The case of contracting out government health services to non-governmental organizations (NGOs) has been weak for maternal, newborn, and child health (MNCH) services, with documented gains being mainly in curative services. We present an in-depth assessment of the comparative advantages of contracting out on MNCH access, quality, and equity, using a case study from Pakistan.An end-line, cross-sectional assessment was conducted of government facilities contracted out to a large national NGO and government-managed centres serving as controls, in two remote rural districts of Pakistan. Contracting out was specific for augmenting MNCH services but without contractual performance incentives. A household survey, a health facility survey, and focus group discussions with client and spouses were used for assessment.Contracted out facilities had a significantly higher utilization as compared to control facilities for antenatal care, delivery, postnatal care, emergency obstetric care, and neonatal illness. Contracted facilities had comparatively better quality of MNCH services but not in all aspects. Better household practices were also seen in the district where contracting involved administrative control over outreach programs. Contracting was also faced with certain drawbacks. Facility utilization was inequitably higher amongst more educated and affluent clients. Contracted out catchments had higher out-of-pocket expenses on MNCH services, driven by steeper transport costs and user charges for additional diagnostics. Contracting out did not influence higher MNCH service coverage rates across the catchment. Physical distances, inadequate transport, and low demand for facility-based care in non-emergency settings were key client-reported barriers.Contracting out MNCH services at government health facilities can improve facility utilization and bring some improvement in  quality of services. However, contracting out of health facilities is insufficient to increase service access across the catchment in remote rural contexts and requires accompanying measures for demand enhancement, transportation access, and targeting of the more disadvantaged clientele. Contracting out involves a formal agreement between a government, as the financier, and a private sector or autonomous government provider for a mutually agreed set of services, in a specified location, over a defined period . InsuffiExisting evidence suggests that contracting healthcare services has resulted in increased utilization of primary healthcare services ,5, but gHerein, we examine the relevance of contracting out health services to NGOs to augment government health facilities and services for MNCH. An attempt is made to fill critical knowledge gaps through a case study of contracting out from Pakistan. In Pakistan, there has been a mushrooming of contracting initiatives in recent years, involving the contracting of government health facilities to large NGOs in rural settings. However, expansion of contracting out schemes has taken place without being accompanied by independent monitoring and evaluations. This paper presents an in-depth assessment of the comparative advantages, if any, of contracted out facilities versus government-managed facilities in remote rural settings. These are compared in terms of (1) utilization of facility and outreach services; (2) equitable utilization by the disadvantaged; (3) quality of services; and (4) patient expenditure. In addition, client-perceived barriers that affect the use of contracted versus government-managed facilities for MNCH services are explored. The paper concludes with a synthesis of how contracting of government health facilities can be strengthened for MNCH in rural disadvantaged settings based on lessons learnt from the experience of Pakistan.Pakistan is the sixth most populous country in the world, with an estimated population of more than 165 million; 12.4% of its population lives below the poverty line . PakistaIn Pakistan, an extensive contracting initiative – the People’s Primary Healthcare Initiative – is already in place, whereby 2,392 BHUs across the country have been contracted out to a national NGO . A thirdThe study was conducted in two contracted-out RHCs, one each from Thatta and Chitral districts, and four matching government-managed RHCs which served as controls, with an intervention to control ratio of 1:2. The contracted RHCs were located in far flung and underdeveloped Talukas (sub-district level); Keti Bunder in district Thatta and Shagram in district Chitral, with a distance of 60 km or more from a RHC to the next government health facility. The control RHCs from both Thatta and Chitral were selected with participation of respective district health offices and objectively based on comparable catchment population size, BCG vaccine coverage, number of LHWs working in RHC catchments, and geographical location such as proximity to road or town centre.The RHCs assessed had been contracted out to a national NGO for provision of MNCH services since 2008. The RHC tier was targeted as it has not been previously explored, allows evaluation of BEmONC as well as routine MNCH services, and is of policy relevance due to continuous expansion of contracting to RHCs. The contractual package included provision of facility-based routine and BEmONC services. In Chitral, the contract additionally stipulated the provision of caesarean delivery as well as administrative control of outreach preventive care programs. The contracts were based on a block grant and did not include specific targets for the agreed service package. Formal controls brought in by the contract included (1) posted government staff made available to the NGO but without transfer and termination authority; (2) additional NGO- supported staff hired with incentivised salary; (3) introduction of an expanded number of essential drug categories and diagnostic tests; (4) authority over maintenance of building and equipment related to MNCH services; (5) introduction of user charges for additional diagnostics that were not covered by RHC budget; and (6) introduction of user charges for antenatal and delivery registration.An end-line, cross-sectional comparison was conducted between contracted RHCs and their designated catchment areas and matching control sites using a case study design. Mixed methods were used to bring together a comprehensive account of case of contracting out , which h2 test and Fisher’s exact test were performed for comparison between contracted and control RHCs. Expenditure data was trimmed for outliers by removing 10% of the data from both tails  after long waiting because nobody paid attention.” .“Clients were also probed on underlying barriers for non-usage of RHCs. Supply side concerns were more commonly reported for control RHCs and included unavailability of basic MNCH services, scarcity of medicines, inadequate attention received from staff and long waiting times. A mother from catchment of control RHC reported,In RHC Shagram, they charge 175 rupees for one X-ray. The registration fee in government hospital is 5 rupees whereas in RHC Shagram it is 75 rupees. They charge high there so we prefer Dai [traditional birth attendant].” .“For clients from contracted sites, the most formidable barrier was high OOP expenditure on transport due to remote distances. Physical access was a cross-cutting concern in both catchments but more widely prioritized by those living in catchment of contracted facilities with complaints of scarce transportation, poor road conditions, and long distances to RHCs. Respondents also cited user charges for diagnostics and registration fee for delivery at contracted facilities, which went against community perceptions of free services at government facilities. A father from catchment of contracted RHC stated,The present study found that utilization of contracted out RHCs was significantly higher for MNCH services and the effect was seen across a range of services including ANC (3+ visits), delivery, PNC, and newborn illness. Prior contracting studies from Bangladesh, Cambodia, Bolivia, Guatemala, and India have reported only a positive increase in ANC visits, but widely variable performance for facility-based births -26. The Equitable utilization remains under-examined. Few studies have looked into utilization of health services by disadvantaged groups, but these are not specific to MNCH services. These studies showed no difference in terms of the poor and the less poor in the use of contracted facilities in Bangladesh and Cambodia ,26, whilOur study on barriers to utilization provides insight into where supportive measures may be placed. Supply side issues at contracted facilities were not a concern despite being the foremost issue at control facilities. Instead, transports costs, difficulties in physical access, and NGO-instituted user charges for registration and diagnostics remained residual barriers at contracted sites. Uneven demand for services was another factor blunting usage with little demand seen for PNC, newborn check-up, and facility-based delivery as opposed to high demand for first antenatal visit, emergency obstetric care, and newborn illness. Our study therefore indicates the need for both demand-inducing measures as well as safety nets for transport expenditure to accompany contracting. User fees applied by contracted NGOs at government facilities also need to be carefully considered as they may go against the popular notions of free services at government facilities.The previous study from Cambodia reports on patient expenditure and is suggestive of reduction in contracted areas . We founThis study also importantly highlighted that contracting out of facilities only translates into better community-based preventive care practices when control over outreach services is also provided. The contracted site lacking a control of outreach services actually had worse indicators than control sites, indicating that bifurcation of facility and outreach responsibilities may in fact have a negative effect. While little is published about preventive care impacts of contracting, two studies from Cambodia and Guatemala show a similar decrease in immunization in contracted sites -26. EvenThe contracted facilities had generally better quality of care but not in all aspects. The health facility assessment shows better functionality of contracted facilities, and higher staff and patient satisfaction, but there is little edge of contracted RHCs in terms of technical process of care and staff capacities. Detailed assessments of quality of contracted primary healthcare services from Afghanistan show high scores in several but not all aspects . Other sThere were certain methodological limitations. Only six facilities were assessed, and although powered to detect utilization differences, our results can be interpreted as a case study that adds insight to contracting literature. The context used here is of remote rural settings and results cannot be generalizable to all settings. For quality assessment we were unable to report the technical process of care for deliveries at control sites as there were only infrequent cases. Finally, due to the absence of baseline data, we cannot establish an increase, but only a comparison of better utilization and quality of care in the contracted over control facilities.The most visible strength of this study was that it moved beyond an assessment of facility outputs as usually performed in other studies , and undOur case study from rural remote Pakistan indicates that contracting out MNCH services at government facilities to NGOs can result in significantly higher facility utilization across a range of MNCH services, better quality of certain services, and can also improve promotive care practices in the community when administrative control over outreach services is also provided as part of the contract. However, contracting in the context of rural remote settings does not result in a beneficial impact on all fronts. Higher facility utilization is confined to literate or better socioeconomic groups. Increased utilization also comes with higher client OOP expenditure on transport and diagnostic fees, and fails to translate into higher population coverage of MNCH services. For contracting to meaningfully increase access in remote settings, accompanying measures are required aimed at behavioural change measures for demand enhancement at village level, transportation access such as through incentivised transport networks or use of transport vouchers, and targeted measures for the more disadvantaged clientele.


Prior studies of risk factors associated with external causes of death have been limited in the number of covariates investigated and external causes examined. Herein, associations between numerous demographic, lifestyle, and health-related factors and the major causes of external mortality, such as suicide, homicide, and accident, were assessed prospectively among 73,422 black and white participants in the Southern Community Cohort Study (SCCS). Hazard ratios (HR) and 95% confidence intervals (CI) were calculated in multivariate regression analyses using the Cox proportional hazards model. Men compared with women , current smokers , and unemployed/never employed participants at the time of enrollment  had increased risk of dying from all external causes, with similarly elevated HRs for suicide, homicide, and accidental death among both blacks and whites. Blacks compared with whites had lower risk of accidental death  and suicide . Blacks and whites in the SCCS had comparable risks of homicide death ; however, whites in the SCCS had unusually high homicide rates compared with all whites who were resident in the 12 SCCS states, while black SCCS participants had homicide rates similar to those of all blacks residing in the SCCS states. Depression was the strongest risk factor for suicide, while being married was protective against death from homicide in both races. Being overweight/obese at enrollment was associated with reduced risks in all external causes of death, and the number of comorbid conditions was a risk factor for iatrogenic deaths. Most risk factors identified in earlier studies of external causes of death were confirmed in the SCCS cohort, in spite of the low SES of SCCS participants. Results from other epidemiologic cohorts are needed to confirm the novel findings identified in this study. These causes of death represent a significant proportion of potentially preventable mortality in the United States (US). In 2010, suicides and accidents occupied two of the top 10 leading causes of death In 2010, US whites had a much higher rate of death due to suicides  than US blacks  The Southern Community Cohort Study (SCCS) is comprised of primarily low-income black and white adults enrolled throughout the Southeastern US. This cohort presents a unique opportunity to examine race- and SES-specific associations between commonly observed risk factors for external causes of death in a population of socioeconomically similar black and white adults. Potential risk factors will be evaluated for the major categories of external cause of death, with information about risk factors obtained at the time of enrollment into the cohort.The SCCS is a prospective cohort study of approximately 85,000 primarily black and white adults designed to study cancer and other health outcomes in underserved populations in the Southeastern US. From 2002–2009, participants 40–79 years of age were enrolled in-person at one of 71 community health centers  or by randomized general population mailings  from the following 12 Southeastern states: Alabama; Arkansas; Florida; Georgia; Kentucky; Louisiana; Mississippi; North Carolina; South Carolina; Tennessee; Virginia; and West Virginia. Participants completed a questionnaire at enrollment which gathered information on demographic, lifestyle, personal and family medical history, and other factors http://www.cdc.gov/nchs/ndi.htm). Alive status is ascertained through contact with the participants and linkage with the Social Security Administration's Service for Epidemiologic Research (http://www.ssa.gov/policy/about/epidemiology.html).SCCS participants are actively followed through administration of follow-up questionnaires, and passively followed through linkages with state and national registers. All-cause and cause-specific mortality in the SCCS is ascertained through linkage with the National Death Index, currently available through 2011  for the population age 40 years and older were calculated for the 12 SCCS states and the 38 remaining states for the years 2002 through 2010. The age-adjusted rates and corresponding standard errors were calculated using version 8.1.2 of SEER*Stat th Revision: all external causes (V01-Y89); accidents ; suicides ; and homicides . Expected numbers of deaths were computed based on age-, calendar year-, race-, and sex-specific rates in the general population of the 12 southeastern SCCS states. Person-years of follow-up began on the participant's enrollment date and continued through the date of death or December 31, 2011, whichever occurred first. Confidence intervals were calculated based on the Poisson distribution for the number of deaths in each external cause of death category.Standardized Mortality Ratios (SMRs), the ratio of observed to expected numbers of deaths, and corresponding 95% CIs were calculated to determine whether the external cause mortality experience of SCCS participants differed from that in the general population in the 12 SCCS states (Panel B of Table1). Observed numbers of deaths were defined according to the International Classification for Disease (ICD) 102; overweight, 25.0 kg/m2≤BMI<30.0 kg/m2; obese, BMI≥30.0 kg/m2; versus normal, 18.5 kg/m2≤BMI<25.0 kg/m2); height (continuous in centimeters); a comorbidity index (continuous); and the self-reported degree to which faith is a source of comfort or strength . The comorbidity index was calculated for each cohort member based on diseases reported on the baseline questionnaire. This index was based on the Charlson index Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% CIs of mortality from external causes of death as an underlying or contributing cause of death among SCCS participants after their entry into the cohort. Covariates used in the models included race (black versus white); sex ; enrollment source (CHC versus GP); alcohol use (continuous number of drinks per day); self-reported doctor diagnosis of or treatment for depression (yes versus no); smoking ; income ; education ; marital status ; employment status (unemployed/never employed versus currently employed); body mass index (BMI) , but no evidence of lack of fit for homicides, suicides, or deaths from other external causes (P>0.2). To assess the impact of the lack of model fit for accidental deaths, logistic regression was used to analyze accidental deaths stratified on year of enrollment. The logistic regression yielded relative risk estimates and CIs very similar to those obtained using the proportional hazards analysis, and thus the results of the proportional hazards analyses will be presented for all categories of external death.In total, there were 695 deaths from all external causes among SCCS participants included in the analysis: 441 deaths (64%) from accidental causes, 98 deaths (14%) from homicide, 57 suicide deaths (8%), and 104 deaths (15%) from other external causes, of which 80 (77%) were the result of complications of medical and surgical care . There was evidence of a lack of fit of the proportional hazards model for accidental deaths .The rate of death from homicide was much higher in male SCCS participants, and was similar in whites and blacks . Death rSuicide rates were much higher in male SCCS participants than in female participants and were much lower in blacks than in whites . The strOverweight and obese participants had reduced risks, and unemployed/never employed participants had increased risks, of dying from all external causes, including accidents, homicides and suicides.The comorbidity index was significantly associated with death rates from external causes other than suicide, homicide, or accident; risk of death increased with an increasing comorbidity index. A significant hazard ratio for the comorbidity index was observed only for the subset of these deaths resulting from iatrogenic causes . There were no significant differences in risk of death from iatrogenic causes by race, sex, or by enrollment source.Blacks in the SCCS had 50% lower risks of suicides and accidental deaths compared with whites, consistent with expectation based on national mortality rates Consistent with most published studies Current cigarette smoking was associated with about a two-fold relative risk for suicide in SCCS participants. Perhaps no risk factor for suicide has been examined more extensively than cigarette smoking, and a direct relation between smoking and suicide has been observed in most studies Cigarette smoking was also strongly associated with death from homicide and accidental death in our study. A recent follow-up study based on the National Health Interview Study  reported relative risk estimates consistent with increased risk in heavy smokers for suicide, homicide, and accidental death Alcohol consumption was significantly associated only with accidental death in the SCCS; the absence of statistical significance for homicides likely reflects the much smaller number of these deaths. Although not studied extensively in epidemiologic studies of homicide or accidental death, a direct association with alcohol consumption is not unexpected Depression was the strongest risk factor for suicide in the SCCS, a finding that was not unexpected Unemployed and never employed participants had a significantly increased risk of external mortality compared with currently employed participants at SCCS enrollment. This is consistent with findings of excess homicide The finding of lower risk of all external deaths in our study, including accidents, homicide and suicides in overweight and obese individuals in the SCCS was a surprise. It is possible that heavier individuals are less likely to engage in certain types of risky activities, and added girth may provide protection in certain types of accidents, but these intriguing findings require confirmation in future studies.Two studies investigating SES and homicide risk in men have found short stature  to be a risk factor for homicide Being married was a strongly protective factor against homicide deaths among SCCS participants. Marital status was not associated with any other external cause of death in the SCCS. However, in a nation-wide follow-up study based on the National Health Interview Study (enrollees interviewed in 1987–1994 and followed for death through 1995) in the United States, being married was protective against deaths from suicide, homicide, and accident The comorbidity index was significantly associated with accidental death and with iatrogenic causes of death. The latter association is plausible, in view of the likely increased need for medical care, including increased use of pharmaceuticals, hospital admissions, and/or surgeries, associated with a greater number of chronic diseases. The association with accidental deaths may reflect increased frailty associated with multiple chronic diseases, or may also possibly be explained by increased use of drugs to treat the greater number of chronic diseases.CHC enrollment was significantly associated with increased homicide and accident deaths compared with GP enrollment, even after adjustment for demographic, lifestyle, and health-related covariates. This may reflect a contribution of factors not covered by the enrollment questionnaire or possibly the influence of community effects. Such effects related to residential environment have been observed in a study of homicide deaths The availability of information from SCCS participants at study enrollment about a variety of demographic, lifestyle, and health-related variables is a strength of the current study. Few studies have evaluated the risk of death for the major external cause of death categories in a prospective cohort study setting, or had the ability to investigate the number and variety of potential risk factors included in the present analyses, though these risk factors were assessed only at study entry. The SCCS population is not representative of the US as a whole, particularly with respect to SES. However, even in this low SES population, most risk factors associated with external causes of death in other populations were also identified as risk factors in the SCCS. Novel findings, such as the inverse associations of obesity with suicides, homicides, and accidents; the similarity of homicide rates among low SES blacks and whites; and the relation between iatrogenic deaths and comorbidities need confirmation in other study populations.


Here, we predict how rapid warming and acidification are likely to affect benthic flora and coastal ecosystems of the northeast Atlantic in this century, based on global evidence from the literature as interpreted by the collective knowledge of the authorship. We predict that warming will kill off kelp forests in the south and that ocean acidification will remove maerl habitat in the north. Seagrasses will proliferate, and associated epiphytes switch from calcified algae to diatoms and filamentous species. Invasive species will thrive in niches liberated by loss of native species and spread via exponential development of artificial marine structures. Combined impacts of seawater warming, ocean acidification, and increased storminess may replace structurally diverse seaweed canopies, with associated calcified and noncalcified flora, with simple habitats dominated by noncalcified, turf-forming seaweeds.Seaweed and seagrass communities in the northeast Atlantic have been profoundly impacted by humans, and the rate of change is accelerating rapidly due to runaway CO Global reviews of the known effects of global warming and ocean acidification  make it clear that although some taxa will benefit, others will be adversely impacted , are also highly productive and play a key role in carbon capture and transfer in coastal ecosystems  dominate algal biomass in the subtidal and fucoids  in the intertidal. Kelp beds are amongst the most productive habitats on Earth Mann  and are ids Mann ; this pr2 conditions as increased inorganic carbon availability may enhance the growth and reproduction of fleshy macroalgae , and Alaria esculenta . We also predict that Fucus distichus will decline based on evidence of loss from its southern limit in the UK  macroalgal species, loss of key habitat-forming kelps at their southerly limits, and indirect factors facilitating dispersal, transportation, and establishment of non-native populations.On the whole, we predict that under a high COAcetabularia, and the brown algal genus Padina. The coralline algae include crustose coralline algae (CCA), free-living coralline algae (rhodolith/maerl), and geniculate (articulated) turfing algae. These form a cosmopolitan group of marine flora, ubiquitous in intertidal and shallow subtidal habitats, where they act as important ecosystem engineers  are benthic microscopic algae including cyanobacteria, diatoms, benthic dinoflagellates, and diminutive life-history stages of macroalgae. They are the base of many food webs, sustaining thousands of species of grazing and deposit feeding invertebrates in the northeast Atlantic, and they form biofilms that affect the colonization of rocky substrata, the biogeochemistry of sediments, and stabilize coastal mud flats. Some MPBs effectively exist via symbiotic relationships with invertebrates such as anemones and corals whilst other MPBs live within shellfish and can be severely toxic to humans.2 vent sites in the Mediterranean Sea where most insight into the potential impacts of high CO2 on the MPB come from. In these vent systems, diatom- and cyanobacteria-dominated biofilms predominate, and broad scale analysis of microeukaryote diversity has shown that MPB communities in high CO2 water are substantially modified compared with ambient conditions  uptake-mechanisms and intracellular pH regulatory mechanisms. The production of CO2 internally from active uptake of + fluxes, with substantial cell surface pH fluctuation in relation to photosynthetic metabolism observed for large diatom cells (Kühn and Raven 2, larger cells are likely to experience substantially larger diurnal pH fluctuations than smaller cells (Flynn et al. 2 on MPB.To allow further predictions, we require a deeper understanding of the mechanistic effects of high CO2 need to be understood at the ecosystem level. For example, biogeochemical impacts of CO2 enhanced MPB communities may be modulated by heterotrophic components of the same community (Witt et al. In addition, MPB responses to high CO2 emissions are curbed, there will be far-reaching consequences for regional biodiversity patterns, trophic linkages, nutrient cycling, and habitat provision for socio-economically important marine organisms. Warming will kill off kelp forests in the south, and ocean acidification will remove maerl habitat in the north. Seagrasses will proliferate, and associated epiphytes switch from calcified algae to diatoms and filamentous species. Invasive species will thrive in niches liberated by loss of native species and spread via exponential development of artificial marine structures. Thus, combined impacts of seawater warming, ocean acidification, and increased storminess may replace structurally diverse seaweed canopies with associated calcified and noncalcified flora with simple habitats dominated by noncalcified, turf-forming seaweeds.Carbon dioxide emissions are causing rates of global warming and ocean acidification that will profoundly affect marine flora worldwide (Pörtner et al. Over the longer term, the ability and rate of species/populations to evolve will be crucial (Sunday et al. 2, are required. Underpinning this is a need to quantify natural variability in carbonate chemistry in the northeast Atlantic to gain a complete understanding of the carbonate chemistry environment experienced by species.Future research must also address the impact that loss of the calcified and fleshy algae and their habitats will have on other benthic flora groups, and benthic, pelagic, and terrestrial fauna that are dependent on such resources. The responses of MPB assemblages, and species-specific information for DMSP and DMS production in algae and seagrasses that will form the benthic floral assemblages under increased COFinally, unless we take action, we will sleepwalk through radical ecological changes to the phycology of our coasts.


Although abbreviated surgery with planned reoperation (damage control surgery) is now widely used to manage major trauma patients, the procedure and its component interventions have not been evaluated in randomized controlled trials (RCTs). While some have suggested the need for such trials, they are unlikely to be conducted because of patient safety concerns. As animal studies may overcome several of the limitations of existing observational damage control studies, the primary objective of this study is to evaluate the efficacy and safety of damage control versus definitive surgery in experimental animal models of injury.We will search electronic databases , conference abstracts, personal files, and bibliographies of included articles. We will include RCTs and prospective cohort studies that utilized an animal model of injury and compared damage control surgery (or specific damage control interventions or adjuncts) to definitive surgery . Two investigators will independently evaluate the internal and external/construct validity of individual studies. The primary outcome will be all-cause mortality. Secondary outcomes will include blood loss amounts; blood pressures and heart rates; urinary outputs; core body temperatures; arterial lactate, pH, and base deficit/excess values; prothrombin and partial thromboplastin times; international normalized ratios; and thromboelastography (TEG) results/activated clotting times. We will calculate summary relative risks (RRs) of mortality and mean differences (for continuous outcomes) using DerSimonian and Laird random effects models. Heterogeneity will be explored using subgroup meta-analysis and meta-regression. We will assess for publication bias using funnel plots and Begg’s and Egger’s tests. When evidence of publication bias exists, we will use the Duval and Tweedie trim and fill method to estimate the potential influence of this bias on pooled summary estimates.This study will evaluate the efficacy and safety of damage control in experimental animal models of injury. Study results will be used to guide future clinical evaluations of damage control surgery, determine which animal study outcomes may potentially be generalizable to the clinical setting, and to provide guidelines to strengthen the conduct and relevance of future pre-clinical studies. Hemorrhage is the leading preventable cause of death after injury worldwide-4. Thus,The conventional surgical approach to managing traumatic hemorrhage is to definitively repair all injured organs in one operation. HoweverTrauma patients who are bleeding heavily therefore often develop a ‘lethal triad’ of hypothermia, acidosis, and coagulopathy, which has been linked with a high risk of mortality-10. In oAs damage control laparotomy was associated with an increase in unexpected survivors during a time that the incidence of high energy and multicavitary penetrating and blunt trauma was rising in the United States and other countries, surgeons rapidly adopted this method over definitive laparotomy for management of severely injured patients,8. The aDespite its potential advantages, damage control laparotomy is associated with several potentially severe complications, reduced quality of life, and significant costs to the health-care system-19. CommAs a result of the perceived lack of clinical equipoise among the surgical community, damage control has not been compared to definitive surgery in a RCT. AlthougAnimal models have the potential to avoid the limitations associated with retrospective reviews of human experiences through the use of stringent inclusion/exclusion criteria, standardized applications of interventions, randomization of animals to treatment groups, allocation concealment, and blinded assessments of outcome. These tIn support of this, a large number of animal studies have evaluated the efficacy of damage control surgery and specific damage control interventions  to definitive surgery  in experimental animal models of injury. We will also evaluate whether estimates of efficacy vary with the construct validity of the model and various study-level characteristics. In the presence of publication bias, we will use the Duval and Tweedie trim and fill method to determine the potential effect of adding a cohort of theoretically unpublished studies to summary estimates of efficacy.This protocol was created according to the Preferred Reporting Items in Systematic Reviews and Meta-analyses statement, the MetIs damage control surgery (or a specific damage control intervention) more efficacious in reducing mortality than definitive surgery  in experimental mammalian models of injury?1) Are particular damage control interventions  more efficacious in reducing mortality than other damage control interventions in experimental mammalian models of injury?2) Are particular damage control adjuncts  more efficacious in reducing mortality than use of no damage control adjunct or other damage control adjuncts in experimental mammalian models of injury?We will modify a sensitive search strategy previously developed for use in identifying studies of damage control surgery and damage control interventions. With asin vivo surgically or through an external blunt or penetrating force; 2) where the experimental intervention was damage control surgery, a damage control intervention, or a damage control adjunct; 3) where the comparator intervention was definitive surgery, a definitive surgical procedure, or an alternate type of damage control intervention or adjunct (or no damage control adjunct); and 4) where the study design was a RCT or prospective cohort study. Both RCTs and prospective cohort studies will be included as many potentially confounding factors are frequently controlled for in non-randomized animal studies. Injuries of interest will include those resulting in solid, hollow, and/or vascular organ damage in the trunk  as well as extremity vascular trauma[Two investigators  will independently screen the titles and abstracts of all citations identified by the search and select those that may have involved animals and which mention use of damage control surgery, interventions, or adjuncts for full-text review. We will include studies: 1) that involved large  or small  animals in which injury was induced r trauma,9. For tr trauma. DefinitAgreement between investigators regarding identification of abstracts for full-text review and inclusion of articles in the systematic review will be quantified using kappa statistics. DisagreThe primary outcome will be all-cause mortality measured at the longest follow-up time after administration of the intervention.Secondary outcomes will include volumes and/or rates of blood loss; laboratory surrogates of blood loss ; and physiologic measurements, including blood pressures , heart rates, urinary outputs, core body temperatures, arterial lactate, base deficit/excess, and pH values, prothrombin and partial thromboplastin times, international normalized ratios, and thromboelastography (TEG) results/activated clotting times.Two investigators  will independently extract data from included studies using a pre-designed data extraction spreadsheet. The design and reliability of the spreadsheet will be pilot tested on a random sample of an equal number of RCTs and prospective cohort studies until it is clear that the form captures all relevant information and consistency in data extraction is achieved (κ statistic ≥0.75). If a noTwo investigators  will independently assess the internal and external/construct validity of included studies. Internal validity will be evaluated using a modified version of the ten-item Collaborative Approach to Meta-Analysis and Review of Animal Data from Experimental Studies (CAMARADES) checklist, which assesses the risk of study design-related biases in animal studies,62,68  for animals utilized in study▪ Explicit statement of exclusion reason(s) for animals removed from analysis of results▪ Explicit statement in study addressing potential confounding factors/sources of bias▪ Evidence of delay in employment of treatment to emulate realities of emergent surgical care▪ Evidence of a pre-specified stopping rule▪ Reporting of a potentially patient-important outcome such as mortalityThe clinical relevance of the study design will be assessed independently by two fellowship-trained trauma surgeons. For the item related to providing evidence of delay in employment of treatment, if the intervention was applied in the ambulance, the delay should be approximately 20 min to account for a 5-min response time and about a 15-min on scene time; if the Both a narrative synthesis and, where possible, a meta-analysis of the results of the individual studies will be presented. Studies will first be grouped according to the types of interventions and controls studied. After studies have been combined into common groups, their characteristics will be presented in summary tables. These groupings will be utilized to determine where categories of studies exist that have similar enough designs to allow for a meta-analysis of their reported outcomes.To address the primary research question, we will calculate individual study estimates of the relative risk (RR) comparing mortality between animals that received damage control (or a specific damage control intervention) versus definitive surgery . Similarly, for the secondary research questions, we will calculate RRs comparing mortality between animals that received different damage control interventions or adjuncts or a damage control adjunct versus no adjunct. As we expect that there will be ‘clinical’ heterogeneity in the design and/or conduct of the included studies, individual study RR estimates will be combined using DerSimonian and Laird random effects models. HoweverI2 inconsistency values and conducting Cochran’s Q hypothesis tests of homogeneity . Heterogeneity will be defined according to the value of the I2 statistic as low (I2 > 25%), moderate (I2 > 50%), and high (I2 > 75%)[We will examine for evidence of between-study heterogeneity by calculating 2 > 75%). In the 2 > 75%). Other c2 > 75%),59,62,69We will assess for the presence of small study effects potentially due to publication bias by plotting funnel plots of the RR of mortality. Evidence for the existence of funnel plot asymmetry will be assessed using Begg’s funnel plot asymmetry test and confirmed using Egger’s regression test,74. WhenAnimal experiments are frequently used to evaluate interventions before they are used clinically. Although animal studies provide evidence of the performance of interventions under relatively ideal conditions, some are limited by study design-related biases and/or a lack of model construct validity. Thus, systematic reviews of these types of studies may be used to outline which interventions tested in animal models do not yet have enough supporting evidence to warrant evaluation in clinical trials,55-57,78Systematic reviews of animal intervention studies are therefore important to guide the transition of scientific findings from the bench to the bedside. These rSystematic reviews of animal studies have also influenced the conduct of pre-clinical trials. Several systematic reviews have suggested how the design, construct validity, methodological rigor, and reporting of animal studies may be improved such that their relevance to human healthcare is enhanced,57,82. IThrough this systematic review and meta-analysis, we seek to establish whether damage control is more efficacious than definitive surgery and if so, which damage control interventions are more efficacious than others. To accomplish this, we will assemble all original scientific research examining the efficacy and safety of damage control in experimental animal models of injury. After considering animal model construct validity, study design-related biases, and whether publication bias may have existed, we will determine which damage control interventions or adjuncts may potentially provide valid and generalizable evidence for further clinical evaluation and suggest how to improve future pre-clinical trials. Thus, our results may be used to both inform clinical research and practice and more appropriately direct future research conducted in animals.In Vivo Experiments.RCT: randomized controlled trial; CAMARADES: Collaborative Approach to Meta-Analysis and Review of Animal Data from Experimental Studies; STREAM: Studies of Translation, Ethics and Medicine; TEG: thromboelastography; MAP: mean arterial blood pressure; REBOA: resuscitative balloon occlusion of the aorta; RR: relative risk; ICU: intensive care unit; AIHS: Alberta Innovates-Health Solutions; ARRIVE: Animal Research: Reporting The authors declare that they have no competing interests.NC drafted the manuscript. NC and DJR contributed to the drafting of the manuscript, formulation of the study selection criteria and risk of bias assessments, and the compiling of tables and the data extraction spreadsheet. DJR and HTS were responsible for formulating the search and for the development of the study design, research question, and statistical analysis/synthesis of data plan. All authors contributed to manuscript revisions and reviews of numerous drafts and agreed upon a final version.NC is an undergraduate Bachelor of Science program student at the University of Calgary. DJR is a surgery and Clinician Investigator Program resident and Surgeon Scientist Program member who is currently pursuing a Doctor of Philosophy degree in Epidemiology and Knowledge Translation with a thesis on trauma damage control surgery at the University of Calgary. HTS is an academic intensive care physician who has an interest in health services research related to critically ill patients.


High rates of partner change in sex work—whether in professional, ‘transactional’ or other context—disproportionately drive transmission of HIV and other sexually transmitted infections. Several countries in Asia have demonstrated that reducing transmission in sex work can reverse established epidemics among sex workers, their clients and the general population. Experience and emerging research from Africa reaffirms unprotected sex work to be a key driver of sexual transmission in different contexts and regardless of stage or classification of HIV epidemic. This validation of the epidemiology behind sexual transmission carries an urgent imperative to realign prevention resources and scale up effective targeted interventions in sex work settings, and, given declining HIV resources, to do so efficiently. Eighteen articles in this issue highlight the importance and feasibility of such interventions under four themes: 1) epidemiology, data needs and modelling of sex work in generalised epidemics; 2) implementation science addressing practical aspects of intervention scale-up; 3) community mobilisation and 4) the treatment cascade for sex workers living with HIV.Decades of empirical evidence, extended by analyses in this collection, argue that protecting sex work is, without exception, feasible and necessary for controlling HIV/STI epidemics. In addition, the disproportionate burden of HIV borne by sex workers calls for facilitated access to ART, care and support. The imperative for Africa is rapid scale-up of targeted prevention and treatment, facilitated by policies and action to improve conditions where sex work takes place. The opportunity is a wealth of accumulated experience working with sex workers in diverse settings, which can be tapped to make up for lost time. Elsewhere, even in countries with strong interventions and services for sex workers, an emerging challenge is to find ways to sustain them in the face of declining global resources. Sex work is central to transmission of HIV and other sexually transmitted infections (STI) due primarily to the large numbers of infections that can rapidly follow each new transmission event. When condoms are used inconsistently, clients quickly infect sex workers who bear the heaviest burden of disease and complications.,2 High rFortunately, high-incidence transmission in sex work can be interrupted. Several countries have demonstrated the feasibility of protecting female sex workers and their clients from HIV/STI transmission, and averting subsequent secondary or ‘downstream’ transmission in the wider population. When interventions are implemented at sufficient scale, as in Thailand, Cambodia and parts of India, for example, established HIV/STI epidemics have been halted and reversed.–8 The coSex work often overlaps with drug-injecting populations, men who have sex with men and transgender persons, expanding transmission potential beyond heterosexual networks. Heterogeneity of sexual behaviour and conditions under which sex work takes place influence to a great extent the degree of vulnerability and risk in sex work, the potential for transmission within larger epidemics, as well as intervention options.,21 For eThis PLoS library collection of eighteen articles extends our understanding of the dynamics of sex work, the potential impact of interventions, and the implementation science behind successful programmes. New research and modelling refine concepts, analytical methods and estimates of the many secondary infections attributable to sex work in generalised HIV epidemics. Other articles, focusing mainly on female sex workers, add to an extensive body of empirical experience which already exists to inform programmes, addressing questions and challenges of sustainability, cost effectiveness, scale and quality.–31Despite an early focus on preventing HIV/STI transmission in sex work, few African countries currently implement interventions in sex work settings to scale.,32–37 SeMishra et al. rigourously deconstruct the logic and evidence behind such assumptions in two papers beginning with a systematic review of empirical and model-based evidence on the role of sex work in HIV transmission. Drawing t) achieved the largest long-term impact. The authors conclude that the MOT is not a valid tool to identify epidemic drivers and is of limited value in guiding HIV prevention priorities. Other analyses have identified similar limitations, while improved methods in Nigeria resulted in considerably higher estimates of transmission attributable to sex work.[The second paper by Mishra et al. critically examines the MOT methods that are widely used to set intervention priorities in different types of epidemics. The valisex work., 19A concrete example of MOT-directed policies can be seen in Swaziland. With one of the highest national HIV prevalence rates in the world, virtually all prevention efforts—behaviour change, male circumcision and ART for its prevention effects—are spread widely across the general population. Yet, Baral et al. surveyed over three-hundred young, active, full-time sex workers who were easy to identify, had HIV prevalence in excess of 70% and reported large sexual networks and low levels of condom use. They conIn contrast, Benin is one of the few African countries that has implemented sex work interventions to scale. Williams et al. used extensive epidemiological and intervention data to parameterise a model which estimates that 96% of HIV infections before the start of interventions were linked directly or indirectly to sex work. Over theDespite the importance of sex work to HIV/STI transmission, resources available to support targeted interventions have been estimated to be less than one percent of programme expenditures in countries with generalised HIV epidemics.  Better aThe actual scale of the response—targeted geographic coverage with adequate intensity and sustainability of cost-effective services—are arguably critical factors that determine the course of epidemics. Notably in Asia, large-scale implementation of basic interventions in sex work settings, supported by structural change, has turned around several rapidly expanding HIV epidemics.–8 Our unTwo papers report on national-level mapping exercises conducted in Africa using methods—including confidentiality safeguards—adapted from Indian experience. In Kenya, interviews with secondary key informants were used by Odek et al. to identify ‘hot spots’, characterise how sex work takes place and estimate numbers of female sex workers. PopulatiAmong direct interventions, condom use reduces STI exposure and incidence, and STI treatment acts on existing prevalent infections. By shortening the duration of infectiousness, chains of infection are interrupted, HIV cofactors removed and risk of complications to individuals reduced. Antiretroviral treatment (ART) also greatly benefits those already infected and reduces the likelihood of onward transmission. Morales-Miranda et al. used routinely reported programme data in Guatemala to document scale-up and increasing clinic attendance, examine issues influencing programme retention, and monitor outcomes. An assesStructural interventions change conditions in sex work settings to reduce vulnerability, support condom use and improve sex workers’ access to services and participation in interventions, both prevention and treatment. In brothels and other venues where sex is sold, condom use policies and ‘house rules’ that shift responsibility for enforcing condom use from individual sex workers to the establishment have overcome inherent power imbalances between sex workers and their clients, and led to rapid increases in condom use and decreased HIV/STI transmission.,6Sex worker mobilisation and empowerment address similar power differentials. Through solidarity and collective action—beginning with participation in peer interventions—sex workers in different settings have changed not only the ground rules concerning condom use but other underlying conditions that affect their work and lives.,28–30,47top down, such as regulations on condom use in sex venues, and bottom up, by mobilising sex worker communities as active partners in prevention—are potentially complementary. [Such structural interventions have been prominent in Asian responses to HIV.,25,26,28mentary. ,49 Recenmentary. ,49 DonorVassall et al. report on a cost-effectiveness analysis conducted in two Avahan districts. A two-stEarly sex worker community mobilisation efforts developed in a step-by-step empirical manner.,28,29,47Due to their generally much higher HIV burden, sex workers are among those most in need of antiretroviral therapy (ART). ART alsoCianci et al. assessed the incremental cost of providing ART to sex workers. Using daSustaining HIV viral suppression and immunological improvement requires that individuals engage and remain in the HIV care cascade with good adherence. Mountain et al. report encouraging levels of ART initiation, adherence, retention, and treatment response among sex workers in a systematic review and meta-analysis of 27 studies, 17 from Africa. ART coveDonastorg et al. developed an integrated programme to promote prevention and care for Dominican female sex workers living with HIV, including individual counseling and education; peer navigation; clinical provider training; and community mobilisation. They repThe articles in this supplement argue for greater policy and programme support for efficient, scaled and targeted interventions with sex workers in order to improve control of HIV and related STI epidemics. At policy level, this includes structural interventions to increase condom use, reduce vulnerability and remove barriers to prevention and treatment. Implementation science shows how to identify areas where sex work takes place, design standardised packages of effective interventions, monitor progress and estimate outcomes—from programme participation to averted infections and retention on treatment. Sex workers should be involved as active participants in improving policies and programmes.The fundamentals have been clear for decades. Interventions such as peer outreach, condom policies and programming, STI services and ART have long been shown to be feasible and effective, and are remarkably consistent across countries and regions.,21,26,28Balance is important. Narrowly conceived programmes with single interventions—to increase condom use, for example, or test sex workers for HIV—run the risk of alienating sex workers and reducing impact. Programmes should thus strive to provide services that sex workers need and value, and to build trust by involving sex workers in decisions about how services are provided, especially those, like HIV testing, which may feel threatening. Experience shows that the more services meet sex workers’ perceived needs, the more likely they will be to utilise them and contribute actively to interventions. A mobilised community that trusts providers is a powerful platform on which to expand services.Programmes should attempt to reach high coverage of the most active sex workers as most of the effect of interventions on HIV transmission is achieved by reaching those with the highest rates of partner change.,17 DeterIn summary, targeted treatment and preventions interventions with sex workers should be scaled up first and foremost in order to reduce the high HIV/STI burden and avert serious morbidity and mortality among sex workers themselves. Feasibility has been demonstrated as has the vital importance of such actions in controlling sexual transmission. The imperative for Africa is rapid scale-up of targeted prevention and treatment, linking outreach and facility-based services, and facilitated by policies and action to improve conditions that place sex workers at high risk and stand in the way of service access. The opportunity is a wealth of accumulated experience working with sex workers in diverse settings, in Africa as well as other regions, which can be tapped to make up for lost time. Elsewhere, even in countries with strong interventions and services for sex workers, an emerging challenge will be sustaining them in the face of declining global resources.Sex work is an important driver of sexual transmission regardless of stage or classification of HIV epidemic. Yet, high-incidence transmission between sex workers and their clients can be interrupted.The disproportionate burden of HIV borne by sex workers calls for expedited and facilitated access to appropriate services. Targeted prevention and treatment interventions should be scaled up first and foremost to reduce high HIV/STI burden and avert serious morbidity and mortality among sex workers themselves.Experience from Asia has demonstrated the feasibility of protecting sex work, averting secondary transmission beyond sex workers and their clients, and, when implemented at sufficient scale, halting established HIV/STI epidemics. Feasibility and effectiveness have also been shown in Africa, but funding for interventions in sex work remains marginal and large-scale responses are rare.Direct interventions should include peer-based outreach, condom programming and appropriate clinical services, and should be supported by structural interventions to reduce vulnerability, facilitate condom use and promote participation and ownership by sex workers.Community mobilisation promotes sex worker participation and uptake of services, helps to overcome structural barriers and build a sustainable response. Provision of more comprehensive services addresses sex workers’ broader health and social needs and, in doing so, may also increase engagement and participation of sex workers, and cost-effectiveness of the response.Sex work takes place in many contexts and takes many forms, from overt and full-time to part-time and ‘transactional’. While any sex worker who seeks services should receive them, programmes should prioritise coverage of overt, high-volume sex work as a first step to interrupting transmission and controlling epidemics.Implementation of both direct and structural interventions should be supported by community mapping and monitoring involving sex workers, where confidentiality and data protection are ensured.The articles in this supplement argue for greater policy and programme support for efficient, scaled and targeted implementation of interventions with sex workers in order to improve control of HIV and related STI epidemics.


Canis dingo/familiaris) and red foxes (Vulpes vulpes) are widespread carnivores in southern Australia and are controlled to reduce predation on domestic livestock and native fauna. We used the occurrence of food items in 5875 dingo/wild dog scats and 11,569 fox scats to evaluate interspecific and geographic differences in the diets of these species within nine regions of Victoria, south-eastern Australia. The nine regions encompass a wide variety of ecosystems. Diet overlap between dingoes/wild dogs and foxes varied among regions, from low to near complete overlap. The diet of foxes was broader than dingoes/wild dogs in all but three regions, with the former usually containing more insects, reptiles and plant material. By contrast, dingoes/wild dogs more regularly consumed larger mammals, supporting the hypothesis that niche partitioning occurs on the basis of mammalian prey size. The key mammalian food items for dingoes/wild dogs across all regions were black wallaby , brushtail possum species (Trichosurus spp.), common wombat (Vombatus ursinus), sambar deer (Rusa unicolor), cattle (Bos taurus) and European rabbit (Oryctolagus cuniculus). The key mammalian food items for foxes across all regions were European rabbit, sheep (Ovis aries) and house mouse (Mus musculus). Foxes consumed 6.1 times the number of individuals of threatened Critical Weight Range native mammal species than did dingoes/wild dogs. The occurrence of intraguild predation was asymmetrical; dingoes/wild dogs consumed greater biomass of the smaller fox. The substantial geographic variation in diet indicates that dingoes/wild dogs and foxes alter their diet in accordance with changing food availability. We provide checklists of taxa recorded in the diets of dingoes/wild dogs and foxes as a resource for managers and researchers wishing to understand the potential impacts of policy and management decisions on dingoes/wild dogs, foxes and the food resources they interact with.Dingoes/wild dogs ( Large- and medium-sized mammalian carnivores influence ecosystem structure and function worldwide through predation and intraguild competition , 2. The Mammalian carnivore species often co-occur, potentially creating complex interspecific interactions and trophic dynamics. If sympatric carnivores use the same food resources, interactions can range from commensalism to mutualism to competition and predation –15. The Understanding the diets of carnivores is important for two main reasons. First, such knowledge can identify prey species that may be impacted by predation. Prey of particular interest are: (i) native species that may be negatively impacted by carnivores , 24–27, Canis dingo), ‘wild’ dogs (C. familiaris) and hybrids of the two (10–25 kg [Vulpes vulpes [5–8 kg]) because of their perceived and actual impacts on native mammals and domestic livestock [As with many areas of the world, south-eastern Australia has a suite of native and introduced mammalian carnivores . Of part10–25 kg , 37), anivestock , 39–42. ivestock , but wilivestock  and are ivestock .Felis catus) [Macropus spp.) [Capra hircus) and feral pigs (Sus scrofa) [Ovis aries), cattle (Bos taurus) and goats [Dingoes, wild dogs and their hybrids (hereafter referred to as ‘wild dogs’ because their scats are indistinguishable) and foxes consume predominantly mammalian prey . Howevers catus) , 54 (mess catus) ). Furtheus spp.) , 56) and scrofa) . Howevernd goats , 58–60, nd goats , 61.Predation by red foxes has been implicated in the decline and extinction of numerous small native mammals, particularly within the Critical Weight Range (CWR: 35–5500g) –66. ConsThe diets of wild dogs and foxes overlap and diet breadth is greater for foxes.The diets of wild dogs and foxes vary geographically.The diet of wild dogs is composed of larger mammals than the diet of foxes and the size-range of mammals in the diet of foxes is nested within the diet of wild dogs.Rusa unicolor)), and large native herbivores (kangaroo species) than the diet of foxes.The diet of wild dogs is composed of more domestic livestock , large introduced herbivores  collected from throughout Victoria during summer, autumn, winter and spring between 1983 and 2014 . AnalystThe locations of scat samples were determined from site descriptions associated with diet analysis data, through cross-referencing with samples entered into the Victorian Biodiversity Atlas , and thrF, of a given food item i is defined as the number of samples N in which that food item occurs, expressed as a frequency of the total number of samples (or of the number of samples that contained food) [Our metric for examining regional variation in the diets of wild dogs and foxes, and to compare the use of mammalian food items from different size-classes by wild dogs and foxes, was percentage frequency occurrence (hereafter ‘frequency occurrence’) of diet categories for each carnivore per region. The frequency occurrence, ed food) :Fi=, medium mammal (0.5–6.9 kg), small mammal (<0.5 kg), bird, reptile/amphibian, insect, other invertebrate and plant material. The mammal size classes follow Pascoe et al.  and are Wallabia bicolor) [Macropus giganteus) [M. fuliginosus) [Equus caballus) [Phascolarctos cinereus) [M. rufus), eastern wallaroo (M. robustus robustus) and sheep [Dasyurus maculatus) were classified as small). The exceptions were glider species that could not be distinguished between the genera Petauroides and Petaurus. These taxa were classed as ‘medium’ because the species identified in the diets from these genera were evenly distributed in the small- and medium-sized classes.Mammalian food items were placed in a size-class according to mean adult body masses obtained from Menkhorst and Knight . Where mbicolor) , easternganteus) , 85, wesginosus) , horse  , koala (inereus) , red kannd sheep . While mnd sheep  and it wTrichosurus spp.) were amongst the more frequent prey items for both wild dogs and foxes. Because hair of mountain brushtail possum (Trichosurus caninus) and common brushtail possum (Trichosurus vulpecula) are difficult to distinguish [We identified mammalian food items that occurred at a frequency of >10% across regions in the diet of wild dogs, and those that occurred at a frequency of >10% across regions in the diet of foxes. For both wild dogs and foxes, we then compared the frequency (counts) of these food items among the nine Victorian regions using the chi-square test for homogeneity . Brushtatinguish  and manyCanis lupus) with modifications by Weaver [Y is the mass of the mammalian food item per scat, and X is the mean mass of an individual of a given mammalian food item. We multiplied Y by the number of scats in which each mammalian food item was recorded to estimate the relative total mass of each mammalian food item consumed per region, and then divided this value by the body mass of individuals of each mammalian prey species to estimate the relative number of individuals of each species consumed per region, as represented by the total sample of scats [Frequency occurrence suffers from several biases, particularly when comparing mammal items of different size in the diet –94. Liney Weaver :Y=0.439of scats . To provDespite the potential for error associated with differential digestion between carnivore families  we appliRattus spp. identified to genus only as these could not be designated as native or introduced) consumed. We then graphically compared the number of individuals consumed by wild dogs and foxes Victoria-wide for CWR mammalian species of conservation significance. We used relative biomass to evaluate regional and interspecific differences in key mammalian food items  were compared graphically for all mammalian prey items identified to species level in wild dog and fox diets across Victoria to explore the relationships between these metrics. We provide a description of this comparison, and explanation of our selection of the metric deemed most appropriate to examine each of our six predictions, in od items . Key mamOjk = Pianka's measure of niche overlap between species j and species k; pij = proportion resource i is of the total resources used by species j; pik = proportion resource i is of the total resources used by species k; n = total number of resources. The value of this index ranges from 0 (no overlap) to 1 (complete overlap). Niche breadth (BA) was calculated using Levins’ standardized measure to compare the proportion (based on frequency occurrence) of food resources exploited by each carnivore [pi = proportion of occurrence of each food resource in the diet and n = the number of possible resources. This measure of niche breadth ranges from 0 to 1, with a value close to 0 indicating a narrow niche and a value close to 1 indicating a broad niche. The BA index gives more weight to commonly eaten resources and less weight to rarely consumed resources [We estimated diet niche overlap between wild dogs and foxes and niche breadth for each species across Victoria and within each region, based on use of the eight diet categories (food resources): large mammal, medium mammal, small mammal, bird, reptile/amphibian, insect, other invertebrate and plant material. To estimate diet overlap we used Pianka’s index :O^jk=∑iarnivore , 101:BAesources .We compiled our data into checklists of taxa recorded in the scats of wild dogs and foxes in Victoria. We summarised scat data as frequency occurrence for each item recorded as ‘definite’ or ‘probable’ prey in the diets of wild dogs and foxes within each of the nine regions and in all regions combined. Summary data from the literature, which largely consisted of unpublished reports, were used to compile presence records for the checklists but were not included in estimates of frequency occurrence of dietary items. In the checklists we identified native species of conservation significance that are listed under state and federal legislation , 77 and/Our checklists  Tables iSixty-two mammal species (48 native species and 14 introduced species) from 42 genera and 25 families (mostly the same families recorded for wild dogs) were identified in the diet of foxes . Five biMammals were the most frequently recorded items in the diets of wild dogs and foxes in Victoria  between wild dogs and foxes when data from all regions were pooled (There was high diet overlap (e pooled . HoweverBA) was greater for the fox than for the wild dog when data from all regions were pooled and in all regions except the Mallee, Wimmera and North Central regions , native macropods and livestock, whereas in the North Central region key food items were the introduced sambar deer and native mammals  in the diet of wild dogs and foxes varied among regions Figs. , as did  mammals . Similar mammals .Birds occurred most frequently in the diet of wild dogs in the Mallee, Wimmera and Central regions, whereas reptiles/amphibians, insects and plant material occurred most frequently in the diet of wild dogs in the Mallee region and, to a lesser extent, in the Wimmera region . Birds cVombatus ursinus), and medium-sized brushtail possum spp. (Pseudocheirus peregrinus) and the small-sized bush rat (Rattus fuscipes) (Mus musculus) and the medium-sized European rabbit (Antechinus swainsonii) and broad-toothed rat (Mastacomys fuscus)  . By contn rabbit  Tables. n rabbit . Additio fuscus) .Ten large introduced mammal species were recorded in the diets of wild dogs and foxes in Victoria, including two livestock species  Tables. Axis porcinus) were recorded in the diets of both wild dogs and foxes in low frequencies  and red deer (Cervus elaphus scoticus) were recorded only in the diet of foxes, at even lower frequencies, and only in the Wimmera region  yet goats were a key mammalian food item for wild dogs in the South West region . These tWhen data from all regions were pooled, biomass intake was greater by wild dogs than foxes for eastern grey kangaroo  and eastBurramys parvus) compared to intake of other threatened species in the CWR and compared to intake of any threatened species in the CWR by wild dogs (Isoodon obesulus) and grey-headed flying-fox   and foxes . Foxes consumed almost twice the number of individuals of species in the CWR than did wild dogs  and 6.1 times the number of threatened CWR species . In partild dogs . Other tephalus) .Sminthopsis leucopus) and New Holland mouse (Pseudomys novaehollandiae)) and two were larger ). Notably, within the CWR the critically endangered mountain pygmy-possum and the endangered Leadbeater's possum (Gymnobelideus leadbeateri) [Pseudomys fumeus) [Eleven mammal species of conservation significance listed under state and federal legislation, and/or on the International Union for Conservation of Nature red list were recorded in the diets of wild dogs and 13 mammal and one crustacean species in the diet of foxes  Tables. beateri)  were rec fumeus)  was recoDasyurus maculatus) was not recorded in the diets of wild dogs or foxes during this study, but has been recorded in the diet of wild dogs in the literature (Foxes occurred in the diet of wild dogs at low frequency (0.2%) and biomass, but this was double the frequency (0.1%) and 1.5 times the biomass that wild dogs occurred in the diet of foxes . In partterature .vice versa. Hence, four of our six predictions were supported, and we found partial support for our remaining two predictions.Understanding the diets of sympatric mammalian carnivores is of central importance for ecological theory (niche partitioning) and for managing their impacts on production and conservation values. Our study revealed substantial overlap in the diets of the larger-bodied wild dog and the smaller-bodied red fox in Victoria. However, the breadth of their diet niches and the extent of diet overlap varied geographically, confirming the opportunistic feeding habits of these carnivores in south-eastern Australia , 39, 80.The diets of wild dogs and foxes in Victoria consisted of similar numbers of mammal species . Scat analysis can be biased towards identification of mammalian prey, for example due to digestion of soft-bodied invertebrates , 103, hiAlthough insects may be eaten in large quantities by young wild dogs , we founAs predicted, the diets of wild dogs and foxes in Victoria varied geographically. The greatest variation was between regions that included large tracts of semi-arid rangeland  and wet montane forest . In general, mammals were more prevalent in the diets of wild dogs and foxes in the wetter, more montane regions of eastern Victoria than in the more arid regions in western Victoria where non-mammalian food groups including reptiles, insects and plant material, were recorded in higher frequencies in the diets of both carnivores. The suites of key mammalian food items varied regionally, supporting observations that intake of native species is greatest in regions with a large proportion of native forest  and alpiEcological separation of sympatric carnivore species around the world is primarily related to dietary differences , 120, anIn contrast to foxes, wild dogs may co-operatively hunt to kill prey much larger than themselves , 124. ItWild dogs hunt domestic livestock, with sheep and goats being particularly vulnerable . HoweverOverall, our findings support our prediction that use of large introduced herbivores is greater by wild dogs than by foxes. Sambar deer were a key mammalian food item in the diet of wild dogs, and to a lesser extent foxes, in several regions where this species is now common , 130, whLarge introduced herbivores other than sambar deer were recorded in the diets of wild dogs and foxes in relatively low frequencies. This result may reflect the low densities and/or limited distributions of some species in Victoria , and theOur prediction that large native herbivores would be more common in the diet of wild dogs than in the diet of foxes was supported for only two of the four large macropod species in Victoria, and kangaroos were key mammalian food items for both wild dogs and foxes. Macropods of all age-sex classes are actively hunted by wild dogs , whereasOur study indicates that wild dogs and foxes eat a wide range of mammals in Victoria, but the majority of their diets are composed of a relatively small proportion of these species, consistent with previous studies , 135. InImportantly, our analysis indicates that the European rabbit is a key food item for wild dogs in the Mallee, Wimmera, Northern Country, North East, Central and South West regions. The European rabbit can be an important component of the diet of wild dogs in arid Australia , 116, buOur prediction that the diet of foxes contained more native species in the CWR than did the diet of wild dogs was supported: foxes consumed 1.8 times the number of individuals of species in the CWR than wild dogs and 6.1 times the number of individuals of threatened species in the CWR. Furthermore, a slightly greater number of mammal species of conservation significance, most of which were within the CWR, were recorded in the diet of foxes. Our results are supported by previous work suggesting that foxes pose a greater risk to mammals within the CWR than do wild dogs , 79, parvice versa [Carnivores may scavenge carrion of other smaller, larger, or their own species , 23. We ce versa . The occce versa , 35, 147ce versa , the larce versa  and wildce versa , 147–149Wild dogs and foxes consumed cats at similarly low frequencies in Victoria. Consumption of cats by wild dogs  and foxeCannibalism and scavenging on dead conspecifics has been documented in wild dogs , 152 andChanges in the availability of foods that frequently occur in the diet may have implications for the abundance and/or impacts of carnivores –155. WilFoxes rather than wild dogs are thought to be a major cause of the decline of Australia’s CWR mammals , 66, 79 Finally, large geographic variation in the diets of wild dogs and foxes indicates that a wide variety of trophic interactions are possible within the State of Victoria . This geS1 Appendix(DOCX)Click here for additional data file.S1 Table(DOCX)Click here for additional data file.S2 Table(DOCX)Click here for additional data file.


Recommendations for identifying age-related muscle dysfunction have recently been published. We aimed to compare definitions for clinically relevant weakness and low lean mass proposed by the Foundation for the National Institutes of Health (FNIH) Sarcopenia project with the definition of sarcopenia proposed by the European Working Group on Sarcopenia in Older People (EWGSOP).A total of 1566 men and women from a British birth cohort had measures of appendicular lean mass, grip strength and timed up, and go speed at ages 60–64. Prevalence of low lean mass, weakness and slowness, identified using the FNIH and EWGSOP recommendations were estimated and compared: using kappa statistics and; by testing cross-sectional associations of both definitions of low lean mass and weakness with slowness and self-reported difficulties walking.The combined prevalence of low lean mass and weakness ranged from 1.1% in men using FNIH criteria to 6.4% in women using EWGSOP criteria. There was limited overlap between the groups identified using the different criteria, driven by limited agreement between the two definitions of low lean mass. Using FNIH criteria, both low lean mass and weakness were associated with higher odds of slowness and difficulties walking; whereas low lean mass classified using EWGSOP criteria was not associated with these markers of mobility impairment.At relatively young ages, signs of skeletal muscle function deficit with potential clinical relevance are already identifiable in the general population. This suggests that implementation of strategies to prevent mobility limitations, related to age-related muscle dysfunction, may need to start at least as early as midlife. A series of articles recently published outline the findings and recommendations of the Foundation for the National Institutes of Health (FNIH) Sarcopenia Project . This poIn direct response to the call made to evaluate the FNIH recommendations in other study populations ,4,5, we The Medical Research Council National Survey of Health and Development (NSHD) is a socially stratified sample of 5362 singleton births that took place in one week of March 1946 in mainland Britain. Between 2006 and 2010 (at 60–64 years), 2856 eligible study members  were invited for assessment at one of six clinical research facilities (CRFs) or to be visited by a research nurse at home; 2229 were assessed (1690 at a CRF) . RelevanAs described in detail elsewhere ,13, meas2).Strength and physical performance were assessed by trained nurses during the CRF or home visit using standardized protocols. Grip strength (kg) was assessed using an electronic handgrip dynamometer . Three v2, ALM:BMI ratio, and walking speed, by multiplying TUG speed by 1.62, based on comparisons of TUG and walking speeds in other British study populations with both measures [n = 17) or TUG (n = 8) assessment for health reasons , were categorised as weak and slow, respectively.After deriving the variables required (ie ALM adjusted for heightmeasures ), the FNn = 1566). Sensitivity analyses, conducted to test the impact of including those people unable to perform the grip strength and TUG assessments in the main analyses and to assess the robustness of findings, are described in Appendix 1.Prevalence estimates of low lean mass, weakness, slowness, and the combinations of these outcomes were calculated. Cohen’s kappa was used to compare the different definitions. Logistic regression was used to estimate the odds ratios of slowness and self-reported difficulty walking associated with the different definitions of low lean mass and weakness. Gender-specific analyses were conducted on the sample with complete data on lean mass, grip strength, and walking speed . As the FNIH criteria are more restrictive , driven by limited agreement between the two definitions of low lean mass ; 31.6% of men and 40.5% of women had low lean mass according to at least one definition, but only 4.8% of men and 5.0% of women were identified by both definitions.Using the FNIH criteria, low lean mass and weakness were both associated with higher odds of slowness and self-reported difficulties walking . Low leaAppendix 1).Findings from sensitivity analyses suggested that there was no major impact on findings of including those people unable to complete the grip strength and TUG assessments for health reasons  . Both deThese analyses respond to the call to evaluate recently proposed criteria for the identification of clinically meaningful age-related changes in muscle mass, strength, and performance in other study populations ,4,5. WhiThat some people in a general population in early old age already fell below cut-points for low lean mass, weakness and slowness may be due to initial developmental differences as well as earlier onset or accelerated rates of age-related decline in some individuals. Future studies, ideally with longitudinal assessment of muscle from earlier in life, should investigate these different pathways which may be associated with different health and disability prospects.That the FNIH definition of low lean mass (which includes adjustment for BMI) was associated with slowness and difficulties walking; whereas, the EWGSOP definition of low lean mass (which includes adjustment for height) was not provided further evidence of the need to take account of BMI or fat mass when identifying those most likely to have insufficient muscle to support movement. As the FNIH definition uses a ratio of ALM to BMI, follow-up work is required to identify whether interventions targeting ALM, fat mass, or both are most effective in preventing future mobility disability.Appendix 1) suggest that this may have led to underestimates of the prevalence of low lean mass, weakness and slowness suggesting that the need for earlier intervention may be even greater than our main results suggest.This study has a number of major strengths as well as limitations which have recently been discussed in detail elsewhere . For exaLean mass and walking speed were not assessed in the NSHD until the most recent data collection, and so we are currently limited to cross-sectional analyses of their associations with other outcomes alongside our prospective studies of their determinants ,13. Howehttp://biomedgerontology.oxfordjournals.org/Supplementary material can be found at: the UK Medical Research Council (Programme code MC_UU_12019/4). The study sponsors played no role in study design, the collection, analysis, and interpretation of data, the writing of the article, or the decision to submit it for publication.This work was supported by None.


New treatments for multidrug-resistant tuberculosis (MDR TB) are urgently needed. Two new drugs, bedaquiline and delamanid, have recently been released, and several new drugs and treatment regimens are in the pipeline. Misuse of TB drugs is a principal cause of drug resistance. As new drugs and regimens reach the market, the need to make them available to patients must be balanced with regulation of their use so that resistance to the new drugs can be prevented. To foster the rational use of new drugs, we propose 1) expanding/strengthening the capacity for drug susceptibility testing, beginning with countries with a high TB burden; 2) regulating prescribing practices by banning over-the-counter sale of TB drugs and enacting an accreditation system whereby providers must be certified to prescribe new drugs; and 3) decentralizing MDR TB care in rural communities by employing trained community health workers, using promising mobile technologies, and enlisting the aid of civil society organizations. The World Health Organization (WHO) recently described the global effects of multidrug-resistant tuberculosis (MDR TB) as a “public health crisis”   of the agents being used. Although standardized DST for the newest drugs is still in development, for other components of MDR TB treatment regimens, DST is more established. However, access to DST for second-line drugs is severely limited in many countries  was established in 2000. The GLC was created by the Stop TB Partnership to ensure that low-cost, quality-assured second-line TB drugs reached approved treatment programs. The committee verified that programs adhered to WHO guidelines and procured all drugs used to treat MDR TB by programs funded by the Global Fund to Fight AIDS, Tuberculosis and Malaria.Although the GLC successfully obtained drugs and verified their appropriate use, after 10 years only 29,000 MDR TB patients had been started on treatment through this mechanism  Project, a collaboration to improve TB laboratory support in 27 countries that contain ≈40% of global MDR TB cases  for community-based management of TB and MDR TB, harnessing new technologies to promote appropriate use of drugs, and enlisting support of existing civil society organizations.CHWs can be trained to monitor patients for treatment compliance, administer injectable second-line drugs, and refer cases with a poor treatment response or severe medication side effects to a higher level of care. CHWs can also utilize new technologies, such as mobile devices, to monitor compliance (Bedaquiline, delamanid, and other forthcoming drugs have the potential to greatly improve MDR and XDR TB treatment outcomes worldwide. The appropriate use of these medications along with other active drugs is essential to prevent resistance. Although the release of new drugs and regimens should not prompt the introduction of potentially harmful treatment restrictions, a nuanced use of some restrictions could be introduced without obstructing appropriate treatment. The arrival of promising new drugs should also be seen as an opportunity to strengthen existing TB diagnostic and treatment efforts, so that the expected benefits of new therapies may reach patients quickly and safely.


In 2001, in anticipation of rotavirus vaccine licensure and introduction, the World Health Organization (WHO) and partners established regional laboratory surveillance networks for rotavirus detection and strain type monitoring among hospitalized children aged <5 years . VaccinaIn 2008, the Global Rotavirus Surveillance Network (GRSN) was established to 1) generate local data for decision making regarding rotavirus vaccine introduction and sustained use, 2) assess and monitor disease trends and genotype distribution over time, 3) develop a platform for vaccine effectiveness studies, and 4) highlight the value of surveillance data. The transition of regional laboratory network coordination to WHO for a global laboratory network within the GRSN then began, with GAVI Alliance funding for surveillance in eligible countries. The Global Rotavirus Laboratory Network (GRLN) is a fundamental component of the GRSN designed to conduct high-quality diagnostic testing for rotavirus diarrhea and characterize the most prevalent genotypes among strains isolated in different countries and regions. As of April 2013, the network includes 107 sentinel hospital laboratories, 36 national laboratories, nine regional reference laboratories, and one Global Reference Laboratory.WHO coordinates the operations of the GRLN and GRSN. WHO surveillance focal persons and laboratory coordinators work closely with ministries of health in participating countries to support surveillance activities, including initial sentinel hospital site selection, specimen and data flow management, laboratory performance monitoring, and regional meeting planning. WHO, partners, and participating countries hold regular meetings at the global and regional levels to discuss surveillance results and progress in network development and to set an agenda of priority activities.Sentinel hospital sites within participating countries enroll children <5 years of age hospitalized with acute gastroenteritis who meet a standard case definition.The GRLN has adapted several approaches from the WHO-coordinated global laboratory networks for poliovirus and for measles and rubella to confirm and improve the accuracy of collected data ,7. TheseIn 2012, WHO established a rotavirus laboratory technical working group to develop approaches to improve laboratory network capacities and increase standardization of key laboratory methods and procedures. Progress on standardization issues includes recommendations to 1) revise standard genotyping data collection forms to record all detected strains; 2) define approaches to reduce the number of untypeable strains; 3) develop standard procedures for sample handling, storage, and shipping that can be adapted in each region; and 4) implement routine confirmation for a subset of genotypes.Monitoring of individual laboratory performance occurs through site assessments using standardized assessment tools for the national laboratories and RRLs; a standard tool for sentinel hospital laboratories is in development. Performance indicators for sentinel hospital laboratories and national laboratories include minimum number of rotavirus tests performed, RRL-confirmed testing accuracy, successful completion of yearly proficiency testing, timely sample analysis, and application of standard operating procedures. Additionally, reviewers assess the biosafety procedures and infrastructure of all laboratories. Site visits offer opportunities to assist laboratories with problem solving and often are combined with trainings.Laboratory data reported through the GRSN include the percentage of hospitalized children positive for rotavirus and strain prevalence in each WHO region and country. The number of reporting countries has grown from 44 in 2008, to 64 in 2011 . During The GRLN is an integral part of the GRSN that provides timely rotavirus disease burden data, which can help guide decisions regarding rotavirus vaccine introduction into national immunization programs. These data also can provide a baseline for assessing the impact of rotavirus vaccines on severe rotavirus disease resulting in hospitalization and on strain prevalence.Substantial progress has been made in expanding the reach of the GRLN, developing standardized data collection procedures, and implementing quality assurance procedures to improve data collection. Lessons learned and applied from the other WHO-coordinated laboratory networks have resulted in a system of national, regional, and global laboratories proficient in rotavirus diagnosis and genotyping. Efforts are underway to optimize critical laboratory procedures used at the global and regional reference laboratories to facilitate interlaboratory data comparability and improve genotyping data quality.Although 2009–2011 data indicate that G1P[8], G2P[4], G3P[8], G4P[8], and G9P[8] strains remain the most prevalent globally, regional and temporal differences in genotypes exist. Strain changes are seen naturally. Careful interpretation is necessary to associate any changes with vaccine use, especially because both vaccines have demonstrated good cross-protection to date. Close monitoring is required and can be accomplished through the GRLN.WHO, in collaboration with key partners, has begun an in-depth review of the past 5 years of data and experience collected through the GRSN. This review will identify strengths and weaknesses of the GRSN, including the GRLN, and will guide decisions on strategies and actions to ensure the network is responsive to information needs of all immunization stakeholders. The review also will provide recommendations related to the potential use of the network for surveillance needs around vaccines in development and other important gastroenteric pathogens.


The Golgi apparatus is an essential cellular organelle for post-translational modifications, sorting, and trafficking of membrane and secretory proteins. Proper functionality of the Golgi requires the formation of its unique cisternal-stacking morphology. The Golgi structure is disrupted in a variety of neurodegenerative diseases, suggesting a common mechanism and contribution of Golgi defects in neurodegenerative disorders. A recent study on Alzheimer's disease (AD) revealed that phosphorylation of the Golgi stacking protein GRASP65 disrupts its function in Golgi structure formation, resulting in Golgi fragmentation. Inhibiting GRASP65 phosphorylation restores the Golgi morphology from Aβ-induced fragmentation and reduces Aβ production. Perturbing Golgi structure and function in neurons may directly impact trafficking, processing, and sorting of a variety of proteins essential for synaptic and dendritic integrity. Therefore, Golgi defects may ultimately promote the development of AD. In the current review, we focus on the cellular impact of impaired Golgi morphology and its potential relationship to AD disease development. The Golgi apparatus is a membranous cellular organelle that mediates proper trafficking, post-translational processing, and sorting of membrane and secretory proteins. The Golgi is often localized to the perinuclear region of the cell, which depends on an intact microtubule network and a motor protein dynein. Golgi membranes form multilayer stacks that are laterally linked into a ribbon. Formation of stable multilayer stacks and ribbons appears to be essential for proper functioning of the Golgi   may be a site where Aβ is generated in the cell  peptides  caused by precipitation of hyperphosphorylated tau protein, which is also related to Golgi structure and function Figure  Morishi. Tau is In AD, hyperphosphorylation of tau results in NFT formation, which impairs microtubule integrity and blocks membrane transport (Patrick et al., Golgi morphological alterations have been observed in neurons of AD patients (Dal Canto, cis-Golgi ribbon-linking and no apparent neurological phenotype (Veenendaal et al., The formation and maintenance of the perinuclear localization of the Golgi ribbon rely on an intact microtubule cytoskeleton emanating from the perinuclear centrosomes (Glick and Nakano, 2+ influx (Zempel et al., The mechanism of Golgi fragmentation in AD has not been well studied, but likely involves multiple mechanisms Figure . One posProper Golgi structure formation controls the sequence and speed of protein transport through the Golgi membranes for proper trafficking, maturation, sorting, and processing of not only APP, but also many neuronal proteins (Dries and Yu, 2+ (Pinton et al., 2+ is a key regulator of membrane fusion (Pang and Sudhof, Long term Golgi defects might also result in a significant change in the composition of proteins, lipids, and polysaccharides at the cell surface Figure . A changThe Golgi apparatus plays an essential role in trafficking and sorting of proteins that are vital for neuronal functions. The Golgi is fragmented in many neurodegenerative diseases, suggesting that Golgi defects may contribute to neurodegeneration. Golgi fragmentation likely involves multiple mechanisms. In a recent study on AD, Golgi fragmentation is caused by phosphorylation of the Golgi structural protein GRASP65 and Golgi fragmentation results in enhanced APP trafficking and Aβ production. Golgi fragmentation is predicted to impair intracellular trafficking of many proteins that are essential for neuronal function. Restoring Golgi morphological defects might be an attractive approach to treating, or even preventing, AD. Understanding the impact of Golgi pathology and determining the molecular mechanisms that cause Golgi fragmentation is expected to shed insight into novel therapeutic approaches for treating AD and potentially other neurodegenerative disorders.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.