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BackgroundOver a quarter of children aged 2-17 years living in Australia are overweight or obese, with a higher prevalence reported in regional and remote communities. Systems thinking approaches that seek to support communities to generate and implement locally appropriate solutions targeting intertwined environmental, political, sociocultural, and individual determinants of obesity have the potential to ameliorate this. There have however been reported challenges with implementation of such initiatives, which may be strengthened by incorporating implementation science methods.MethodsThis pilot randomised controlled trial protocol outlines the development and proposed evaluation of a multicomponent implementation strategy (Action-RESPOND). to increase the implementation of community-based systems thinking child obesity prevention initiatives The target of this intervention is ten rural and regional communities (or local government areas as the unit of allocation) within Northeast Victoria who were participants in a whole-of-systems intervention (RESPOND). Action-RESPOND builds on this intervention by assessing the impact of offering additional implementation strategies to five communities relative to usual care. The development of the multicomponent implementation strategy was informed by the Promoting Action on Research Implementation in Health Services (PARIHS) framework and consists of seven implementation strategies primarily delivered via 'facilitation' methods. Implementation strategies aimed to ensure initiatives implemented are i) evidence-based, ii) address community's specific needs and iii) are suitable for local context. Strategies also aimed to increase the community's capacity to implement, through iv) improving the health promotion team's implementation knowledge and skills, fostering v) leadership, vi) physical resources and vii) community culture to drive implementation. The feasibility, acceptability, potential impact, and cost of the strategy will be assessed at baseline and follow up using surveys administered to key representatives within the community and internal records maintained by the research team.DiscussionBy leveraging an existing community-based whole-of-systems intervention, Action-RESPOND offers a unique opportunity to collect pilot feasibility and early empirical data on how to apply implementation and systems science approaches to support obesity prevention in rural and regional communities in Victoria.

BackgroundWorld-wide, health service providers are moving towards innovative models of clinical home-based care services as a key strategy to improve equity of access and quality of care. To optimise existing and new clinical home-based care programs, evidence informed approaches are needed that consider the complexity of the health care system across different contexts.MethodsWe present a protocol for working with health services and their partners to perform rapid identification, prioritisation, and co-design of content-appropriate strategies to optimise the delivery of healthcare at home for older people in rural and regional areas. The protocol combines Systems Thinking and Implementation Science using a Consensus Mapping and Co-design (CMC) process delivered over five workshops.DiscussionThe protocol will be implemented with rural and regional healthcare providers to identify digital and non-digital solutions that have the potential to inform models of service delivery, improve patient experience, and optimise health outcomes. The combination of system and implementation science is a unique approach for optimising healthcare at home for older populations, especially in the rural context where need is high. This is the first protocol to integrate the use of systems and implementation science into one process and articulating these methods will help with replicating this in future practice. Results of the design phase will translate into practice through standard health service planning methods to enhance implementation and sustainability. The delivery of the protocol will include building capacity of health service workers to embed the design, implementation, and evaluation approach into normal practice. This protocol forms part of the DELIVER (Delivering Enhanced heaLthcare at home through optImising Virtual tools for oldEr people in Rural and regional Australia) Project. Funded by Australia's Medical Research Future Fund, DELIVER involves a collaboration with public health services of Western Victoria, Australia.

BackgroundSevere acute respiratory infections (SARI) pose a great global burden. The contribution of respiratory viruses to adult SARI is relatively understudied in Asia. We aimed to determine viral aetiology of adult SARI patients in Kuala Lumpur, Malaysia.MethodsThe prevalence of 20 common (mainly viral) respiratory pathogens, and MERS-CoV, SARS-CoV and 5 bacterial select agents was investigated from May 2017 to October 2019 in 489 SARI adult patients in Kuala Lumpur, Malaysia, using molecular assays (Luminex NxTAG-RPP kit and qPCR assays). Viral metagenomics analysis was performed on 105 negative samples.ResultsViral respiratory pathogens were detected by PCR in 279 cases (57.1%), including 10 (2.0%) additional detections by metagenomics analysis. The most detected viruses were rhinovirus/enterovirus (RV/EV) (49.1%) and influenza virus (7.4%). Three melioidosis cases were detected but no SARS-CoV, MERS-CoV or other bacterial select agents. Bacterial/viral co-detections and viral co-detections were found in 44 (9.0%) and 27 (5.5%) cases respectively, mostly involving RV/EV. Independent predictors of critical disease were male gender, chronic lung disease, lack of runny nose and positive blood culture with a significant bacterial pathogen. Asthma and sore throat were associated with increased risk of RV/EV detection, while among RV/EV cases, males and those with neurological disease were at increased risk of critical disease.ConclusionsPrior to the COVID-19 pandemic, the high prevalence of respiratory viruses in adults with SARI was mainly attributed to RV/EV. Continued surveillance of respiratory virus trends contributes to effective diagnostic, prevention, and treatment strategies.

Background: Over a quarter of children aged 2–17 years living in Australia are overweight or obese, with a higher prevalence reported in regional and remote communities. Systems thinking approaches that seek to support communities to generate and implement locally appropriate solutions targeting intertwined environmental, political, sociocultural, and individual determinants of obesity have the potential to ameliorate this. There have however been reported challenges with implementation of such initiatives, which may be strengthened by incorporating implementation science methods. Methods: This pilot randomised controlled trial protocol outlines the development and proposed evaluation of a multicomponent implementation strategy (Action-RESPOND). to increase the implementation of community-based systems thinking child obesity prevention initiatives The target of this intervention is ten rural and regional communities (or local government areas as the unit of allocation) within Northeast Victoria who were participants in a whole-of-systems intervention (RESPOND). Action-RESPOND builds on this intervention by assessing the impact of offering additional implementation strategies to five communities relative to usual care. The development of the multicomponent implementation strategy was informed by the Promoting Action on Research Implementation in Health Services (PARIHS) framework and consists of seven implementation strategies primarily delivered via 'facilitation' methods. Implementation strategies aimed to ensure initiatives implemented are i) evidence-based, ii) address community's specific needs and iii) are suitable for local context. Strategies also aimed to increase the community's capacity to implement, through iv) improving the health promotion team's implementation knowledge and skills, fostering v) leadership, vi) physical resources and vii) community culture to drive implementation. The feasibility, acceptability, potential impact, and cost of the strategy will be assessed at baseline and follow up using surveys administered to key representatives within the community and internal records maintained by the research team. Discussion: By leveraging an existing community-based whole-of-systems intervention, Action-RESPOND offers a unique opportunity to collect pilot feasibility and early empirical data on how to apply implementation and systems science approaches to support obesity prevention in rural and regional communities in Victoria. [ABSTRACT FROM AUTHOR]

BackgroundGovernments commonly fund research with specific applications in mind. Such mechanisms may facilitate 'research translation' but funders may employ strategies that can also undermine the integrity of both science and government. We estimated the prevalence and investigated correlates of funder efforts to suppress health behaviour intervention trial findings.MethodsOur sampling frame was lead or corresponding authors of papers (published 2007-2017) included in a Cochrane review, reporting findings from trials of interventions to improve nutrition, physical activity, sexual health, smoking, and substance use. Suppression events were based on a previous survey of public health academics. Participants answered questions concerning seven suppression events in their efforts to report the trial, e.g., [I was…] "asked to suppress certain findings as they were viewed as being unfavourable." We also examined the association between information on study funder, geographical location, targeted health behaviour, country democracy rating and age of publication with reported suppression.FindingsWe received responses from 104 authors (50%) of 208 eligible trials, from North America (34%), Europe (33%), Oceania (17%), and other countries (16%). Eighteen percent reported at least one of the seven suppression events relating to the trial in question. The most commonly reported suppression event was funder(s) expressing reluctance to publish because they considered the results 'unfavourable' (9% reported). We found no strong associations with the subject of research, funding source, democracy, region, or year of publication.ConclusionsOne in five researchers in this global sample reported being pressured to delay, alter, or not publish the findings of health behaviour intervention trials. Regulation of funder and university practices, establishing study registries, and compulsory disclosure of funding conditions in scientific journals, are needed to protect the integrity of public-good research.

BackgroundThis systematic review described the association between electronic nicotine delivery systems and electronic non-nicotine delivery systems (ENDS/ENNDS) use among non-smoking children and adolescents aged MethodsWe searched five electronic databases and the grey literature up to end of September 2020. Prospective longitudinal studies that described the association between ENDS/ENNDS use, and subsequent tobacco use in those aged < 20 years who were non-smokers at baseline were included. The Joanna Briggs Institute Critical Appraisal Checklist was used to assess risk of bias. Data were extracted by two reviewers and pooled using a random-effects meta-analysis. We generated unadjusted and adjusted risk ratios (ARRs) describing associations between ENDS/ENNDS and tobacco use.FindingsA total of 36 publications met the eligibility criteria, of which 25 were included in the systematic review (23 in the meta-analysis) after exclusion of overlapping studies. Sixteen studies had high to moderate risk of bias. Ever users of ENDS/ENNDS had over three times the risk of ever cigarette use (ARR 3·01 (95% CI: 2·37, 3·82; pConclusionThere is an urgent need for policies that regulate the availability, accessibility, and marketing of ENDS/ENNDS to children and adolescents. Governments should also consider adopting policies to prevent ENDS/ENNDS uptake and use in children and adolescents, up to and including a ban for this group.

INTRODUCTION:The standard clinical approach to non-occupational HIV post-exposure prophylaxis (nPEP) focuses on biomedical aspects of the intervention, but may overlook co-occurring or 'syndemic' psychosocial problems that reinforce future vulnerability to HIV. We therefore sought to determine the prevalence of syndemic health problems in a cohort of Ontario nPEP patients, and explored the relationship between syndemic burden and HIV risk. METHODS:Between 07/2013-08/2016, we distributed a self-administered questionnaire to patients presenting to three clinics in Toronto and Ottawa seeking nPEP for sexual HIV exposures. We used validated screening tools to estimate the prevalence of depression (CES-D score ≥16), harmful alcohol use (AUDIT ≥8), problematic drug use (DUDIT ≥6 men/≥2 women), and sexual compulsivity (SCS ≥24) among men who have sex with men (MSM) respondents. In exploratory analyses, we examined the relationships between syndemic conditions using univariable logistic regression models, and the relationship between syndemic count (total number of syndemic conditions per participant) and HIV risk, as estimated by the HIRI-MSM score, using linear regression models. RESULTS:The 186 MSM included in the analysis had median age 31 (IQR = 26-36), including 87.6% having a college/undergraduate degree or higher. Overall, 53.8% screened positive for depression, 34.4% for harmful alcohol use, 30.1% for problematic drug use, and 16.1% for sexual compulsivity. Most participants (74.2%) had at least one syndemic condition and 46.8% had more than one. Exploratory analyses suggested positive associations between depression and harmful alcohol use (OR = 2.11, 95%CI = 1.13, 3.94) and between harmful alcohol use and problematic drug use (OR = 1.22, 95%CI = 0.65, 2.29). Syndemic count was associated with increased HIRI-MSM risk scores in univariable (2.2, 95%CI = 1.0, 3.3 per syndemic condition) and multivariable (2.1, 95%CI = 0.6, 3.6) linear regression models. CONCLUSIONS:The prevalence of syndemic conditions in MSM seeking nPEP for sexual exposure is alarmingly high, and is associated with underlying HIV risk. Routine screening for these conditions may identify opportunities for intervention and could alleviate future vulnerability to HIV.

Pyrexia of unknown origin (PUO) is defined as a temperature of >38.3°C that lasts for >3 weeks, where no cause can be found despite appropriate investigation. Existing protocols for the work-up of PUO can be extensive and costly, motivating the application of recent advances in molecular diagnostics to pathogen testing. There have been many reports describing various analytical methods and performance of metagenomic pathogen testing in clinical samples but the economics of it has been less well studied. This study pragmatically evaluates the feasibility of introducing metagenomic testing in this setting by assessing the relative cost of clinically-relevant strategies employing this investigative tool under various cost and performance scenarios using Singapore as a demonstration case, and assessing the price and performance benchmarks, which would need to be achieved for metagenomic testing to be potentially considered financially viable relative to the current diagnostic standard. This study has some important limitations: we examined only impact of introducing the metagenomic test to the overall diagnostic cost and excluded costs associated with hospitalization and makes assumptions about the performance of the routine diagnostic tests, limiting the cost of metagenomic test, and the lack of further work-up after positive pathogen detection by the metagenomic test. However, these assumptions were necessary to keep the model within reasonable limits. In spite of these, the simplified presentation lends itself to the illustration of the key insights of our paper. In general, we find the use of metagenomic testing as second-line investigation is effectively dominated, and that use of metagenomic testing at first-line would typically require higher rates of detection or lower cost than currently available in order to be justifiable purely as a cost-saving measure. We conclude that current conditions do not warrant a widespread rush to deploy metagenomic testing to resolve any and all uncertainty, but rather as a front-line technology that should be used in specific contexts, as a supplement to rather than a replacement for careful clinical judgement.

Cladophialophora bantiana is a dematiaceous fungus with a predilection for causing central nervous system (CNS) infection manifesting as brain abscess in both immunocompetent and immunocompromised patients. In this paper, we report comprehensive genomic analyses of C. bantiana isolated from the brain abscess of an immunocompetent man, the first reported case in Malaysia and Southeast Asia. The identity of the fungus was determined using combined morphological analysis and multilocus phylogeny. The draft genome sequence of a neurotrophic fungus, C. bantiana UM 956 was generated using Illumina sequencing technology to dissect its genetic fundamental and basic biology. The assembled 37.1 Mb genome encodes 12,155 putative coding genes, of which, 1.01% are predicted transposable elements. Its genomic features support its saprophytic lifestyle, renowned for its versatility in decomposing hemicellulose and pectin components. The C. bantiana UM 956 was also found to carry some important putative genes that engaged in pathogenicity, iron uptake and homeostasis as well as adaptation to various stresses to enable the organism to survive in hostile microenvironment. This wealth of resource will further catalyse more downstream functional studies to provide better understanding on how this fungus can be a successful and persistent pathogen in human.

Sleep apnea syndrome, characterized by intermittent hypoxia (IH), is linked with increased oxidative stress. This study investigates the mechanisms underlying IH and the effects of IH-induced oxidative stress on cerebellar astrocytes. Rat primary cerebellar astrocytes were kept in an incubator with an oscillating O2 concentration between 20% and 5% every 30 min for 1-4 days. Although the cell loss increased with the duration, the IH incubation didn't induce apoptosis or necrosis, but rather a G0/G1 cell cycle arrest of cerebellar astrocytes was noted. ROS accumulation was associated with cell loss during IH. PARP activation, resulting in p21 activation and cyclin D1 degradation was associated with cell cycle G0/G1 arrest of IH-treated cerebellar astrocytes. Our results suggest that IH induces cell loss by enhancing oxidative stress, PARP activation and cell cycle G0/G1 arrest in rat primary cerebellar astrocytes.

Besides regulating calcium homeostasis, the effects of vitamin D on vascular tone and metabolic disturbances remain scarce in the literature despite an increase intake with high-fructose corn syrup worldwide. We investigated the effects of calcitriol, an active form of vitamin D, on vascular relaxation, glucose tolerance, and visceral fat pads in fructose-fed rats. Male Wistar-Kyoto rats were divided into 4 groups (n = 6 per group). Group Con: standard chow diet for 8 weeks; Group Fru: high-fructose diet (60% fructose) for 8 weeks; Group Fru-HVD: high-fructose diet as Group Fru, high-dose calcitriol treatment (20 ng / 100 g body weight per day) 4 weeks after the beginning of fructose feeding; and Group Fru-LVD: high-fructose diet as Group Fru, low-dose calcitriol treatment (10 ng / 100 g body weight per day) 4 weeks after the beginning of fructose feeding. Systolic blood pressure was measured twice a week by the tail-cuff method. Blood was examined for serum ionized calcium, phosphate, creatinine, glucose, triglycerides, and total cholesterol. Intra-peritoneal glucose intolerance test, aortic vascular reactivity, the weight of visceral fat pads, adipose size, and adipose angiotensin II levels were analyzed at the end of the study. The results showed that the fructose-fed rats significantly developed hypertension, impaired glucose tolerance, heavier weight and larger adipose size of visceral fat pads, and raised adipose angiotensin II expressions compared with the control rats. High- and low-dose calcitriol reduced modestly systolic blood pressure, increased endothelium-dependent aortic relaxation, ameliorated glucose intolerance, reduced the weight and adipose size of visceral fat pads, and lowered adipose angiotensin II expressions in the fructose-fed rats. However, high-dose calcitriol treatment mildly increased serum ionized calcium levels (1.44 ± 0.05 mmol/L). These results suggest a protective role of calcitriol treatment on endothelial function, glucose tolerance, and visceral adiposity in fructose-fed rats.

BACKGROUND: In Singapore, as diabetes is an increasingly important public health issue, the cost-effectiveness of pursuing lifestyle modification programs and/or alternative prevention strategies is of critical importance for policymakers. While the US Diabetes Prevention Program (DPP) compared weight loss through lifestyle modification with oral treatment of diabetes drug metformin to prevent/delay the onset of type 2 diabetes in pre-diabetic subjects, no data on either the actual or potential cost effectiveness of such a program is available for East or South-east Asian populations. This study estimates the 3-year cost-effectiveness of lifestyle modification and metformin among pre-diabetic subjects from a Singapore health system and societal perspective. METHODOLOGY: Cost effectiveness was analysed from 2010-2012 using a decision-based model to estimate the rates of getting diabetes, healthcare costs and health-related quality of life. Cost per quality-adjusted life year (QALY) was estimated using costs relevant to the time horizon of the study from Singapore. All costs are expressed in 2012 US dollars. PRINCIPAL FINDINGS: The total economic cost for non-diabetic subjects from the societal perspective was US$25,867, US$28,108 and US$26,177 for placebo, lifestyle modification and metformin intervention respectively. For diabetic patients, the total economic cost from the societal perspective was US$32,921, US$35,163 and US$33,232 for placebo, lifestyle modification and metformin intervention respectively. Lifestyle modification relative to placebo is likely to be associated with an incremental cost per QALY gained at US$36,663 while that of metformin intervention is likely to be US$6,367 from a societal perspective. CONCLUSION: Based on adaptation of the DPP data to local conditions, both lifestyle modification and metformin intervention are likely to be cost-effective and worth implementing in Singapore to prevent or delay the onset of type 2 diabetes. However, the cost of lifestyle modification from the societal perspective would have to be reduced in order to match the cost-effectiveness of metformin intervention.

BackgroundN-butylidenephthalide (BP) exhibits antitumor effect in a variety of cancer cell lines. The objective of this study was to obtain additional insights into the mechanisms involved in BP induced cell death in human prostate cancer cells.Methods/principal findingsTwo human prostate cancer cell lines, PC-3 and LNCaP, were treated with BP, and subsequently evaluated for their viability and cell cycle profiles. BP caused cell cycle arrest and cell death in both cell lines. The G0/G1 phase arrest was correlated with increase levels of CDK inhibitors (p16, p21 and p27) and decrease of the checkpoint proteins. To determine the mechanisms of BP-induced growth arrest and cell death in prostate cancer cell lines, we performed a microarray study to identify alterations in gene expression induced by BP in the LNCaP cells. Several BP-induced genes, including the GADD153/CHOP, an endoplasmic reticulum stress (ER stress)-regulated gene, were identified. BP-induced ER stress was evidenced by increased expression of the downstream molecules GRP78/BiP, IRE1-α and GADD153/CHOP in both cell lines. Blockage of IRE1-α or GADD153/CHOP expression by siRNA significantly reduced BP-induced cell death in LNCaP cells. Furthermore, blockage of JNK1/2 signaling by JNK siRNA resulted in decreased expression of IRE1-α and GADD153/CHOP genes, implicating that BP-induced ER stress may be elicited via JNK1/2 signaling in prostate cancer cells. BP also suppressed LNCaP xenograft tumor growth in NOD-SCID mice. It caused 68% reduction in tumor volume after 18 days of treatment.ConclusionsOur results suggest that BP can cause G0/G1 phase arrest in prostate cancer cells and its cytotoxicity is mediated by ER stress induction. Thus, BP may serve as an anticancer agent by inducing ER stress in prostate cancer.

It is unknown whether human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) can improve the renal function of patients suffering from acute kidney injury. Moreover, before beginning clinical trials, it is necessary to investigate this renoprotective effect of hUC-MSCs in a xenogeneic model of acute kidney injury. However, no previous studies have examined the application of hUC-MSCs to immunodeficient mice suffering from acute kidney injury. The objectives of this study were to examine whether hUC-MSCs could improve renal function in nonobese diabetic-severe combined immune deficiency (NOD-SCID) mice suffering from acute kidney injury, and to investigate the mechanism(s) for hUC-MSCs to improve renal function in this xenogeneic model. Early (3 hr) and late (12 hr) administrations of hUC-MSCs (10(6) cells) were performed via the external jugular vein into NOD-SCID mice suffering from either folic acid (FA) (250 mg/kg body weight) or vehicle. The results showed that early administration of hUC-MSCs improved the renal function of NOD-SCID mice suffering from FA-induced acute kidney injury, as evidenced by decreased serum urea nitrogen and serum creatinine levels, as well as a reduced tubular injury score. The beneficial effects of hUC-MSCs were through reducing apoptosis and promoting proliferation of renal tubular cells. These benefits were independent of inflammatory cytokine effects and transdifferentiation. Furthermore, this study is the first one to show that the reduced apoptosis of renal tubular cells by hUC-MSCs in this xenogeneic model is mediated through the mitochondrial pathway, and through the increase of Akt phosphorylation.

Evidence accumulated over the last decade has shown that allopolyploid genomes may undergo drastic reorganization. However, timing and mechanisms of structural diploidization over evolutionary timescales are still poorly known. As transposable elements (TEs) represent major and labile components of plant genomes, they likely play a pivotal role in fuelling genome changes leading to long-term diploidization. Here, we exploit the 4.5 MY old allopolyploid Nicotiana section Repandae to investigate the impact of TEs on the evolutionary dynamics of genomes. Sequence-specific amplified polymorphisms (SSAP) on seven TEs with expected contrasted dynamics were used to survey genome-wide TE insertion polymorphisms. Comparisons of TE insertions in the four allopolyploid species and descendents of the diploid species most closely related to their actual progenitors revealed that the polyploids showed considerable departure from predicted additivity of the diploids. Large numbers of new SSAP bands were observed in polyploids for two TEs, but restructuring for most TE families involved substantial loss of fragments relative to the genome of the diploid representing the paternal progenitor, which could be due to changes in allopolyploids, diploid progenitor lineages or both. The majority of non-additive bands were shared by all polyploid species, suggesting that significant restructuring occurred early after the allopolyploid event that gave rise to their common ancestor. Furthermore, several gains and losses of SSAP fragments were restricted to N. repanda, suggesting a unique evolutionary trajectory. This pattern of diploidization in TE genome fractions supports the hypothesis that TEs are central to long-term genome turnover and depends on both TE and the polyploid lineage considered.

BACKGROUND: Health outcomes in developing countries continue to lag the developed world, and many countries are not on target to meet the Millennium Development Goals. The private health sector provides much of the care in many developing countries (e.g., approximately 50 percent in Sub-Saharan Africa), but private providers are often poorly integrated into the health system. Efforts to improve health systems performance will need to include the private sector and increase its contributions to national health goals. However, the literature on constraints private health care providers face is limited. METHODOLOGY/PRINCIPAL FINDINGS: We analyze data from a survey of private health facilities in Kenya and Ghana to evaluate growth constraints facing private providers. A significant portion of facilities (Ghana: 62 percent; Kenya: 40 percent) report limited access to finance as the most significant barrier they face; only a small minority of facilities report using formal credit institutions to finance day to day operations (Ghana: 6 percent; Kenya: 11 percent). Other important barriers include corruption, crime, limited demand for goods and services, and poor public infrastructure. Most facilities have paper-based rather than electronic systems for patient records (Ghana: 30 percent; Kenya: 22 percent), accounting (Ghana: 45 percent; Kenya: 27 percent), and inventory control (Ghana: 41 percent; Kenya: 24 percent). A majority of clinics in both countries report undertaking activities to improve provider skills and to monitor the level and quality of care they provide. However, only a minority of pharmacies report undertaking such activities. CONCLUSIONS/SIGNIFICANCE: The results suggest that improved access to finance and improving business processes especially among pharmacies would support improved contributions by private health facilities. These strategies might be complementary if providers are more able to take advantage of increased access to finance when they have the business processes in place for operating a successful business and health facility.

BackgroundIn 2008, over 300,000 women died during pregnancy or childbirth, mostly in poor countries. While there are proven interventions to make childbirth safer, there is uncertainty about the best way to deliver these at large scale. In particular, there is currently a debate about whether maternal deaths are more likely to be prevented by delivering effective interventions through scaled up facilities or via community-based services. To inform this debate, we examined delivery location and attendance and the reasons women report for giving birth at home.Methodology/principal findingsWe conducted a secondary analysis of maternal delivery data from Demographic and Health Surveys in 48 developing countries from 2003 to the present. We stratified reported delivery locations by wealth quintile for each country and created weighted regional summaries. For sub-Saharan Africa (SSA), where death rates are highest, we conducted a subsample analysis of motivations for giving birth at home. In SSA, South Asia, and Southeast Asia, more than 70% of all births in the lowest two wealth quintiles occurred at home. In SSA, 54.1% of the richest women reported using public facilities compared with only 17.7% of the poorest women. Among home births in SSA, 56% in the poorest quintile were unattended while 41% were attended by a traditional birth attendant (TBA); 40% in the wealthiest quintile were unattended, while 33% were attended by a TBA. Seven per cent of the poorest women reported cost as a reason for not delivering in a facility, while 27% reported lack of access as a reason. The most common reason given by both the poorest and richest women for not delivering in a facility was that it was deemed "not necessary" by a household decision maker. Among the poorest women, "not necessary" was given as a reason by 68% of women whose births were unattended and by 66% of women whose births were attended.ConclusionsIn developing countries, most poor women deliver at home. This suggests that, at least in the near term, efforts to reduce maternal deaths should prioritize community-based interventions aimed at making home births safer.

BACKGROUND: Health systems in Sub-Saharan Africa (SSA) are in urgent need of improvement. The private health sector is a major provider of care in the region and it will remain a significant actor in the future. Any efforts by SSA governments to improve health systems performance therefore has to account for the private health sector. Regional and international actors increasingly recognize importance of effectively engaging with the private health sector, and initiatives to improve engagement are underway in several countries. However, there is little systematic analysis of private health providers' view and experience with engagement. METHODOLOGY/PRINCIPAL FINDINGS: In this study we surveyed private health facilities in Kenya and Ghana to understand the extent to which and how governments interact and engage with these facilities. The results suggest that government engagement with private health facilities is quite limited. The primary focus of this engagement is "command-and-control" type regulations to improve the quality of care. There is little attention paid to building the capacity of health care businesses through either technical or financial assistance. The vast majority of these facilities also receive no government assistance in meeting public health and social goals. Finally, government engagement with private pharmacies is often neglected and clinics receive a disproportionate share of government assistance. CONCLUSIONS/SIGNIFICANCE: Overall, our findings suggest that there may be considerable untapped potential for greater engagement with private health facilities--particularly pharmacies. Improving engagement will likely help governments with limited resources to better take advantage of the private sector capacity to meet access and equity objectives and to accelerate the achievement of the Millennium Development Goals.

BACKGROUND: The role of the private health sector in developing countries remains a much-debated and contentious issue. Critics argue that the high prices charged in the private sector limits the use of health care among the poorest, consequently reducing access and equity in the use of health care. Supporters argue that increased private sector participation might improve access and equity by bringing in much needed resources for health care and by allowing governments to increase focus on underserved populations. However, little empirical exists for or against either side of this debate. METHODOLOGY/PRINCIPAL FINDINGS: We examine the association between private sector participation and self-reported measures of utilization and equity in deliveries and treatment of childhood respiratory disease using regression analysis, across a sample of nationally-representative Demographic and Health Surveys from 34 SSA economies. We also examine the correlation between private sector participation and key background factors (socioeconomic development, business environment and governance) and use multivariate regression to control for potential confounders. Private sector participation is positively associated with greater overall access and reduced disparities between rich and poor as well as urban and rural populations. The positive association between private sector participation and improved health system performance is robust to controlling for confounders including per capita income and maternal education. Private sector participation is positively correlated with measures of socio-economic development and favorable business environment. CONCLUSIONS/SIGNIFICANCE: Greater participation is associated with favorable intermediate outcomes in terms of access and equity. While these results do not establish a causal link between private sector participation and health system performance, they suggest that there is no deleterious link between private sector participation and health system performance in SSA.

Polyploidy, frequently termed "whole genome duplication", is a major force in the evolution of many eukaryotes. Indeed, most angiosperm species have undergone at least one round of polyploidy in their evolutionary history. Despite enormous progress in our understanding of many aspects of polyploidy, we essentially have no information about the role of chromosome divergence in the establishment of young polyploid populations. Here we investigate synthetic lines and natural populations of two recently and recurrently formed allotetraploids Tragopogon mirus and T. miscellus (formed within the past 80 years) to assess the role of aberrant meiosis in generating chromosomal/genomic diversity. That diversity is likely important in the formation, establishment and survival of polyploid populations and species.Applications of fluorescence in situ hybridisation (FISH) to natural populations of T. mirus and T. miscellus suggest that chromosomal rearrangements and other chromosomal changes are common in both allotetraploids. We detected extensive chromosomal polymorphism between individuals and populations, including (i) plants monosomic and trisomic for particular chromosomes (perhaps indicating compensatory trisomy), (ii) intergenomic translocations and (iii) variable sizes and expression patterns of individual ribosomal DNA (rDNA) loci. We even observed karyotypic variation among sibling plants. Significantly, translocations, chromosome loss, and meiotic irregularities, including quadrivalent formation, were observed in synthetic (S(0) and S(1) generations) polyploid lines. Our results not only provide a mechanism for chromosomal variation in natural populations, but also indicate that chromosomal changes occur rapidly following polyploidisation.These data shed new light on previous analyses of genome and transcriptome structures in de novo and establishing polyploid species. Crucially our results highlight the necessity of studying karyotypes in young (