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Sanitation in neighbourhood and household domains can provide primary protection against diarrhea morbidity, yet their distinct health benefits have not been succinctly distinguished and reviewed. We present here the first systematic review and meta-analysis of the distinct effect of neighbourhood and household sanitation conditions on diarrhea morbidity. We identified studies reporting the effect of neighbourhood-level exposure to wastewater or household sanitation facilities on diarrhea, by performing comprehensive search on five databases, namely the Cochrane library, PubMed, Embase, Scopus and Web of Science, from the earliest date available to February 2015. Twenty-one non-randomized studies and one randomized controlled trial met the pre-determined inclusion criteria, consisting of six datasets on neighbourhood sanitation conditions (total 8271 subjects) and 20 datasets on household sanitation (total 20021 subjects). We calculated the pooled effect estimates of neighbourhood and household sanitation conditions on diarrhea morbidity using the inverse variance random-effects model. The pooled effect estimates showed that both neighbourhood sanitation conditions (odds ratio = 0.56, 95%CI: 0.40-0.79) and household sanitation (odds ratio = 0.64, 95%CI: 0.55-0.75) are associated with reduced diarrheal illness, and that the magnitudes of the associations are comparable. Evidence of risk of bias and heterogeneity were found in the included studies. Our findings confirm that both neighbourhood sanitation conditions and household sanitation are associated with considerable reduction in diarrhea morbidity, in spite of a number of methodological shortcomings in the included studies. Furthermore, we find evidence that neighbourhood sanitation conditions is associated with similar magnitude of reduction in diarrhea morbidity as household sanitation. The findings suggest that, in addition to household sanitation provision, dual emphasis on neighbourhood sanitation through public sanitation infrastructure provision and community-wide sanitation adoption is advisable for effective reduction of diarrheal disease burden.

Improvements in life expectancy have been considerable over the past hundred years. Forecasters have taken to applying historical trends under an assumption of continuing improvements in life expectancy in the future. A linear mixed effects model was used to estimate the trends in global and regional rates of improvements in life expectancy, child, adult, and senior survival, in 166 countries between 1950 and 2010. Global improvements in life expectancy, including both child and adult survival rates, decelerated significantly over the study period. Overall life expectancy gains were estimated to have declined from 5.9 to 4.0 months per year for a mean deceleration of -0.07 months/year2; annual child survival gains declined from 4.4 to 1.6 deaths averted per 1000 for a mean deceleration of -0.06 deaths/1000/year2; adult survival gains were estimated to decline from 4.8 to 3.7 deaths averted per 1000 per year for a mean deceleration of -0.08 deaths/1000/year2. Senior survival gains however increased from 2.4 to 4.2 deaths averted per 1000 per year for an acceleration of 0.03 deaths/1000/year2. Regional variation in the four measures was substantial. The rates of global improvements in life expectancy, child survival, and adult survival have declined since 1950 despite an increase in the rate of improvements among seniors. We postulate that low-cost innovation, related to the last half-century progress in health-primarily devoted to children and middle age, is reaping diminishing returns on its investments. Trends are uneven across regions and measures, which may be due in part to the state of epidemiological transition between countries and regions and disparities in the diffusion of innovation, accessible only in high-income countries where life expectancy is already highest.

Protein phosphatase 2A (PP2A) is a ubiquitous phospho-serine/threonine phosphatase that controls many diverse cellular functions. The predominant form of PP2A is a heterotrimeric holoenzyme consisting of a scaffolding A subunit, a variable regulatory B subunit, and a catalytic C subunit. The C subunit also associates with other interacting partners, such as α4, to form non-canonical PP2A complexes. We report visualization of PP2A complexes in mammalian cells. Bimolecular fluorescence complementation (BiFC) analysis of PP2A subunit interactions demonstrates that the B subunit plays a key role in directing the subcellular localization of PP2A, and confirms that the A subunit functions as a scaffold in recruiting the B and C subunits to form a heterotrimeric holoenzyme. BiFC analysis also reveals that α4 promotes formation of the AC core dimer. Furthermore, we demonstrate visualization of specific ABC holoenzymes in cells by combining BiFC and fluorescence resonance energy transfer (BiFC-FRET). Our studies not only provide direct imaging data to support previous biochemical observations on PP2A complexes, but also offer a promising approach for studying the spatiotemporal distribution of individual PP2A complexes in cells.

Planning for the reliable and cost-effective supply of a health service commodity such as medical oxygen requires an understanding of the dynamic need or 'demand' for the commodity over time. In developing country health systems, however, collecting longitudinal clinical data for forecasting purposes is very difficult. Furthermore, approaches to estimating demand for supplies based on annual averages can underestimate demand some of the time by missing temporal variability.A discrete event simulation model was developed to estimate variable demand for a health service commodity using the important example of medical oxygen for childhood pneumonia. The model is based on five key factors affecting oxygen demand: annual pneumonia admission rate, hypoxaemia prevalence, degree of seasonality, treatment duration, and oxygen flow rate. These parameters were varied over a wide range of values to generate simulation results for different settings. Total oxygen volume, peak patient load, and hours spent above average-based demand estimates were computed for both low and high seasons.Oxygen demand estimates based on annual average values of demand factors can often severely underestimate actual demand. For scenarios with high hypoxaemia prevalence and degree of seasonality, demand can exceed average levels up to 68% of the time. Even for typical scenarios, demand may exceed three times the average level for several hours per day. Peak patient load is sensitive to hypoxaemia prevalence, whereas time spent at such peak loads is strongly influenced by degree of seasonality.A theoretical study is presented whereby a simulation approach to estimating oxygen demand is used to better capture temporal variability compared to standard average-based approaches. This approach provides better grounds for health service planning, including decision-making around technologies for oxygen delivery. Beyond oxygen, this approach is widely applicable to other areas of resource and technology planning in developing country health systems.