Odocoileus virginianus) and other forest herbivores. Liming is a mitigation technique that can be used to restore forest health in acidified areas, but little is known about how it affects the growth or nutrient content of deer forage. We examined the effects of dolomitic limestone application on the growth and chemical composition of understory plants in an acidified forest in central Pennsylvania, with a focus on vegetative groups included as white-tailed deer forage. We used a Before-After-Control-Impact study design with observations 1 year before liming and up to 5 years post-liming on 2 treated and 2 untreated 100-ha sites. Before liming, forage availability and several nutrients were below levels considered optimal for white-tailed deer, and many vegetative characteristics were related to soil chemistry. We observed a positive effect of liming on forb biomass, with a 2.7 fold increase on limed sites, but no biomass response in other vegetation groups. We observed positive effects of liming on calcium and magnesium content and negative effects on aluminum and manganese content of several plant groups. Responses to liming by forbs and plant nutrients show promise for improving vegetation health and forage quality and quantity for deer.Acidic deposition and subsequent forest soil acidification and nutrient depletion can affect negatively the growth, health and nutrient content of vegetation, potentially limiting the availability and nutrient content of forage for white-tailed deer ( Odocoileus virginianus) Soil nutrient availability and related forage quality are known correlates of diet, health and morphometrics of many cervid species Strong relationships from soil nutrient availability to forage quality to white-tailed deer morphometrics have been established While we predicted that soil acidification could negatively affect deer through reduced forage quality and quantity, little is known about the effects of soil acidification on understory vegetation. Much of this small body of research focuses on tree saplings As a starting point to experimentally determine the effects of soil acidification and nutrient depletion on white-tailed deer, we mitigated acidic soil conditions using dolomitic limestone application and measured the response of white-tailed deer forage availability and nutrient content. Lime application is a common mitigation technique for waters and forests affected by acidic deposition This study was conducted in the Mosquito Creek watershed located in Clearfield, Cameron, and Elk counties in central Pennsylvania over the summers of 2003, 2004, and 2008. This study was part of a larger study evaluating the effects of watershed and riparian liming as a mitigation technique Seiurus aurocapilla) clutch sizes, very little regeneration of most tree species (with the exception of Acer rubrum), and dominance of the understory in hay-scented fern (Dennstaedtia punctilobula), bracken fern (Pteridium aquilinum), and mountain laurel  The study area receives some of the highest levels of acidic deposition in the country We conducted this study in 2003, 2004, and 2008 using a Before-After-Control-Impact (BACI) study design 2 plots at survey points. We completed vegetation collection in July and August. Our plots were located in 3 different locations around points located 10 m from the center of each survey point in the directions of 30°, 120°, 210°, and 300°. The 3 plots were located above and to the right, above and to the left, and centered below the points, with a different plot sampled each year. We clipped all of the current year’s growth in each plot and grouped it in 11 categories: oak species , red maple (Acer rubrum.), other tree species , blueberry/huckleberry (mostly Vaccinium spp. and Gaylussacia baccata), other shrub species , teaberry (Gaultheria procumbens), greenbrier (Smilax spp.), forbs, bracken fern (Pteridium aquilinum), other fern species (mostly Dennstaedtia punctilobula), and grasses. For herbaceous plants, we clipped the entire aboveground portion. For woody species, we identified the current year’s growth using bud scars and stem coloration. For species where current year’s growth was difficult to identify, we collected material from the end of the twig to 2 cm below the last leaf on primary and secondary stems. Because sampling was spread across up to 5 weeks, we stratified sampling to rotate among sites to ensure the timing of cutting would not bias our results.We used a clipped-plot method similar to Conroy et al. The vegetation categories were based on deer forage, distribution and abundance, and sampling ease. Six categories – oak species, red maple, other tree species, Smilax species, forbs, and grasses – were classified as white-tailed deer forage, and the other 5 categories were classified as non-forage After drying and weighing, we ground the samples of the deer forage vegetation in a Wiley mill with a 1-mm mesh screen, and analyzed them for nutrient content. We analyzed individually the samples collected at each survey point for oak species, red maple, and forbs. We pooled samples collected across each site for other tree species, greenbrier, and grass because we did not have enough vegetation to analyze by point. Two representative samples were drawn from the pooled samples for analysis. We did not chemically analyze the other vegetation groups because they were not considered forage of white-tailed deer. We analyzed the 2003 and 2004 vegetation for calcium, magnesium, potassium, phosphorus, and crude protein. We analyzed the 2008 vegetation for calcium, magnesium, potassium, phosphorus, aluminum and manganese. We included aluminum and manganese in 2008 because liming was predicted to result in decreases in the availability of aluminum and manganese to plants (both increase in availability as soil become acidified) We used the Oa-horizon soil samples collected by Rummel www.r-project.org). We used the glm function to perform generalized linear models relating initial (before liming) understory vegetation availability and nutrient content to soil conditions. We assessed the relationship between vegetation and soil variables using 95% confidence intervals to indicate magnitude and uncertainty in slope estimates. We considered slope estimates with confidence intervals that excluded zero to indicate significant relationships between the soil measure and vegetation variable. We modeled biomass for each vegetation group, for total deer-forage vegetation, for total non-forage vegetation or for the proportion of total vegetation that was forage as the response variable and Oa-horizon soil pH, calcium, magnesium, potassium, or phosphorus as the predictor variable. We modeled the calcium, magnesium, potassium, phosphorus, and crude protein content of the vegetation groups with point-level data  as response variables, with soil variables as predictor variables. We also modeled biomass of deer-forage vegetation as the response variables and biomass of non-forage vegetation as the predictor variables to examine the potential for competition. All models had a Gaussian error structure and biomass and nutrient-content variables were log transformed for normality.All statistical analyses were completed in R  and time  effects, fixed treatment by time interaction effect, random site (four sites) effect, and random point within site (eight points within each of the four sites) effect. For the nutrient content variables of other preferred deer browse categories, the model included the same fixed- and random-effects, except the random point within site was changed to random sample from within site because we took two samples from the combined point samples for chemical analyses. The random terms in the model structure the error to allow the use of point-level, repeated measures data without committing pseudoreplication mcmcsamp function in the R package lme4HPDinterval function in the R package codaWe assessed the uncertainty in the time by treatment interaction parameter estimates using 95% confidence limits by generating Markov Chain Monte Carlo (MCMC) samples from the posterior distribution of each parameter estimate using the lmer function from the lme4 package in R to analyze these data We only collected data on understory vegetation aluminum and manganese content in 2008, therefore, we could not analyze these data as a BACI experiment. We used the Before liming, the biomass and chemical composition of vegetation were variable among plant categories and many were related to soil condition  and 2. AFor nutrient content, oak calcium content was positively related to soil pH and calcium, and oak magnesium content was positively related to soil pH and magnesium . Red mapWe also observed a negative relationship between the biomass of deer forage and non-forage vegetation (slope (95% CI): −0.043 ).We observed a positive effect of liming on forb biomass . Forb biWe observed effects of liming on many of the chemical characteristics of plants. We observed positive effects of liming on oak species magnesium content, red maple magnesium content, forb magnesium content, other tree species phosphorus and magnesium content, grass calcium and magnesium content, and greenbrier calcium and magnesium content . Liming We observed several differences between aluminum and manganese content in the vegetation from control and limed sites five years after liming. Control site vegetation had higher concentrations of manganese than limed sites in oak species and red maple . Grass fDeer forage availability and nutrient content were both related to and affected by soil conditions in this study. While we did not study how soil conditions affect white-tailed deer, we experimentally established a causal pathway for the quality of deer forage to be affected by changes in soil acidity and nutrient availability, and other studies have observed relationships between both soil and forage quality and deer health and morphometrics Results from before liming indicate that forage biomass and nutrient content are of moderate to low quality for white-tailed deer, although comparable biomass and nutrient content information was difficult to find. Also, the relationships between soil pH, calcium, and magnesium and the biomass and nutrient content of deer forage indicates a potential for soil acidification to negatively affect deer forage availability and quality, however, these were correlative results and only indicate a potential causative link.Kalmia latifolia), blueberry (Vaccinium spp.), and fern. These vegetation types are known to have associations with acidic soils and can outcompete forage vegetation and reduce tree regeneration We observed low deer forage biomass compared to other studies In general, crude protein content of deer forage exceeded minimum requirements but were not considered “optimum” by many studies. None of the forage categories we measured had levels optimal for post weaning fawns, antlerogenesis, or lactating females Liming successfully increased soil pH, calcium and magnesium on our study sites Increases in calcium and magnesium content of browse could benefit deer because they require large amounts of calcium and lesser amounts of magnesium for antler growth Also, in areas with low soil nutrient availability (like at our study sites), forage mineral content can become a more important factor in diet selection than protein and energy, to the point where vegetation selected may have lower levels of protein and energy than other available vegetation The forage group containing tree saplings other than oaks and red maple showed a positive response in phosphorus content to liming and several other forage groups also showed positive trends. Long et al. While we observed many positive effects of liming on understory plant nutrient levels and forb biomass, we observed no significant effect on the vegetation biomass in other categories. The amount and type of understory vegetation within plots varied widely and potentially our sample size was not large enough to detect treatment effects within that variability. In fact, we detected a pattern that the biomass of deer forage tended to respond in a positive direction to liming while non-forage vegetation tended to respond in a negative direction. However, in another measure of understory vegetation used to examine bird habitat As predicted, we also observed lower concentrations of aluminum and manganese in the vegetation on limed sites, which can be toxic to plants and can affect nutrient balance, and photosynthesis Liming had positive effects on understory forb biomass and vegetation chemistry, with increases in calcium, magnesium, and phosphorus contents and decreases in the metals aluminum and manganese five years post-liming. These changes in vegetation represent improved habitat quality for white-tailed deer. This study was designed to evaluate a method of liming that could be used easily by a land managers to mitigate the effects of acidic deposition with several goals  and our results show promise for the technique to improve vegetation quality for deer forage. A longer-term study may be required to determine if liming is improving understory vegetation composition and tree regeneration, further improving habitat composition for deer. The next step should be to monitor deer population and health responses to experimental lime application.Table S1Dry mass (kg/ha) of the current year’s growth of each understory plant group, separated by deer forage and non-forage for white-tailed deer, and the proportion of total vegetation classified as forage on control and lime-treated sites before (2003) and after  lime application with standard errors, and the estimates of the time by treatment interaction term with confidence intervals (CI).(PDF)Click here for additional data file.Table S2Percent dry weight (SE) of calcium (Ca), magnesium (Mg), potassium (K), phosphorus (P), and crude protein (CP) in the six categories of deer forage sampled in control and lime-treated sites before (2003) and after  lime application, and the estimates of the time by treatment interaction term with confidence intervals (CI).(PDF)Click here for additional data file.


It has been suggested that lay community health workers (LHWs) could play a role in primary and secondary prevention of Mental, Neurological and Substance use (MNS) disorders in low resourced settings. We conducted a systematic review of the literature with the aim of assessing the existing evidence base for the roles and effectiveness of LHWs in primary and secondary prevention of MNS disorders in low and middle income countries (LMICs).Internet searches of relevant electronic databases for articles published in English were done in August 2011 and repeated in June 2013. Abstracts and full text articles were screened according to predefined criteria. Authors were asked for additional information where necessary.A total of 15 studies, 11 of which were randomised, met our inclusion criteria. Studies were heterogeneous with respect to interventions, outcomes and LHWs’ roles. Reduction in symptoms of depression and improved child mental development were the common outcomes assessed. Primary prevention and secondary prevention strategies were carried out in 11 studies and 4 studies respectively .There was evidence of effectiveness of interventions however, most studies (n = 13) involved small sample sizes and all were judged to have an unclear or high risk of bias.LHWs have the potential to provide psychosocial and psychological interventions as part of primary and secondary prevention of MNS disorders in LMICs, but there is currently insufficient robust evidence of effectiveness of LHW led preventive strategies in this setting. More studies need to be carried out in a wider range of settings in LMICs that control for risk of bias as far as possible, and that also collect indicators relating to the fidelity and cost of interventions. Community based health care is becoming one of the preferred approaches to increasing accessibility to public health services, especially in low and middle income countries (LMICs) . It commThe renewed focus on the use of LHWs has its rationale primarily in the recognition that service needs, particularly in remote and underprivileged communities, are not met by existing health services . These LThere is an increased demand for a similar approach to be used in mental health service provision including prevention programmes , particuMental disorder prevention aims at “reducing incidence, prevalence, recurrence of mental disorders, the time spent with symptoms, or the risk condition for a mental illness, preventing or delaying recurrences and also decreasing the impact of illness in the affected person, their families and the society” .Prevention can be classified into primary, secondary and tertiary . PrimaryIt has been suggested that LHWs could play a role in primary and secondary prevention of MNS disorders through health education, case identification and referral . PreviouThis review complements an existing Cochrane review which examines the effectiveness of non-specialist health workers in delivering mental health care in LMICs and includes tertiary but not primary or secondary prevention strategies . The objSearch terms were developed by dividing the research question into four concepts; a) lay community health workers b) mental, neurological and substance use disorders, c) prevention strategies and d) low and middle income countries. Key words and subject headings were identified from the literature on the subject. For each concept, key words with truncation or wild card symbols and medical subject headings (MeSH) were combined with “OR”. The four concepts were then combined with “AND” to generate the final list of records identified.The search strategy was initially developed and run in MEDLINE, then adapted as required for the following complementary electronic databases: EMBASE, PsycINFO, Global Health, Cochrane Library and Cochrane Register of Controlled trials, ELDIS, Africa Wide Information, IMEMR, IMSEAR, LILACS, MedCarib and WPRIM. The above databases were chosen to ensure a comprehensive literature search relevant to the study question. No restriction was placed on date of publication. Searches were initially conducted in August 2011 and were then repeated in June 2013.The systematic review’s focus was on primary and secondary prevention programmes hence studies in which the respondents were community members of all age groups with no previously diagnosed MNS disorders, including those at risk (primary prevention) and with early stage of the illness (secondary prevention), were included.Studies that involved patients that were admitted to or resident in a hospital or health facility setting were excluded because the review’s focus was on community based care provided outside of a health facility. There were no other restrictions, on the types of patients for whom data was extracted in the studies.Studies involving any lay health worker (paid or voluntary) including community health workers, village health workers, lay counsellors etc., were included. Lay community health workers in this review were defined as “any health worker working outside of a health care facility as part of a community based health care programme that met the following criteria: carried out functions related to health care delivery, were trained in some way in the context of the intervention and had no formal professional or paraprofessional certificated or tertiary education degree” . InterveAny community based health intervention for MNS disorders that utilised LHWs in the delivery of primary and secondary prevention programmes in LMICs was included. Interventions that involved tertiary prevention or that only targeted persons with fully established MNS disorders as measured by diagnostic instruments were excluded.The literature review included studies that compared MNS prevention strategies delivered by LHWs with a control. Of these, only randomised controlled trials, controlled clinical trials, controlled prospective studies and, controlled before and after studies were considered for inclusion so that evidence from interventions provided plausibility or probability of effectiveness . UncontrInterventions that involved “Head-to-head” comparisons of different LHW interventions and multi-faceted interventions that included LHWs and professionals working together but did not include a comparison group that allows for separate assessment of the effects of the LHW intervention, were excluded .Primary outcome: Studies were included if they assessed the proportion of the study population with improved mental health status, determined by changes in incidence or prevalence of MNS disorders measured by validated instruments.Secondary outcomes: studies were included if they assessed any of the following outcome categories;1) Consumer- oriented outcomes including: knowledge and understanding; health status and wellbeing; health behaviours such as changes in risk taking behaviour and other MNS treatment outcomes including adverse outcomes resulting from the intervention.2) Health provider -oriented outcomes related to consultation processes such as rate of provision of services.Outcomes were assessed depending on whether the intervention targeted primary or secondary prevention.The longest follow up period to the end of the intervention was the time point considered for the review. This list of outcomes was adapted from the list of outcomes of interest to the Cochrane Consumers and Communication Review Group .The potential relevance of all titles and abstracts identified from the databases was examined according to these inclusion and exclusion criteria by the first author. The screened titles and accompanying abstracts were imported into Endnote reference manager and duplicates removed. The titles and abstracts of citations were screened again to determine whether each paper met the predetermined criteria. In case of doubt, the full text of the article was retrieved and reviewed against the inclusion and exclusion criteria. The reference section of the articles was reviewed to identify any other potentially relevant studies.A data extraction form was developed using the data collection checklist developed by the Cochrane Effective Practice and Organisation of Care Review Group  and the A qualitative synthesis of included studies was done with a focus on effectiveness of interventions and roles of LHWs. Studies that evaluated similar outcomes were grouped together and standardized mean differences and proportions were calculated. Effect sizes were then used to construct forest plots to illustrate individual study results, however because of clinical and methodological heterogeneity of included studies, there was no pooling of results and meta-analyses were not done .The database searches yielded a total of 2104 records. Records from each database considered to be relevant to the review were identified on the basis of whether the study titles or abstracts reported on MNS disorders and whether studies had been conducted in LMICs. A total of 168 records were identified and 21 additional records obtained through searches of reference lists. Removal of duplicates resulted in 124 records, of which 45 were considered potentially relevant to the study question after further title and abstract screening.The full text articles of these 45 records were retrieved and subjected to a more thorough screening against the inclusion criteria. A total of 20 articles reporting on 15 studies fulfilled the full inclusion criteria and were selected for the final analysis and data extraction. Figure The included studies represented six LMICs including India -23, PakiThe majority of studies 93%, n = 14) involved a home visiting intervention ,23-34. T4 involveThe selection, training and supervision of LHWs varied between studies and information on some of these aspects was lacking for a number of the included interventions. In four of the studies, LHWs were recruited on the basis of being part of the community, literate, motivated to participate in the intervention and able to communicate with community members -24,28. MThe description of the education level of LHWs varied from those with limited schooling, ability to read and write or completed primary education to some who had completed secondary school or university education ,27-34. TA wide range of intervention recipients were studied including infants ,33 and tIn seven of the studies, LHWs provided psychosocial stimulation to children ,30-34. IA minority of studies  did not have the evaluation of mental health status as the primary objective (27–28). Studies used a variety of tools to assess different mental health outcomes. The tools commonly used included the World Health Organisation wellbeing index (WHO-5), General Health Questionnaire (GHQ), Post Traumatic Stress Disorder (PTSD) Scales and the Zarit Burden scale. Interestingly, even among studies which had similar interventions such as those which involved psychosocial stimulation of children, the outcome measures varied . In the seven studies that assessed symptoms of depression, the Becks depressive inventory (21), the Aga Khan University Anxiety and Depression Scale (AKUADS) (24–25), the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) diagnosis (SCID) (27–28), the Kessler 10 item questionnaire (22), the Edinburgh postnatal depression scale (28) and the Centre for Epidemiological Studies Depression scale (34) were all tools that were used.Children’s mental development was assessed using a variety of tools dependent on the age of the child. Infants were assessed using the Griffiths mental development scale, intentional problem solving tests, behaviour rating scales and the Bayley scales of infant development . Tools used to assess older children and adolescents included the Wide Range Achievement Test (WRAT:26), Stanford Binet test, Wechsler intelligence scales for children (Revised), Peabody picture vocabulary test (PPVT), Ravens progressive matrices and the Wechsler Adult Intelligence Scales (WAIS) .Other outcomes assessed included level of stimulation in the home, functional impairment, and disability and social support . Adverse outcomes were reported by only two studies and these related to number of suicide attempts (21) and mortality rates (23) of study participants.Five studies reported on dichotomous outcomes  with the rest of the studies reporting continuous outcome measures (mean scores and mean difference measures). An Additional file The studies included in the final analysis showed wide ranging heterogeneity with respect to study participants, setting, nature of intervention delivered, roles of LHWs and outcomes measured. For a number of studies p-values and/or confidence interval estimates were not provided, making judgement of study effectiveness difficult  evaluated interventions aimed at reducing depressive symptoms in adults ,27,28,34Ten studies (62.5%) assessed aspects of child mental health including mental development, behaviour and mother child interaction -28,30-34Two studies provided evidence of effectiveness of interventions that targeted symptoms of Post-Traumatic Stress Disorder (PTSD) ,29. The Additional file This review presents findings from 15 controlled interventions led by LHWs, of which 11 studies were randomised controlled trials. Studies were heterogeneous with respect to interventions and outcomes assessed, although there were outcomes common to some of the interventions including those related to child mental development and to symptoms of adult depression. Heterogeneity in the studies is also reflected in the settings, study participants, assessment tools, follow up periods and outcomes measured, and hence a meta-analysis was deemed inappropriate.A variety of secondary outcomes related to the mental health of consumers were reported but were difficult to analyse across studies as they were specific to the interventions. Despite its importance, reporting on adverse outcomes such as mortality or symptom progression in study subjects was absent in all but two studies ,23. MostPrimary prevention includes selective, indicated and universal preventive strategies ,9. In thUniversal prevention entails the provision of an intervention at general population level and not on the basis of increased risk of a particular population -10. NotaEven with results showing that primary prevention can be effective, emphasis is usually put on treatment of identified illnesses rather than primary prevention which is thought to be the only sustainable method for reducing the burden of mental disorders ,10. ImpoNo study targeted secondary prevention of MNS disorders in children. Secondary prevention strategies mainly targeted adults with symptoms of MNS disorders and showed statistically significant reductions in prevalence ,28 or meMost studies (87.5%) involved a home visiting intervention though the mode of delivery varied across studies. Interventions were also different with respect to basic education, selection and training of LHWs which could have resulted in the diversity of LHW roles seen in the various studies. The level of education and or training determines the role(s) that LHWs have in a particular intervention . This thIn keeping with evidence from other LHW led interventions carried out in similar settings, the review findings indicate that MNS prevention interventions led by LHWs are effective for particular outcomes . HoweverA multitude of factors are thought to contribute towards effectiveness of an intervention led by LHWs. These include: health system factors such as supervision of LHWs; national political and socioeconomic factors; and community factors related to leadership, infrastructure and community empowerment . StudiesThe sustainability of community health worker programmes is a common challenge, probably as a result of the many factors which have a bearing on their successful implementation . Six of Much of the evidence in this review has been generated from randomised controlled trials that indicate a high probability of effectiveness, with less of the evidence provided by non-randomised studies which show plausibility of effectiveness of an intervention . HoweverThe review was subject to a number of limitations. Only literature published in the English language were considered for inclusion and these were largely from databases that contain peer reviewed published journal articles. The reviewer was not able to carry out extensive hand searches of unpublished literature and hence could have missed some relevant studies. To try and address the gaps in information in some studies, seven authors were contacted for additional information and one responded with the sufficient information.Lack of a common terminology describing LHWs made the search and identification of relevant studies difficult, and could have resulted in some relevant information being missed, particularly in Latin America and Europe which were underrepresented in this review. However, every attempt was made to ensure that the search criteria were comprehensive enough to capture all potential MeSH terms and keywords related to LHWs.All data extraction and synthesis was carried out by the first author alone thereby introducing the potential for bias. Only fifteen studies representing six countries were found for inclusion in the review hence limiting applicability of the results to other LMICs. The majority of studies had small sample sizes and were judged as having unclear or high risk of bias, which may bring into question the quality of evidence generated. The description of the target population in some of the studies was not adequate to allow definitive judgement on whether prevention was primary and/ or secondary. This could have resulted in some studies missing out that would otherwise have been included in the review. In such cases, authors were contacted for more information.Most of the studies indicated a positive outcome for the intervention. However, sensitivity analyses to determine if statistical significance varied with different subgroup characteristics was not done. The reviewer would also have wished to investigate further for publication bias towards studies with positive findings. A number of included studies were conducted and reported by the same authors increasing the risk of citation bias. Nevertheless, a systematic methodology was followed in searching the literature and the review results are likely to be a true indication of the current available evidence for LHW led MNS disorder prevention interventions in LMICs.This review provides some evidence of effectiveness of using LHWs in MNS disorder prevention programmes. It also indicates that LHWs’ roles in such programmes could involve provision of psychological and psychosocial interventions. From a policy perspective, it would therefore seem that LHW led prevention programmes demonstrate potential for implementation in other LMICs.However, only a few studies from a limited number of countries have been conducted and the evidence base is heterogeneous with respect to intervention design, target population and outcomes measured. In addition, most of the included studies evaluated small populations and were judged to have potential for bias, indicating that the evidence for effectiveness is weak.A need therefore exists for similar and larger studies to be carried out in other settings in LMICs that also allow for recording of indicators related to adverse outcomes, delivery of care processes, fidelity of interventions and cost effectiveness. Such information is necessary for the comprehensive evaluation of the feasibility and impact of large scale mental, neurological and substance use disorder prevention programmes led by lay health workers in low and middle Income countries.AKUADS: Aga Khan University anxiety and depression scale; BDI: Becks depressive inventory; CESD: Centre for epidemiological studies depression scale; CHW: Community health worker; DSM IV: Diagnostic and statistical manual of mental disorders fourth edition; ELDIS: Institute of development studies database; EMBASE: Excerpta medica database; EPOC: Effective practice and organisation of care; GHQ: General health questionnaire; HIV: Human immunodeficiency virus; HOME: Home observation for the measurement of the environment; IMEMR: Index medicus for Eastern Mediterranean database; IMSEAR: Index medicus for South East Asia region database; IQ: Intelligence quotient; LHW: Lay health worker; LILACS: Latin American and Caribbean literature on health sciences database; LMICs: Low and middle income countries; MC-HOME: Middle childhood home observation for the measurement of the environment; MDI: Mental development indices; MedCarib: Caribbean health sciences literature database; MEDLINE: International database for medical literature; MESH: Medical subject headings; MG: Monitoring group; MNS: Mental Neurological and substance use; NET: Narrative exposure therapy; OR: Odds ratio; PDI: Psychomotor development indices; PDS: Post traumatic stress disorder scale; PPVT: Peabody picture vocabulary test; PRISMA: Preferred reporting items for systematic reviews and meta-analysis; PsycINFO: Psychological information database 5; PTSD: Post traumatic stress disorder; SCID: Structured clinical interview for diagnostic manual of mental disorders; SDQ: Strengths and difficulties questionnaire; TC: Trauma counselling; VHW: Village health worker; WAIS: Wechsler’s adult intelligence scales; WHO: World health organisation; WHO-5: WHO wellbeing index; WPPSI-111: Wechsler preschool and primary scale of intelligence; WPRIM: Western Pacific region index medicus database; WRAT-26: Wide range achievement test.The authors declare that they have no competing of interest.BM developed the initial draft and performed the database searches and screening for articles. NV, LS, DS participated in the drafting of the manuscript and helped with discussion of the review. SW provided statistical input. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1472-6963/13/412/prepubCharacteristics of included studies.Click here for fileSummary of findings from included studies.Click here for fileRisk of bias assessment.Click here for file


This study correlated assessment tools for evaluating the severity of skin, nail, and joint symptoms in patients with psoriasis (Pso) and psoriatic arthritis (PsA). Adults with plaque Pso (with or without PsA) were enrolled from four U.S. institutions. Patients were evaluated using a novel 10-area Linear Psoriasis Area and Severity Index (XL-PASI), Psoriatic Arthritis Assessment (PsAA), Psoriatic Arthritis Screening and Evaluation Questionnaire (PASE), Nail Assessment (NA) and Joint Assessment (JA) tools, Psoriasis Weighted Extent and Severity Index (PWESI), and Lattice Physician Global Assessment (LS-PGA). Correlations between assessment tools and individual items in the assessment tools were performed. Data from 180 patients (55 with PsA) were analyzed. Highest correlations between tools (r = 0.77–0.88) were between the XL-PASI, PWESI and LS-PGA. Individual items in the XL-PASI correlated with items in the PWESI for extent skin symptoms, but not for all body areas. Overall, correlations were seen between hands and feet, between face and scalp, and between buttocks, chest, and back. Only low correlation was seen between items assessing joint symptoms with items assessing skin symptoms. These data support the notion that the complex phenotype of psoriatic disease requires instruments that assess the severity of skin, nails, and joints separately. Psoriasis (Pso) is a chronic, systemic, inflammatory, multigenic disease, that manifests in the skin and has significant impact on quality of life Genes within the Major Histocompatibility Complex and genes encoding cytokines have been linked to Pso and PsA Biological evidence also supports a physiological differentiation. For example, selected key immune mediators of disease in the skin and joints differ. Pathologic events in the skin are mediated by autoreactive T cells Hence, there is a need to optimize the diagnosis and recording of the appearance and progression of Pso and PsA for both clinical research purposes and clinical practice, thus optimizing treatment modalities and outcomes. The goal of this paper is to determine from existing tools the smallest number of independent scoring dimensions needed to measure the presence and severity of skin, nail and joint involvement in the broadest psoriatic patient population. Various assessment tools were then evaluated in a phase II-type clinical trial.The clinical portion of the study was conducted from November 2007 to August 2008 in four U.S. institutions; Baylor Research Institute, Dallas; Central Dermatology, St. Louis; University of Utah, Salt Lake City; and Tufts Medical Center, Boston. The study protocol and informed consent forms were approved by all institutional review boards and all patients signed a written consent form before initiation of study-specific procedures. All statistical analyses were performed at the Rockefeller University, Center for Clinical and translational Science, New York.Eligible patients were >18 years old and had plaque Pso (with or without PsA) with ≥5% and ≤90% body surface area (BSA) affected.As described below, the assessment tools comprised two categories: those that involved a physician examination and those submitted to the patient by questionnaire. Some tools were modified slightly to derive more detailed information and consequently, these are included as supplemental figures.The PASI is the most commonly used tool to assess disease severity in patients with Pso in clinical trials Psoriatic Arthritis Screening and Evaluation Questionnaire (PASE). This validated questionnaire  Electronic versions of the instruments were generated using the Web-based Interactive Study Design, Organization, and Management (WISDOM) software, and are available for download at http://mustat.rockefeller.edu) for computing u-scores of the binary, discrete, continuous, and interval-censored data. JMP® 7.0 software  was used to generate the heatmap of the scores and Pearson correlations, equivalent to Spearman rank correlations http://cran.r-project.org) was used to compute odds ratios.Statistical analyses were conducted using the μStat server at the Rockefeller University  and NA are likely inflated at the expense of the correlation between hands/feet and Pso of the other body areas (lower right corner) because of the design and wording of the questionnaires. Moreover, the NA items were highly correlated among each other, but had poor correlation with XL-PASI and PWESI items. Again, hands and feet were an exception, most notably for the severity by PWESI, which explicitly includes “fingernails” and “toenails” in its “hands” and “feet” categories. In particular, there were no secondary structures indicating that the joint and nail symptoms affect the same digits, an observation in contrast to the commonly believed theory.The results of this study do not support the hypothesis that a “least common denominator” of individual components will suffice to define the severity of the spectrum of disease along the axes of both psoriasis and psoriatic arthritis. Thus, at this time, the need for a single measurement tool that is broadly utilizable with the ability to measure the presence and severity of all clinical aspects of psoriasis remains unmet.Our results provide evidence against an association between the severity of joint and skin involvement in patients with Pso and PsA, with the possible exception of hand symptoms. There have been few studies that have directly addressed the controversial relationship between the complexities of skin, nail and joint disease in psoriatic patients. Several small studies have reported no P<0.001) for skin involvement and “any joints involved” and “any nail involved” among toes and a moderate odds ratios  for fingers. The lack of a quantitative association requires further investigation but might involve additional genetic risk factors.However, in support of previous observations regarding a qualitative association between skin and joint disease Several inconsistencies in the design of individual instruments may have affected our results. The PWESI explicitly includes nails with hands and feet, but the guidelines provided on the form do not allow even the most severe nail disease to be marked more than “noticeable” in terms of extent. The XL-PASI (like the PASI), in contrast, does not mention nails at all. The diversity of Pso manifestations on the hands and feet  for example hyperkeratosis vs pustular or combinations thereof, further complicates the issue . The relatively high correlation between severity of disease and extent of disease in nails and hands/feet and the extremely low correlation between extent of disease in hands/feet and extent of disease in all other body areas may suggest that the examiners attempted to reflect severe nail disease by inflating extent and severity of skin disease of hands and feet. The XL-PASI includes a column for severity of arthritis, so that physicians were less likely to reflect joint problems by increasing the severity indicators meant to reflect skin conditions. The PWESI, by contrast, has no separate category for arthritis and, in support of this argument, had a higher correlation with severity of arthritis than the PASI.Analysis of data to evaluate nail disease was complicated by wording of the assessment tools. The NA includes a request for a list of all involved digits (fingers and toes), but then continues with “Select the most involved fingernail and evaluate.” Several completed questionnaires indicated that the examiner had included toenails in the assessment, but others may have followed the instructions literally so that the assessment could be biased to disease forms more frequently seen with hands, such as pitting. This issue highlights the importance of validating assessment tools in the appropriate clinical setting. These observations suggest that Pso of the nails might be more clearly separated from Pso of the skin if examiners were allowed to distinguish explicitly between involvement of nails and skin on both hands and feet.The pathophysiology of nail dystrophy has been postulated to be more closely associated with joint symptoms than with skin symptoms GWAS and family-based association tests for Pso as a whole have had only limited success in defining causative alleles. The results presented here, however, offer a strategy for future genetic studies with a high potential for success in elucidating genetic risk factors for Pso. More specific and statistically validated assessment instruments will allow for the clinical classification of Pso patients into specific categories based on skin, joint, and nail involvement. In addition, the identification of genetic discriminators between these categories, using novel multivariate The clinical evidence presented herein likely signifies the existence of different psoriatic disease phenotypes, thus supporting the hypothesis that different genetic risk factors are involved in the etiology of skin, joint, and possibly nail forms of psoriatic disease. Our results suggest that the complex phenotype of psoriatic disease can only be assessed with instruments that allow the examiner to judge severity of skin, nails, and joints separately (in addition to extent of skin involvement). Moreover, the data analysis suggests that a minimum of two summary scores (one for skin and one for joints), and potentially a third for nails, are required to accurately assess severity across the full spectrum of psoriatic disease. The optimal design of such assessment tools remains the objective of this research project, with efforts continuing to identify the most meaningful contributing elements that define the full spectrum of the psoriatic disease state. Accordingly, this information is likely to be of significant benefit clinical practice as well as in the future design of clinical trials investigating developmental therapies for Pso and PsA.Figure S1Psoriatic Arthritis Assessment (PsAA) is a composite measurement of PsA that includes questions regarding patient and family history and 6 multipart components of a physical examination.(TIF)Click here for additional data file.Figure S2Psoriatic Arthritis Screening and Evaluation (PASE) is a validated patient questionnaire that comprises questions on symptoms and functions.(TIF)Click here for additional data file.Figure S3Nail Assessment (NA) and Joint Assessment (JA) evaluates nail involvement (score 0 for no involvement and score 1 for involvement by digit) and joint involvement (0/1 by digit) on the hands, as determined by physician assessment.(TIF)Click here for additional data file.Figure S4Psoriasis Weighted Extent and Severity Index (PWESI) is used to evaluate the extent and severity of skin disease across multiple areas of the body. The extent of skin disease is measured on a scale of 0 (none) to 4 (extensive) and severity of disease on a scale of 0  to (intensely inflamed). Ten areas are assessed: scalp/hairline, face/neck, arms/axillae, hands/fingers/fingernails, anterior chest/abdomen, back/shoulders, genitalia/perineum/natal cleft, buttocks/thighs, knees/lower legs/ankles, and feet/toes/toenails. This physician assessment delivers a maximal composite score of 50.(TIF)Click here for additional data file.Figure S5Extended 10-area Linear Psoriasis Area and Severity Index (XL-PASI) combines the PASI and PWESI scoring methods. This measure includes assessment of surface area involved, as well as dimensions for scaling, erythema, thickness and joint involvement for specific areas of psoriatic involvement. As with the PASI, severity indicators range from 0 (none) to 4 (extremely severe). As with the PWESI, body surface area is divided into ten (“X”) areas and each area is quantified. The scale of the XL-PASI ranges from 0 to 148.(TIF)Click here for additional data file.


Traditionally, probiotics on the base of live microorganisms are considered to be both beneficial and safe. Unfortunately, their effects may have short-term success or are absent or uncertain. Some symbiotic (probiotic) microorganisms with known beneficial health affects may cause opportunistic infections, increase incidence of allergic sensitization and autoimmune disorders, produce microecological imbalance, modify gene expression, transfer antibiotic resistant and virulence genes, cause disorders in epigenome and genome integrity, induce chromosomal DNA damage, and activate signaling pathways associated with cancer and other chronic diseases. The commercially available probiotics should be considered as a first generation means of correcting microecological disorders. Further, their development will include the selection of natural metabiotics and/or working out the synthetic (or semi-synthetic) metabiotics that will be analogies or improved copies of natural bioactives, produced by symbiotic (probiotic) microorganisms. Metabiotics are the structural components of probiotic microorganisms and/or their metabolites and/or signaling molecules with a determined (known) chemical structure that can optimize host-specific physiological functions, regulator, metabolic and/or behavior reactions connected with the activity of host indigenous microbiota. Metabiotics have some advantages because of their exact chemical structure, well dosed, very safe and long shelf-life. Thus, now metabiotics should not consider myth; they are the result of the natural evolution of probiotic conception. Neither microbial genes nor microbial names cause any harm to the body, but microbial product may do. The presence of very active microbial biological compounds in the gut may have physiological and pathophysiological consequences for the host. Tore Midtvedt (2008)Eukarya, Bacteria, Archaea, and Viruses. Various host indigenous microorganisms should be considered as essential complex extracorporal physiological systems that play a fundamental role in human health and disease. Host microbiota and other functional and metabolic systems, connected with host eukaryotic cells, are working together profitably for the whole organism and for its separated components in the concrete environment conditions. Unfortunately various unfavorable biotic or abiotic factors and stress agents  can produce microecological disorders resulting in tissue, organ and regulatory systems disturbances that can lead to an increase of a disease development risk  inside the intestinal tract can induce the expression of overran additional 400 new genes involved in immune response and inflammation, cell growth and differentiation, apoptosis, cell-to-cell signaling, and cell adhesion resulting in a wider impact on the host's gene expression than thought before the era of macroarray technologies  that the DNA methyltransferases represent potential threats to the epigenomic integrity of cell genomes. When the methylation system enters the cell and begins to methylate the host genome, the methylated DNA-specific microbial DNAse senses the epigenetic changes, causing cell death via chromosomal cleavage (E. coli Nissle 1917) possess a set of genes (pks island) that are responsible for the production of double-strand breaks in host cell DNA. Bacteria containing the pks genes induce in eukaryotic cells a process called megalocytosis, in which the cell body and nucleus become enlarged and mitosis stops. Sometimes 4 hour is enough for the pks island carrying bacteria with eukaryotic cells resulting in the increase of DNA double-strand breaks level. A total of 34% of E. coli strains isolated from healthy human intestine content had such pks islands. A small number of bacterial cells caused minimal DNA damage in eukaryotic cells; in contrast, exposure to 100 or more bacteria per cell has broken the most nuclear DNA. Thus, the breaks in host cell DNA caused by peptide-polyketide genotoxins of some indigenous (probiotic) bacteria could trigger the various cells disorders, including intestinal cancer development  and decrease a safety concern.Investigations of the last 10–20 years have demonstrated that gut microorganisms (including probiotic strains) are able to break down and metabolize complex food nutrients and endogenous substances  resulting in the formation of low molecular weight (LMW) bioactives that may be localized both inside and/or out of microbial cells and found in the intestinal content or passing across the intestinal epithelium barrier determined in the various human fluids, organs and tissues. These compounds derived from probiotic (symbiotic) microbes form what has been called the probiotic metabolome. Interacting with corresponding prokaryotic and eukaryotic cell targets, these biological and pharmacological active compounds may control many genetic, epigenetic, and physiological functions; biochemical and behavior reactions; and intra- and intercell exchange of information. Some commensal microbes including probiotics can secrete a variety of signaling molecules that can modify the inter-bacterial signaling (quorum quenching) and suppress the expression of virulence genes in pathogens or stimulate the growth of beneficial indigenous gut microorganisms , 55–62. Specific representatives of these groups of LMW compounds isolated from symbiotic (probiotic) microorganisms or their cultural liquids may be used for manufacturing microbe-free food supplements, functional foods, and drugs for prophylaxis and treatment of chronic human diseases, as well as sport and anti-aging foods, etc. The above -mentioned approaches and tools for the design of new types of bio-actives on the base of LMW molecules of symbiotic microbiota origin for nutrition and medicine are already being developed in some countries .l or d, and α, β or γ forms; valency and isotope state of incoming chemical elements; substance solubility; dispersiveness, ligand binding, oxido-reduction potential of metabiotic ingredient(s), its(their) interaction with other components that can be both as enhancers or inhibitors; competitive inhibitors for specific transport proteins or absorption site) as well as host physiological status, illness, constituents of the diet, medication, and so on.Current probiotic strains in such situations may become starter strains for industry manufacturing of such microbial bioactive molecules. The knowledge of quality and quantity of LMW molecule profile of each industry used or potential probiotic strain will help researchers to design novel metabiotics with increased health effectiveness, and determine the optimal frequency, dose, and mode of their administration. Industrial production of metabiotics could become the novel prophylaxis and therapeutic approach to address human health in the near future because of their potential ability to interfere in the processes associated with stability of host genome and microbiome; modulation of epigenomic regulation of gene phenotypic expression in eukaryotic cells; improvement of the information exchange, signaling and metabolic pathways in numerous bacteria, bacteria–host and host systems that play an important role in the control for many genetic, epigenetic, physiological functions, biochemical and behavior reactions; in cell growth and host development; in supporting host health in general. We should always remember that real health effectiveness of suggested metabiotics depends on our knowledge of the physicochemical characteristics of metabiotic molecules  for nutrition and medical aims. There is no doubt that the future metabiotics created on the base of strains belonging to the widen spectrum dominant microorganisms may be more effective at conferring health benefits than the LMW bioactives received only on the basis of classical probiotic strains (bifidobacteria and lactobacilli). The known and potential microbial starter cultures of human microbiota origin that could be used as a platform for metabiotic production should firstly be investigated on the synthesis of structural and excreted bioactive substances participating or regulating in pathways associated with carbohydrate, fat, and cholesterol metabolism; work of immune, hormone, and nervous systems; metagenome and epigenome stability; and gene expression regulation. Undoubtedly among human gut microbiota there are species and strains which are potential sources of small diffusible antimicrobial agents, regulators of host energy balance, cholesterol-lowering compounds, modifiers of immune reactions, stimulants, antidepressants, cognitive enhancers, etc. . This bacteria-free liquid medicine for oral use contains metabolic products of Escherichia coli DSM 4087 (25 g), Streptococcus faecalis DSM 4086 (12.5 g), Lactobacillus acidophilus DSM 4149 (12.5 g), and L. helveticus DSM 4183 (50 g). The benefits of this sterile liquid drug are explained by the presence of SCFA, lactic acid, and some other non-identified microbial metabolites in this drug. There are data that ‘Hylak Forte’ promotes the health of adults and children thanks to producing positive shifts in intestine microbiota, host acid-alkaline, water–salt metabolism, vitamins B and K balance, energy provision to intestinal epithelia and local immune cells (E. coli glycoprotein with anorexic activity (Lactobacillus casei (LEx) polysaccharide – glycopeptide with antihypertension effect  inhibiting angeotensin convert enzyme (ACE) and resulting in the decrease of blood pressure  (www.stada.ru/products/baktistatin.html); lactic acid bacteria SCFA and other organic acids   bioactives of microbial origin in the last decade have already been introduced into medical practice and have proven their effectiveness in reducing infectious and metabolic diseases. For example, nowadays on the international market of drugs there is the most known metabiotic with trade mark ‘ne cells . Among one cells ; E. coliactivity ; Lactoban effect , 75; L. pressure , 77; lyo‘Frodo’) ; Quorum croflora , 66. Potcroflora , 56, biocroflora , lectinecroflora , 82, nuccroflora  connectecroflora  and outecroflora  as attraMetabiotics, as modifiers of physiological functions, biochemical and behavior reactions, have some advantages. They have exact chemical structure, well dosed, very safe and long shelf-life. Besides, metabiotics possess the better absorption, metabolism, distribution, and excretion abilities compared with classic probiotics on the base of live microorganisms. A detailed molecular understanding can permit metabiotics to become significant specific and active contributors to the benefits derived from probiotics , 15, 20.I now consider metabiotics not to be a myth; they are a natural evolution of the probiotic conception. In the near future on the base of probiotic LMW bioactives with proven specific benefit effect(s), a set of semi- and/or completely synthetic metabiotics will be designed that are analogies or improved copies of the natural microbial bioactives. This is a similar route of development to the traditional antibiotics that have been coming out during the last 50 years. LMW bioactives of indigenous microbiota origin being even chemically similar with the molecules of other origin  have advantages in principle. For many millions years of evolution, a human superorganism has been selecting prokaryotic and eukaryotic microorganisms from the environment that were functionally and metabolically the most optimal for human life and development. It means that metabiotics manufactured on the base of LMW bioactives of indigenous microbiota origin are the most beneficial and the safest.The metabiotics of next generations will promote the further development of probiotic concept, improve effectiveness and benefit specificity of classic probiotics, and reduce environmental and health hazards of the current microecological approaches in the prevention and treatment of diseases associated with the imbalance of host microbiota.


The need to develop capacity for health services and systems research (HSSR) in low and middle income countries has been highlighted in a number of international forums. However, little is known about the level of HSSR training in Sub-Saharan Africa (SSA). We conducted an assessment at four major East and Southern African universities to describe: a) the numbers of HSSR PhD trainees at these institutions, b) existing HSSR curricula and mode of delivery, and c) motivating and challenging factors for PhD training, from the trainees’ experience.PhD training program managers completed a pre-designed form about trainees enrolled since 2006. A desk review of existing health curricula was also conducted to identify HSSR modules being offered; and PhD trainees completed a self-administered questionnaire on motivating and challenging factors they may have experienced during their PhD training.Of the 640 PhD trainees enrolled in the health sciences since 2006, only 24 (3.8%) were in an HSSR field. None of the universities had a PhD training program focusing on HSSR. The 24 HSSR PhD trainees had trained in partnership with a university outside Africa. Top motivating factors for PhD training were: commitment of supervisors (67%), availability of scholarships (63%), and training attached to a research grant (25%). Top challenging factors were: procurement delays (44%), family commitments (38%), and poor Internet connection (35%).The number of HSSR PhD trainees is at the moment too small to enable a rapid accumulation of the required critical mass of locally trained HSSR professionals to drive the much needed health systems strengthening and innovations in this region. Curricula for advanced HSSR training are absent, exposing a serious training gap for HSSR in this region. Health systems and services research (HSSR)has been defined as ‘a field of study that examines the organization, financing, and delivery of public health services within communities and the impact of those services’ . HSSR caOver the past decade, numerous calls have been made to strengthen HSSR capacity in low and middle income countries (LMICs) as one of the ways to improve health care delivery in these settings. The calls have been made through scientific publications -7 and a It is widely recognized that if health care delivery in SSA is to improve, health systems strengthening is a key factor towards this effort -15. ProgThe African Regional Capacity Development for Health Services and Systems Research (ARCADE-HSSR) project aims at increasing the number of HSSR professionals through development of web-based and freely available modules and blended courses delivered in a collaborative way across several universities; which it is hoped will increase access to specialized training . The ARCThe assessment was conducted between May and October 2011, at the four East and Southern African universities that are part of the ARCADE-HSSR consortium. Only health science departments within these universities were involved in the assessment. Respondents included current and recently graduated PhD trainees, academic program registrars, and PhD training program managers.PhD training program managers in the health science departments were contacted and requested to complete a pre-designed form that sought information on the number of current PhD trainees and those that graduated between 2006 and 2011. The information collected included: trainees’ age, sex, field of study, academic department, year of enrollment, and year of graduation for those that had already graduated. No identifying information such as names and registration numbers were collected. In-depth interviews were also conducted with PhD training program managers to assess available infrastructure and information and communication technology (ICT) facilities at these institutions that can facilitate advanced training in the health sciences, including computer facilities, Internet connectivity and video-conferencing equipment for students.To identify motivating and challenging factors towards PhD training from the trainees’ experience, current PhD students that had been on the training program for at least two years, and those that had graduated no longer than two years prior to 2011 and could be traced, were sent a self-administered questionnaire via Email or direct contact, which they were requested to complete and return. The self-administered questionnaire sought information on demographics, year of enrollment and graduation, field of study, and type of training arrangement, that is, whether the student studied full-time at the home university, or was part of a ‘sandwich’ arrangement . The questionnaire also sought information on their experiences on: a) motivating and challenging factors to enroll into the PhD training program, b) motivating and challenging factors faced during the PhD training, and, c) any gender and social issues that may have affected their enrollment or that they had faced during the PhD training.Finally, a desk review of existing health curricula at these institutions was conducted to identify the various HSSR related modules being offered for masters and PhD training; and the mode of delivery for each module, that is, whether the module was offered in face-to-face mode or in distance-learning mode, and/or if it was freely available on the web.Descriptive statistics were used to describe the characteristics of the PhD trainees. To describe the various fields of study of the PhD trainees, the fields of study were classified into nine categories including: a) health systems, b) health service delivery/research, c) health policy/planning, d) health economics/financing, e) health human resource, f) governance in health, g) biomedical sciences, h) clinical sciences, and i) others.During the review of health science curricula, a number of HSSR related modules being offered were identified, and although some of these had varying names at the different universities, the content for some was generally similar. Modules with generally similar content description were classified under the following categories: a) health services research, b) health systems management and research, c) health policy, d) health planning, e) health economics, f) quality of health care, and g) cost-effectiveness analysis. We report the number of modules in these categories, and the percentage being offered via each of the three modes of delivery, that is, face-to-face mode, distance-learning mode, and web-based freely available.The motivating and challenging factors described by the PhD trainees are reported as percentages of trainees mentioning the given factors.Minimum, median and maximum values were used to describe the number of computers with Internet connection reported by PhD training program managers as being available for use by PhD trainees in the various health science departments. Similarly, minimum, median and maximum values were used to describe the number of video-conferencing equipment available for use by PhD trainees in the various health science departments.The study was approved by the respective Institutional Review Boards of the four participating universities, that is, from the Higher Degrees Research and Ethics Committee (HDREC) of Makerere University’s School of Medicine; from the Research Ethics Committee of Muhimbili University of Health and Allied Sciences; from the Health Research Ethics Committee (HREC) of the University of Stellenbosch; and from the College of Medicine Research and Ethics Committee (COMREC) of the University of Malawi. Written informed consent was also obtained from each participant completing the self-administered questionnaire.A total of 640 PhD trainees enrolled in a health science field at the four participating universities between 2006 and 2011. Of these, 359 (56%) were females. The median age at enrollment into the PhD training programs was 37 years with an inter-quartile range of 30 to 44 years. The numbers enrolled progressively increased from 82 in 2006 to 141 in 2011  were reported to be training, or had trained in the fields of biomedical sciences, followed by 254 in the clinical sciences (40%). Only 24 PhD trainees (3.8%) were training or had trained in a HSSR related field, specifically: 23 trainees in health systems (3.6%), and only one in health policy (0.2%). All the 24 students had trained as part of a ‘sandwich’ training program in partnership with a university outside of Africa. No PhD trainee at these institutions had trained in the fields of health service research/delivery, health economics/financing, health human resources or governance in health  completed and returned the questionnaire, whereas of the 18 current PhD trainees, 16 (89%) completed and returned the questionnaire; giving an overall total of 48 or overall response rate of 50%. The most commonly cited motivating factors to enroll, or experienced during the PhD training included: high level of supervisors’ commitment (67%), availability of funds to support PhD research (63%), PhD training attached to a research grant (25%), availability of a regular stipend (25%), and availability of downloadable training modules (23%). The leading challenges during PhD training cited were: equipment or materials procurement delays largely due to institutional procedural bureaucracies (44%), lack of funding/scholarships for the training (38%), family commitments (38%), poor Internet connection (35%), conflicting job responsibilities (31%), and inadequate institutional/administrative support (27%). Table The median number of computers with Internet connection reported in the health departments was ten, with a maximum of sixty. These facilities were open for use to all graduate students (masters and PhD). Moreover, some departments reported having video-conferencing facilities with a median number of zero, and a maximum of three. At all the three institutions, the video-conferencing facilities were reported to serve multi-purposes including video-conferencing with research collaborators and teaching/learning purposes; and were open for use by graduate students and faculty members Table .Findings from this study show that there has been an average of only five PhD graduates per year in the field of HSSR across the four universities, constituting only 3.8% of all health science PhD trainees. Further, there were no PhD trainees in some of the HSSR fields such as health services research, health economics/financing, governance in health and health human resources. The number of HSSR PhD graduates being produced per year at these universities is very small and is not enough to enable accumulation of the required critical mass of locally trained HSSR professionals to drive the much needed health systems strengthening and innovations in this region. This is a serious training gap in the fields of HSSR that needs to be urgently addressed. There is general agreement that HSSR needs to be driven by local experts who have an intimate understanding of their own health systems and the challenges that they face ,13,15. Met al.[We also found that HSSR related curricula to facilitate advanced academic training is lacking. All the HSSR related modules being offered at these universities were part of either Masters of Public Health, or Masters of Health Services Research. Absence of HSSR related curricula to support PhD training is most likely one of the reasons why there are few PhD HSSR related training at these universities. Bennett et al. have poiet al.. Our finet al.. We beliet al. [One of the factors pointed out by the PhD trainees that motivated them enrolling into respective PhD training programs was availability of web-based freely available modules that they could access remotely. Trainees that mentioned this were those in a ‘sandwich’ training arrangement under which they were able to freely access web-based modules at a partner northern university. Furthermore, a number of challenges that may limit access to PhD training were also highlighted, for example the need to continue working to earn a living, and family commitment. These findings highlight the need to develop learning modules that can be remotely accessed by those who are not able to leave work, family or other responsibilities, to attend face-to-face training. Innovative ways to increase access to advanced HSSR training in SSA, such as development of web-based freely available modules, like those being developed under the ARCADE-HSSR project , need toet al.  found thet al. . InterneWe recognize that our assessment was conducted at only four universities in East and Southern Africa; therefore our findings may have limited generalizability. Nonetheless, the four universities we selected are among the major tertiary training institutions in health sciences in this region. Therefore the numbers and proportion of HSSR trainees may not be very different from other universities within the region. We therefore believe that the gaps in training exposed by our study reasonably reflect the situation in the region.Secondly, although we found low numbers of HSSR trained PhDs from these universities, HSSR research capacity in this region is enhanced by graduates who are being trained outside of Africa, but return to work in their home countries. Our study did not assess this component; therefore the number of HSSR graduates working in the region might be higher. The desire, however, is to build enough local HSSR training capacity within the region. The ARCADE-HSSR project is trying to address this gap.Finally, we recognize that our study did not evaluate the number of trainers (faculty) and their capacity to train in the area of HSSR. This investigation was also only conducted at institutions of learning targeting formal education in HSSR, and therefore did not assess other capacities for HSSR training including: perceptions of HSSR capacity and challenges faced by other stakeholders such as donor agencies and non-governmental organizations, networking, sharing information, and transferring knowledge. Thus, our assessment is deficient of other components of capacity for HSSR training. These could be areas for further investigation in the future.The current level of HSSR PhD training at SSA institutions is too low to enable the rapid creation of a critical mass of locally trained HSSR professionals to drive health system strengthening and innovations. Further, curricula for advanced HSSR training are absent, exposing a serious training gap for HSSR in this region. HSSR related curricula/modules for advanced HSSR training need to be developed at SSA institutions, in order to enhance the number of experts in this field.ARCADE: African regional capacity development; HSSR: Health services and systems research; ICT: Information and communication technology; LMIC: Low and middle income countries; MDG: Millennium development goals; PhD: Doctor of philosophy; SSA: Sub-Saharan Africa; WHO: World Health Organization.The authors declare that there is no conflict of interest.DG drafted the manuscript all authors provided comment, read and approved the final version of the manuscript. Study conceptualization: JKT, CO, DG, MZ. Data collection: FB, DG, JKT, LD, LC, GHL, ELM, NK, MP, SA. Data management and analysis: DG and FB.