To assess the concurrent validity of a wireless patch sensor to monitor time lying, sitting/standing, and walking in an experimental and a hospital setup.Healthy adults participated in two testing sessions: an experimental and real-world hospital setup. Data on time lying, sitting/standing, and walking was collected with the HealthPatch and concurrent video recordings. Validity was assessed in three ways: 1. test for mean differences between HealthPatch data and reference values; 2. Intraclass Correlation Coefficient analysis (ICC 3.1 agreement); and 3. test for mean differences between posture detection accuracies.Thirty-one males were included. Significant mean differences were found between HealthPatch data and reference values for sitting/standing  and walking  in the experimental setup. Good correlations were found between the HealthPatch data and video data for lying (ICC: 0.824) and sitting/standing (ICC: 0.715) in the hospital setup. Posture detection accuracies of the HealthPatch were significantly higher for lying and sitting/standing in the experimental setup.Overall, the results show a good validity of the HealthPatch to monitor lying and poor validity to monitor sitting/standing or walking. In addition, the validity outcomes were less favourable in the hospital setup. Low mobility during hospital stay is common in patients  and indeThe HealthPatch  Fig 1)  Fig 1) iA cross-sectional, experimental study design was used to assess the concurrent validity of the HealthPatch  . All parth version, 19-10-2013) were followed and ethical approval was granted by the advisory board Practice oriented research, Faculty of Health, Behaviour and Society, HAN university of applied sciences, Nijmegen, the Netherlands (EACO 57.02/17). Written informed consent for study inclusion and anonymous collection of data was obtained from each respondent.A convenience sample of students was recruited between February 2017 and July 2017 at the HAN university of applied sciences, Nijmegen, the Netherlands. Students were informed and asked to participate via social media, e-mail, and their digital learning environment. Healthy male students between 18 and 30 years were eligible for inclusion. Healthy was operationalized as the absence of cognitive or physical disability to lie on a bed, sit, stand, and walk for a total of sixty minutes. The current study aimed to include at least 30 participants, which is considered fair in the COSMIN checklist . PrincipThe measurement procedure started with a standard measurement of body weight (Seca 761), length, and breast girth. Horizontal placement of the patch on the skin at left midclavicular line under the pectoralis minor muscle (position 3) showed the highest accuracy for posture detection in previous research  and was 2, with a hospital bed, nightstand, table, two seats, and a closet  to change level of mobility after standardized blocks of three minutes without breaks according to a predefined format: lying on the hospital bed , sitting on the hospital bed , walking in the hospital room ; sitting on the comfortable chair (block 4). In the real-world hospital setup, the observers provided no specific instructions to change the mobility of participants. In addition, participants were not informed about the purpose of measurements to empower natural behaviour. The hospital room had a surface of 30ma closet . The parHealthPatch data, device under investigation–The primary outcome in the current study was time lying, sitting/standing, or walking. The HealthPatch continuously measured level of mobility with a 3-axis micro electro-mechanical system accelerometer resulting in counts with a frequency of 1 Hertz . The timVideo data, golden standard–Analysis of video recordings on mobility in participants was considered as the golden standard to determine actual time lying, sitting/standing, or walking of the participants. Second-by-second analysis of the video data was performed by the observers  and reported in a standardized case report form. In this form, the observers reported the time lying, sitting/standing, and walking of the participants. In addition, details were provided on the start and end of measurements, problems with data collection, and name of observers. Definitions of different levels of mobility were described by Pedersen et al.  and usedHealthPatch data was stored  and double checked  for incorrect data and missing values. In case of incorrect or missing data, data files  and case report forms (video data) were checked to correct the data entry. Prior to data analysis, a syntax was written  to provide independent data analysis in IBM SPSS statistics, version 23 . DescripHealthPatch data on individual level were presented and analyzed with a scatter plot to observe differences in HealthPatch data between participants. Mean differences were calculated between the HealthPatch data and reference values  with a one sample t-test. The video data showed exactly three minutes lying, sitting/standing or walking per block in all participants as predetermined, securing solid use of the reference values. Outcomes with a two-tailed p-value < 0.05 were considered significant.The HealthPatch data were analyzed for correlation with the golden standard video data in the hospital setup. Firstly, data on individual level were presented for lying, sitting/standing and walking with a scatter plot of both HealthPatch and video data. Secondly, Intraclass Correlation Coefficients (ICCs) were calculated between the HealthPatch and video data using a two-way mixed effect model (ICC 3.1 agreement) with 95% confidence intervals (CI). A correlation of ICC < 0.70 was considered poor or moderate, ICC ≥ 0.70 as good and ICC ≥ 0.90 as excellent , 24. ThiA comparison of ICC outcomes between the experimental and hospital setup would provide information on differences in outcomes related to the specific setup. However, correlation coefficients cannot be calculated for data in the experimental setup as there was no variance in time lying, sitting/standing, and walking in all participants. With no variance in the independent variable, the standardized time lying, sitting/standing, or walking, a correlation coefficient cannot be calculated . An indeThirty-one males were included in the current study with a mean age of 22 years, ranging between 18 and 29 years. The demographics were: mean weight 80 kilograms (range: 60-104kg), mean length 183 centimetres (range: 171-195cm), and mean breast girth 90 centimetres (range: 81-100cm). HealthPatch data were missing on four participants in the experimental setup  and hospital setup  as a result of connectivity problems. One HealthPatch (case 24) disconnected as the chest hair of the participant impaired the connection between the HealthPatch and his skin. Three participants sat with their arms folded for their chest, causing the HealthPatch to stop register and transfer data. No explanation was found for the missing data in the remaining four participants. As a result, the current study included data on 27 participants (810 minutes) per setup. Analysis of the inter-observer reliability on pilot test video data showed ICC’s (agreement) between 0.971 and 0.999.Video data during the hospital setup measurements showed that the participants were lying mean 4.7 minutes (SD: 9.0), sitting/standing mean 22.0 minutes (SD: 9.9), and walking mean 3.3 minutes SD: 5.6). Figs .6. Figs The posture detection accuracies of the HealthPatch ranged between 72.3% and 99.3% . The mosThis is the first study to assess the concurrent validity of the HealthPatch to determine time lying, sitting/standing, and walking in both an experimental and a hospital setup. Experimental setup outcomes show poor validity of the HealthPatch to determine time sitting/standing and walking, indicated by statistically significant differences with reference values. The HealthPatch is able to validly monitor lying and sitting/standing in a real-world hospital setup reflected by good ICC’s. These findings implicate that the HealthPatch might be a promising tool to assess the time lying and sitting/standing of patients during hospital stay. However, the ICC between HealthPatch and video data for walking in the hospital setup is poor and Bland-Altman analysis shows a high and increasing measurement error. The posture detection accuracies show low walking detection accuracies and statistically significant differences on all posture detection accuracies between the experimental and the hospital setup. With this knowledge, the use of HealthPatch walking data could not be used interchangeable with the golden standard (video data) and should be considered as biased . The staEarlier research on posture detection accuracies of the HealthPatch by Chan et al.  shows reStrengths of the current study include the analysis of video recorded data as a golden standard for mobility observation . In addiFirstly, the differences between outcomes in the experimental and real-world hospital setup show the need for a real-world setup to determine the validity of accelerometry. The validity for examination of time lying, sitting/standing, and walking is different between setups indicated by analysis on both individual Figs –8 and grAssessment of mobility in patients during hospital stay is of great clinical importance. Valid and accurate assessment of in-hospital mobility contributes to early detection of patients at risk for development of new disability during their hospital stay as a result of physical inactivity. Furthermore, mobility assessment is crucial for monitoring purposes in interventions aiming to increase in-hospital mobility of patients. Wireless devices with accelerometry, such as the HealthPatch, provide an opportunity to continuously monitor mobility in patients without mobility limitations.This is the first study to assess the concurrent validity of an accelerometer to monitor levels of mobility in both an experimental and a hospital setup. Overall, the results show a good validity of the HealthPatch to monitor lying and poor validity for sitting/standing and walking. In addition, the validity outcomes were less favourable in the hospital setup. The use of an experimental and a hospital setup within this study provides a blue-print for future studies to analyze validity of accelerometry.S1 FigThe measurements were performed in the research zone with a hospital bed, nightstand, table, two seats, and a closet. Two cameras (GoPro HERO 4) were used to videotape the mobility of participants.(TIF)Click here for additional data file.S1 Dataset(ZIP)Click here for additional data file.S2 Dataset(ZIP)Click here for additional data file.S3 Dataset(ZIP)Click here for additional data file.S4 Dataset(ZIP)Click here for additional data file.


Supplemental Digital Content is available in the text. Unlike in older people, it has been suggested that elevated blood pressure (BP) in young people is because of high cardiac output accompanied by normal total peripheral resistance (TPR)—a hyperkinetic/hyperdynamic circulation. We investigated this in a large, United Kingdom-based birth cohort of adolescents. The study was conducted on 2091 17-year-old participants in the ALSPAC —a prospective population-based birth cohort study. BP measurement and echocardiography were performed, and heart rate (HR), stroke volume (SV), and TPR were calculated. Data are means (SD). Higher quintiles of systolic BP were associated with higher SV, higher HR, and higher TPR. The proportional contribution made by SV, HR, and TPR to mean arterial pressure differed little by systolic BP quintile . Higher BP is attributable to a combination of higher cardiac output  and higher TPR in a population-based sample of adolescents. There is no evidence of a disproportionate contribution from elevated cardiac output at higher BP levels. Several previous studies17 have suggested that high BP in young people may be explained by elevated CO rather than elevated TPR, whereas the latter is more typical in older people with established hypertension.17 This high CO state has been termed a hyperkinetic (or hyperdynamic) circulation.18 This has been proposed to be a precursor to adult hypertension, with a transition from a high CO-normal TPR to a normal CO-high TPR state with aging.19 However, not all studies have confirmed these observations21 and those that have observed hyperkinetic hemodynamics have often been based on small sample sizes or have studied selected individuals , which may bias relationships or render them nongeneralizable.Elevated blood pressure (BP) accounts for two thirds of all strokes and a half of all coronary heart diseases, and the relationship between BP and risk is continuous and log-linear across the range of BP.We, therefore, aimed to investigate whether higher BP in young people is explained by a hyperkinetic state and whether elevated HR and SV made a disproportionate contribution to elevated BP in a large, population-based cohort of adolescents.http://www.alspac.bris.ac.uk).22 Since 7 years of age, surviving participants have been invited to regular follow-up clinics. The study website contains details of all the data that are available through a fully searchable data dictionary  and also includes details of representativeness of the sample. Five thousand two hundred seventeen participants attended the clinic assessment at 17 years of age. Because of limited time and equipment availability, 1 in 2 of daily clinic attenders were invited to undergo echocardiography. This study is based on these individuals. Ethical approval was obtained from the ALSPAC Law and Ethics Committee and the Local Research Ethics Committee. Participants provided written informed consent.The ALSPAC  is a prospective population-based birth cohort study that recruited 14 541 pregnant women residents in Avon, United Kingdom, with expected dates of delivery between April 1, 1991, and December 31, 1992 , diastolic BP, and HR were measured using an Omron 705 IT oscillometric BP monitor. Arm circumference was measured, and an appropriate cuff size was chosen according to manufacturer’s instructions. The average of the final 2 of 3 readings was used in the analysis. Pulse pressure was calculated as the difference between SBP and diastolic pressures. MAP was calculated as diastolic BP+1/3 (SBP−diastolic BP).23 LV mass was indexed (LVMI) to height2.7 and TPR was calculated as MAP/CO. Quality control was performed throughout the study, and reproducibility of echocardiographic measurement was assessed by recalling 30 participants and repeating their measurements. The intraclass correlation of repeated echocardiographic measurements was excellent: 0.75 to 0.93 (intraobserver) and 0.78 to 0.93 (interobserver).Echocardiography was performed using a HDI 5000 ultrasound machine (Phillips) equipped with a P4-2 Phased Array Ultrasound Transducer by 1 of 2 echocardiographers using a standard examination protocol. All measurements and calculations were made according to American Society of Echocardiography guidelines.2 (m2).Age at clinic assessment and sex were recorded. Other demographic and lifestyle data were ascertained from questionnaire data; socioeconomic position was assigned by paternal occupation, education was classified as in full-time education or not, alcohol consumption was assessed as the number of drinks containing alcohol consumed on a typical day, smoking was categorized as never, ever but not current, or current. Weight and height were measured while the subjects were wearing light clothing and no shoes. Weight was measured to the nearest 0.1 kg by using scales . Height was measured to the nearest 0.1 cm by using a Harpenden stadiometer . Body mass index (BMI) was calculated as weight (kg)/heightIndividuals with diabetes mellitus (n=21), familial hypercholesterolemia (n=7), and known heart disease (n=3) or women who were pregnant (n=15) were excluded. Data from a further 25 individuals without information on sex or BP were also not used. MAP and LVMI were subdivided into quintiles to examine associations with SV, HR, and TPR without assuming linear relationships across the entire range of variables. The primary analysis was performed on both sexes combined, but we also examined both sexes separately. MAP was used for these analyses because on a priori grounds, HR and TPR would not be expected to contribute to pulse pressure, but a further sensitivity analysis was performed using quintiles of SBP because this is more widely clinically used as a measure of BP than MAP. Associations between LVMI or relative wall thickness (RWT) and SV, HR, and TPR were examined by multiple linear regression with age, sex, height, BMI, socioeconomic position, education status, alcohol consumption, and smoking as potential confounders; both LVMI and BMI are indexed to height, which could introduce some colinearity between these measures, so we also constructed models in which weight was substituted for BMI.Descriptive statistics for continuous variables are presented as means (SD) or medians (interquartile ranges) for skewed data. The primary analysis was performed as a complete-case analysis; however, to check that missingness did not influence results, multiple imputation was also used to impute missing outcome or covariable data for participants who met the inclusion criteria. The imputation equations included all outcomes, exposures, and covariables, and 20 imputed datasets were created. Because imputation had minimal effects on results, these results are not presented.online-only Data Supplement). Characteristics of the individuals allocated to quintiles of MAP are shown in Table S2.Characteristics of those included in analyses are shown in Table P<0.001). There was no evidence of modification by sex for any of the findings; analyses stratified by sex are shown in Figure S1.The values of SV, HR, CO, and TPR in each quintile of MAP are shown in Table The proportional contribution made by SV, HR, and TPR to MAP hardly differed across MAP quintiles Figure , and theIn a multiple regression model adjusted for potential confounders, higher SV and TPR were associated with higher LVMI Table , whereas24 Our data provide no evidence that elevated HR, SV, or their product CO  makes the sole or even predominant contribution to elevated BP at this age. Greater LVMI was associated with higher SV and TPR but not HR, suggesting that the greater wall mass may largely represent an adaptation to increased work related to preload and afterload. There was no evidence of interactions by sex indicating that these findings apply to both men and women.Higher BP in adolescence is because of a combination of higher HR, SV, and TPR as is commonly observed in adults.17 Reasons for these differences between studies are uncertain: possibly sample categorization and selection contribute to the observed differences. Julius et al16 subdivided hypertensive individuals in Tecumseh into normokinetic and hyperkinetic subgroups, both groups had elevated TPR, although only the hyperkinetic group had an elevated CO—it is noteworthy that the normokinetic group predominated by almost 2:1 (62 compared with 37). Lund Johanssen17 observed higher CO in 19 hypertensive individuals compared with 11 normotensive individuals aged 17 to 29 years, a comparable difference was not seen in older people; however, TPR was higher on average in hypertensive individuals at each age group studied. In the ENIGMA study of university students in the United Kingdom,25 young people with essential hypertension had elevated TPR, higher HR, and lower SV (and consequently a similar CO) to normotensive individuals, whereas young people with isolated systolic hypertension had higher MAP and SV, but HR and TPR did not differ from normotensive individuals. In ENIGMA, the normotensive, essential hypertensive, and isolated systolic hypertensive groups differed in terms of height, sex, and BMI, and it is likely that these differences may have contributed to the different hemodynamic patterns observed.Our observations do not lend support to the idea of a specific hyperkinetic or hyperdynamic state in young people with high BP as proposed previously.27 and suggest that LV adaptation to hemodynamic load is similar in adolescence to that observed in later life. The strong association between SV (or end-diastolic volume) on LVMI and RWT is also in keeping with previous findings in adults27 and is likely to reflect the strong influence of volume load on chamber size, wall stress, and LV hypertrophy.28Our observations relating HR, SV, and TPR to LVMI and RWT are consistent with previous studies in older adults29 As is expected in adolescence,6 the prevalence of hypertension was low; therefore, we cannot exclude that selected hypertensive adolescents may show different hemodynamic characteristics. All participants were of similar age when studied minimizing the influence of age on our findings but limiting the generalizability of our findings to other ages. The ALSPAC cohort is predominantly of white European origin, and it should not be assumed that our results will apply to other populations.Our study has strengths and limitations. ALSPAC is an unselected general population study that is reasonably representative of the contemporary UK population.30 after adjustment for age and baseline BP, no hemodynamic variables were significantly associated with the incidence of hypertension during a 4-year follow-up period, and in a study of young Swedish men, there was no significant correlation between baseline CO and BP measured 30 years later.31Although nested within a cohort, this study was cross-sectional, and, therefore, the question of whether people with high CO and normal TPR are at higher risk of essential hypertension or whether there are age-dependent differences in the trajectories of the hemodynamic determinants of MAP cannot be addressed. However, in the Framingham studyHigher BP in adolescents is attributable to a combination of higher SV, higher HR, and higher TPR. Relationships between measures of hemodynamic load and LV mass and RWT were qualitatively similar to those reported previously in older adults. There is no evidence of a disproportionate contribution from elevated HR or SV that explains higher BP levels in youth.We are extremely grateful to all the families who took part in this study, the midwives for their help in recruiting them, and the whole ALSPAC  team, which includes interviewers, computer and laboratory technicians, clerical workers, research scientists, volunteers, managers, receptionists, and nurses. C. Park and A.D. Hughes had full access to the data and took responsibility for the integrity of the data and its analysis.The Medical Research Council (MRC), the Wellcome Trust (092731), and the University of Bristol provide core funding support for ALSPAC . A. Fraser, L.D. Howe, G. Davey Smith, D.A. Lawlor, N. Chaturvedi, and A.D. Hughes work in units that receive funding from the UK MRC . A. Fraser and L.D. Howe are funded by UK MRC fellowships . Additional funding for this study came from the Wellcome Trust (086676/7/08/Z) and the British Heart Foundation (PG/06/145 and CS/15/6/31468). The views expressed in this article are those of the authors and not necessarily those of any funding body or others whose support is acknowledged. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.None.


Supplemental Digital Content is available in the text Nonalcoholic steatohepatitis (NASH)-related cirrhosis and cryptogenic cirrhosis (CC) have become leading indications for liver transplantation (LT) in the US. Our aim was to compare the trends, clinical presentation, and outcomes for transplant candidates with NASH and CC.The Scientific Registry of Transplant Recipients (1994–2016) was used to select adult LT candidates and recipients with primary diagnoses of NASH and CC without hepatocellular carcinoma.P < .0001). For most of the study period, patients with CC or NASH were similarly more likely to be taken off the list due to deterioration or death, with to patients with other CLDs. Post-LT data were available for 14,052 transplant recipients with NASH or CC. With the exception of post-transplant diabetes, the outcomes of patients transplanted for CC and NASH were similar to those of other CLD patients.Two lakh twenty-three thousand three hundred ninety-one LT candidates were listed between 1994 and 2016. Of these, 16,214 (7.3%) were listed for CC and 11,598 (5.2%) for NASH. Before 2004, NASH was seldom coded for an indication for LT, but became more common after 2009. Averaged across the study period, CC candidates compared with NASH candidates were younger and had fewer conditions of metabolic syndrome (MS). CC patients were more likely to have MS components in comparison to candidates with other chronic liver diseases (CLDs) (all Number of LT due to CC and NASH cirrhosis is increasing. In the past decade, there is a shift from LT listing diagnosis from CC to NASH potentially related to increased awareness about NASH in transplant centers in the US. In fact, nonalcoholic steatohepatitis (NASH) as an indication for LT has risen substantially so that it is currently the second most common indication for LT in the US,,6 synchronously with a steady increase in the prevalence of nonalcoholic fatty liver disease (NAFLD) and its complications in the US.–4 This trend is also affected by a simultaneous decrease in the number of patients with HCV requiring LT because of highly effective and safe antiviral treatments for HCV infection,–9 while no similarly effective treatment option exists for NAFLD. In fact, it is predicted that the combination of these 2 factors could push NASH or the progressive form of NAFLD, to become the most common indication for LT in the near future.–12Despite hepatitis C virus (HCV) being the leading indication for liver transplantation (LT) in the United States (US),,14 In fact, over a decade ago, evidence suggested that the majority of patients with CC in the US may have had “burnt out” NASH.,13,15–20 Nevertheless, controversy remains if patients transplanted for CC have NASH with the same on-list and post-LT outcomes or whether the 2 diagnoses indeed can be used interchangeably for most of the affected patient population. Therefore, the objective of this analysis is to use longitudinal data from the national registry to compare the trends and outcomes of patients listed or transplanted for NASH or CC in the US.It is important to remember that, until relatively recently, most of the clinical research related to NASH combined the diagnostic category of NASH-related cirrhosis and cryptogenic cirrhosis (CC).22.1In this study, we used data from the Scientific Registry of Transplant Recipients (SRTR), which includes data on all donor, wait-listed candidates, and transplant recipients in the US, submitted by the members of the Organ Procurement and Transplantation Network (OPTN). The Health Resources and Services Administration (HRSA), U.S. Department of Health and Human Services provides oversight to the activities of the OPTN and SRTR contractors.For this study, we included all liver transplant candidates and recipients of at least 18 years of age who were waitlisted or transplanted in 1994 through 2016 with the primary diagnosis of NASH or cryptogenic or idiopathic cirrhosis (the NASH+CC cohort). Patients with hepatocellular carcinoma (HCC) and acute liver failure were excluded from that cohort. Patients with all other causes of chronic liver disease  who had been waitlisted or transplanted in the same years were used as non-NASH non-CC controls.For all candidates, the studied outcomes were transplantation and wait list dropout; the latter included death or deterioration while waiting. For transplant recipients, the outcomes were being discharged alive after transplantation versus inpatient death before discharge, being obese (BMI ≥30) and having type 2 diabetes in follow-up, as well as postdischarge mortality , and graft loss . Patients undergoing retransplants were included in the mortality analysis only with their most recent transplants. Patients with no documented date of death were presumed alive as of March 1, 2017. Candidates who were presumed alive and had no documented wait list removal indication were presumed to be still waitlisted.2.2P values of .05 or less were considered significant.All collected clinical and demographic parameters of included waitlisted candidates and transplant recipients were summarized as mean ± standard deviation or N (%) and were compared between patients with NASH, CC, and with other CLD using Chi-square or Mann–Whitney test without and with accounting for the year of listing/transplantation. For assessment of time trends, Kendall correlation coefficients were calculated. All analyses were run in SAS 9.4 . The study was granted a nonhuman subject research status by Inova Institutional Review Board.33.1Over the study period 1994–2016), a total of 223,391 adult LT candidates were listed. Of these, 16,214 (7.3%) were listed for CC and 11,598 (5.2%) for NASH without HCC, with both accounting for >12.5% of all candidates were listed for LT. From 1994 to 2016, there have been partially mutually exclusive trends in the rates of CC and NASH listings among transplant candidates . Candidates with CC were also more likely to be male than patients with NASH (52.7% vs 50.3%). White race comprised (82.3%) of NASH candidates and only (75.3%) of CC candidates (P < .001). The model for end-stage liver disease (MELD) scores were highest among NASH candidates (22.4) followed by candidates with CC (21.1), and the rates of cirrhosis complications and some comorbidities  were also higher in NASH , but both were still older than patients listed for LT with other CLDs 51.9 years)   Fig. A.A similar trend in pretransplant obesity and a less pronounced but correlated trend in pretransplant hypertension were also observed Fig. B, C.3.3P > .10). When all CC and NASH candidates were compared with candidates listed with all other CLDs (average transplant rate 53.7%), there was also no significant difference . On the contrary, the average dropout rate from LT list for candidates with CC (27.3%) was significantly higher than candidates with NASH (24.0%); this, however, was completely explained out by the difference in timing (P > .025 in each given year). Despite this, the dropout rate in NASH and CC was consistently higher in comparison to patients with other CLDs  , mortality .Transplant data were available for 8137 CC, 5915 NASH, and 79,153 other CLD recipients (which is 94–96% of candidates removed from the wait list due to receiving a transplant). Clinicodemographic data were similar to that reported above for listed candidates. Post-LT prevalence of diabetes was similar in NASH and CC at all time points, and was higher than in other CLD until 2012 when the rates of post-transplant diabetes decreased substantially in all cohorts  (Fig. 4–25This study compares the trends in the prevalence, clinical characteristics, and outcomes of candidates who were listed or transplanted with the diagnosis of NASH and CC in the United States. Our data show a clear increase in the number of cases who are listed for LT in the US with the combined diagnoses of NASH and CC. In addition, there is a clear shift in the listing diagnosis from CC to NASH. This is most likely due to better recognition of NASH as a diagnostic category for listing for LT and the increasing number of cases with NASH-related cirrhosis seen in the US. Interestingly, in comparison to CC, NASH subjects who were listed or transplanted were older and more likely to be white and female. This is consistent with the demographic profile of NAFLD and NASH patients from the general population.–32 On the contrary, it is important to note that NASH patients were primarily listed in more recent years, so that increasing relaxation of contraindications for LT plays a role, in consistence with the increasing trends in the prevalence rates of comorbidities in all diagnostic groups. Furthermore, the rates of metabolic syndrome components were still substantially higher in CC in comparison to other CLD patients. On the basis of the pretransplant diabetes rates, we believe that a large proportion of CC patients listed for LT have underlying NASH. The exact proportion of CC patients with burned-out NASH cannot be determined but can be estimated between 50% and 75%.,34,35 This estimate is based on pretransplant diabetes and other metabolic abnormalities, which are very susceptible to the development of severe liver disease.An important finding of our study is that, in comparison to patients with CC, patients with NASH have a higher prevalence of components of metabolic syndrome, other comorbidities, and higher MELD scores. Again, this is consistent with a number of other studies showing that NASH subjects who are listed for LT have more obvious evidence for metabolic abnormalities than those listed with the diagnosis of CC. suggested that NASH/CC had a lower chance of receiving LT than patients with HCV.In comparison to other CLDs, a similar proportion of patients with CC and NASH eventually received LT, and the dropout rates were also similar in NASH versus CC, although those rates were higher than in other CLD, primarily due to lower proportion of NASH+CC patients being removed from the list because of improvement. In contrast to this finding, a report by O’Leary et alPost-transplant outcomes in patients with CC, NASH, and other CLD were largely similar with the exception of post-transplant diabetes, which was similarly higher in CC and NASH in comparison to other CLD patients. These data suggest that CC and NASH patients have similar potential for recurrence of metabolic abnormality and probably share the same pathogenic pathway that led to their cirrhosis. It is important to note that more recently, post-LT diabetes has decreased regardless of the diagnostic group. This could probably be explained by the use of less diabetogenic immunosuppressants in the recent years. who reported that both graft and patient survival rates at 1, 3, 5, and 10 years after LT were worse for patients with CC than NASH, even though NASH patients were older, and had metabolically worse picture than CC before LT. It is important to note, however, that that study did not account for patients with NASH being listed and transplanted primarily in more recent study years when all post-transplant outcomes improved solely due to recent advances in the transplant procedure and post-transplant management.Our data also showed that post-transplant mortality and graft failure was not different between CC and NASH, after adjustment for the year of transplant. These findings are not consistent with a study by Singal et alAlthough this study has many strengths, our main limitation was the availability of the initial data in the SRTR database, which has many missing records across fields, especially in earlier study years. In particular, pretransplant diabetes was not recorded until 2004, which does not allow for more robust estimates of metabolic profile of patients with CC.In conclusion, NASH as an indication for LT has become increasingly more recognized in the past decade. This may be due to both increasing prevalence of NASH and increasing recognition that most CC patients do, in fact, have NASH. Nevertheless, CC patients without components of metabolic syndrome before LT may have other etiologies rather than pure NASH. Despite this possibility, LT candidates with CC and NASH have similar on-list and post-LT outcomes. Further prospective studies are needed to determine why and how some patients with NASH lose hepatic steatosis, as they develop more advanced cirrhosis labeled as CC.PG, HB, IY, and CTL participated in the study design, helped the interpretation of the data, and drafted the manuscript. MS performed the statistical analysis and helped the interpretation of the data. AM, GT, ME, CV, and ZG participated in the interpretation of the data and revised the manuscript. ZG, IMJ, and ZMY conceived the study, participated substantially in its design and coordination, and helped to draft the manuscript. All authors read and approved the final manuscript.Conceptualization: Alita Mishra, Gregory Trimble, Madeline Erario, Zobair M. Younossi.Data curation: Maria Stepanova, Zachary Goodman.Formal analysis: Maria Stepanova.Investigation: Pegah Golabi, Haley Bush, Chapy Venkatesan, Issah Younossi.Methodology: Maria Stepanova.Resources: Issah Younossi, Zachary Goodman.Supervision: Ira M. Jacobson, Zobair M. Younossi.Validation: Ira M. Jacobson, Chapy Venkatesan, Zachary Goodman, Zobair M. Younossi.Writing – original draft: Pegah Golabi, Haley Bush, Maria Stepanova, Cameron T. Locklear, Alita Mishra, Chapy Venkatesan, Issah Younossi.Writing – review & editing: Ira M. Jacobson, Gregory Trimble, Madeline Erario, Zachary Goodman, Zobair M. Younossi.Author name: Orcid number:Zobair M. Younossi: 0000-0001-9313-577XPegah Golabi: 0000-0001-9818-0983


The dimensions of wellness and engagement in physical activity both are crucial for a healthy lifestyle, adjustment, and attainment of professional excel among young female health students.The purpose of the study is to determine adherence to physical activity and dimensions of wellness among students of the College of Health and Rehabilitation Sciences, Princess Nourah bint Abdulrahman University (n = 198).This study is based on a Cross-sectional design.Students of College of Health and Rehabilitation Sciences, Princess Nourah bint Abdulrahman University in Riyadh, Saudi Arabia. The study was carried out from May to December, 2018.Perceived Wellness scale was used to measure six dimensions of wellness. The frequency of physical activity was measured by self-report 5-point Likert scale. Data was collected through survey research forms.2 = .113, F  = 12.371, p < .01) with perceived wellness. The department-wise comparison of wellness perception revealed that all the departments score differently on various wellness dimensions.Results revealed that the physical wellness dimension was significantly correlated with all physical activity, exercising last year, social, intellectual, and overall wellness (p < .01) and with psychological, emotional, and spiritual wellness (p < .05). Furthermore, regression analysis confirmed the predictive relationship of frequency of physical activity and exercising last year (RComprehensively, association with all dimensions of wellness and physical activity was found among students of the College of Health and Rehabilitation. It further validates the impact of their well-designed curriculum and encouragement to engage with a healthy lifestyle. Further programs can work out to dimensions of wellness where weakness was found to achieve overall wellness. Psychology; Wellness; Physical activity; Health; Rehabilitation; Students; Saudi Arabia Health Wellness encompasses the complete health of the individual . WellnesSocial wellness makes individuals have successful interaction, communication, relationship and to feel appreciated and belonging . Health Spiritual dimension involves an individual having a set of guiding beliefs that help to direct one's life. It involves having an unwavering faith and unending commitment in ones' belief that provide a sense of meaning and purpose in life . PsycholHealth professionals have found that physical activity can improve immensely on health and reduce the risk of several diseases . There aThe World Health Organization defined wellness as the optimal state of health of individuals and groups . CohesivThis study is based upon the Social cognitive theory that emphasises that behaviour can be learned by social interaction while living in a particular situation . FurtherThe medical/health science students, future doctors, and therapists can not underestimate their importance about wellness . They haHypothesis 1Physical activity will be associated with perceived wellness among students of Health and Rehabilitation Sciences.Hypothesis 2Department wise students of Health and Rehabilitation Sciences will score significantly different on dimensions of wellness .As far as research evidence from Saudi Arabia is concerned related to physical activity among Saudi female medical students, some evidence was found in the literature. One of the studies based on BMI and dietary habits of Saudi female , another2Research design: The present study used a cross-sectional, descriptive, correlational research design. The research method applied is quantitative. Survey technique was used, including standardised self-report questionnaires, rating scale, and demographic information sheets. The study was conducted to investigate the relationship between physical activity and perception of wellness among students of CHRS, PNU, in Riyadh during May–December, 2018.n = [DEFF*Np(1-p)]/[(d2/Z21-α/2*(N-1)+p*(1-p)]) (Sampling: PNU has five (5) colleges in Health Campus. College of Health and Rehabilitation CHRS is the biggest and comprises a variety of programs and consists of four (4) departments, including Radiological Science, Rehabilitation Sciences, Health Sciences, and Communication Sciences. Furthermore, there are 13 program divisions within four departments . The sam*(1-p)]) . Total p*(1-p)]) . HoweverInclusion/exclusion criteria: The study was based on the perceived wellness of the students based on their physical activity engagement. The age range was 21–25 years (M±SD: 21.74 ± 0.837). There were a total of 255 students enrolled in final year BS programs at the CHRS. Students other than the final year and not meeting the age criteria were excluded. One of the Programs from the Rehabilitation department is Masters-degree program was excluded to avoid the maturity factor. Moreover, the Nuclear Medicine Technology program from the Radiology department was also excluded due to not offering final year levels for students. Therefore, the sample was collected from 11 programs.2.1i.Demographic information sheet: A personal information questionnaire prepared by the researchers was used to determine the age, department, track, and educational level.ii.Physical activity rating scale: Physical activity rating scale was developed by iii.Perceived wellness scale: Perceived wellness scale  of Princess Nourah bint Abdulrahman University before initiating the study, and permission was sought (IRB Log number: 18–0181). Consent forms, explaining the purpose of study, privacy, the confidentiality of data, indicating the role and responsibilities of the researcher, were provided to the subjects. After screening through demographic information, participants were given standardised scales. Data were collected by using individual administration of survey forms.Statistical analysis: Collected data were analysed by using SPSS (V. 24). Descriptive Statistics of measures of central tendency and dispersion were calculated. Pearson product-moment correlation and multiple linear regression analysis were computed to find out the relationship and predictive association of physical activity and perceived wellness scores. Further, one-way ANOVA was conducted to measure the differences in wellness dimensions between the scores of students from four departments.3Overall, 198 individuals participated in the survey. The response rate was 97%, with a refusal rate of 3%. Results in 2 = .113, F  = 12.371, p < .01) on the variable of wellness perception. Therefore, the first hypothesis of physical activity and perceived wellness association among students of Health and Rehabilitation Sciences has been accepted.Scheffe post-test comparison  indicate4The general awareness of the concept of wellness makes the health sciences students value the importance of the relationship that exists between the sound nourishment and functioning of the body. Moreover, the wellness perception motivates the students toward engagement in physical exercises. The medical students require several dimensions of wellness perception in order to enhance their lifestyles in a healthy manner and aid in the achievement of general wellness .Physical activity has been found to contribute immensely to the general well-being of an individual . The benResearch has found that the wellness of human beings comprises several dimensions that must be attained to fully achieve wellness, including spiritual wellness, emotional wellness, psychological wellness, intellectual wellness, social wellness, physical wellness, and even financial wellness . In the Concerning other dimensions of wellness, the Health and Rehabilitation students scored relatively low on specific domains. It may be due to the rigorous training in their specific discipline. Previous studies have established that medical training exposed more psychosocial stress among female students than other types of education . Therefo5In conclusion, the students from health and rehabilitation sciences showed an exceptional awareness of the perception of all the six dimensions of wellness, including psychological, social, emotional, spiritual, physical, intellectual wellness, and overall wellness as well. Physical activity was found associated and can predict wellness among health students. What was established is that the health and rehabilitation students were found different in various dimensions of wellness. Moreover, overall, students are responding to their wellness and practicing physical activities regularly.U. Zaidi: Conceived and designed the experiments; Performed the experiments; Analyzed and interpreted the data; Contributed reagents, materials, analysis tools or data; Wrote the paper.Deanship of Scientific Research at Princess Nourah Bint Abdulrahman University, Saudi Arabia through the Fast-track Research Funding Program.This research was funded by the The authors declare no conflict of interest.No additional information is available for this paper.


Low-grade inflammation (LGI) has been suggested to be involved in the development of chronic diseases. Healthy dietary patterns, such as the Mediterranean diet (MD), may decrease the markers of LGI. Healthy Nordic diet (HND) has many similarities with MD, but its effects on LGI are less well known. Both of these dietary patterns emphasize the abundant use of fruits and vegetables (and berries in HND), whole grain products, fish, and vegetable oil (canola oil in HND and olive oil in MD), but restrict the use of saturated fat and red and processed meat. The aim of this narrative review is to summarize the results of studies, which have investigated the associations or effects of HND on the markers of LGI. Altogether, only two publications of observational studies and eight publications of intervention trials were found through the literature search. Both observational studies reported an inverse association between the adherence to HND and concentration of high sensitivity C-reactive protein (hsCRP). A significant decrease in the concentration of hsCRP was reported in two out of four intervention studies measuring hsCRP. Single intervention studies reported the beneficial effects on interleukin 1Ra and Cathepsin S. Current evidence suggests the beneficial effects on LGI with HND, but more carefully controlled studies are needed to confirm the anti-inflammatory effects of the HND. Low-grade inflammation (LGI) has been linked with the pathogenesis of several chronic diseases, such as cardiovascular diseases, type 2 diabetes, certain cancers, and neurodegenerative diseases ,2,3,4. IObesity, especially abdominal obesity and the accumulation of visceral fat, is associated with LGI, and weight loss is the key treatment for LGI in overweight and obese people . Weight Healthy Nordic diet (HND) has many similarities with the Mediterranean diet . Both diRecently, Kaluza and colleagues developed a questionnaire-based Anti-Inflammatory Diet Index (AIDI), which could predict systemic chronic inflammation in the Nordic population . It was The aim of this narrative review is to summarize the results of studies, which have investigated the associations or the effects of the HND on markers of LGI in observational and intervention studies, respectively. There are several different biomarkers that are used for assessing LGI in dietary studies. In these studies, the markers have been CRP, hsCRP, IL-6, IL-1 Ra, leptin, high-molecular weight adiponectin, TNF-α, IL-1β, IL-10, TNF RII, and Chatepsin S. Furthermore, inflammation on the level of expression of genes that are linked to inflammation in adipose tissue and peripheral blood mononuclear cells (PBMC) is an interesting approach to examine the impact of diet on LGI in the target tissues ,21.We carried out a literature search of the Nordic diet and LGI and related biomarkers in PubMed. We used the following search term:  AND (inflammation OR biomarker OR metabolomics) AND human NOT animal. The search was performed until the 30th of April 2019 and it gave, altogether, 38 publications. Relevant articles were selected based on the review of the abstracts . All of Thus far, there are two observational studies (including data from three cohorts) investigating the association between the HND  and LGI. Those studies have consistently shown an inverse association between the HND and hsCRP A.n = 4579), and in the Helsinki Birth Cohort Study  [p < 0.01) in all adjusted models, which included relevant confounding factors, such as age, sex, energy intake, education, smoking, physical activity, waist circumference, medication for diabetes, and the use of statins. Participants’ mean concentration of hsCRP was 1.14 mg/L in the lowest BSDS quintile and 1.03 mg/L in the highest BSDS quintile. Unexpectedly, HMW-adiponectin concentrations also inversely associated with the BSDS (p < 0.05). Adjustments for the above-mentioned confounding factors strengthened this association (p < 0.01). Other measured inflammatory markers did not associate with BSDS in the DILGOM study. Alcohol intake was the only component that significantly associated with the HMW-adiponectin concentrations of the single BSDS components. Participants with a high intake of alcohol had higher HMW-adiponectin concentration than individuals with low alcohol intake (p < 0.001). This finding is consistent with earlier findings that were related to alcohol consumption and adiponectin [p < 0.01). Other measured inflammatory markers did not associate with BSDS in the HBCS study. Among the single BSDS components, the higher intake of Nordic fruits, berries, and cereals, and the lower intake of red and processed meat and moderate alcohol intake significantly associated with lower hsCRP concentrations in both of the studies.The association between the HND and inflammatory markers was independently investigated in two large cross-sectional studies in Finnish participants: in the DIetary, Lifestyle, and Genetic determinants of Obesity and Metabolic syndrome (DILGOM) study ( = 1911) . In bothponectin . In the Both the DILGOM and the HBCS study were included among the Health 2000 Survey in the meta-analysis investigating associations with BSDS and cardiometabolic risk factors, including hsCRP  Table 2Table 2A.In summary, it has been consistently shown that a high adherence to the HND lowers the risk of low-grade inflammation, but, so far, the studies are scarce and only conducted among Finns.p < 0.01 and p < 0.05, respectively) and the change in hsCRP in the WGED group was significantly different from that in the control group (p < 0.05) (Only three intervention studies have investigated the effects of the HND pattern on LGI B. Furthe < 0.05) . Interes < 0.05) .ad libitum. CRP and TNF-R2 was significantly decreased by the prudent breakfast when compared with the control breakfast (p < 0.005). The percentual changes in CRP and TNF-R2 between baseline and 12 weeks were +37% for the control breakfast and −30% for the prudent breakfast, and +9% for the control breakfast and +2% for the prudent breakfast, respectively. There were no changes in body weight, but sagittal abdominal diameter, which is a marker of visceral fat, was reduced in the prudent breakfast group.The effect of a prudent low-fat breakfast (based on Nordic foods) as compared with usual breakfast was studied in a parallel controlled 12-week study with 79 healthy overweight . The pruad libitum New Nordic Diet (NND) versus Average Danish Diet (ADD) in adults (18–65 y) with central obesity and components of the metabolic syndrome could reduce body weight and improve the risk markers of the metabolic syndrome, type 2 diabetes, and cardiovascular diseases [p = 0.007) [p = 0.043). TNF-α was measured for the subset of the study population (n = 64), and it did not change significantly [The effect of the HND pattern on LGI has been investigated in three randomized controlled trials B. In thediseases ,28. The diseases . The con= 0.007) . The decficantly . It is wficantly . Howeverficantly .ad libitum Nordic prudent diet or a control  diet for six weeks [ad libitum nature of the HND diet. Cathepsin S is a proteolytic enzyme that has been associated with LGI [p = 0.03). However, the decrease was not significant after adjusting for change in body weight and LDL-cholesterol concentration, which may indicate that the decrease of the level of S cathepsin was mediated by weight loss or lowered LDL cholesterol concentration. There were no changes in CRP (p = 0.40) [In the NORDIET trial, 88 normal to slightly overweight hyperlipidemic men and women were randomly assigned to ix weeks ,27. Altowith LGI ,38. Comp = 0.40) .In the SYSDIET study , altogetA Mediterranean type diet, which is much more studied when compared to Nordic diet, has consistently shown to be anti-inflammatory . MediterOverall, currently, it is not possible to draw definite conclusions of anti-inflammatory effects of HND, since there are quite few studies investigating this issue. Furthermore, several different markers of inflammation have been applied in the studies. It might be seen as a strength that favorable effects have been seen in the circulating markers of inflammation as well as in gene expression level in adipose tissue and PBMCs ,30. ReceAll of the studies investigating the health effects of HND, and reported in this review, were conducted in the Nordic countries, which enables a reasonable compliance to the HND in the intervention groups. The control diet was usually the average diet in the Nordic countries. However, as seen e.g., in the SYSDIET study , the peoOne limitation in these studies is that there was a significant weight loss during the intervention in some of these ,28. ThesThis narrative review overviews and summarizes all the published papers covering the HND and LGI. Only 10 papers describing seven studies were found, including three observational studies and four interventions. The authors are not aware of other reviews investigating this issue in detail. Quite few studies have investigated the effect of HND on LGI so far. Two observational studies have shown an inverse association between the adherence to the HND and concentration of hsCRP. In the intervention studies, a significant decrease in the concentration of hsCRP has been reported in two studies ,29 out o


With the widespread nature of wireless internet and internet of things, data have bloomed everywhere. Under the scenario of big data processing, privacy and security concerns become a very important consideration. This work focused on an approach to tackle the privacy and security issue of multimedia data/information in the internet of things domain. A solution based on Cryptographical Digital Signal Processor (CDSP), a Digital Signal Processor (DSP) based platform combined with dedicated instruction extension, has been proposed, to provide both programming flexibility and performance. We have evaluated CDSP, and the results show that the algorithms implemented on CDSP all have good performance. We have also taped out the platform designed for privacy and security concerns of multimedia transferring system based on CDSP. Using TSMC 55 nm technology, it could reach the speed of 360 MHz. Benefiting from its programmability, CDSP can be easily expanded to support more algorithms in this domain. We have entered the era of Big Data. The widespread nature of internet of things and wireless network, is making multimedia communication systems, such as on-line chatting, video conference and surveillance systems, becoming more and more popular. Since the process of multimedia communication systems involves data generation, storage, sending, receiving, sharing and so on, various security issues should be concerned. Data encryption algorithms could be adopted in multimedia communication systems to guarantee the security of data. Many kinds of data encryption algorithms have been released. This provides people with more options to choose according to their own needs. However, it also imposes a challenge for hardware design to have a large level of flexibility to adapt to different kinds of data encryption algorithms with limited time.In this work, we focused on solving the privacy and security issue of multimedia surveillance system in internet of things domain, where high quality video and audio recorded by cameras needs to be compacted, encrypted and transferred to the control center through network, and be replayed in real-time on the monitors.Data in the stream always contain private information, so encryption of the raw data is required to protect the data stream from disclosure before transferring. Thus data encryption algorithms need to be supported.Since surveillance audio and video can be used as legal evidence to justify the fact, it is necessary to ensure the truth and reliability of the data stream. Hash functions and authentication could be of use for this.Sometimes it is required to verify whether the audio and video are from a specific user. Thus digital signature should also be supported.Requirement of real-time. Time delay from the scene to the control center should be less than 170 ms, which means that the work of video/audio encoding, encryption, decryption and video/audio decoding should be finished in 170 ms. According to the practical application, the peak throughput of the data stream should reach 150 Mbps.When evaluating the feature of the data stream of multimedia surveillance system, one finds that:Thus, the middleware platform of this kind of surveillance system should support a lot of different kinds of data encryption algorithms. In this work, we present our middleware solution based on CDSP, combining the programmability of DSP and the high efficiency of dedicated designed special operations. Benefiting from the programmability of DSP, new kinds of algorithms can be easily implemented, providing a high level of flexibility. Furthermore, the special operations designed dedicated for some algorithms can significantly reduce the code size, and largely enhance the performance. This is a new attempt in cryptographic DSPs, and the results show that our approach is both feasible and efficient.The remainder of this paper is organized as follows: Our middleware solution is built based on a DSP called CDSP, which is designed as a 6-issue VLIW DSP. It provides high instruction level parallelism, and can greatly improve the performance on cryptographic algorithms execution. In this section we will introduce it in more detail.CDSP core  is compoIFU reads instruction packets from PMEM. Each instruction packet is 256-bit width, containing eight to 16 instructions.IDU seeks available instructions in the package and hands them out to EU. At most, six instructions can be dispatched each cycle.EU is clustered, and the two clusters are named as X cluster and Y cluster. EU includes six function units, which are named as XA, YA, XM, YM, XD and YD separately. XA, XM and XD belong to X cluster. YA, YM and YD belong to Y cluster. XA and YA are arithmetic units, executing arithmetic and logic instructions, such as ADD, SUB, AND, XOR, ASL and LSR. XM and YM are multiplication units, executing multiplication instructions, and some arithmetic logic instructions. XD and YD are load/store units, loading data from DMEM to register, or storing data from register to DMEM. Some arithmetic logic instructions and branch instructions can also be executed in XD and YD units.CDSP includes 11 pipeline stages, as shown in PCG (PC generation): This stage generates the next PC, which is chosen from the interrupt PC, branch PC and PC + 4.PCS (PC send): This stage passes the generated PC to the next stage.PWT (PC wait): This stage checks whether the instruction is valid in the instruction cache or not. If the instruction is invalid, instructions should be fetched from the PMEM.IR (instruction return): We get the instructions in this stage.EXP (instruction expansion): As the instructions are either 16-bit or 32-bit, we expand the instructions to the same length in this stage.IDP (instruction dispatch): Instruction dispatch is completed in this stage. Since the function unit information is encoded in the instructions, we can get this information and dispatch the instructions to the corresponding function units. This procedure can be interpreted as predecode and dispatch.IDC (instruction decode): This stage decodes the instructions.EX1∼EX4 (instruction execution): Instructions are executed in this stage. Different instructions need 2∼4 stages to complete execution.CDSP has three register files, which are also clustered. Register files are also shown in X and Y are two symmetrical clusters. Taking advantage of the symmetrical architecture, CDSP can access 56 registers using only 5 bits of the instruction. Usually, 5 bits can only address 32 registers. A large number of registers can help exploit Instruction Level Parallelism (ILP) and increase the performance. Some algorithms can also take advantage of the symmetrical architecture to run in parallel.CDSP is a RISC processor, and its Instruction Set consists of both general instructions and dedicated designed special instructions. General instructions include arithmetic and logic instructions, shift instructions, multiplication instructions, load instructions and branch instructions. Dedicated instructions are designed for specific cryptographic algorithms in order to improve the performance. General instructions will be described in this part.Arithmetic instructions: Addition (ADD/ADC) and subtraction (SUB/SUBB). The operands could be 32-bit signed or unsigned numbers, and the operation could be addition with carry or subtraction with borrow.Logic instructions: Bitwise AND, bitwise OR, bitwise XOR and bitwise Negate (NOT). Operands can be immediate data or come from registers.Move instructions: Move a data from one register to another (MOV).Shift instructions: Arithmetic Shift Right (ASR), Logic Shift Right (LSR), Arithmetic Shift Left (ASL), and Barrel Rotate Left (ROL).Multiplication instructions: Multiplication (MUL) and Accumulation (ACC). Multiplication instructions occupy two pipeline stages.Pack instructions: Pack instructions switch the byte sequence in a 32-bit operand, or select some bytes from two operands and build up a new word.LOAD/STORE instructions: Load (LD) data from data memory to registers, or store (ST) data from register to data memory. A RISC processor always uses powerful load-store instructions to finish data transfer between registers and memory. CDSP LD instructions use base register and offset register to calculate the memory address, and the base register can increase or decrease automatically.Branch instructions: Branch to the target PC and flush the instructions in pipeline (B); Branch to the target PC without flushing the instructions in pipeline (BD); Call subroutine (CALL); Return from subroutine (RET).The architecture of CDSP system is shown in An embedded Direct Memory Access (DMA) with an AXI master interface is designed in CDSP, which is used to read and write data stream though AXI bus, with high bandwidth. The DMA can be controlled either by CDSP or AXI-lite.The CDSP platform we presented combines both the programmability of DSP and the high efficiency of dedicated designed special instruction to: (1) provide flexibility for implementing of different kinds of encryption algorithms, and (2) achieve high performance. Dedicated instruction design for cryptographic algorithms is an important feature of CDSP, and is also an innovation in cryptographic DSP design.Block cipher algorithms ,3,4,5, iHash  functionMany kinds of data encryption algorithms have already been implemented on our platform:In this section, the design of dedicated instructions for DES and AES algorithms will be introduced.DES encrypts 64-bit plain text, and generates a 64-bit cipher text, using a 64-bit key. DES algorithm could be divided into three function units as shown in (1)(2)Result of step (1) xor with round key ((3)Result of step (2) is substituted using lookup table S-box;(4)Result of step (3) is rearranged with a new Permutation (P).If only general instructions are used to implement the DES algorithm, then a large number of instructions will be needed, considering the performing of the permutation, which would result in large code size. And also the performance might be low.DESIP: Deigned to implement the IP operation. The source operand is a 64-bit data from a register pair, and the result is also 64-bit width and stored in a register pair.DESFP: Deigned to implement the FP operation. Function of this instruction is the same as DSEIP.DESRND: Designed to implement the DES round transformation. The source operand is a 64-bit intermediate result and a 48-bit round key. The output is a 64-bit intermediate result for the next round.Three dedicated instructions are designed for the implementation of DES algorithm:The comparison of code size is shown in SubBytes: Each byte is used as an address to look up a SubBytes table and output a new byte, substituting for the initial byte.ShiftRows: The last three rows of the matrix shift left cyclically for 1 byte, 2 bytes and 3 bytes separately, as shown in MixColumns: Combines 4 bytes in each column. It can be implemented by using a fix value matrix to multiply the mid-state, as shown in AddRoundKey: Round key is a 128-bit key expanded from the initial key. AddRoundKey conducts bitwise XOR operation between mid-state and the round key.AES encrypts 128-bit plain text, and generates a 128-bit cipher text, using a 128-bit key. AES consists of 10 round transformations. The intermediate result between two rounds is a 16-byte data called mid-state, which is usually arranged in a 4 × 4 matrix. AES round transformation is based on this matrix. AES could be divided into four main operations as shown in ShiftRows can be moved to the front of SubBytes, and the sequence will become ShiftRows→SubBytes→MixColumns→AddRoundKey.Using general instructions only to implement SubBytes, ShiftRows and MixColumns operations will result in low throughput and large code size. Dedicated instructions are designed to enhance the performance of AES.AESSHF: AESSHF conducts ShiftRows, as shown in AESSUBMIX: AESSUBMIX conducts two operations, SubBytes and Mixcolumns, as shown in AESSUB: AESSUB conducts SubBytes operation, as shown in Three dedicated instructions are designed for the implementation of DES algorithm:As shown in There is not much research reported on the implementation of cryptographic algorithms on a DSP platform combined with dedicated instruction extension, while some are similar to ours. We divide them into two categories.T. Wollinger et al.  researchTMS320C6201 DSP has 32 32-bit registers and eight independent functional units. The architecture of TMS320C6201 DSP is also divided into two parts and each part includes four functional units and 16 registers.They compare the result with Pentium-Pro processor, both working under 200 MHz. It shows that the performance of TMS320C6201 is better than Pentium-Pro processor by about 32.3% on average.K. Itoh et al.  also impY. S. Zhang et al.  have desIntel proposes Advanced Encryption Standard (AES) new instruction set in 2010 . The newThe IBM Power8  processoOur implementation combines the features of these two approaches, which realizes cryptographic algorithms on a DSP with an extended instruction set.Function simulation of CDSP is achieved by Synopsis VCS and Verdi joint simulation, working under Redhat system. FPGA verification is conducted on XC5VLX330T from Xilinx vertex 5 series. Verification is based on Synopsis VMM , using system Verilog. Using VMM, we can generate random test cases or test cases with constraints.C language is used to build a C-model for certain cryptographic algorithm. Furthermore, we use C-model to generate the correct result, called the golden result.The programs implementing different cryptographic algorithms are written in CDSP assembly language. The assembler of CDSP is designed based on GNU Binutils binary tool set. We compiled the assembly programs, sent the firmware, together with the test cases, to the DSP, and got the simulation result. The result will be compared with the golden result, and whether the result is correct will be reported.Performance comparison of AES128 with general purpose processors is shown in We also compare the performance of CDSP with other approaches of ISA extension, as shown in In the third column, the number of multiplication operations are evaluated based on the assumption that half of the binary bits in a big number are 1, which is a worst case. Choice of the key and window width can affect the result significantly. In this paper, the window width is 2, and the performance can be raised by 8.7% on average compared with the performance when the window width is 1.In conclusion, CDSP shows satisfactory performance in cryptographic algorithms. Compared with other DSPs, CDSP shows far better performance for algorithms with dedicated instructions and close performance for algorithms without dedicated instructions. Compared with processor with dedicated cryptographic instructions, CDSP shows better performance than Power8 and close performance with Intel under CBC mode.We have implemented the multimedia surveillance system based on CDSP platform. The chip of the surveillance system is taped out and mass-produced. Using TSMC 55 nm technology, the synthesized frequency of CDSP achieves 360 MHz. The critical path is in the instruction dispatch stage. The dedicated instruction extension does not reduce the working frequency. The area is 186,000 gates and 40 KB SRAM (16 KB DMEM and 24 KB PMEM). Area consumption caused by ISA extension are 7862 gates, which is about 4% of the total area. The power consumption is 58 mW. This paper proposes our approach and experiences for designing a platform based on CDSP, a clustered VLIW DSP with ISA extension for cryptographic algorithms. CDSP is designed to target the solving of privacy and security issues in multimedia surveillance system. CDSP has 11 pipeline stages, making it achieve high frequency of 360 MHz. CDSP has six function units, and can run up to six instructions in one cycle, largely enhancing the calculation density. The architecture of CDSP is advantageous in exploiting instruction level parallelism and achieving better performance.ISA of CDSP consists of both general instructions and dedicated instructions. In this work, we presented our experience for design dedicated instructions for DES and AES algorithms. The result shows that those dedicated designed instructions can significantly improve the performance, and reduce software code size. Since cryptographic algorithms usually consist of special complex computation-intensive operations, making software solution yield poor throughput, according to our results, adding dedicated instructions is a good choice to improve performance, and is more convenient compared with the co-processor scheme.Many common cryptographic algorithms are already implemented in CDSP, including block cipher algorithms, hash functions and public key cryptographic algorithms. Using our approach, new data encryption algorithms could be easily implemented on CDSP platform, making CDSP a practical solution for building, establishing a complete network security system.


Callithrix jacchus) may offer several advantages over other non-human primates in terms of its smaller size, shorter life-span, and dental anatomy identical to humans. The purpose of this study was to determine the viability of using the marmoset as a human oral disease model. We collected saliva samples from eight marmosets and eight human subjects. Prokaryotic DNA was extracted from the saliva samples, and 16S bacterial rRNA gene sequencing was performed on each of the samples. Our results indicated that the types of oral microbiomes detected among human and marmoset samples were nearly indistinguishable. In contrast, the oral microbiomes of our human and marmoset subjects were distinctly different from those reported for rats and dogs, which are currently popular research animals. The oral microbiomes of marmosets showed greater diversity than those of humans. However, the oral microbiota of marmosets exhibited less variation than those of humans, which may be attributed to the fact that the marmoset subjects were kept in a controlled environment with identical lifestyles. The characteristics of its oral microbiota, combined with other technical advantages, suggest that the marmoset may provide the best animal model thus far for the study of oral health. This study characterized the oral microbes of the marmoset, thereby providing information to support future application of the marmoset as a model for age-related oral disease.With rapid aging of the world’s population, the demand for research, for a better understanding of aging and aging-related disorders, is increasing. Ideally, such research should be conducted on human subjects. However, due to ethical considerations, animals such as rodents and monkeys are used as alternatives. Among these alternative models, non-human primates are preferred because of their similarities with humans. The small South American common marmoset ( Callithrix jacchus) offers a number of advantages over other non-human primates given their relatively small size and shorter life-span [Aging is a complex phenomenon affecting all organs of the body. In the field of basic science, experimental subjects such as cells, worms, flies, and rodents have provided extensive groundwork for aging research . Howeverife-span . ConsequDue to rapid aging of the world’s population, an increasing number of studies have articulated the importance of maintaining oral health. For instance, the prevalence of periodontitis increases with age, as shown by epidemiological studies , 4. IndeA substantial number of studies have examined the influence of oral health status, especially the existence of periodontitis, on general health. Examples include the association between the severity of periodontitis and cardiovascular disease, diabetes mellitus, and neurodegenerative diseases , 8–12. PEight healthy common marmosets aged between 10 and 18 years were selected from the colony at Clea, Japan . Human subjects were recruited among the patients who visited the Dental Hospital, Tokyo Medical and Dental University. Finally, eight healthy human subjects  were selected after excluding those with any prescribed medication, periodontitis, or systemic diseases.Marmosets were fasted on the day of saliva collection to obtain undisturbed oral microbiota from each animal. Saliva samples were collected by probing sterilized cotton swabs  in the oral cavity and allowing the marmosets to habitually chew on the cotton swabs. After 2–3 minutes, the cotton swabs were removed and suspended in 1 ml of sterile distilled water in sterile 1.0-ml tubes. The tubes were then stored at −80°C, until assayed for DNA analysis.As for human subjects, they were asked to refrain from eating, drinking, brushing their teeth, and rinsing their mouth on the day of saliva collection to obtain undisturbed oral microbiota from each subject. Saliva was obtained by requesting them to spit saliva into sterile tubes while sitting in an upright position in a chair; saliva samples were frozen immediately and then stored at −80°C until analysis. To minimize the effects of circadian rhythm, samples from the two species were collected between 9:00 a.m. and 11:00 a.m.All subjects underwent a standard oral examination. Oral examinations for marmosets and humans were conducted by registered dentists. Data such as types of teeth present, teeth condition , and gingival inflammation were collected. During the oral examination, the marmosets were manually held by the veterinary staff using hands and arms. The mouth was kept open by placing a wooden chopstick between the marmoset’s posterior teeth. To minimize physical and emotional distress to the animals, anesthesia or special restraint devices were not used.DNA was extracted using a NucleoSpin Soil  according to the manufacturer’s instructions. The quantity and quality of extracted DNA were determined using a NanoDrop spectrophotometer , Quant-iT dsDNA HS Assay Kit , and agarose gel electrophoresis.5’-TCGTCGGCAGCGTCAGATGTGTATAAGAGA CAGCCTACG GGNGGCWGCAG-3’) and 806R (5’-GTCTCGTGGGCTCGGAGATGTGTATAAGAGACAG GGACTACHVGGGTWTCTAAT-3’) with dual index were used for amplifying the V3–V4 regions of the bacterial 16S rRNA gene using a melting temperature of 50°C and 28 cycles. The sequencing was performed on the Illumina MiSeq platform .The fusion primers 341F , CD-HIT-OTU (version 0.0.2) was utilized. Sequences were clustered into OTUs at 97% similarity using CD-HIT-OTU software. Taxonomic assignments for the 16S rRNA was performed using the RDP classifier program (version 2.2). A total of 51,135 sequences remained and were automatically used for clustering after quality control screening.No animals were sacrificed during this study. All animals were cared for according to the protocol approved prior to the start of the study by the Animal Welfare Committee of Clea Japan Co. . All study animals were kept on a 12-hour light/dark cycle (7 a.m./7 p.m.) and were individually housed in isolated cages. The size of the cage was as follows: length 39 cm, width 55 cm, and height 70 cm. All were fed with commercially available monkey food for breeding and stud feed CMS-1M  twice a day. Daily care was provided by the same staff, and the veterinary staff took care of the animals in case of any health problems. The veterinary staff also examined the conditions of animals before and after the study. As for the human subjects, the study was performed in accordance with the World Medical Association Declaration of Helsinki, and the study protocol and consent procedures were approved by the institutional ethics committee at Tokyo Medical and Dental University prior to commencement of the study .Statistical analyses were performed using the Statistical Package for Social Sciences (SPSS) for Windows, version 11.5 . OTU numbers, Shannon diversity index, Chao 1 diversity index, and unweighted UniFrac were calculated using QIIME (v. 1.8.0). The Mann-Whitney U test was used to compare the microbial composition between the two species. A two-sided p value < 0.05 was used as a level of statistical significance.Human participants were provided written and verbal explanation with respect to the purpose of this study. The eight subjects signed the consent forms and agreed to enroll in the study. As for the animal subjects, eight healthy marmosets were randomly selected. Distribution of age among the human subjects and marmosets is shown in The oral conditions compared are shown in The distribution of the number of OTUs are shown in The overall bacterial community composition was compared using the UniFrac. UniFrac represents a phylogeny-based distance metric ranging from 0  to 1 (completely different). A principal-coordinate analysis plot based on unweighted UniFrac values revealed distinct clustering of samples from marmosets and humans, indicating the difference in microbial compositions between the two species . As for Firmicutes, Bacteroides, Proteobacteria, Actinobacteria, Fusobacteria, TM7, and Spirochaetes. The other phyla, Tenericues, Synergistetes, and SR1 were detected in traceable small percentages among the whole oral microbiome in our study samples. The average relative abundance of these seven phyla is shown in Firmicutes, Bacteroides, and Proteobacteria were the major phylotype in human saliva, which accounted for 33%, 27%, and 21% of relative abundance on an average, respectively. The fourth abundant phylotype was Actinobacteria, which accounted for 9%. On the other hand, in the marmoset samples, Proteobacteria, Bacteroides, Fusobacteria, and Firmicutes were the major phylotype, which accounted for 26%, 24%, 21%, and 19%, respectively. Their relative abundance was statistically examined using the Mann-Whitney U test. Compared with humans, Actinobacteria and Firmicutes were statistically less abundant in marmosets , and Fusobacteria and Spirochaetes were statistically more abundant in the marmosets (p < 0.001).Furthermore, taxonomic distribution of the numerically abundant bacteria derived from the 16S rRNA gene sequences in all samples were examined . Most ofIn this present study, we analyzed oral microbes from marmosets and humans for comparison. This is the first known report revealing the viability of marmosets as an animal model for oral diseases and oral physiology. Our study has demonstrated important similarities between oral microbes in marmosets and humans, particularly in relation to microbiome phyla, and revealed that oral microbes in marmosets exhibit higher diversity with less individual variations than human oral microbes.Anatomically, both humans and marmosets have common dental physiology in terms of the number and types of teeth . A marmoThis study revealed that oral microbe samples from marmosets showed relatively higher diversity at the OTU level since the difference is close to the statistical level. Although, in general, the oral microbiome varies dynamically over one’s life-time, this diversity is known to be maintained via healthy oral conditions through an optimal balance between the oral microbiota and the host’s immune system . Any onsFirmicutes, Bacteroidetes, Proteobacteria, Actinobacteria, and Fusobacterium, were detected in both humans and marmosets. This result is consistent with those reported in previous human and non-human-primate studies [Spirochaetes–reported to include species of the genus Treponema,—were detected in all samples of the marmoset subjects, but not in the human subjects. This may be attributed to the fact that the marmosets in this study were old, with calculus deposited on their teeth, implicating the existence of periodontitis or gingivitis, whereas the humans were healthy middle-aged subjects without any significant oral or systemic disease. In previous studies, Spirochaetes were reported to be detected in the saliva of patients with oral cancer, periodontitis, and systemic diseases [We found important similarities in the salivary microbiome between humans and marmosets. Five of the most abundant phyla in humans,  studies , 29, whidiseases , 26, 30.Spirochaetes–which is generally found in root canal infections, gingivitis, and periodontitis [Marmoset subjects showed inflammation of their gum, but human subjects did not. This explains why the phylum dontitis –was detedontitis , 32. Thedontitis , 34. WitLaboratory rats, such as Wistar rats, and dogs have been widely used in scientific experiments as models for human oral disease. The oral microbiomes of laboratory rats  and dogsA major limitation of this study was that our sample consisted exclusively of old-aged marmosets. Although we selected marmosets with a wide age range (10 to 18 years), our sample turned out to be surprisingly homogeneous in terms of the oral microbiome and oral-health status. Therefore, we could not determine any associations between these factors  within our sample. Nevertheless, it is reasonable to assume that such associations not only exist, but also that they can be teased out in future studies by including marmosets of younger age-groups and by collecting more detailed data on the marmosets’ oral health status, such as the severity of gingival inflammation, depth of periodontal pockets, and extent of dental decay. Such studies shall reinforce the feasibility of the marmoset as an ideal, promising oral health model for future research.In the context of the marmoset’s dental physiology, shorter life-span, and smaller body mass, our findings suggest that the marmoset could be a model for studying general oral health and its relationship with aging. In conclusion, this study is the first to describe and discuss the oral microbes of the marmoset, thereby providing important information for the application of the marmoset as a model in studies of age-related oral diseases.


Background: Elicitors and symptoms of anaphylaxis are age dependent. However, little is known about typical features of anaphylaxis in patients aged 65 years or more.Methods: The data from the Network for Online Registration of Anaphylaxis (NORA) considering patients aged ≥65 (elderly) in comparison to data from adults (18–64 years) regarding elicitors, symptoms, comorbidities, and treatment measures were analyzed.Results: We identified 1,123 elderly anaphylactic patients. Insect venoms were the most frequent elicitor in this group (p < 0.001), followed by drugs like analgesics and antibiotics. Food allergens elicited less frequently anaphylaxis (p < 0.001). Skin symptoms occurred less frequently in elderly patients . The clinical symptoms were more severe in the elderly (51% experiencing grade III/IV reactions), in particular when skin symptoms (p < 0.001) were absent. Most strikingly, a loss of consciousness  and preexisting cardiovascular comorbidity  were more prevalent in the elderly. Finally, adrenaline was used in 30% of the elderly  and hospitalization was more often required .Discussion and Conclusion: Anaphylaxis in the elderly is often caused by insect venoms and drugs. These patients suffer more often from cardiovascular symptoms, receive more frequently adrenaline and require more often hospitalization. The data indicate that anaphylaxis in the elderly tends to be more frequently life threatening and patients require intensified medical intervention. The data support the need to recognize anaphylaxis in this patient group, which is prone to be at a higher risk for a fatal outcome. The incidence of anaphylaxis, which may occur at any age, is rising in Western countries , 2. WhilOverall, elderly patients have a higher risk for severe and fatal reactions .The main elicitors of anaphylaxis are insect venoms, drugs and food items . While fRecommendations for the emergency treatment of anaphylaxis are similar for all age groups and are supported by current guidelines . Some coIn this study, we analyzed data from adult patients differentiated by age from the European Anaphylaxis Registry registered between 2007 and 2017. The aim was to better understand anaphylaxis in patients ≥65 years. Data regarding elicitors, symptoms, comorbidities, and emergency treatment were considered.The European Anaphylaxis Registry collects information on anaphylactic reactions through a web based electronic data capture system as described previously . ParticiAfter completion of diagnostics, patients' data were retrieved from medical treatment, laboratory measurements, and emergency protocols as available. Using a pseudonym, the data were entered by trained study personnel into an online questionnaire in each study center. The questionnaire and data entry is described elsewhere . Data coAge at reaction was categorized in two groups: patients aged 18–64 years (adults), and patients 65 years and older (elderly). The gathered variables are described elsewhere .2 tests with Holm's correction for multiple comparisons. The values P < 0.05 were considered statistically significant.The analysis of the data was carried out using R. The Shapiro-Wilk's test was used to assess the normality of distribution of interval variables. Interval variables were expressed as mean ± standard deviation. Distribution of categorical variables were expressed as percentages. Differences in categorical variables were tested using pairwise Chin = 4,474), Switzerland (n = 777), France (n = 529), Austria (n = 461), Spain (n = 267), Italy (n = 188), Bulgaria (n = 100), and Poland (n = 95).The European Anaphylaxis Registry collected data of 10,203 cases between July 2007 and March 2017. Six thousand eight hundred ninety-one patients met the criteria of Ring and Messmer ≥grade II and were aged ≥18 years. The cases were registered from 78 study centers in seven countries: Germany .The recent medical history in elderly patients is characterized by significantly more frequent cardiovascular diseases, thyroid and malignant diseases than in younger adults. In contrast, in the younger adult group, atopic diseases were significantly more common than in the elderly (p < 0.001) and there was a considerable association between the age and the concomitant drug intake, under which ace inhibitor, AT-2 antagonist, beta-blocker, acetylcholine, and proton pump inhibitor were taken into account (p < 0.001). Twenty-eight percentage of elderly patients reported a previous allergic reaction to the same elicitor. Of these 75% reported a previous milder reaction, 19% had a similar or even more severe reaction (data not shown).Potential cofactors of any type  were sigp < 0.001; n = 633; 56%; p < 0.001), with yellow jacket  being the cause in the majority of cases. Drugs were the second main causative agent of anaphylaxis across adults again being more prevalent in the elderly . Analgesics  and antibiotics  were the most frequent single elicitors of drug anaphylaxis in the elderly. Food was a predominant elicitor in adults  than in the younger adult group . A major cardiovascular symptom was loss of consciousness  while dizziness and tachycardia were more prevalent in adults . Gastrointestinal symptoms occurred in a similar proportion in both adult groups (p < 0.001), especially dyspnea . Hospitalization was required in 60 and 19% of elderly patients were treated in an intensive care unit (ICU) (p < 0.01).First-line treatment was carried out by emergency physicians in 5,481 (92%) of 5,971 patients who received first-line treatment. The administration rate of adrenaline by professionals in elderly patients was 30 and 26% in younger adults (it (ICU) . RegardlThis is the first large-scale analysis of anaphylactic patients including 1,123 cases aged 65 years or more. The European Anaphylaxis Registry covers a heterogenic sample of patients across all age groups and a wide range of elicitors, from different European countries .The most frequent elicitor in both adult groups was insect venom, but elderly patients had significantly more insect elicited cases than younger adults (56 vs. 47%). The data indicate that the clinical reactivity to insect venoms increases with age, although the individual exposure to insect stings might be comparable among adults, whereas one could speculate that retired elderly spend more time outdoor, e.g., in the garden. However, supposing comparable exposure, one reason for this observation might be the higher frequency of comorbidities, which may enhance the clinical response pattern particularly in patients with preexisting cardiovascular diseases increasing the risks for severe cardiovascular symptoms like tachyarrhythmia or syncope.Moreover, we identified drugs as frequent elicitors in the elderly. This finding is in line with previous data from the registry and most likely associated with a higher drug intake in this patient group , 14. AlsFurthermore, the distribution of elicitors differ by country . This obThe skin is the most frequently involved organ system in anaphylaxis as shown by many different studies including our own data . Most inCardiovascular manifestations of anaphylaxis occurred more frequently in our elderly patient cohort. Most interestingly, loss of consciousness was the predominant symptom in this patient group and has been observed by us in a previous analysis . ConsideAdrenaline is the first treatment of choice in anaphylaxis and recommended by several international guidelines . HoweverThis data indicate the need of educational measures regarding the acute treatment of anaphylaxis not only among patients but also among professionals. In particular, in emergency medical professionals the recognition of barriers against the use of adrenaline by an intramuscular route requires more attention. Recently, also guidelines from the resuscitation council are in favor of the first line intramuscular route and are an important step forward to change current clinical practice .Finally, we observed increased hospital admission rates and treatment in ICU in elderly patients. Such an observation has been reported in previous studies from the US , 22. MosWe report on a large group of elderly European anaphylactic patients covering a 10-year observational period. The web-based assessment tool for registration covers several aspects of an anaphylactic reaction in a standardized manner, including elicitors, symptoms, co-factors, and emergency treatment. The online questionnaire was consistently revised and piloted .The data are limited to patient records and not representative for a population as only patients are registered when seen for an allergy assessment after a given reaction.In this large-scale description of anaphylaxis in patients aged 65 years and older, we report on characteristic age-dependent elicitors, comorbidities, symptoms, and emergency treatment. Features of anaphylaxis in patients aged 65 or more years differ from those of the younger adult group. The elderly are more likely to have anaphylaxis without skin symptoms which is associated with more difficulties to make diagnosis of anaphylaxis and more severe reactions. Moreover, the risk for insect venom anaphylaxis raises with age. The hospitalization and ICU admission rate were higher in elderly patients independent from the severity grade indicating that such patients require intensified medical intervention.This study is one of the first comprehensive studies on patients ≥65 years who experienced anaphylaxis. It contributes to a better management and identification of specific medical needs in an aging population.The study was approved by the Ethics Committee at Charité-Universitätsmedizin Berlin (the coordinating center) and by the local Ethics Committees.SA and SD-B acquired data and were responsible for the concept and design of the manuscript, for interpretation of the data, writing and final approval of the manuscript. SD-B and WF were responsible for the data analysis and interpretation. MB, GC, MF-R, TH, CP, IP-G, J-MR, EO, and KS acquired data, revised the manuscript critically for important intellectual content, and approved the final manuscript. MW and RT performed conceptualization of the study and were responsible for supervised interpretation of the data, writing, and final approval of the manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.