dictated by a set of universal priorities that are largely focused on global measurable goals that do not necessarily match the everyday values of people with disabilities. We invite researchers and practitioners to consider ways to find a better balance between public and private aspects of life, and between utilitarian and emotional values. Both approaches have a significant impact on the lives of people with disabilities.
Ultimately, as AT researchers we need to actively engage with people with disabilities to uncover their priorities, understand what different people with disabilities most value in life, and identify how current and future APs might help to make a positive impact on wellbeing. Aspects of life such as friendship, socialization, sexuality, love and play might indeed be more frivolous than practical ones such as education, health, employment and civil rights, but they are inherent to our shared humanity and fundamental to our happiness.
Cite
A right to the frivolous? Renegotiating a wellbeing agenda for AT research
Giulia Barbareschi & Tom Shakespeare (2021) A right to the frivolous? Renegotiating a wellbeing agenda for AT research, Assistive Technology, 33:5, 237, DOI:10.1080/10400435.2021.1984112
| https://www.disabilityinnovation.com/publications?page=4&type=article+working-paper+editorial+toolkit+phd |
2023 Mazda CX-50 S specifications, technical data, performance
2023 Mazda CX-50 S - full technical specs sheet, including performance data, economy and emissions, dimensions, weight and engine particulars.
Mazda CX-50 S , 2023 MY US
CX-50
This car has a 5 door suv/sports utility vehicle body style with a front mounted engine driving through all four wheels.
It's powered courtesy of a naturally aspirated engine of 2.5 litre capacity. This powerplant features double overhead camshaft valve gear, 4 cylinder layout, and 4 valves per cylinder. It has an output of 187 bhp (190 PS/139 kW) of power at 6000 rpm, and maximum torque of 252 N·m (186 lb·ft/25.7 kgm) at 4000 rpm.
The engine transmits power to the wheels via a 6 speed automatic gearbox.
It weighs a claimed 1681 kg at the kerb. Full specs
Key facts
What body style? 5 door suv/sports utility vehicle with 4/5 seats How long? 4719 mm How heavy? 1681 kg What drivetrain? naturally aspirated petrol What size engine? 2.5 litre, 2488 cm 3 How many cylinders? 4, Straight How much power? 190 PS / 187 bhp / 139 kW @ 6000 rpm How much torque? 252 Nm / 186 ft.lb / 25.7 kgm @ 4000 rpm How economical? 24/30/27 US MPG EPA city/highway/combined
2023 Mazda CX-50 S
2023 Mazda CX-50 S Language Français Deutsch Nederlands Italiano Español English Applicable to the USA domestic market(s). Carrosserie Carrosserie 4/5 seater suv/sports utility vehicle Nombre de portes 5 Designer Dimensions et poids Empattement 2814 110.8 Voies AV Voies AR Longueur 4719 185.8 Largeur 1920 75.6 Hauteur 1613 63.5 Garde au sol 211 8.3 1.68 Poids avec pleins 1681 kg 3706 Répartition poids AV Réservoir à essence 60.2 litres 13.2 [15.9] UK [US] gal. Caractéristiques aérodynamique Coefficient de pénétration maître-couple SCx naturally aspirated petrol Constructeur du moteur Mazda Type moteur Cylinders Straight 4 Cylindrée 2.5 litre 2488 cc (151.827 cu in ) Alésage × Course 89 × 100 mm 3.5 × 3.94 in Rapport alésage / course 0.89 Distribution double overhead camshaft (DOHC) 4 Soupapes par cylindre 16 Total vannes Puissance maximale 190 PS (187 bhp ) (139 kW ) à 6000 tr/mn Couple maximale 252 Nm (186 ft·lb ) (25.7 kgm ) à 4000 tr/mn Specific output 56 kW/litre 76.2 ps/litre 75.2 bhp/litre 1.23 bhp/cu in 101.29 Nm/litre 1.22 ft·lb/cu 3 Construction carter Carter humide Taux de compression 13:1 Carburant direct petrol injection bmep (brake mean effective pressure) 1272.8 kPa (184.6 psi ) Régime maximal 6500 tr/mn Nombre de paliers de vilebrequin 5 Refroidissement Water Cylindrée Unitaire 622 cc Aspiration Normal Compressor N/A Intercooler None Catalyseur Y Performances 0-80km/h 0-60mph 0-100km/h 0-160km/h 0-400m 0-1000m Vitesse Power-to-weight ratio Higher is better 112.79 PS/tonne (1000 kg ) 0.11 PS/kg 82.95 kW/tonne (1000 kg ) 0.08 kW/kg 111.24 bhp/tonne (1000 kg ) 0.11 bhp/kg 0.05 bhp/lb Weight-to-power ratio Lower is better 12.05 kg/kW 20.14 lb/bhp Consommation Consommation 24/30/27 US MPG EPA city/highway/combined universal fuel consumption (calculated from the above) litres/100km 9.8/7.8/8.7 l/100km city/highway/combined km/litre 10.2/12.8/11.5 km/l city/highway/combined UK MPG 28.8/36.0/32.4 UK MPG city/highway/combined US MPG 24.0/30.0/27.0 US MPG city/highway/combined Emissions de CO₂ Carfolio Calculated CO 2 ? VED band (UK) CO 2 Effizienz (DE) Châssis Emplacement de moteur front Engine layout transverse Traction all wheel drive Répartition du couple Direction turns lock-to-lock 2.700 Turning circle Suspension AV Suspension AR Roues AV 7J x 17 Roues AR 7J x 17 Pneumatiques AV 226/65 R 17 Pneumatiques AR 226/65 R 17 Freins AV/AR VeDi/Di-S-ABS Diamètre des freins AV 326 mm Diamètre des freins AR 325 mm Braked area Transmission 6 Rapport de démultiplication supérieure 0.6 Rapport de pont 4.37 Généralités Carfolio.com ID 775236 Production total Type mines RAC rating 19.6 Insurance classification No information available Tax band No information available 2023 Mazda CX-50 S added 2022-11-15. Last modified 2022-11-18.
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AIM25 collection description
Records of Saint George's Hospital including admission and discharge registers, fever ward admission books, high dependency unit admission books, regi...
SAINT GEORGE'S HOSPITAL
Identity Statement
Reference code(s) : H68/SG Held at : London Metropolitan Archives Click here to find out how to view this collection at https://www.cityoflondon.gov.uk/lma › Full title : SAINT GEORGE'S HOSPITAL Date(s) : 1827-1998 Level of description : Collection Extent : 8.28 linear metres Name of creator(s) : St George's Hospital | London
Context
Administrative/Biographical history:
Saint George's Hospital opened in 1733 at Lanesborough House, Hyde Park Corner. It owes its existence to four men, Henry Hoare, William Wogan, Robert Witham and the Reverend Patrick Cockburn, who collectively founded the Westminster Public Infirmary in Petty France in 1720. The ever increasing needs of the sick forced the Westminster Public Infirmary to seek improved and enlarged premises. A disagreement between members of both the Governors and medical staff on the choice of building led to the founding of both Westminster Hospital in Castle Lane and Saint George's Hospital on Hyde Park Corner.
In 1735, Saint George's Hospital purchased the freehold of Lanesborough House, two adjoining houses and two acres of land. Under the direction of Isaac Ware of the Board of Works, the hospital was enlarged to accommodate 200 patients. By 1825 the hospital was falling into disrepair. A competition was held for the design of a new hospital. It was won by William Wilkins, and the new building was opened at Hyde Park Corner in 1829.
Since its foundation, Saint George's Hospital has been training medical students. In 1834, a medical school was established in Kinnerton Street and it was incorpotated into the hospital in 1868.
Just before the beginning of the Second World War, it was decided that Saint George's needed to be rebuilt on its Hyde Park Corner site. The plan was however abandoned by the commencement of hostilities. During the War, against a background of the population shift from central London, discussions took place which paved the way for Saint George's to be rebuilt and transferred out of the city centre.
With the introduction of the National Health Service in 1948, the hospital became part of the Saint George's Hospital Teaching Group of the South West Metropolitan Regional Hospital Board. Soon after, the Board of Governors persuaded Aneurin Bevan, the Minister of Health, that the new hospital should be built on the Grove Fever Hospital and Fountain Hospital sites in Tooting. Patients began to be admitted into the Grove Hospital in 1951 and, by 1953, the Grove Hospital was designated to Saint George's and responsibility for it was transferred from the Wandsworth Hospital Group to the Board of Governors of Saint George's. The Fountain Children's Hospital site adjacent to the Grove Hospital was added to the land available for the Saint George's Hospital redevelopment when the Fountain transferred to Queen Mary's Hospital, Carshalton. The building of the new Saint George's at Tooting began in 1973.
Following the reorganisation of the National Health Service in 1974, the Board of Governors was disbanded, and the responsibility for Saint George's Hospital was passed to the Wandsworth and Merton District of the Merton, Sutton and Wandsworth Area Health Authority. South West Thames Regional Health Authority assumed responsibility for the rebuilding of the new Saint George's. The first phase of the new Saint George's Hospital Medical School opened in 1976. Lanesborough Wing, the first of the ward blocks opened in 1980. The same year marked the closure of Saint George's Hospital at Hyde Park Corner.
In 1993, Saint George's Hospital came under the control of Saint George's Healthcare NHS Trust.
The hospital has been administered by the following:
1733-1948: Saint George's Hospital
1948-1974: Saint George's Hospital Teaching Group of South West Metropolitan Regional Hospital Board
1974-1982: Merton, Sutton and Wandsworth Area Health Authority of South West Thames Regional Hospital Board
1982-1993: Wandsworth District Health Authority of South West Thames Regional Hospital Board
1993- : Saint George's Healthcare NHS Trust.
Content
Scope and content/abstract:
Records of Saint George's Hospital including admission and discharge registers, fever ward admission books, high dependency unit admission books, registers of maternity patients, death registers, deaths under anaesthetic registers, post mortem and case books, post mortem examination books, case books, registers of anaesthetics and operations, operating theatre lists, porters accident books, casualty registers, registers of transfers from casualty, brandy book, book of patient sayings, registers of officers and servants, registers of nurses, registers of probationary nurses, registers of candidates for nursing posts, registers of nurses leaving the hospital, registers of sick leave and special leave, officers' signature books, lists of the number of operations carried out by surgeons, papers and correspondence relating to staff matters, staff certificates, staff reminiscences, staff handbooks and rules, baptism registers.
Administrative, financial and other records are uncatalogued as of February 2012, please see staff for further details.
Access & Use
Language/scripts of material:English.
System of arrangement:
These records are arranged as follows:
H68/SG/B/01 Patients' records: admission and discharge registers;
H68/SG/B/02 Patients' records: fever ward admission books;
H68/SG/B/03 Patients' records: high dependency unit admission books;
H68/SG/B/04 Patients' records: registers of maternity patients;
H68/SG/B/05 Patients' records: death registers;
H68/SG/B/06 Patients' records: deaths under anaesthetic registers;
H68/SG/B/07 Patients' records: post mortem and case books;
H68/SG/B/08 Patients' records: post mortem examinations;
H68/SG/B/09 Patients' records: case books;
H68/SG/B/10 Patients' records: registers of anaesthetics and operations;
H68/SG/B/11 Patients' records: operating theatre lists;
H68/SG/B/12 Patients' records: porters accident books;
H68/SG/B/13 Patients' records: casualty registers;
H68/SG/B/14 Patients' records: registers of transfers from casualty;
H68/SG/B/15 Patients' records: brandy books;
H68/SG/B/16 Patients' records: books of patient sayings;
H68/SG/C/01 Staff records: registers of officers and servants;
H68/SG/C/02 Staff records: registers of nurses;
H68/SG/C/03 Staff records: registers of probationary nurses;
H68/SG/C/04 Staff records: registers of candidates for nursing posts;
H68/SG/C/05 Staff records: registers of nurses leaving the hospital;
H68/SG/C/06 Staff records: registers of sick leave and special leave;
H68/SG/C/07 Staff records: officers' signature books;
H68/SG/C/08 Staff records: lists of the number of operations carried out by surgeons;
H68/SG/C/09 Staff records: papers and correspondence;
H68/SG/C/10 Staff records: certificates;
H68/SG/C/11 Staff records: reminiscences;
H68/SG/C/12 Staff records: handbooks and rules;
H68/SG/G/01 Chaplain: registers of baptisms.
Conditions governing access:
These records are available for public inspection, although records containing personal information are subject to access restrictions under the UK Data Protection Act, 1998.
Conditions governing reproduction:
Copyright to this collection rests with the depositor.
Finding aids:
Please see online catalogues at:http://search.lma.gov.uk/opac_lma/index.htm
Archival Information
Archival history:
Immediate source of acquisition:
Records deposited in 1996, 2005 and 2007.
Allied Materials
Related material:
See also South West Metropolitan Regional Hospital Board (LMA/4431/A), South West Thames Regional Health Authority (LMA/4431/B), South Thames Regional Health Authority (HA/ST).
Further records of the hospital are held at the Wellcome Library and Royal College of Surgeons. Post mortem reports, and papers relating to Sir Benjamin Collins Brodie, Surgeon; John Hunter, anatomist and surgeon; Saint George's Hospital Whist Club; Saint George's Hospital Hunterian Society (formerly Medical and Surgical Society) and Saint George's Hospital Medical School Library are held at Saint George's, University of London.
Publication note:
Description Notes
Archivist's note:
Rules or conventions
:
Compiled in compliance with General International Standard Archival Description, ISAD(G), second edition, 2000; National Council on Archives Rules for the Construction of Personal, Place and Corporate Names, 1997.
Date(s) of descriptions:February 2012.
Medical%20sciences Medical sciences
Nursing Nursing
| https://aim25.com/cgi-bin/vcdf/detail?coll_id=19207&inst_id=118&nv1=search |
(PDF) INTRODUCTION. CONSERVATION, TOURISM, AND IDENTITY OF CONTEMPORARY COMMUNITY ART
PDF | After the Mexican Revolution of the twentieth century, a new concept of nation was created, which therefore required a new identity. In this... | Find, read and cite all the research you need on ResearchGate
Chapter
PDF Available
INTRODUCTION. CONSERVATION, TOURISM, AND IDENTITY OF CONTEMPORARY COMMUNITY ART
January 2017
In book: CONSERVATION, TOURISM, AND IDENTITY OF CONTEMPORARY COMMUNITY ART (pp.1-19)
Publisher: Apple Academic Press
Editors: Santamarina-Campos, Virginia Carabal-Montagud, María Ángeles DE-Miguel-Molina, María De-Miguel-Molina, Blanca De-Miguel-Molina
Authors:
Virginia Santamarina-Campos
Universitat Politècnica de València
María Ángeles Carabal-Montagud
Universitat Politècnica de València
María De-Miguel-Molina
Universitat Politècnica de València
Stephan Kröner
Universitat Politècnica de València
Abstract and Figures
After the Mexican Revolution of the twentieth century, a new concept of nation was created, which therefore required a new identity. In this democratizing movement, the participation of the artists played a key role, redefining a new concept of art, using the murals as a communication channel 2with the population. This movement crosses the Mexican boundaries through the muralist Siqueiros (Informant 1), who called the new American generation of artists, inviting them to construct a monumental, human, public, and identitarian art.
Demetrio Urruchúa, Amalia Polleri, Carmen Garayalde and María Rosa de Ferrari. The man's partner, 1941 (detail) library from the Artiga Professors Institute, Montevideo. Social Realism. Source: Graphical record of the R&D Project PUCM, 2010. …
Norberto Berdía. San Rafael Casino-Hotel.1948. Punta del Este. Social realism. Source: Graphical record of the R&D Project PUCM, 2010. …
Norberto Berdía. Press Freedom, 1953. El Pais, Montevideo. Social realism. Source: Graphical record of the R&D Project PUCM, 2013. …
Luis Mazzey and Carlos González. Works of ANCAP, 1949. ANCAP Building. Montevideo. Social Realism. Source: Graphical record of the R&D Project PUCM, 2011. …
Augusto Torres. Constructivism in sand stone, 1964. Montevideo. Constructivism. Source: Graphical record of the R&D Project PUCM, 2013. …
Figures - uploaded by
Virginia Santamarina-Campos
Author content
Content may be subject to copyright.
Content uploaded by Virginia Santamarina-Campos
CONSERVATION, TOURISM, AND
IDENTITY OF CONTEMPORARY
COMMUNITY ART
A Case Study of Felipe Seade’s Mural
“Allegory to Work”
Edited by
Virginia Santamarina-Campos, PhD
Mar í a Á ngeles Carabal-Montagud, PhD
Mar í a De Miguel-Molina, PhD
Blanca De Miguel-Molina, PhD
mural “Allegory to work” / edited by Virginia Santamarina Campos, PhD, María Ángeles Carabal
Montagud, PhD, María de Miguel Molina, PhD, Blanca De Miguel Molina, PhD.
Includes bibliographical references and index.
Issued in print and electronic formats.
ISBN 978-1-77188-401-3 (hardcover).--ISBN 978-1-315-20958-6 (PDF)
1. Seade, Felipe, 1912-1969. Alegoría al trabajo. 2. Mural painting and decoration--Conservation and
restoration--Uruguay--Case studies. 3. Cultural property--Conservation and restoration--Uruguay--Case
studies. 4. Social realism--Uruguay--Case studies. 5. Art and society--Uruguay--Case studies. 6. Art and
globalization--Uruguay--Case studies. 7. Sustainable tourism--Uruguay--Case studies. 8. Hospitality
industry--Uruguay--Case studies. I. Carabal Montagud, María Ángeles, editor II. Santamarina Campos,
Virginia, editor III. Miguel Molina, María de, editor IV . Miguel Molina, Blanca de, editor
ND429.S43A44 2017 759.9895 C2017-905556-9 C2017-905557-7
Library of Congress Cataloging-in-Publication Data
Names: Santamarina Campos, Virginia, editor . | Uruguay. Comisiâon del Patrimonio Cultural de la
Naciâon. | Universidad Politâecnica de V alencia.
Title: Conservation, tourism, and identity of contemporary community art : a case study of Felipe
Seade’s mural “Allegory to work” / editors: V irginia Santamarina Campos, María Ángeles Carabal
Montagud, María de Miguel Molina, Blanca De Miguel Molina.
Description: Toronto; W aretown, NJ : Apple Academic Press, 2018. | Includes bibliographical references
and index.
Identiers: LCCN 2017037302 (print) | LCCN 2017042123 (ebook) | ISBN 9781315209586 (ebook) |
ISBN 9781771884013 (hardcover : alk. paper)
Subjects: LCSH: Art and society--Uruguay--Case studies. | Heritage tourism--Uruguay--Case studies. | Mu -
ral painting and decoration, Uruguayan--Conservation and restoration--Uruguay--Colonia del Sacramento.
| Seade, Felipe, 1912-1969. Alegorâi al trabajo.
Classication: LCC N72.S6 (ebook) | LCC N72.S6 C5924 2018 (print) | DDC 701/.03--dc23
LC record available at https://lccn.loc.gov/2017037302
Apple Academic Press also publishes its books in a variety of electronic formats. Some content that appears in print may
not be available in electronic format. For information about Apple Academic Press products, visit our website at www.
appleacademicpress.com and the CRC Press website at www .crcpress.com
About the Editors......................................................................................... ix
List of Contributors .................................................................................. xiii
List of Abbreviations ...................................................................................xv
Acknowledgments ..................................................................................... xvii
Introduction ................................................................................................ 1
V . Santamarina-Campos, M. Á. Carabal-Montagud,
M. De-Miguel-Molina, and S. Kröner
PAR T I: CONTEMPORARY MURAL AND FELIPE SEADE ................... 21
1. Contemporary Uruguayan Mural Painting,
Tradition, and Relevance .........................................................................23
A. E. Sánche z-Guillén and A. A. Berriel-Benvenuto
2. Social Realism in Contemporary Mural Painting ................................. 49
V . Santamarina-Campos
3. Felipe Seade as the Main Figure of the Uruguayan Social Realism ....... 65
M. Fernández-Oscar, V . Santamarina-Campos,
M. Á. Carabal-Montagud, and M. J. Guirado-Ruano
4. The Contemporary Mural Painting “Allegory to Work” ..................... 79
M. Á. Carabal-Montagud, V . Santamarina-Campos,
M. Fernández-Oscar, and M. J. Guirado-Ruano
PAR T II: ETHNOGRAPHIC RESEARCH OF THE P AINTING
“ALLEGORY T O WORK” .................................................................... 93
5. “On the Face of It”: Wall-to-W all Home Ethnography ......................... 95
J. Skinner
CONTENTS
vi Contents
6. Participatory Action Research (P AR) in Contemporary
Community Art ....................................................................................... 105
V . Santamarina-Campos, E. M. Martínez-Carazo,
M. Á. Carabal-Montagud, and M. De-Miguel-Molina
P ART III: SCIENTIFIC RESEARCH OF THE PAINTING
“ALLEGORY T O WORK” .................................................................. 137
7. PhysicalIdenticationandDigitalRecordofPainting ...................... 139
J. C. V alcárcel-Andrés, M. Fernández-Oscar, E. M. Martínez-Carazo,
and M. Sánchez-Pons
8. Colorimetric Characterization .............................................................. 163
M. L. Martínez-Bazán, M. Fernández-Oscar, D. J. Yusá-Marco,
and E. M. Martínez-Carazo
9. Study of the Chemical Composition Through Cross Sections:
Optical Microscopy, Scanning Electr on Microscopy, and
X-Ray Microanalysis .............................................................................. 181
D. J. Yus á-Marco, X. Mas-i-Barberà, M. Fernández-Óscar ,
and M. J. Guirado-Ruano
10. T echnical Documentation Sheet of Painting:
ScienticCataloging ................................................................................ 195
M. Sánchez-Pons, M. Fernández-Oscar, J. C. V alcárcel-Andrés,
and M. L. Martínez-Bazán
P ART IV : INTERVENTION PROCESS OF THE PAINTING
“ALLEGORY T O WORK” .................................................................. 209
11. State of Conservation ............................................................................. 211
J. L. Regidor-Ros, M. A. Zalbidea-Muñoz, and M. Fernández-Oscar
12. Restoration Process ................................................................................ 225
M. A. Zalbidea-Muñoz, J. L. Regidor-Ros, V . Muhvich Meirelles,
and A. R. Benítez Alcieri
P ART V : MUSEOGRAPHIC AREA AND SUSTAINABLE
TOURISM OF THE P AINTING “ALLEGORY TO WORK” .......... 255
13. The Use and Social Enjoyment of Murals: ‘The People’s Art,’
Its Publics and Cultural Heritage ......................................................... 257
S. Carden
Contents vii
14. Preventive Conservation Policies .......................................................... 271
X. Mas-i-Barberà, M. Sánchez-Pons, and J. Osca-Pons
15. Guidelines to Stimulate Use and Social Enjoyment ............................ 283
M. De-Miguel-Molina, B. De-Miguel-Molina, and
M. V . Segarra-Oña
Conclusions: Management, T ouristic Promotion, and Social
Enjoyment of Contemporary Mural Painting ..................................... 301
V . Santamarina-Campos, M. Á. Carabal-Montagud,
M. De-Miguel-Molina, and B. De-Miguel-Molina
Index ......................................................................................................... 317
INTRODUCTION
V. SANTAMARINA-CAMPOS 1 , M. Á . CARABAL-MONTAGUD 2 ,
M. DE-MIGUEL-MOLINA, 3 and S. KR Ö NER 4
1 Associate Professor , Research Micro-Cluster Globalization,
T ourism and Heritag e, Department of Conservation and Restoration
of Cultural Heritage, UPV , 3N Building, Camino de V era s/n,
46022 V alencia, Spain, T el.: +34-963879314/79414,
E-mail: virsanca@upv .es
2 Associate Professor , Research Micro-Cluster Globalization,
T ourism and Heritage, Department of Conservation and Restoration
of Cultural Heritage, UPV , 3N Building, Camino de V era S/N,
46022 V alencia, Spain, T el.: +34-963877000/73132,
E-mail: [email protected] .es
3 Associate Professor , Research Micro-Cluster Globalization, T ourism
and Heritage, Department of Management, UPV , Camino de Vera,
S/N, 46022, V alencia, Spain, T el.: +0034963877680/76821,
Ext. 76844, E-mail: [email protected] .es
4 External Staff, Department of C onservation and Restoration of
Cultural Heritage, Polytechnic Univ ersity of Valencia. Camino de
Vera S/N, 46022 V alencia, Spain, T el.: +34-664711624,
E-mail: [email protected]
After the Mexican Revolution of the twentieth century, a new concept of
nation was created, which therefore required a new identity. In this democ -
ratizing movement, the participation of the artists played a key role, rede-
fining a new concept of art, using the murals as a communication channel
2 Conservation, Tourism, and Identity of Contemporary Community Art
with the population. This movement crosses the Mexican boundaries
through the muralist Siqueiros (Informant 1), who called the new Ameri-
can generation of artists, inviting them to construct a monumental, human,
public, and identitarian art.
As a result, in the Southern Cone we nd a huge muralist production
along the twentieth century that reects a subversion to the international
art conceptions and shows local contents, favoring an esthetics based on a
nationalism with equalitarian tendencies and interpreting reliably their cul-
tural origins. It leads to murals with artistic and historic qualities related to
social realism, constructivism, and formal tradition, painted by an exclu-
sive minority of artists, and located in indoor and centralized places, linked
to the ‘high culture’ (Figures 1–6). This nonconformist character can be
reected not only at the concept level, but also at a technological one with
an experimentation period where traditional techniques are substituted by
new procedures and commercial products (Figure 7).
FIGURE 1 Demetrio Urruchúa, Amalia Polleri, Carmen Garayalde and María Rosa
de Ferrari. The man’s partner , 1941 (detail) library from the Artiga Professors Institute,
Montevideo. Social Realism. Source: Graphical record of the R&D Project PUCM, 2010.
Introduction 3
FIGURE 2 Norberto Berdía. San Rafael Casino-Hotel.1948. Punta del Este. Social
realism. Source: Graphical record of the R&D Project PUCM, 2010.
FIGURE 3 Norberto Berdía. Press Freedom, 1953. El Pais, Montevideo. Social realism.
Source: Graphical record of the R&D Project PUCM, 2013.
4 Conservation, Tourism, and Identity of Contemporary Community Art
Nowadays, in Uruguay there is a lack of resources and training in heritage
management, whose consequence is the loss of conscience about the symbolic
dimension of these murals, forgetting their social purpose, and increasing their
deterioration due to the absence of social interest as their values being mani -
festations of cultural practices are unknown. As Bulanti (2008:57), one of the
principal researchers on these topics, points out ‘our country should analyze in
profound the esthetic signicance of these murals.’ Moreover, following this
idea, Hugo Achúgar (2001:73), in relation to the mural artists who started their
activity with the encouragement of Siqueiros, wrote:
‘What happened with all of them? They are dead, forgotten. It is not
worth to remember their names. The people who will read this autobiogra-
phy would not have any idea about who they were. They would not know
if they were painters or poets. They would not know that those days they
were fundamental actors of the Uruguayan art or at least they thought it.’
FIGURE 4 Luis Mazzey and Carlos González. W orks of ANCAP , 1949. ANCAP
Building. Montevideo. Social Realism. Source: Graphical record of the R&D Project
PUCM, 2011.
Introduction 5
T o this complexity, we have to add the difculty of facing the con -
servation of these works, as many of them were painted with exper -
imental materials that have generated complex problems difcult to
manage. Finally, the lack of restoration specialists and the nonexis -
tence of a regulation for this profession, have allowed professional
intrusiveness and, therefore, inadequate interventions. This fact can
be contrasted in the following transcript found at the National General
Archive:
Issue: The Assistance Centre of the Medical Union of Uruguay
(CASMU) requests to the National Cultural Heritage Committee of
the Education and Culture Ministry of the Oriental Republic of Uru -
guay the restoration of the mural painted by Augusto Torres that was
declared as National Historic Monument (decision no. 128/998), and
located at the CASMU Sanitarium no. 1, Floor 2, Arenal Grande and
Colonia Street. Signed by Raúl Germán Rodríguez (Accountant of the
FIGURE 5 Augusto T orres. Constructivism in sand stone, 1964. Montevideo.
Constructivism. Source: Graphical record of the R&D Project PUCM, 2013.
6 Conservation, Tourism, and Identity of Contemporary Community Art
Board of Directors), 23th June, 2008. The transcript includes the report
of Miguel Umpiérrez, Head of the Restoration Department at CCHN-
ECM, explaining the impossibility of succeed to the restoration due to
the reduced staff that have and the tasks priorities pending and recom -
mending the request to a private company, but taking into account some
guidelines:
1. to control if the damage zone is dried, to consolidate the existing
paint and to repair the missing areas.
2. to consolidate the crackles since they will become firmed.
3. to clean totally the mural from all the existing dirties, especially
oil, as it has to be cleaned carefully.
4. to use varnish retouching in the entire surface to separate the new
reintegration of color.
5. final protective varnish.
FIGURE 6 Edwin Studer . Sand Stone Mural with surface for a building in Juan María
Pérez and Ellauri, 1956. Montevideo, Uruguay. Constructivism. Sour ce: Graphical record
of the R&D Project PUCM, 2010.
Introduction 7
In addition, they request that the company that will conduct the restora-
tion send a descriptive report of the works to be done, so that the depart-
ment could audit them, as it is a National Historical Monument (Transcript
no. 2008.11.008–316/08, 24 June, 2008).
The last document includes the decision from the CCHN-ECM, signed
by the Director Alberto Quintela and the Architect Renée Fernández,
approving the report from the Restoration Atelier and giving permission
to the work from a private company if it follows the mentioned guidelines
by the Restoration Department of the CCHN-ECM.
The heritage enjoyment in Uruguay, enhanced with the inclusion in
1995 of the Historical Neighborhood of Colonia del Sacramento into the
world heritage list, attracts a cultural tourism more and more exigent, and
these murals spaces become highly vulnerable. The triad tourism, heri-
tage, and market presents in the present Uruguay new ‘glocalizated’ maps
FIGURE 7 Miguel Ángel Battegazzore, Entropy II, 1988. Located in the outdoor facade
of the firemen building, in Magallanes street, Montevideo. Synthetic vinyl painting, on
synthetic preparation. Highly deteriorate. Source: Graphical record of the R&D Project
PUCM, 2010.
8 Conservation, Tourism, and Identity of Contemporary Community Art
(glocalization: from local to global and vice versa). In addition, in this
context, it is necessary to enhance researchers about new models of sus-
tainable management that will guarantee the required resources for this
social art.
The recent declaration of new heritage elements has generated a
wider and spreader perception of the cultural assets, being observed as
a tool to offer essential goods for the human welfare, so that their accu-
rate management is essential to construct a process of social, economic
and environmental sustainable development. T ourism, globalization, and
heritagization of new cultural assets, require the revision and proposal of
new management models that will include sociocultural aspects, their use,
formal and symbolic/identitarial value. That is, the restoration should bear
in mind the actors’ perspective and contain it in the intervention process.
It will be necessary for the involvement and interaction of the different
stakeholders to develop a sustainable conservation.
In this framework, the research project ‘social function of the Uru-
guayan muralism of the twentieth century as a tool and model of sustain-
able heritage activation’ has been developed, with the participation of the
Polytechnic University of V alencia, University of V alencia (participated in
the rst stage of the research project, dealing with the area of ethnographic
research), University of the Republic Uruguay, the Unit of Restoration of
the Cultural Heritage Commission and the National Cultural Board of the
ECM of Uruguay. The main objective was to use Colonia del Sacramento
as a strategic location in Uruguay , to create a management program that
could be re-created in other heritage places of the country, with the main
objective of being sustainable by employing the tool of activation of the
social function of the Uruguayan muralism of the twentieth century .
One of the specic objectives of the project was to give urgently a peri -
odic support to a complex process of intervention; in this case the “Alle-
gory to work” by Felipe Seade (Figure 8), by developing a sustainable
model of restoration-management, while at the same time covering the
three principal problems of the Uruguayan muralism. This goal could be
achieved through three interconnected national subprograms nanced by
the Spanish government and the UPV . These included intervened works
that experienced a complete process of illusionist chromatic reintegration;
murals that, for different reasons, had to be moved as the only measure
Introduction 9
to preserve the work of art; works painted in schools that have experi-
enced a heritage deactivation and a lack of management; paintings from
the twentieth century with problems of conservation, as a consequence
of the period of experimentation when they were created; murals created
in the twenty-rst century with problems of instability due to the lack of
technical knowledge regarding the methodology for outdoor paintings.
The rst program of research-intervention included, on the one hand,
the statement and heritage activation of the mural “Allegory to work” in
its wider and extended vision through the scientic record of it, and, on
the other hand, the analysis of the problems of mural intervention, devel-
oping a sustainable model of restoration-management, replicable in other
murals located throughout the country, from an economi c, cultural and
locally participative perspective. The second program (training), had the
FIGURE 8. Detail of the artwork “Allegory to work” by Felipe Seade, located in the
conference room of the culture house (old High School of Colonia del Sacramento), before
the intervention process. Source: Graphical record of the R&D Project PUCM, 2010.
10 Conservation, Tourism, and Identity of Contemporary Community Art
objective of creating step-by-step of a decentralized project to implement
a University teaching area of heritage intervention. The approach was, in
a rst step, to train the human resources using the work of Felipe Seade as
an object for practice in order to gain access to information, which could
help those people work independently. Moreover , this will at the same
time promote the protection of artworks in general, and also the cultural
expression as a tool. Finally, the program of sensibilization and dif fusion
was focused on:
a. promoting a program of social sensibilization to favor the syner-
gies with the cultural and development policies; and
b. helping to conduct ethnographic researches in the framework of
the mural “Allegory to work,” in order to contextualize the reasons
for its heritage deactivation and to understand the mechanisms of
its deterioration.
Enhancing the value of the cultural heritage ‘contemporary muralism’
and, in particular, the object of study , special attention is paid to integrate the
local community and the most vulnerable groups, focusing each action to
a concrete public by using the participatory action research (P AR) method.
Moreover, diffusion of the results is done in the academic area to promote
the sensibilization of interculturalism values and to improve the research
methodologies to manage sustainably the contemporary muralism.
The mural “Allegory to work,” located in the Cultural House of Colo-
ing problems of heritage deactivation and conservation, and previous
interventions that had modied totally the original work.
In addition, Felipe Seade was a key artist in the Uruguayan contem-
porary muralism of the twentieth century. He was follower of the Mexi-
can and the political-social movement (Informant 24) and one of the top
examples of the artistic Social realism movement (Informant 32), which is
opposed to the Constructive Universalism of T orres-García’s Attelier that
had a huge improvement in the Uruguayan artistic panorama since the 30s,
when it started to be dened the social function of the artist and its plastic
application. The mural “Allegory to work” is one of the most signicant
paintings of this artist (Informant 32).
With this background, one can understand that the commitment of pre-
serving the heritage is a shared responsibility , not only of the government
Introduction 11
but also of the different stakeholders (social groups, educational organiza-
tions and NGOs). For this reason, it is necessary to benet from the syner -
gies that a heritage intervention project in local areas is able to generate:
sharing knowledge and experience. Following this idea, the participation
and collaboration of four stakeholders was targeted: (i) public institutions,
(ii) academics, (iii) NGOs, and (iv) local community.
With these stakeholders, a horizontal structured team with capacity
of decision making by consensus, based on communication and active
was formed. A process of co-training was started to help them to design
new projects based on the experience acquired of this project, correcting
detected problems. Those institutions are aware of the complexity of the
work to be intervened and the ways to enjoy the Uruguayan heritage.
Furthermore, the local community dened the symbolic dimension of
this mural, and redened its social function and its capacity of proposing
fantastic discourses. They demonstrated us the knowledge of its values
as signicant expressions of a cultural tradition. To incorporate them and
have an effective feedback, the cooperation actors and the local associa-
tions played a key role.
The methodology used had as objective to consider the mural by Felipe
Seade as a whole and with its intrinsic nality. During the heuristic (pre -
paratory) phase the inventory process of the mural was developed, adding
the principal data for later extend the information at the scientic cata -
loguing process during the analytical phase, with the objective to obtain a
wider knowledge of the mural, considering its background, signicance,
and value.
Filling in the scientic cataloguing form at the mural’s place, was a
fundamental step and it became a coherent report of the critical research
about the mural in its identity. It was a tool to cover all the morphological,
historical-critical, technical, administrative, and legal information in an
organic synthesis.
cia (synthesis phase). The materials and the possible interactions with
the conservation and restoration processes of the work were studied and,
together with this information, a nal catalogue, a proposal for the mural
intervention and the design of the museographic program was created.
12 Conservation, Tourism, and Identity of Contemporary Community Art
The activities for that program were:
1. Analysis of Secondary Source
Archives’ r esearch. Search of documents in the principal public and
private archives that could have information about the conceptions,
uses and functions of the cultural heritage, and specially referred
to contemporary Uruguayan muralism and the mural “Allegory to
work” by Felipe Seade.
Study of bibliography. Books, journals, monographs, official
documents, autobiographies, experts’ reports, films, video records,
and documentary films about Uruguayan contemporary muralism
and its intervention, focusing the research in the object of study .
The work plan for the analysis of the secondary source was:
a. Find, collect, and manage public and private archives.
b. Scan and record the documents.
c. Organize and register the information.
2. Ethnographic Study
The ethnographic fieldwork was mainly developed in two loca-
mento. In each of these urban locations, we used the same analytic
methodologies (semistructured interviews with people from dif-
ferent backgrounds to have a first impression of the perception
and valuation of the Uruguayan muralism and, secondly of Felipe
Seade’s work), focusing on the valuation and social uses of the
contemporary Uruguayan muralism, but adapting them to the spe-
cific objectives in each location.
In the city of Montevideo, the study was oriented to analyze the
Uruguayan muralism of the twentieth century. The main objective,
from the ethnographic point of view , was to observe the way the cul-
tural manifestations transcend the historic-artistic value to become
important identitarian symbols for the community . Moreover, the
quantitative (because of the huge amount of murals in Latin Amer -
ica and, particularly in Uruguay) and qualitative (because their rec-
ognized technical quality) importance of the muralism, it appends
new dimensions regarding its symbolic value and its capacity to
strengthen identity. For this reason, it was fundamental to under -
Introduction 13
stand the perception, comprehension, use and social function of
the contemporary Uruguayan muralism. From this point of view,
the need to reassess the mural art and highlighting its influence in
society was studied.
conducted, using a previous planned set of questions, with the aim
to focus them on main research objectives. The informants have
been interviewed from different professional profiles to elaborate
a complete framework of the comprehension and valuation of the
Uruguayan muralism and the works of Felipe Seade. The infor-
mants were selected based on a set of criteria (age, professional
career related to the intervention of mural works, relevance of their
work, and so on) and grouped together, according to their profes-
sional characteristics, as follows:
a. Relevant plastic artists in the Uruguayan environment
(muralists and family members of muralists of the twenti -
eth century), with technical knowledge of contemporary
muralism. For example, an interview with Miguel Ángel
Battegazzore, one of the prestigious artists (and muralists)
in Uruguay, who has written many books, and is one of the
inheritors of the Felipe Seade’s Atelier (Informant 24), was
included. This interview , and one by Seade’s sons, were rel -
evant testimonials to collect the information regarding the
life and work of this renowned artist of the first term of the
twentieth century.
b. Technical and research institutional staff (universities, institu-
tional centers), with observed experience in intervention, man-
relevance to the results of the staff from the National Cultural
Heritage Committee of the Education and Cultural Ministry
was attributed; and above all, the restorers (active or retired)
who have worked in the conservation and restoration of murals,
as a public service or working for private organizations. Many
of them had a wide experience in the senior management of
a restoration atelier, as well as in the interventions of murals
made from them. The most important intervention could be the
14 Conservation, Tourism, and Identity of Contemporary Community Art
one of the murals in the Saint Bois Hospital, executed by the
T orres-García Atelier.
c. Civil society (cultural associations). In particular, the Saint
Bois Association, that leads the movement for recuperation
and return to their original context of the murals of the Saint
Bois Hospital that were removed from there and then located
in Antel Tower , where they are at present.
d. Relevant critics and art historians in the study of Uruguayan art
(and, specially, muralism).
The work plan includes:
a. Digital record of the interview (audiovisual record).
b. Transcription of the interview.
c. Analysis of the most relevant documents to categorize analyti-
conclusions.
The information was processed following the ethical guidelines of
anthropology, with the informants’ consent for using the materials
for research and diffusion purposes.
3. Sensibilization Program
The workshop ‘heritage, participation, and collective action’; and
‘dialogues on Colonia del Sacramento heritage town,’ using the
methodology participatory action research (P AR) was held. The
topics of the activities were related to the heritage applications and
the intervention-management of murals, focusing each activity on
a specific public, depending on their age, and grouping them in
adolescents, teenagers, adults and elderly people.
W ork teams should:
• ‘draw your heritage’ and ‘treasure search’ (8–16 years).
• ‘from participation to action: sustainable heritage action plan
for Colonia del Sacramento’ (18–55 years).
• ‘before and after: alive memories of Colonia’ (over 55 years).
The sensibilization workshops were developed in the conference
room, where the mural “Allegory to work” by Seade is located,
as it was not only the key object of the project but also a mural-
ist icon of the Colonienses. T o generate more sensibilization with
performed activities, the professional staffs were working on the
record and proposal steps, encouraging interaction of the restores
with the participants so that they could know directly some of the
processes that conform a mural intervention project.
At this research phase, the work plan was:
a. Preparation and performance of the workshops.
b. Photographic and video-graphic record.
c. Information digitalization.
d. Analysis and interpretation of the information.
e. Conclusions.
4. Training Program
Development of the teaching program of a specific learning module in
the Republic University of Uruguay, through the postgraduate course
‘Sustainable management of the Latino-American cultural heritage,’
which practical part was made about the mural “Allegory to work,” to
give a real and close vision. The course lasted 72 h (40 h of theory and
32 h of practice), divided into five independent modules:
• Module 1: Cultural heritage.
• Module 2: Tools for cataloguing and inventorying the cultural
heritage.
• Module 3: Photography applied to the analysis of art works.
• Module 4: Research of nondestructive methods in heritage
intervention. Characterization and colorimetric monitoring.
• Module 5: Design of the technical project on mural intervention.
5. Graphical Record and Physical-Chemical Analysis of the W ork
a. Physical identification, localization, and description of the work
for the inventory process. Record of the principal data of the
mural: author, title, technique, measures, support, year of cre -
ation, intervention, conservation status, and so on, using a stan -
dard form.
Work plan :
i. Compelling data,
ii. Database development, and
iii. Reports.
b. Scientific cataloguing based on the inventory data of the mural
and enhanced with specific record devices: video-endoscopy,
16 Conservation, Tourism, and Identity of Contemporary Community Art
laser distance-metric, temperature and humidity measurer, lux-
metric, GPS, and contact video-microscopy. The technical data
were inserted in an excel database to be processed later and
added to the designed cataloguing forms.
Work plan :
i. Compelling data,
ii. Database development, and
iii. Reports.
c. Scientific cataloguing based on chemical analyses. Compila-
tion of microsamples of the pictorial film, esplanades, and sup-
port, following a patron related with the rest of records and the
information needed. The analysis were:
• Stratigraphic study: morphological and chemical analysis
MO and SEM/EDX.
• Identification of pictorial binders: through FT-IR and Pyr-
GC/MS.
• Chemical-mineralogical characterization of mortars: through
FT -IR.
• Compelling of microsamples of external elements from
the pictorial film (dirtiness, repainting, and so on). One
part was made in situ with the conduct-meter and analysis
strips for the semiquantitative determinations.
Work plan :
i. Compelling samples.
ii. Laboratory analyzes.
iii. Reports.
d. Scientific cataloguing based on physical analyses, includ -
ing colometric characterization and digital photographic
documentation.
• Colorimetric characterization through visible spectropho-
tometric.
W ork plan :
i. Colorimetric measurements with contact techniques
by selection of sample points.
ii. Data processing.
iii. Results of the analyzes.
Introduction 17
• Digital photographic documentation of the mural.
W ork plan :
i. Photos with visible radiation of the original status of
the painting, including photos with raking light, mac-
rophotos and reflected light with incident angle of 90º.
ii. Photography with nonvisible light. Red reflectography
for the study of internal paint layers and ultraviolet
photography of fluorescence to detect the presence of
repainting and identify materials.
iii. Laboratory analyzes.
iv. Reports.
e. Creation context based scientific cataloguing. Precise bio-
graphic data from the author and the work was collected, as
well as more specific aspects according to their particularities.
6. Restoration Process of the Mural “Allegory to Work” by Felipe
Seade
Intervention for conservation (consolidation processes) and resto-
ration (cleaning process and volumetric and pictorial reintegration)
was executed directly on the artwork. During the whole process,
the different steps have been monitored/evaluated with photog-
raphy with visible and invisible radiations and colorimetric mea-
surement, using contact techniques by selecting samples points, in
order to compare results (values) from the different conservation/
restoration processes.
W ork plan :
i. Direct intervention for conservation,
ii. Direct intervention for restoration, and
iii. Reports.
7. Design of a New Use and Social Enjoyment Scheme of the
Mural “Allegory to W ork” by Felipe Seade
After the intervention project, we defined the policies for preven-
tive conservation (minimize the deterioration, create maintenance
routines, manage guidelines for the staff and users, development of
security measures and contingency plans in case of disaster, design
of protective measures to reduce deterioration processes, presenta-
tion and photography processes, and so on) and the guidelines to
18 Conservation, Tourism, and Identity of Contemporary Community Art
enhance the use and social enjoyment of the mural (routines for
guided visits, new activities, and so on).
W ork plan :
i. Definition of policies for preventive conservation.
ii. Design of guidelines to enhance the uses and social enjoyment.
iii. Reports.
KEYWORDS
• contemporary muralism
• heritage activation
• PAR
• participatory action research
• scientific cataloguing
• sensibilization program
• social sensibilization
• Uruguayan muralism
REFERENCES AND BIBLIOGRAPHY
Achúgar, H. (2001). “ Falsas memorias: Blanca Luz Brum.” Montevideo: Ediciones T rilce.
ISBN: 9974-32-219-7.
Bulanti, M. L. (2008). “ El taller T orres-García y los murales del hospital Saint Bois.”
Montevideo: Ediciones Tradinco. ISBN: 978-9974-675-17-9.
Expedte. no. 2008.11.008-316/08, con fecha de 24 de junio de, 2008. Archivo General de
la Nación, Uruguay.
Santamarina, V ., & Carabal, M. A. (2013). Informe Final del proyecto Función social del
muralismo uruguayo del siglo XX como vehículo y modelo de activación patrimonial
sustentable. Descentralización, identidad y memoria . Ministerio de Asuntos Exteri-
ores y de Cooperación.
Santamarina, V ., & Carabal, M. A. ( 2014 ). Informe Final del proyecto Función social del
muralismo uruguayo del siglo XX como vehículo y modelo de activación patrimonial
sustentable . Universitat Politècnica de V aléncia.
Santamarina, V ., & Carabal, M. A. ( 2016 ). Informe finaldel proyecto Diseño e implemen-
tación de políticas culturales inclusivas: el muralismo uruguayo contemporáneo
como herramienta de activación patrimonial sustentable . Ministerio de Economía y
Competitividad, Dirección General de Investigación Científica y Técnica.
Introduction 19
INTERVIEWS
• Informant 1. Didier Calvar. Profile: Lecturer of Arts History, Faculty of Humanities
and Education Science (RU) and Professor of the University ORT , Montevideo. Date
of Interview: 28–09–2010.
• Informant 24. Miguel Angel Battegazzore. Profile: Artist and lecturer . Date of Inter-
view: 02–04–2011.
• Informant 32. Carolina and Juan Felipe Seade. Profile: Artists of recognized pres-
tige in Uruguay. Descendants of muralist Felipe Seade. Date of Interview: 14–04–
2011.
... The study was performed using qualitative research, focusing on documentary research, photographic documentation, and field research. The field work focused on the use of tools such as participant observation, participatory action research (PAR), semistructured interviews, and focus groups
[41]
. Specifically, PAR is based on critical-reflective thinking carried out via citizen participation, which seeks to combine theory and practice. ...
... On the other hand, the study on mural production in Uruguay is presented as a symbol of contemporary Uruguayan cultural heritage, despite the fact that it had previously been understood as an anecdotal art form subordinated to other disciplines, such as easel painting and architecture [3,
41]
. That is why this study aims to reactivate these spaces as tourist products [13][14][15], stimulating the community and public and private institutions to preserve and extend these mural landscapes [49,50]. ...
... It is worth mentioning that there was only broad research on the mural work made by constructive universalism in the hands of Torres García and the TTG. In this way, it was essential to broaden the knowledge, focusing the study on the following artistic movements: constructive universalism, social realism, abstraction, mural public art, graffiti, and street art [30,
41,
51,52,58,59]. Furthermore, it is also noteworthy that, linked to some of these mural landscapes, we have found a society's sense of belonging, identified by the local communities themselves as part of their patrimonial legacy. ...
Creative Mural Landscapes, Building Communities and Resilience in Uruguayan Tourism
Article
Full-text available
May 2021
Eva Martinez Carazo
Virginia Santamarina-Campos
María De-Miguel-Molina
The purpose of this research was to analyze open-air mural painting museums in Uruguay as a model of tourism resilience, sustainability, and social development, being one of the first Latin American examples to demonstrate the ability to adapt to change and overcome external shocks through the creation of creative community landscapes. To do so, documentary research, photographic documentation, and field research were carried out in order to explore the opportunities of mural tourism in small locations in Uruguay. In the nineties, a new type of artistic production was created in Uruguay, initially characterized by its decentralization. This was somewhat of a revolution in the muralist field as, until this time, Montevideo had been the center of cultural tradition, considered the intellectual focus of the country, and had concentrated the largest number of murals. For this reason, the birth of new muralist nuclei in small rural enclaves, which traditionally had not had much access to culture and no link to muralism, is remarkable. Secondly, this new movement sought to diversify economic activity given the consequences of the severe economic crises and environmental catastrophes that were and are still prevalent in these areas. Therefore, these new creative landscapes were conceived as important examples of the resilience of cultural tourist destinations. The results emphasize that, until now, the idea of giving muralism a new use as a tool for local economic development had not been envisaged with reference to mural art in Uruguay. This new rethinking has given rise to the so-called Regionalization Processes of Uruguayan wall production. The most relevant cases are those developed in the municipalities of San Gregorio de Polanco (1993), Rosario (1994), and Pan de Azúcar (1998).
Falsas memorias : Blanca Luz Brum / H. Achugar.
Article
Hugo Achugar
Blanca Luz Brum (1905-1985), escritora y pintora uruguaya, aunque residente durante muchos años en Chile. Con una presencia política y cultural similar a la de Frida Kahlo, Tina Modotti o Nahui Ollin en los movimientos de intelectuales comunistas en América Latina durante las décadas de 1920 y 1930. Pareja del poeta peruano Juan Parra del Riego y del pintor mexicano David Alfaro Siqueiros, pasó de comunista en los años treinta, a peronista en los cincuenta, para terminar paradójicamente apoyando al régimen dictatorial de Augusto Pinochet. Entre las obras de Brum se encuentran: Las llaves ardientes; Atmósfera arriba; Cantos de la América del Sur; El reloj de las imágenes caídas; Un documento humano; Blanca luz, contra la corriente; Mi vida: cartas de amor a Siqueiros; y, El último Robinson.
El taller Torres-García y los murales del hospital Saint Bois
Jan 2008
978-9974
Portugal / Y. Bottineau ; tr. por Ma. Dolores Raich Ullán.
Yves Bottineau
Traducción de: Portugal Amplia descripción de Portugal, que presenta una revisión de cada región de este país europeo con sus características propias (religión, costumbres, aspectos económicos, etcétera) y sus principales manifestaciones artísticas.
| https://www.researchgate.net/publication/323152470_INTRODUCTION_CONSERVATION_TOURISM_AND_IDENTITY_OF_CONTEMPORARY_COMMUNITY_ART |
Improving Resource Utilization and Outcomes Using a Minimally Invasive Pilonidal Protocol - Journal of Pediatric Surgery
Improving Resource Utilization and Outcomes Using a Minimally Invasive Pilonidal Protocol
Hajar R. Delshad
Affiliations
Department of Surgery, Boston Children's Hospital, Harvard Medical School, Boston, MA
Owen Henry
Owen Henry
Affiliations
Department of Surgery, Boston Children's Hospital, Harvard Medical School, Boston, MA
David P. Mooney
David P. Mooney
Correspondence
Corresponding author at: Department of Surgery, Boston Children's Hospital, Hunnewell 345, 300 Longwood Avenue, Boston, MA 02115.
Contact
Affiliations
Department of Surgery, Boston Children's Hospital, Harvard Medical School, Boston, MA
Abstract
Key words
References
Abstract
Purpose
The purpose of this study was to evaluate the resource utilization and outcome of
a minimally invasive pilonidal protocol (MIPP) versus surgical excision (SE) in adolescents
with pilonidal disease.
Methods
Improved hygiene, laser epilation (LE), and sinusectomy were implemented as a minimally
invasive pilonidal protocol (MIPP) in March 2016. Following IRB approval, 34 consecutive
MIPP patients with moderate and severe disease were compared with a random sample
of 17 SE patients treated prior to MIPP implementation. Number of visits, laser epilation
(LE) treatments, care duration, operations, operating room (OR) time, charges, and
condition at last visit were analyzed. Charges were standardized for 2018.
Results
No differences were found in age or body mass index between groups. SE patients underwent
an average 1.6 excisions/patient (cumulative 2598 OR minutes) and no LE. MIPP patients
underwent an average 1.4 sinusectomies and 3.5 LEs/patient. Six sinusectomies (0.17/patient)
were performed in OR (cumulative 258 OR minutes). No differences in number of visits
or care duration were found between groups. At last follow-up, 82% of MIPP and 18%
of SE patients were healed or asymptomatic (p < 0.01). Average charges were $29,098
for SE versus $8440 for MIPP (p < 0.01).
Conclusion
A minimally invasive pilonidal protocol reduces charges and improves outcome compared
with surgical excision in adolescents.
Level of evidence
III.
Type of study
Retrospective comparative study.
Key words
Pilonidal
Sinusectomy
Pit picking
Laser epilation
Resource utilization
Quality improvement
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Footnotes
☆How this paper will improve care:Compared to surgical excision, a minimally invasive pilonidal protocol (improved hygiene, outpatient sinusectomy, laser epilation, and close clinical follow-up) reduces charges and increases the percentage of patients who enjoy symptom resolution, thus improving resource utilization and clinical outcomes.
Identification
DOI:https://doi.org/10.1016/j.jpedsurg.2019.09.074
Copyright
ScienceDirect
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