Loss of arm-hand performance due to a hemiparesis as a result of stroke or cerebral palsy (CP), leads to large problems in daily life of these patients. Assessment of arm-hand performance is important in both clinical practice and research. To gain more insight in e.g. effectiveness of common therapies for different patient populations with similar clinical characteristics, consensus regarding the choice and use of outcome measures is paramount. To guide this choice, an overview of available instruments is necessary. The aim of this systematic review is to identify, evaluate and categorize instruments, reported to be valid and reliable, assessing arm-hand performance at the ICF activity level in patients with stroke or cerebral palsy.A systematic literature search was performed to identify articles containing instruments assessing arm-hand skilled performance in patients with stroke or cerebral palsy. Instruments were identified and divided into the categories capacity, perceived performance and actual performance. A second search was performed to obtain information on their content and psychometrics.Regarding capacity, perceived performance and actual performance, 18, 9 and 3 instruments were included respectively. Only 3 of all included instruments were used and tested in both patient populations. The content of the instruments differed widely regarding the ICF levels measured, assessment of the amount of use versus the quality of use, the inclusion of unimanual and/or bimanual tasks and the inclusion of basic and/or extended tasks.Although many instruments assess capacity and perceived performance, a dearth exists of instruments assessing actual performance. In addition, instruments appropriate for more than one patient population are sparse. For actual performance, new instruments have to be developed, with specific focus on the usability in different patient populations and the assessment of quality of use as well as amount of use. Also, consensus about the choice and use of instruments within and across populations is needed. Regarding arm-hand training, most treatment approaches target a specific patient population, and almost all arm-hand assessment instruments are currently applied in only one particular pathology. This leads to a myriad of patient-specific assessment tools. However, patients with different disorders with similar clinical characteristics might benefit from similar treatments, and assessment instruments might be suitable for more than one patient population. Dobkin  stated tIn stroke and CP, loss of arm-hand function and, consequently, loss of arm-hand performance leads to large problems in the everyday life of these patients. It limits the execution of activities of daily living, which results in greater dependency, restricted social participation , and a dAssessment of arm-hand function and performance is important in both clinical practice and research e.g. to determine the effectiveness of rehabilitation treatments and to monitor the progress of patients. In the present study, the term 'instrument' will refer to measurement instrument, i.e. instrument used to measure arm-hand function and/or performance.Next to its intended use, the International Classification of Functioning, Disability and Health (ICF) framework  can be uIn the last decades, the focus of rehabilitation on arm-hand disorders is slowly shifting from ICF function level towards activity and participation level , i.e. toRegarding activity level, it should be noted that outcomes of capacity measures and performance measures may differ strongly, since different constructs are measured, i.e. the highest level of functioning versus functioning in daily life situations. When assessing performance, like AHSP, two kinds of instruments are available. On the one hand, questionnaires can be used to measure perceived performance. On the other hand, actual performance can be measured by direct and objective assessment in the real-life situation.For clinicians and researchers it is important to evaluate and compare the effects of therapies and treatments, in order to make a well-founded choice for the best therapy or treatment for the patient. This choice necessitates appropriate measurement instruments. Besides the differences in ICF levels and concepts (e.g. capacity or performance) instruments are quantifying, a large diversity in the content between instruments exists. To guide the choice of instruments, an overview of available instruments and their content is necessary. The aim of this systematic review is 1) to identify and evaluate the available instruments to assess AHSP in patients with stroke or CP and 2) to categorize the available instruments into the categories capacity, perceived performance and actual performance. Instruments for which no data about the validity and reliability was available were not included in this study.This review consists of 5 steps: 1) A systematic literature search was performed to identify articles which included instruments assessing AHSP in patients with stroke or CP. 2) Articles were selected based on predetermined inclusion criteria. 3) All measurement instruments reported within the articles selected were extracted. 4) Only instruments that fitted a second set of predetermined inclusion criteria were kept. All other instruments were discarded. 5) The included instruments were further evaluated and classified, yielding a final set of instruments that is reported on.A systematic search was performed to identify relevant articles published until November 2010, selected from the following databases: PubMed, CINAHL, EMBASE, Chochrane, PsychINFO, IEEE and Scopus. The search strategy consisted of 4 elements, focusing on 1) patient population; 2) upper extremity; 3) outcome domain and 4) measurement instrument. The combination of search terms used is listed in Table Articles were included if they met all of the following inclusion criteria: 1) the article should include instruments developed for and/or used in patients with stroke or CP; 2) the instrument used in the article should assess AHSP; 3) the article should be written in English, Dutch, German or French.All titles and abstracts of the articles retrieved from the literature search were divided among 4 reviewers and were screened for the inclusion and exclusion criteria. In cases where insufficient information was available from the title or the abstract, the full text of the article was examined. In cases of uncertainty, the title and abstract was screened by one of the other three reviewers. If it remained uncertain whether or not to include the article, the article was discussed between all 4 reviewers until consensus was reached. At the end of this step, a list of eligible articles was available.In this study several definitions have been used, adopted from the ICF . In someThe articles gathered from step 2 were analysed to identify instruments. Abstracts of these articles, and in case of insufficient information the full text, were screened to extract potential instruments. From several instruments more than one version was available. In such case, only 1 version of the instrument was included in this systematic review. The version which was tested on its validity and reliability in the target population and most often used was chosen.All instruments retrieved from step 3 were screened by 1 reviewer on the following inclusion and exclusion criteria. Inclusion criteria: 1) instrument assesses AHSP; 2) instrument has to be reported valid and reliable in the target population (stroke and/or CP). Exclusion criteria: 1) instrument is a classification instrument; 2) measuring AHSP is not the main goal of the instrument; 3) instrument is not uniquely used to asses AHSP.Information about the properties and content of the instruments, necessary to apply the inclusion and exclusion criteria, were retrieved from several sources, i.e. from: 1) the articles included after the second step; 2) a new search on database Pubmed, using the name of the instrument ; 3) other internet sources such as databases of instruments; 4) contact with authors describing the instruments. After this step, a final list of included instruments was composed.The instruments from the final list were classified into the following categories: capacity, perceived performance and actual performance, based on the definitions presented earlier. In case of uncertainty about the classification, the instrument was discussed among the 4 reviewers, who are also experts in the field of arm-hand rehabilitation, until consensus was reached. The following information about each instrument was examined: target population, total number of items included in the test, number of items concerning measurement of the upper extremity, ICF levels measured with the instrument, inclusion of unimanual and/or bimanual items, assessment of amount of use and/or quality of use and the responsiveness.The systematic literature search (step 1) resulted in a total of 2216 articles, of which 747 were included after step 2. A total of 188 measurement instruments were identified from these articles (step 3) of which 30 were included (step 4), and further evaluated (step 5). A flowchart depicting this process is presented in Figure In Tables The most noticeable difference is the number of instruments included per category. In the categories capacity and perceived performance, 18 and 9 instruments were included respectively, whereas only 3 instruments were categorized as measuring actual performance. In addition, more instruments are available for patients with stroke compared to patients with CP, with only 10% of the instruments used and tested for their psychometric properties in both patients groups. For 2 instruments, two versions exist, one for adults and one for children.In the category capacity, about half of the instruments solely measure at ICF activity level. The other half of the instruments also measure at function level. In the category perceived performance almost 90% of the instruments solely measure at ICF activity level, whereas all instruments in the category actual performance measure only at ICF activity level.In the category capacity, instruments consist of unimanual or bimanual items, or a combination of unimanual and bimanual items. In the category perceived performance, all instruments include both unimanual and bimanual items. In daily life, measured with instruments for actual performance, both unimanual and bimanual tasks are present. Most instruments include a combination of basic activities of daily living and extended activities of daily living.Only a few instruments in the categories capacity and perceived performance measure quality of use (QOU), whereas no instruments measure the amount of use (AOU). Most instruments use another description to measure upper limb use for example how much assistance does the patient need to perform the task. Instruments assessing actual performance measure mostly AOU, but the Assisting Hand Aassessment (AHA) measures QOU of the affected arm-hand. For about half of all measurement instruments that were reported to be valid and reliable, responsiveness was also tested in the target population.A total of 30 instruments were included in this review, 18 of which measure capacity, 9 measure perceived performance and 3 measure actual performance.Even though stroke patients and cerebral palsy (CP) patients share most of their clinical symptoms, almost all of the upper extremity outcome measures are developed for, tested in and used in only one patient population, i.e. either stroke or CP. To gain more insight in the possibilities of common therapies, transcending diagnosis boundaries, agreement about the choice of common instruments is needed.Regarding stroke or CP rehabilitation, many instruments are available in the categories capacity and perceived performance. However, instruments assessing actual performance are less abundantly available for these patients. This is in sharp contrast to the importance that patients, clinicians and researchers in the field of stroke and CP rehabilitation attribute to high quality arm-hand skilled performance (AHSP) in real life.For capacity and perceived performance only a few instruments assess quality of use (QOU) of the affected arm and hand, whereas no instruments assess the amount of use (AOU). Many instruments use other descriptions of upper limb use, such as "how much assistance is needed to perform the task?".In addition, this systematic review revealed that a large diversity in the content of the instruments exists, making it more difficult to compare different outcome measures with each other.It can be concluded that a wide range of measurement instruments for the categories capacity and perceived performance exists. This systematic review identified 30 instruments currently available to assess AHSP in patients with stroke or CP, which are reported to be both valid and reliable. More than 155 instruments were excluded, mainly because no information was published about the psychometric properties in patients with stroke or CP. Other reasons for exclusion were for example "instrument does not include items to assess the upper extremity" and "instrument is a classification instrument". Nineteen instruments were excluded because next to arm-hand items, they contain also items not related to the upper extremity. Although instruments containing only arm-hand items are used most and are most appropriate to assess arm hand performance, the abovementioned nineteen instruments that were excluded might also be of interest in arm-hand assessment. For the sake of completeness, these instruments are listed in table 8 in the Additional file The chance of consistent use of outcome measures between studies decreases as the range of available instruments increases. The use of different outcome measures makes it more difficult to compare similar studies with each other. It is very important that a future agreement about the choice and the use of common instruments is achieved. This may facilitate comparison between studies, may result in more powerful meta-analyses, and enables the use of published data for group size calculations for new studies .This systematic review demonstrated that only 3 out of 30 instruments were used in both patients with stroke and patients with CP  may be very useful, it does not reveal valid information about the functioning of a patient in daily life (performance). It is known that a large difference may exist between capacity and performance. This difference may be caused, among others, by the learned non-use phenomenon , developPatients, clinicians and researchers may have questions on both aspects of AHSP: capacity and performance. Depending on the information needed, the outcome measure should be chosen accordingly.For the assessment of performance in stroke and CP, most instruments currently available evaluate perceived performance, whereas only 3 instruments assess actual performance. The questionnaires used to assess perceived performance take the perspective of the patient into account, which may be desirable but also has disadvantages. These questionnaires rely on recall and valid reporting of the patient. The cognitive problems stroke patients may have might influence the recall. In addition, the Hawthorn effect may play a role, i.e. the overestimation of arm-hand performance by the patient because his/her desire to improve or to please the examiner . FurtherCapacity and perceived performance are both relevant for the assessment of AHSP, but actual performance should equally be taken into account, since this reflects the real functioning of a patient in daily life. Actual performance is measured objectively. One example is video observation, in which the performance of a patient is unobtrusively monitored, while performing activities of daily living. A disadvantage of video observation is that the video material has to be assessed by (multiple) experts, which makes this method potentially subjective and very time consuming. Other disadvantages are the possible intrusion on the patient's privacy and the problems of installing the system in a patient's home.Although the video-based AHA instrument is not applied in the home situation, it was classified as a measure for actual performance, because the spontaneous use of the affected arm during a 15 minutes free play is determined using video observation.Another method to assess actual performance is accelerometry, measuring the actual AOU of the arm-hand in daily life. Wearing accelerometers is unobtrusive and data can be collected for several consecutive days. Because data collection is done during the whole day, the registered activity will include specific task-related movements, but also non-functional movements and unintentional arm activity. Accelerometry does not provide information about the QOU of the affected arm-hand. The latter is especially of interest for patients, clinicians and researchers. The QOU of the affected arm and hand is associated with the ability to use the affected arm and hand in the home situation, performing activities of daily living.Currently several promising new instruments to assess actual performance have not yet been tested as to their psychometric properties and were therefore not included in this systematic review. Two examples of such instruments are the Strathclyde Upper Limb Activity Monitor (SULAM)  and the In order to assess actual performance in stroke and CP, it is important that the systems under development will be tested more extensively to determine their utility and psychometric properties in both patient populations. In addition, measurement instruments for the assessment of actual performance have to be (further) developed, assessing also other aspects of AHSP such as QOU or information about the type of activity performed. Considering the importance of instruments transcending diagnosis boundaries, such instruments should be able to be used in different patient populations.A large diversity in the content of the instruments to assess AHSP in patients with stroke or CP exists. About half of the instruments included in the category capacity, solely measure at ICF activity level, whereas the other half of the instruments cover more ICF levels. About 89% of the instruments included in the category perceived performance and 100% of the instruments in the category actual performance solely measure at ICF activity level. If the aim of the study is to measure on ICF activity level, instruments assessing solely on ICF activity level are to be preferred. Whenever more ICF levels are included, the interpretation of the results becomes more difficult, especially when the outcome exists of a total score covering the different ICF levels.The inclusion of unimanual and/or bimanual items differs among instruments. To determine the capacity of the affected arm-hand, unimanual tasks are useful because these tasks force the use of the affected arm-hand, which can be assessed. However, in daily life, many tasks are bimanual requiring both hands to perform the tasks. Moreover in daily life, the affected arm-hand is rarely used for unimanual tasks . TherefoAlthough there are some differences in the inclusion of basic and/or extended activities of daily living, the majority of the instruments included both basic and extended activities of daily living.Some considerations can be made regarding this systematic review. Based on the definitions stated earlier, some instruments which, in other studies, were classified as activity measures, were excluded in this systematic review, for example the nine hole peg test and box and block test . HoweverInstruments used as classification instruments rather than assessment tools for AHSP were excluded. Examples of such instruments are the Manual Ability Classification Instrument (MACS)  and the Some instruments, such as the COPM and the GAS can be used to assess individual goals of patients. These instruments can be used to assess AHSP  and have been demonstrated to be valuable in the assessment of AHSP . TherefoThis systematic review has some limitations that have to be addressed. One limitation might be the fact that the articles retrieved from the search strategy were divided among four reviewers. However, strict a priori rules were applied in the selection and evaluation of articles and instruments, and in case of even the slightest doubt, the article was reviewed by another reviewer and if needed discussed among all four reviewers.A second limitation might be that in this systematic review, instruments were included whenever they were reported to be valid and reliable. No criteria were applied to determine the methodological quality of the studies describing the psychometrics. However, the aim of this review was to identify and evaluate instruments available for assessing AHSP in patients with stroke or CP, rather than to give an extended overview of the psychometric properties of these instruments. The latter one is an important next step.This systematic review provides an overview of available instruments to assess AHSP in patients with stroke and patients with CP. This overview may be used as a guide for instrument selection.Currently, a limited number of valid and reliable instruments assessing actual performance for patients with stroke or CP are available. Furthermore, the 3 instruments available do not cover all domains interesting for AHSP. In order to assess actual performance, existing tools have to be adapted and new tools have to be developed, which will be applicable in more than one patient population. In addition, quantifying the QOU of the affected arm-hand should be taken into account while assessing activities of daily living.Furthermore, only a few instruments are applicable for both patients with stroke and patients with CP. To better compare studies, and to gain more insight in the possibilities of common therapies for different patient populations with similar clinical characteristics, consensus should be reached regarding the choice and use of outcome measures which can be used in different patient populations.This paper was funded by Adelante, Centre of Expertise in Rehabilitation and Audiology, Hoensbroek, the Netherlands.The authors declare that they have no competing interests.RL participated in drafting the manuscript, carried out the literature search, participated in the screening of the articles, identified and evaluated the included instruments and participated in interpreting the results. AT, YJ and HS participated in drafting the manuscript, screening the articles and interpreting the results. Furthermore, AT, YJ and HS critically revised the intellectual content of the article. RS participated in drafting the manuscript and interpreting the results and critically revised the intellectual content of the article. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2377/12/21/prepubExcluded instruments [truments -203Click here for file


Background: Cuba is a unique country, and despite limited economic development, has an excellent health system. However, the prevalence of asthma symptoms in children in Havana, Cuba, is unusually high.Aim: As early life exposures are critical to the aetiology of asthma, we have studied environmental influences on the risk of wheezing in Cuban infants.Design: Cross-sectional study.Methods: A random sample of 2032 children aged 12–15 months living in Havana was selected for inclusion in the cohort. Data were collected using questionnaires administered by researchers.Results: Of 2032 infants invited to participate, 1956 (96%) infants provided data. The prevalence of any wheeze was 45%, severe wheeze requiring use of emergency services was 30% and recurrent wheeze on three or more occasions was 20%. The largest adjusted risk factors for any wheeze were presence of eczema , family history of asthma , poor ventilation in the house , attendance at nursery , male sex  and the number of smokers in the house (P < 0.03 for trend), OR 1.64 (95% CI 1.17–2.31) for three or more smokers in the house compared to no smokers in the household.Conclusion: We have identified several risk factors for any wheeze in young infants living in modern day Cuba. As the prevalence of smoking in the house is high (51%), intervention studies are required to determine effective strategies to improve infant health. Asthma is a disease that often presents during the first decade of life, with an estimated global prevalence of wheezing in 6- to 7-year–old children of ∼12%.,Cuba is a large island in the Caribbean with a unique cultural and historical experience, that has a system of universal health coverage,All children aged between 12 and 15 months who were living in Havana, Cuba between March 2010 and March 2011 and who attended one of the randomly selected 17 polyclinics, nested in four municipalities in Havana, Cuba, were eligible to be selected to participate in the study . Individuals with a pre-existing diagnosis of neuropathy, myopathy, heart disease, genetic disease, such as cystic fibrosis, severe somatic malformations and those with limited life expectancy were excluded from the study. In total, 2195 infants were randomly selected to participate in the study proportionate numbers to each municipality population and after consent was obtained from the parents/guardians, the child was enrolled in the study. About 163 individuals were initially enrolled but subsequently found not to be eligible for inclusion in the study as they lived outside the polyclinic or municipality catchment area. The study protocol was approved by National Institute of Hygiene, Epidemiology and Microbiology, the local Havana Scientific Committee in Cuba and also by the University of Nottingham Medical School ethics committee in the UK.The baseline data collection consisted of an interviewer-administered questionnaire that collated the responses from the parent/caretaker about prenatal and postnatal exposures of the child, their living environment and the medical history of the family. Specific questions focussed on paracetamol exposure and exposure to environmental tobacco smoke. Data on the height and weight at the time of the interview were also collected. The primary outcome was wheeze and used the Spanish translation of the ISAAC questionnaire ‘¿Ha tenido su bebé sibilancias o silbido, jipidos o ruidos en el pecho durante el primer año de vida?’ after piloting in the local community. Recurrent wheezing was characterized as wheeze on three or more occasions in the infant’s life, whereas the use of the emergency services to obtain treatment for wheezing was used to categorize severe wheeze. Where possible, a stool sample was also taken and analysed for parasite infection using direct method with eosin and Lugol solutions and concentration technique of Willis–Malloy using protocols from the Pedro Kouri Institute of Tropical Medicine, Havana.P ≤ 0.05) were then entered into a mutually adjusted multivariable model and a step-wise modelling procedure followed to obtain a final model of only statistically significant (P ≤ 0.05) variables. Sex and number of smokers in the household were considered as a priori confounding factors. As many measures of smoke exposure, such as maternal, paternal and grandparental smoking were associated with increased wheeze in the univariate analysis; a composite measure of environmental tobacco exposure was computed as the total number of smokers in the household was included in all final models. No further post hoc modelling was performed on the dataset to maintain transparency and simplicity.The data were entered into an electronic database, cleaned and checked for obvious errors or implausible values. All statistical analyses were carried out in Stata v12  using the survey commands to allow for the clustered survey design. Univariate analyses were initially performed using logistic regression and crude odds ratios (ORs) and associated 95% confidence intervals (CIs) were computed for each exposure variable. Variables that were statistically significant in univariate analysis , OR 1.64 (95% CI 1.17–2.31) for three or more smokers in the house compared to no smokers in the household. The Habana del Este municipality has a consistently lower risk of any wheeze, recurrent wheezing and severe wheeze than the other municipalities which was not explained by any of the variables adjusted for in the analysis. There was no association between paracetamol administration to the infant in the first year of life  and risk of wheezing .After mutual adjustment for confounding, the independent risk factors for any wheeze in the first year of life are presented in This is the first population-based study to investigate exposures that are associated with increased risk of wheeze in Havana, Cuba, a relatively unique environment that is considered to possibly have a high prevalence of wheezing in children. Our initial cross-sectional analysis of the baseline data at the age of 12–15 months has identified a number of risk factors for any wheeze in these individuals. The exposures that are associated with an increased risk of any wheeze include family history of asthma, self-reported eczema, poor ventilation, male gender, smaller height at birth, the presence of other siblings, attendance at daycare facilities, living with smokers in the household and living in either Cerro, Arroyo Naranjo or La Lisa municipalities of Havana City.The strengths of these dataset include the recruitment of four areas in Havana that are considered to be representative of the population of Havana, and the high response rate of 96% of those who were eligible and invited to participate, giving confidence that the results are unlikely to be susceptible to response bias. The data were collected by staff at the local participating polyclinics who ensured that all questions were answered and hence there is little missing data. The questions on exposures that were considered to be potentially important with regard to the aetiology of asthma in this population were devised by Cuban epidemiologists familiar with the environment, and we were thus able to test hypotheses that had been formulated locally. As emergency medical treatment is easily accessible in Havana and mothers are encouraged to have a low threshold for accessing this care, the latter category of severe wheeze may not be generalizable to other populations.As we were trying to identify important risk factors for wheezing in a relatively unstudied population, we necessarily have tested many exposures leading to the risk that some of our apparently statistically significant associations are artefacts of multiple hypothesis testing. The cross-sectional nature of the study will not permit causality to be identified, simply associations and in particular, is unable to exclude the possibility of reverse causality or residual confounding by unmeasured exposures. As the phenotype of asthma takes a while to develop, it is important to clarify that this is a study of risk factors for wheezing in young children, rather than simply asthma. This is particularly important in this population of infants aged 12–15 months, as much wheeze is likely to be viral in nature,Although we were not surprised to identify that consistent with the literature, family history of asthma,It is unclear why living in Habana del Este should be associated with a substantially lower risk of wheezing than other areas of Havana. Habana del Este is situated in a coastal location with relatively less heavy industry and a lower density of motor traffic than the other municipalities that contributed to the study population, suggesting that urbanization and pollution may contribute to the geographical differences in risk of wheezing. Future studies of the risk of wheezing in Havana would benefit from objective measures of air pollution to test the hypothesis that this may contribute to the disease burden of asthma in this setting.In conclusion, we report data from a cohort of infants aged 12–15 months living in Havana which has a high frequency of any wheeze, with 45% having any wheeze reported since birth. The location of residence is an important risk factor for wheezing, as are others such as exposure to environmental tobacco smoke, the presence of poor ventilation in the house, the presence of siblings and smaller mean height at birth. Interventions to reduce environmental tobacco exposure in this population are required.


Housing-led regeneration has been shown to have limited effects on mental health. Considering housing and neighbourhoods as a psychosocial environment, regeneration may have greater impact on positive mental wellbeing than mental ill-health. This study examined the relationship between the positive mental wellbeing of residents living in deprived areas and their perceptions of their housing and neighbourhoods.A cross-sectional study of 3,911 residents in 15 deprived areas in Glasgow, Scotland. Positive mental wellbeing was measured using the Warwick-Edinburgh Mental Wellbeing Scale.Using multivariate mulit-nomial logistic regressions and controlling for socio-demographic characteristics and physical health status, we found that several aspects of people's residential psychosocial environments were strongly associated with higher mental wellbeing. Mental wellbeing was higher when respondents considered the following: their neighbourhood had very good aesthetic qualities ; their home and neighbourhood represented personal progress ; their home had a very good external appearance  and a very good front door (both an aesthetic and a security/control item) ; and when satisfaction with their landlord was very high . Perception of poor neighbourhood aesthetic quality was associated with lower wellbeing .This study has shown that for people living in deprived areas, the quality and aesthetics of housing and neighbourhoods are associated with mental wellbeing, but so too are feelings of respect, status and progress that may be derived from how places are created, serviced and talked about by those who live there. The implication for regeneration activities undertaken to improve housing and neighbourhoods is that it is not just the delivery of improved housing that is important for mental wellbeing, but also the quality and manner of delivery. It is well established that physical and mental health are related to the physical and built environment -4. In geFurthermore, housing and neighbourhoods are not just defined by their physical aspects but can also be considered as a psychosocial environment, similarly to the way they are considered in studies of health inequalities and the workplace . That isTo date, however, cross-sectional, longitudinal and intervention studies that explore associations between mental health and residential circumstances have mostly used measures of mental illness, with little evidence relating to more positive mental wellbeing -12. MentIn this paper we focus on some of the poorest communities in Glasgow  to better understand what aspects of residents' perceptions of their housing and neighbourhoods are associated with their mental wellbeing. The high-level aim is to inform targeted individual- and area-based strategies, including urban regeneration programmes that attempt to improve residents' mental health and quality of life in disadvantaged areas.People living in deprived areas have poorer mental health than those in less deprived areas ,15, and Changes in mental health problems over time have not been shown to be strongly related to residential neighbourhoods. For example, a study of mental health outcomes over a ten-year period showed that, whilst mental health scores  were worse on average for social renters living in the most deprived areas, there was no effect of area deprivation on trajectories of mental health over the study period .Studies which have examined the effect on mental health of housing improvements or housing-led regeneration have shown some positive impacts on mental health, although the evidence is stronger for targeted housing improvement -21. ThosA limitation of these studies, we argue, has been the way mental health has been assessed. Most studies examining the effects of housing and neighbourhood on mental health have used measures of mental illness  e.g. -12). Onl. Onl12])There are two issues with using mental ill health measures in assessing positive mental health in the general population. Firstly, relatively few people in the general population have symptoms of mental illness, thus scoring low or zero on these measures. It is therefore arguable whether such instruments are 'fit for the purpose of establishing ...[ways]... to improve mental health at the general population level'  and quesSecondly, and perhaps more important, is the recognition that mental health or wellbeing is not equivalent to the absence of mental illness. The WHO has defined mental health as: 'a state of wellbeing in which every individual realises his or her own potential, can cope with the normal stresses of life, can work productively and fruitfully, and is able to make a contribution to her or his community.'. PositivReducing health inequalities is a key policy priority for both the UK and Scottish governments with both 'mental illness and mental wellbeing [being] specific priorities...' . The neeImproving mental wellbeing, and reducing inequalities in mental wellbeing, is also a stated aim of regeneration . Regenermight be expected as an outcome of regeneration activities, and, if so, which aspects of residential circumstances appear most likely to have an impact in that they seem strongly associated with levels of mental wellbeing. In all cases, we are looking at residents' perceptions of their residential environments rather than independent measures of them, since mental wellbeing is about a psychological dynamic, i.e. whether it is possible to change people's general state of mind/wellbeing, through changing how they assess their residential circumstances. Furthermore, the focus is on perceptions measured at the level of individuals.This article, therefore, looks at the associations between aspects of housing and neighbourhoods and mental wellbeing to see whether higher mental wellbeing Ultimately, the aim of this paper is to examine the associations of individually perceived aspects of housing and neighbourhoods with the mental wellbeing of residents in deprived areas, after adjusting for individual characteristics.Specifically, we:might act;• examine whether mental wellbeing scores for residents of deprived areas are associated with residents' perceptions of aspects of housing and neighbourhoods upon which regeneration • estimate the relative strength of those associations so as to identify the relative importance of different aspects of the residential environment for mental wellbeingUsing the Warwick-Edinburgh Mental Wellbeing Scale (WEMWBS), a comprehensive measure of wellbeing ,33, we c• Residential circumstances and psychosocial benefits• Dwelling type and perceived housing quality• Perceived neighbourhood qualityThis paper draws on data from the second cross-sectional survey of GoWell, a long-term study of 15 deprived communities in Glasgow undergoing major housing investment and area regeneration over a 10-15 year period. All but one of the 15 study areas is in the 15% most deprived areas in Scotland on the Scottish Index of Multiple Deprivation, with six of the areas in the very worst, or most deprived, 5% . We selected households in each study area from the addresses in the most recent version of the Royal Mail Postal Address File within the postcode units that define the study areas. Where selected homes had more than one householder, only the householder with the most recent birthday was interviewed (i.e. one householder was interviewed per selected household). Households selected for cross-sectional surveys were posted information sheets and letters inviting them to take part. Study information leaflets were produced in English, Arabic, Urdu, Cantonese and Turkish. Fieldworkers made up to five attempts to contact selected homes in person to seek consent to participate.A face-to-face questionnaire lasting around 40 min was verbally administered by fieldworkers at participants' homes with responses recorded using CAPI . Interpreters were available or assistance from other household members obtained if the interviewee did not speak English . The achieved sample of householders was 4,657, with an overall response rate of 47.5%, which is good for a survey of deprived area populations.Ethics approval for the study was given by the NHS Scotland B MREC (no. 05/MRE10/89).The outcome of interest here is mental wellbeing. To consider how regeneration might impact upon wellbeing, the other independent variables are organised into groupings related to residential circumstances and psychosocial factors, and perceptions of residents' house and neighbourhood.Mental wellbeing was assessed using the Warwick-Edinburgh Mental Wellbeing Scale (WEMWBS) ,33. The The scale has 14 items covering: positive affect ; positive functioning ; and relationships with others. Respondents are asked to what extent they have been feeling that way over the past two weeks. Responses are summed, with higher scores indicating greater wellbeing. Internal consistency of the scale in this study was high . Low, average and high wellbeing in the current analyses were defined as: < 1 standard deviation below the population mean in Scotland (50.7), +/-1 standard deviation (9.9) around the mean, and > 1 standard deviation above the mean, respectively. We chose to trichotomise the WEMWBS scores to better show the associations with average and high wellbeing, rather than the effect of a one-point increase in the continuous wellbeing score.We included the following socio-demographic factors in our analysis: gender, ethnicity, age, household type , and educational attainment. Economic status was assessed using three variables: employment status, income source, and regular access to a private vehicle.In this analysis we used the first item of the SF-12v2 Health Survey --a self-Here we include housing tenure and the length of time the respondent had lived in their home and neighbourhood, as well as their perceptions of the internal and external reputation of the neighbourhood, whether their neighbourhood had changed for better or worse in the previous two years, satisfaction with their home, neighbourhood and landlord, and whether their home or neighbourhood made them feel they were doing well in their life.Tenure can be considered to convey material and psychosocial advantages . HousingFurthermore, and perhaps more importantly, the preference for private consumption, possession and ownership of goods--especially housing--has been explained by sociologists as a 'cultural phenomenon rather than something inherent to the objects themselves', providing benefits of identity, autonomy and ontological security , p.328-9. This haLength of residence is also included here as it serves as a proxy for place attachment, the two having been shown to have a strong relationship in recent research in the UK . Place aResidents provided information about type of residence , the existence of internal and external problems, access to a garden, perception of overall condition of the residence, and specifically about insulation, the external appearance and repair, and the condition of their front door. They were also asked about their satisfaction with any improvements that had been made to their residence. We have included dwelling type here for similar reasons to those mentioned above in relation to housing tenure. Dwelling type also contributes to psychosocial benefits pertaining to identity, status and self-esteem, with strong general preferences for houses over flats, and for larger properties with more rooms and additional space over and above smaller properties . This isResidents were asked whether the following environmental incivilities in their local neighbourhood were a serious or a slight problem, or not a problem: vandalism, graffiti, other deliberate damage to property or vehicles; abandoned or burnt-out cars; rubbish or litter lying around; vacant or derelict buildings and sites; and untidy gardens. The number of serious problems was summed and then coded as: 3 or more serious incivilities, 1-2 serious incivilities, or no serious incivilities.Quality of local amenities  was assessed. The number of amenities assessed as 'poor' or 'very poor' was counted and coded as 3 or more, 1 or 2, or none.Residents were asked to rate the attractiveness of the buildings and environment in their neighbourhood and whether it was quiet and peaceful. Neighbourhood quality was based on the number of 'fairly' or 'very poor' responses to questions about attractive buildings, attractive environment, and a quiet and peaceful environment.Multinomial logistic regression was used to assess the associations between housing and neighbourhood environment and average or high wellbeing compared with low wellbeing, adjusting for individual socio-demographic factors, and taking account of clustering within GoWell areas. STATA Version 9 was used for all analyses .From the sample of 4,657 complete data were available from 3,911 households for this study. Forty-three percent of respondents were male. Table Multivariate analyses of the socio-demographic  factors are shown in Table The associations between residential factors and mental wellbeing are shown in Table Table Table This study has examined the associations between housing, neighbourhood and mental wellbeing after controlling for personal characteristics  and found that the residential and environmental aspects of people's houses and neighbourhoods were significantly associated with positive mental wellbeing. In particular, for residential aspects, perceiving the area as having a good internal reputation, being satisfied with house and landlord and feeling that both the home and neighbourhood contribute to a sense of doing well were all associated with average or higher than average levels of mental wellbeing. In terms of environmental aspects, average and high levels of wellbeing were associated with living in a house (rather than a flat), having a home in good repair, living in an area perceived as having attractive buildings, and living in an attractive, quiet and peaceful environment.not once environmental quality was included in the model. Depression has previously been associated with the built form  and disused buildings but not with open spaces, graffiti or access to a private garden [Our findings are generally in agreement with studies examining the associations between the built environment and mental health ,49. The e garden .In his review, Evans  proposedOverall, our study confirms that there is merit in considering the residential domain as a psychosocial environment that affects residents' mental wellbeing. The most important aspects of the residential domain for mental wellbeing for those people living in deprived areas were not found to be housing tenure or houses as a built form (aspects that policy for disadvantaged communities has often focused on), but rather a set of psychosocial factors which are all relational in nature: satisfaction with one's landlord ; a sense of personal progress derived from one's home and neighbourhood ; and the internal reputation of one's neighbourhood . Several aesthetic aspects of the home and neighbourhood were also found to be significantly associated with mental wellbeing , and these may also be considered as potentially relational and psychosocial since they are concerned with appearance and its role in attributed status, helping to make people feel good about themselves and their position in society. With the exception of general health, these psychosocial factors had stronger associations with mental wellbeing than most of the socio-demographic and resource-based variables, as might be expected.This study contributes to a greater understanding of how perceptions of neighbourhood might contribute to mental wellbeing. Importantly, we found that not only are the quality and aesthetics of housing and neighbourhoods associated with mental wellbeing, but so, too, are feelings of respect, status and progress derived from how places are created, serviced and talked about by those who live there. The residential domain is both an important source and signifier of one's position in society in terms of relative position and advancement, self-esteem and self-efficacy. These are precisely those things also found to be important in respect of other psychosocial environments such as the workplace ,50.The cross-sectional design of this study precludes attribution of cause. While the associations we have found between mental wellbeing and many of the aspects of residential and environmental capital are strong, we cannot yet conclude that the built or psychosocial environment contributes to positive wellbeing. Most of the outcomes are self-reported and therefore subject to bias related to common method variance. It might also be hypothesised that some self-reported outcomes might be more susceptible to common method variance than others . Unfortunately, using more objective measures, usually proposed as a way of avoiding this problem, is not appropriate for many of the constructs or factors we are interested in, these being residents' perceptions of their environment. Our planned longitudinal study of residents staying in their original areas or moving to other parts of the city will help give a clearer indication of whether mental wellbeing scores are responsive to changes in residential circumstances. Another useful approach, which we have not been able to adopt here, may have been to measure personality types to account for the fact that different kinds of people may respond in different ways to unfavourable circumstances, with some people adjusting their expectations and evaluations to better accord with the reality they face .This study, on the other hand, has many strengths. It is a large study with a relatively good response rate (~50%) for a survey of this type in deprived areas. It examined a large number of housing and neighbourhood factors and used an appropriate measure of mental wellbeing.According to philosophers and sociologists, the rise of meritocracy and the growing importance of status in society  has led Scottish regeneration policy is said to be about people and place , with miThe authors declare that they have no competing interests.LB, AK, CT, PM and ME contributed to the GoWell study and participated in its design and coordination. EW undertook the statistical analysis and contributed to the interpretation of the results. All contributed to drafting the manuscript and read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2458/12/48/prepub


The recent development of high-density technologies has enabled a dramatic extension of the exploration of living organisms. Such exploration typically consists in the parallel measurement of large numbers of compounds, at different developmental stages or following the application of contrasted environmental stimuli. Correlation analysis or more sophisticated statistical approaches are then used to identify clusters of co-varying compounds with the aim of reconstructing the underlying regulatory network governing system responses. Such approaches are now routinely used to identify predictive biomarkers , without considering the subcellular localization of the measured compounds. Plant cells distinguish from other cells in possessing a large central vacuole, which size may vary dramatically between tissues, genotypes  and developmental stages. Whereas young cells have small vacuoles, mature cells have large vacuoles that can encompass more than 95% of the cell volume.Here, we will demonstrate that without taking into account the volumes of the cell compartments, the analyses of the dynamics of the compounds and the subsequent compound-compound correlation analyses might be biased, especially when the functional significance of the study is bound to concentrations, as it is the case for enzymes and metabolites. Possible correction strategies are discussed, with special emphasis to their pertinence and applicability to specific questions.M. In many studies the metabolite concentration is expressed per volume  of the whole tissue, asLet us consider for the sake of simplicity a cytosolic metabolite Mt] = M/Vt with Vt the volume of the tissue and M the metabolite quantity in this tissue. The metabolite being cytosolic, its concentration, to be physiologically meaningful, should be calculated as[Mc] = M/Vc with Vc the volume of cytosol in the tissue.[Mt] underestimates [Mc] because Vt is often much bigger than Vc due to the presence of other subcellular compartments . More importantly, the ratio [Mc]/[Mt] = Vt/Vc, may not be constant among genotypes or during the development of organs where the ratio Vt/Vc strongly increases as the cell vacuole enlarges. This may lead to an erroneous interpretation of changes in metabolite concentration when comparing different experiments. Let's make an example. Assuming that Vc is constant and Vt increases with time, Figure Mt] can be strongly different from the real cytosolic concentration, both quantitatively and qualitatively. In the extreme case, a decrease of [Mt] can be measured instead of an increase when the growth of the volume is faster than the metabolite accumulation in the cytosol .It is striking that in many studies fresh weight is used as the reference to express concentrations of biomolecules, irrespective of their subcellular localization. We show here that considering subcellular compartments is of primary importance for the correct interpretation of experimental results, especially when dealing with a system level perspective. Note that in the example we used, the organ volume was assumed to change with time but our conclusions are valuable for any other factor inducing organ volume variation, such as carbon or water stress, temperature, or genotypic traits. As a consequence, the bias induced by growth can potentially affect not only studies on dynamic profiling . If in addition to water, the content in storage compounds  is expected to change, the above strategy can be iterated by expressing the concentration with respect to the structural dry mass (SDM) of the tissue, as:Another standardization used in water stress studies consists in expressing data on fresh mass at full turgor (Hummel et al., In the case of studies on leaf tissues, normalization with respect to leaf surface (Krapp et al., Another way to circumvent the problem bound to subcellular volumes is to express data in a “semi-quantitative” way, i.e., not an absolute amount per unit of biomass but a relative amount. In the simplest case a signal obtained for a given analyte is divided by the signal obtained by another analyte, either internal, or external to the system under study. In the case of mass spectrometry-based metabolomics (Katajamaa and Oresic,


Diabetes in pregnancy, which includes gestational diabetes mellitus (GDM) and type 2 diabetes mellitus (T2DM), is associated with poor outcomes for both mother and infant during pregnancy, at birth and in the longer term. Recent international guidelines recommend changes to the current GDM screening criteria. While some controversy remains, there appears to be consensus that women at high risk of T2DM, including indigenous women, should be offered screening for GDM early in pregnancy, rather than waiting until 24-28 weeks as is current practice. A range of criteria should be considered before changing screening practice in a population sub-group, including: prevalence, current practice, acceptability and whether adequate treatment pathways and follow-up systems are available. There are also specific issues related to screening in pregnancy and indigenous populations. The evidence that these criteria are met for indigenous populations is yet to be reported. A range of study designs can be considered to generate relevant evidence for these issues, including epidemiological, observational, qualitative, and intervention studies, which are not usually included within a single systematic review. The aim of this paper is to describe the methods we used to systematically review studies of different designs and present the evidence in a pragmatic format for policy discussion.The inclusion criteria will be broad to ensure inclusion of the critical perspectives of indigenous women. Abstracts of the search results will be reviewed by two persons; the full texts of all potentially eligible papers will be reviewed by one person, and 10% will be checked by a second person for validation. Data extraction will be standardised, using existing tools to identify risks for bias in intervention, measurement, qualitative studies and reviews; and adapting criteria for appraising risk for bias in descriptive studies. External validity  will also be appraised. The main findings will be synthesised according to the criteria for population-based screening and summarised in an adapted "GRADE" tool.This will be the first systematic review of all the published literature on diabetes in pregnancy among indigenous women. The method provides a pragmatic approach for synthesizing relevant evidence from a range of study designs to inform the current policy discussion. Gestational diabetes mellitus (GDM) is defined as "any degree of glucose intolerance with onset or first recognition during pregnancy" . GDM canDIP is associated with increased risks at birth for the mother (caesarean section) and the T2DM is a serious metabolic disorder, in which blood sugar is no longer controlled, and can lead to heart disease, stroke, renal disease, kidney failure, amputations and blindness . The preThe current recommendations for screening and diagnosis of GDM were written over 40 years ago by adapting methods for screening non-pregnant women in order to identify those at high risk for T2DM after pregnancy  has, howThe aim of population-based screening is to reduce the burden of disease in the community by earlier detection of disease, thus providing an opportunity for intervention and improvement of health-related outcomes . Early dA number of factors should be considered, however, before introducing population-based interventions, including; the prevalence and natural history of the condition, current screening practice and rates, acceptability , efficacy and cost and the availability of adequate treatment pathways and follow-up . In addiThe evidence for these factors will be generated by studies with a number of different designs, including epidemiological studies, qualitative studies, measurement studies, intervention studies and even opinion pieces. Systematic review offers a rigorous process for appraising the quality of evidence; however, such reviews are often restricted, as they include only a limited number of study designs in order to focus on the internal validity of the design and not to consider the external validity or generalizability of the results for the intended purpose . Thus, rOur aim in this paper is to describe a method for systematically reviewing all published studies relevant to informing future discussions about screening for DIP among indigenous women in Australia, Canada, New Zealand and the United States.The inclusion criterion will be broadly defined as "any publication that includes analysis or discussion of diabetes in pregnancy among indigenous women in Australia, New Zealand, Canada or the United States".This broad definition was used so that all studies would be included and information to address the relevant screening criteria  could beWe will search the Cochrane Database of Systematic Reviews (1995-July 2010), Medline (1950-July 2010), Embase (1949-July 2010), CINAHL (1937-July 2010), and PsychINFO (1905-July 2010). The following key words in the titles and abstracts and subsequent MeSH headings will be searched:pregnan* or antenatal or prenatal, or neonatal or newborn or infan* or fetal or fetus or foetal or foetusAND diabet* or hyperglyc?mi* or glucose intoleran* or obes* AND aborigin* or indigen* or native* or first nation*See table Endnote© for removal of duplications, and all abstracts will be reviewed by two people to determine whether the publications potentially meet the criterion for inclusion in this review.Citations identified by the search of the five databases will be downloaded into The full text of all publications that potentially meet the inclusion criterion will be reviewed by one assessor, and 10% will be independently reviewed by a second assessor for validation. When there is disagreement, a third person will make the final decision. The proportions of agreement between the first and second reviewer and between the first and final reviewer will be reported to provide an estimate of the degree of possible variation in interpretation.Kappa scores will not be calculated, as there is a high rate of expected agreement that would require a larger sample size of co-reviewed papers than is feasible within the resource constraints of this review. All publications that do not meet the inclusion criterion, with reasons specified, will be available from the contact author on request.Microsoft Excel© to extract standardised data items from the included publications. One person will extract data from all the included publications, and 10% will be extracted independently by a second reviewer and checked for agreement. When there is disagreement, a third person will make the final decision. The proportions of agreement between the first and second reviewer and the first and final reviewer will be reported in order to provide an estimate of potential variation in interpretation. Again, kappa scores will not be calculated because of the high level of expected agreement.A spreadsheet will be prepared in Publications will be coded according to their focus on indigenous people in the following countries:Australia ;Canada ;New Zealand (Maori);United States ; and"Other" .research purposes [study designs [Publications will be coded under one of the purposes -30 and s designs  outlinedoutcome data will be extracted: rationale, aims, number of people included, journal title, outcomes reported, main findings and conclusions, funding source, data source, GDM incidence, diagnostic criteria used and years of measurement.The following key criteria" of the population-based screening framework [The publication topics will be grouped according to the "ramework  as: epidThe external validity will be appraised by coding the studies according to:whether the population is rural, urban, remote or mixed; andwhether the data were collected from clinics, individual communities or broader populations.risk for bias will be critically appraised with specific tools for different study designs. Intervention and measurement studies, reviews and qualitative descriptive studies will be appraised with the following tools:The Intervention studies will be appraised with the Centre for Evidence-Based Medicine (CEBM) Critical Appraisal Skills Programme (CASP) tool for intervention studies [ studies .Measurement studies will be appraised with the CEBM CASP tool for studies of diagnostic accuracy [accuracy .Reviews will be appraised with the CEBM CASP tool for systematic reviews [ reviews .Qualitative research will be appraised with tools adapted from the Australian Department of General Practice and other experts for qualitative studies [ studies ,36.As no tool exists for appraising descriptive studies, we adapted an instrument from Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) , a recenMicrosoft Excel©. The outcomes reported will include: the rates of publications per country and over time, the type of research that has been published, the internal validity and risks for bias identified in the research, the published findings relevant to population-based screening criteria and the generalisability of the findings.Data will be analysed with A detailed "characteristics of included studies table" will be available on request, in which the included studies will be summarised in alphabetical order with: description of the population, study details, main findings and a summary of the risks for bias.The conclusions about the strength of the evidence within each of the criteria will be clearly communicated to the reader by presenting a summary table adapted from the "GRADE" criteria, which is used to assess guideline evidence ,40 , a strength of evidence symbol and a comment about the generalisability of each statement .This paper outlines a process for systematic review and appraisal of both the internal and external validity of the published literature and for presenting it in a framework to inform decisions about population-based screening for GDM among indigenous women in Australia, Canada, New Zealand and the United States.The heterogeneity of the study designs and the heterogeneity between studies of the same design  will preclude a meta-analysis of the studies. Nevertheless, the authors consider it valuable to present a narrative synthesis of the relevant research that has been published under each of the population-based screening criteria.Calculating kappa scores was not feasible, as the high rate of expected agreement for some criteria would have required co-review by a second person of approximately half of the 123 included publications. Resources permitting, it would be desirable to have all the data extracted by two people.The inclusion criterion for this review does not include potentially relevant evidence on other population groups or topics such as cancer screening. We do not propose that the evidence from the published academic literature on a specific topic for population groups with some similarities would, in itself, provide sufficient information to enable informed decision-making. However, this review should be a useful resource to contribute to the evidence base for developing interventions in this area.reporting rather than for the methods of research. The tool presented here for appraising quantitative descriptive studies was adapted for the studies in this review. Specific consideration was paid to the potential for selection bias, which can be from a non-representative source, and the criteria used for identifying indigenous status (e.g. blood quantum specifications). As we were unable to develop clear objective criteria for assessing analytical bias, we adapted a tool that was already available [The vast majority of the studies are observational, descriptive and quantitative, for which there are no commonly used or widely accepted critical appraisal tools. The STROBE guidelines provide a useful reference point; however, they are designed for vailable . As therOne of the common criticisms of academic literature is that the criteria for internal validity are too restrictive and relevant evidence is not presented in a way that is useful for policy-makers . A strenThe method for our review was adapted to allow inclusion of the perspectives and experiences of indigenous women and communities, which are clearly relevant to policy-makers. At the time of writing, we were unable to find any structured research about DIP that was explicitly reported from an indigenous perspective, thus highlighting a critical gap, or "perspective bias", in the research. This gap may be due to a number of factors, such as an under-representation of indigenous people in academic institutions, lack of trust between indigenous communities and academic institutions and the notion that "objectivity" is desirable in public health research, thus negating the validity of perspectives.all the relevant data for which both the internal and external validity have been rigorously appraised and the evidence gaps clearly identified, to ensure that decisions made on the basis of limited evidence are carefully evaluated.Indigenous women in Australia, Canada, New Zealand and the United States have one of the highest prevalence rates of T2DM in the world; therefore, there is consensus that they should be offered changes to current screening practice in the near future. However, there are unique social and health considerations for this vulnerable population group which requires active collaboration and careful reflection on the existing evidence base. Policy-makers need information presented in a format that is useable and that includes This paper has described a process of adapting rigorous systematic review methods to include different study designs, in order to produce relevant evidence for a contemporary discussion about screening policies for DIP among pregnant indigenous women.DIP: diabetes in pregnancy; GDM: gestational diabetes mellitus; T2DM: type 2 diabetes mellitus.The authors declare that they have no competing interests.CC prepared the protocol, developed and piloted the appraisal tools in collaboration with local experts, and drafted the manuscript. DY developed and pilot-tested the appraisal tools, reviewed 10% of the full texts to confirm inclusion and exclusion of studies and to check data extraction quality, and provided feedback on drafts. HL developed and pilot-tested the appraisal tools, acted as the third reviewer when there was a discrepancy in appraisals, and provided feedback on drafts. EW co-reviewed abstracts of all search results for included studies and provided feedback on drafts. BM assisted in development of appraisal tool and provided feedback on drafts. BO had input into the review protocol and provided feedback on drafts. JO had input into the review protocol and provided feedback on drafts. SE had input into review protocol, advised on relevant indigenous comparisons, and provided feedback on drafts. All authors read and approved the final manuscript.This paper was written by Catherine Chamberlain as part of a PhD program investigating gestational diabetes among Aboriginal and Torres Strait Islander women in Australia.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2393/11/104/prepub


David H Farb is Professor and Chair of the Department of Pharmacology and Experimental Therapeutics at Boston University School of Medicine. Dr. Farb is Principal Investigator and Director of the Laboratory of Molecular Neurobiology and Director of the university-wide NIGMS training program in Biomolecular Pharmacology. A renowned neuropharmacologist, his research integrates existing electrophysiological, behavioral, pharmacological, and molecular genetics technologies in a novel systems-level platform to establish a molecular dissection of spatial memory. In this interview we find out a little more about the key issues in this field of research.A receptors in the development of anxiety disorders, ranging from generalized anxiety to post-traumatic stress. As a post-doctoral fellow, I worked with then MD/PhD student Dennis W. Choi and Gerald D. Fischbach in the Department of Pharmacology at Harvard Medical School to uncover the cellular mechanisms of action of benzodiazepines-the class of agents that serve not only as anxiolytics, but sedative hypnotics and anticonvulsants as well. We showed that benzodiazepines act by positive allosteric modulation of GABAA receptors [++-dependent mechanism, a finding that may further the development of treatments not only for schizophrenia, but also for other conditions associated with malfunctioning NMDA receptors, such as age-related decreases in memory and learning ability [I suppose anxiety was one of the early motivators in my career; more specifically, the study of the role of GABAeceptors , and we eceptors . My reseeceptors . For exaeceptors . We have ability .BMC Pharmacology and Toxicology has been in the forefront of this educational endeavor. In particular, the journal has played a major role in facilitating the timely publication of new scientific research, creating an open forum for discussion of current research trends, and enabling a versatile platform for publication of research findings. My aspirations for the ‘Basic Pharmacology’ section are to continue this timely direction of the journal, publishing translational content that reflects emergent trends in biomedical research and bridges the fields of pharmacology, clinical pharmacology and toxicology. To this end, we encourage submission of research reports in all therapeutic areas broadly encompassing pharmacology and signaling, with incorporation of basic science drug discovery and translational medicine. We are also enthusiastic in our goal to disseminate research that incorporates existing and rapidly evolving leading edge technologies to bridge systems-level inquiries with those at the cellular and molecular levels, as well as research such as computational modeling of systems based on technology platforms that can lead to a greater understanding of the genetic basis of disease [In recent years, open access journals have become extremely influential in shaping the exchange of scientific knowledge, and  disease .BMC Pharmacology and Toxicology may serve to counterbalance the pressures on scientists by focusing more on solid science. We intend to be nimble, staying on the leading edge of translational and basic research through a policy of openness to new ideas that are supported by convincing, reproducible evidence.We are also striving to balance two competing, but not diametrically opposed, forces in scientific publishing: “prestige” science versus less trendy but still exciting and, ideally, solid science. Clearly, citation rates are a useful indicator for measuring the interest given to a publication over a meaningful period of time. It is important to recognize, however, that the growing emphasis on impact factors in scientific publishing is problematic ,8, and tIt’s about publishing all of the science that’s fit to digitize, to spin a phrase. I believe our readership would benefit from research that explores the increasingly pivotal role of personalized medicine in the development of more precise therapeutic approaches to a range of diseases. Genome-wide association studies have enabled a greater understanding of individual differences in disease susceptibility, age of onset, and sexual differentiation in the response to treatment, and greatly underscore the need for an expansion of these types of approaches. For example, it would be of interest to assess how, or even whether, antiviral therapeutics differentially affect the responsiveness of female patients to treatment for sexually transmitted diseases. I am particularly interested in seeing research that embraces new technologies to facilitate in-depth scientific inquiry in any area of pharmacological sciences.A receptors are a classic example of early successes utilizing this approach [Despite intense drug discovery efforts, disorders of the central nervous system have suffered the most from a lack of newly developed therapeutics. Target-based drug discovery, or the process of identifying a drug candidate that acts at a validated target molecule, is the most widely used approach. Although this approach has been successful in identifying drugs for previously validated targets, it has been less successful when novel targets are involved. This is especially true in neuropsychiatric disorders with multifaceted etiologies, and we should consider that a systems-level approach will be needed to model these disease states. Renewed efforts to identify allosteric modulators of multiple receptor types (G protein-coupled receptors in particular) are expected to yield rich dividends in the near future . Severalapproach ,11. Thesapproach . BreakinBMC Pharmacology and Toxicology can provide a useful venue for communicating broad-ranging advances that bridge molecular identities with clinical endpoints without having to assert claims to having solved the problem. We welcome the excitement of the discovery process!Another key challenge in pharmacology is optimizing the use of the ever-increasing amount of genetic information available to us. While the Human Genome Project was rightly heralded as a milestone by those who referred to it as a new platform for aiding medical research, it is nonetheless misleading to think of it as a “roadmap” as we normally understand the term. The genotype may identify a particular phenotype, but does not guide us in one direction or another therapeutically, at least at this time; rather, it provides clues to a complex roadway of potential therapeutic targets . In thisEndeavors to develop allosteric modulators are complemented by drug discovery efforts incorporating a multitude of innovative approaches. A prime example is the use of designer receptors to aid in deciphering the involvement of specific receptors and transmitters in disease . The cloThere are several fields that I think are of particular promise moving forward, including molecular genetics, nanomedicine, optogenetics, tissue engineering, and stem cell technology. To start with genetics as an example, Cre-mediated genetic manipulation in animal models is likely to be of great utility in querying receptor involvement in various disease states and identifying relevant signaling cascade entities. In addition, remarkable progress has been achieved in understanding the significance of microRNAs (miRNA) in the regulation of multiple physiological and pathological conditions. The successful use of antagomirs (a novel class of synthetic oligonucleotides that inhibit miRNAs) in clinical applications for cancer treatment highlights the impact that this class of small RNAs is likely to have on diagnostics and therapeutics in the future ,16. Epigin silico or in vitro toxicology workflows. The importance of biomarkers, both as diagnostics of disease and as indicators of toxicity associated with drug treatments, cannot be over emphasized. In addition, drug delivery continues to be hindered by the inability of targeted therapeutics to cross various cellular barriers, such as the blood-cancer cell cluster barrier or the blood–brain and blood-nerve fiber barriers. New technologies-including nanotechnology/nanomedicine, in silico drug screening, and biophysical research on barrier surfaces-are crucial for addressing these limitations to drug delivery. The importance of translational studies in pharmacology is underscored by the federal endorsement of translational studies, as evidenced by the recent launching of a National Center for Advancing Translational Sciences (NCATS) [Toxicity is still the major obstacle in drug development, and overcoming this obstacle will require the development of more streamlined  (NCATS)  in partn (NCATS) . To achiBMC Pharmacology and Toxicology.David H Farb is a Section Editor for DHF wrote and approved the final text.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/2050-6511/14/42/prepub


Nearly 80% of the 50 million people with epilepsy worldwide reside in developing countries that are least equipped to tackle the enormous medical, social and economic challenges posed by epilepsy. These include widespread poverty, illiteracy, inefficient and unevenly distributed health care systems, and social stigma and misconceptions associated with epilepsy. Several studies have reported that a large proportion of patients with epilepsy in developing countries never receive appropriate treatment for their condition, and many, though diagnosed and initiated on treatment, soon discontinue treatment. Unaffordable cost of treatment, unavailability of antiepileptic drugs, and superstitious and cultural beliefs contribute to high epilepsy treatment gap in resource-poor countries. A significant proportion of the current burden of epilepsy in developing countries can be minimized by educating the public about the positive aspects of life with epilepsy and the primary and secondary physicians about current trends in the management of epilepsies, scaling up routine availability of low-cost antiepileptic drugs, and developing cost-effective epilepsy surgery programs. The Last Lecture” by Randy Pausch, a real life story of a computer science professor. Randy opines that the last lecture should convey, based on the analysis of one’s own life experiences, the following:It is indeed a great honour to serve the Indian Academy of Neurology as the President for the last one year. For the last several weeks, I have been pondering on as to what message I want to get across to the esteemed members of the Academy, junior and senior, at the end of my tenure as its President. Some of you might have read the inspiring novel “If we were to vanish tomorrow, What would we want to be remembered as our legacy? and What wisdom would we want to impart to our junior colleagues?”“Father of Neuroepidemiology”. Len taught me the art of how to meticulously select, plan and execute clinical research, and unambiguously communicate the results to the medical community. I was fortunate to receive training in electroencephaloghraphy from Donald Klass of the Mayo Clinic, the most reputed living legend in electroencephaloghraphy. The training in electroencephaloghraphy and epilepsy from the Mayo Clinic shaped my subsequent career. When I returned to India in 1994 and joined as the Head of the Department of Neurology, Sree Chitra Tirunal Institute of Medical Sciences and Technology, Trivandrum, these multinational experiences helped me to shape my career as a neurologist, neuroepidemiologist and epileptologist, and in establishing the R. Madhavan Nayar Center for Comprehensive Epilepsy Care. I hope through this paragraph, dealing briefly with my autobiography, I could convey the driving principle that has helped me to achieve what I am today. To quote from Mathatma Gandhiji, the “Father of our Nation”:I started my career in neurology at the Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, one of the foremost institutes of national importance for postgraduate studies in our country. I was fortunate enough to be mentored by Professor Jagjit Singh Chopra, a great teacher and researcher, the then Head of the Department of Neurology, PGIMER, Chandigarh. What can be more satisfying for me than the fact that I am delivering today this oration as the President of the organization founded by my own mentor? It is from Professor Chopra that I learned how one can effectively amalgamate the three functions as doctors we have to undertake, namely, patient care, teaching and research. During my stay in Medical University, Benghazi, Libya, I became interested in neuroepidemiology, the study of the distribution and determinants of neurological diseases in the community. The outstanding publications emanated from the studies conducted there came to the notice of the late Leonard Kurland of the Mayo Clinic, Rochester, MN, USA, who is often refereed to as the “Men often become what they believe themselves to be. If I believe I cannot do something, it makes me incapable of doing it. But when I believe I can, then I acquire the ability to do it even if I didn’t have it in the beginning”.“more of we and less of me”.I wish to thank my colleagues in the R. Madhavan Nayar Center for Comprehensive Epilepsy Care for the help they rendered throughout the last 15 years. Our success is due to team approach, which means “Epilepsy is a major public health problem as it affects an estimated 50 million people worldwide, and an additional 500 million people are involved as family members and care givers of the afflicted. Nearly 80% of the burden of epilepsy worldwide is borne by the resource-poor developing countries. DevelopiIn developed countries, the lifetime prevalence rates of epilepsy per 1000 person-years range from 3.5 to 10.7, and the incidence rates per 100,000 person-years range from 24 to 53.2 These wiThe diagnosis of epilepsy is fundamentally a clinical judgement based on history. The accuracy of the diagnosis of epilepsy depends on the skill and experience of the physician and the quality and reliability of the information provided by the witness. The ratio of neurologists to population varies in resource-poor countries from one neurologist to 3–5 million people, and in many Latin American and African regions, there are no neurologists at all. India, wSeveral studies have reported that a large proportion of patients with epilepsy in developing countries do not receive appropriate treatment for their condition, a phenomenon known as the treatment gap.13 The tret al,[In developing countries, a large proportion of patients with epilepsy, though diagnosed and initiated on AED treatment, soon discontinue the treatment. In epidemiological surveys, such patients would be categorized as not being on treatment. Das et al, has coinet al, Among thet al, Unfortunet al, Among thNearly one-third of patients with newly diagnosed epilepsies on long-term follow-up will have their seizures unsatisfactorily controlled by treatment with AEDs. The remaEpilepsy surgery centers in resource-poor countries lack the full range of state-of-the-art technologies usually available in the developed world to perform presurgical evaluation and surgery. Although the total direct cost of presurgical evaluation and surgery in resource-poor countries amounts to a small fraction of the cost incurred in the developed countries, this expenditure is beyond the reach of the majority. Very few20Despite these challenges, in the last one and a half decades, several epilepsy surgery centers in developing countries have successfully implemented epilepsy surgery programs and produced results comparable to those from developed countries.22 The R.Throughout the world, misunderstanding and the resulting social stigma often cause more suffering to a person with epilepsy than the seizures themselves. The progressive emergence of positive public attitudes toward persons with epilepsy has been demonstrated in recently conducted knowledge, attitude practice surveys in developed countries.–26 Unfor4727The psychosocial consequences of the stigma potentials of epilepsy in developing countries are nowhere more evident than in the case of women with epilepsy of the marriageable age. Unlike western culture, in most Asian countries, it is the responsibility of the parents to find a suitable match for their daughter and arrange marriage. Parents of a woman with epilepsy often get her married without informing the spouse and family of the disease.–31 SeizuFather of Indian Epileptology” were nearly identical.[In 1997, the WHO, in collaboration with ILAE and IBE, launched the Global Campaign Against Epilepsy to improve the care of people with epilepsy in resource-poor countries. To test dentical.A model for epilepsy care in resource-poor countries from community to national levels should take into consideration the heterogeneity of epileptic disorders and a need-based approach to their management. While a majority of the patients with epilepsy can be treated at the primary or secondary care facilities, few with difficult to control epilepsies will require referral to tertiary and comprehensive epilepsy care facilities. To improve care at all levels, a close interaction between general practitioners, physicians, neurologists and epileptologists, a partnership between governmental and non-governmental health care agencies, and help from high-income countries in training epilepsy specialists in advanced diagnostic and therapeutic techniques are essential. Several WHO/ILAE/IBE recommended epilepsy care initiatives are being successfully implemented in the recent years by national and regional chapters and governmental and non-governmental organizations. For example, the Indian Epilepsy Society recently brought out Guidelines for the Management of Epilepsy in India (GEMIND) focusing on practical issues that will aid general practitioners in diagnosing epileptic seizures, initiating the most appropriate AED and in making need-based decision to refer a patient for specialized care.Nearly 80% of the global burden of epilepsy is borne by the resource-poor developing countries, which are least equipped to tackle the enormous medical, social and economic challenges posed by this condition. Consequently, a large proportion of patients with epilepsy in resource-poor countries never receive appropriate treatment for their condition, and many, though diagnosed and initiated on treatment, soon discontinue the treatment. The current high treatment gap in developing countries can be considerably minimized by scaling up the routine availability of low-cost AEDs like phenobarbitone. Because of the marked scarcity of comprehensive epilepsy care centers, only a miniscule of patients with difficult to control epilepsies in resource-poor countries ever get a chance to undergo presurgical evaluation and surgery. If the care of persons with epilepsy in developing countries has to improve at the community level, undergraduate medical curriculum should have more emphasis on this common disorder, primary and secondary care physicians need to be regularly educated about the recent advances in its management, low-cost AEDs should be made available to poor patients free of cost, and cost-effective epilepsy surgery programs should be developed in selected centers. A comprehensive epilepsy care model should take into consideration the marked heterogeneity of the disorder and its variable impact on the patient, family and community.