Quantitative Analysis and Modeling Probe Polarity Establishment in C.?elegans Embryos

Cell polarity underlies many aspects of metazoan development and homeostasis, and relies notably on a set of PAR proteins located at the cell cortex. How these proteins interact in space and time remains incompletely understood. We performed a quantitative assessment of polarity establishment in one-cell stage Caenorhabditis elegans embryos by combining time-lapse microscopy and image analysis. We used our extensive data set to challenge and further specify an extant mathematical model. Using likelihood-based calibration, we uncovered that cooperativity is required for both anterior and posterior PAR complexes. Moreover, we analyzed the dependence of polarity establishment on changes in size or temperature. The observed robustness of PAR domain dimensions in embryos of different sizes is in agreement with a model incorporating fixed protein concentrations and variations in embryo surface/volume ratio. In addition, we quantified the dynamics of polarity establishment over most of the viable temperatures range of C. elegans. Modeling of these data suggests that diffusion of PAR proteins is the process most affected by temperature changes, although cortical flows appear unaffected. Overall, our quantitative analytical framework provides insights into the dynamics of polarity establishment in a developing system.     

Is Health Aid Reaching the Poor? Analysis of Household Data from Aid Recipient Countries

Objective

To determine the extent to which the narrowing of child mortality across wealth gradients has been related to foreign aid to the health sector in low- and middle-income countries.

Methods

Mortality and wealth data on 989,901 under-5 children from 957,674 households in 49 aid recipient countries in Africa, Asia, South America, and the Caribbean between 1993 and 2012 were used in the analysis. Declines in under-5 mortality in the four poorest wealth quantiles were compared to the decline among the wealthiest at varying levels of health aid per capita using fixed effects multivariable regression models and controlling for maternal education, urbanization, and domestic spending on health among recipient countries.

Results

Each additional dollar in total health aid per capita was associated with 5.7 fewer deaths per 10,000 child-years among children in the poorest relative to the wealthiest households (p<0.001). This was also true when measured in percent declines (1.90% faster decline in under-5 mortality among the poorest compared with the wealthiest with each dollar in total health aid, p = 0.008). The association was stronger when using health aid specifically for malaria than total health aid, 12.60% faster decline among the poorest compared with the wealthiest with each dollar in malaria aid, p = 0.001.

Conclusions

Foreign aid to the health sector is preferentially related to reductions in under-5 mortality among the poorest compared with the wealthiest. Health aid addressing malaria, which imposes a disproportionate burden among the poor, may explain the observed effect.     

What To Do About Helicobacter pylori? A Decision Analysis of its Implication on Public Health

Objectives. Public health measures to eradicate Helicobacter pylori in the general population may prevent the occurrence of nonulcer dyspepsia (NUD), peptic ulcer (PUD) and gastric cancer, but may at the same time increase the prevalence of gastroesophageal reflux disease (GERD). A decision analysis is carried out to quantify the counteracting influences of H. pylori and resolve the controversy about a public policy to eliminate H. pylori from the general population. Methods. A compartment model is structured to analyze the jointly beneficial and adverse effects of H. pylori. Gastric acid, H. pylori infection, and other pathophysiological mechanisms influence the occurrence of reflux disease, peptic ulcer and dyspepsia, which all contribute to the occurrence of upper abdominal symptoms. Each influence is modeled as a separate compartment with various connections to other compartments. The simulation is carried out on an electronic spreadsheet. Results. A decision in favor or against eradication of all H. pylori depends primarily on the relative contribution of reflux disease vs. peptic ulcer and dyspepsia to upper abdominal symptoms in the general population. If reflux‐related symptoms contribute twice more than peptic ulcer plus dyspepsia to the overall occurrence of abdominal symptoms, a strategy to eradicate H. pylori would actually lower rather than raise public health. Below this threshold such strategy may improve general well‐being. In the individual patient infected with H. pylori, it remains beneficial to eradicate H. pylori, irrespective of the symptoms’ nature. Conclusions. Although it is advisable to treat H. pylori infection in the individual patient who comes to medical attention, a general policy directed towards complete elimination of H. pylori from the population would not be beneficial. A compartment model provides a simple yet powerful method to assess complex disease behavior.     

Linking Human Health and Livestock Health: A “One-Health” Platform for Integrated Analysis of Human Health,Livestock Health,and Economic Welfare in Livestock Dependent Communities

Background

For most rural households in sub-Saharan Africa, healthy livestock play a key role in averting the burden associated with zoonotic diseases, and in meeting household nutritional and socio-economic needs. However, there is limited understanding of the complex nutritional, socio-economic, and zoonotic pathways that link livestock health to human health and welfare. Here we describe a platform for integrated human health, animal health and economic welfare analysis designed to address this challenge. We provide baseline epidemiological data on disease syndromes in humans and the animals they keep, and provide examples of relationships between human health, animal health and household socio-economic status.

Method

We designed a study to obtain syndromic disease data in animals along with economic and behavioral information for 1500 rural households in Western Kenya already participating in a human syndromic disease surveillance study. Data collection started in February 2013, and each household is visited bi-weekly and data on four human syndromes (fever, jaundice, diarrhea and respiratory illness) and nine animal syndromes (death, respiratory, reproductive, musculoskeletal, nervous, urogenital, digestive, udder disorders, and skin disorders in cattle, sheep, goats and chickens) are collected. Additionally, data from a comprehensive socio-economic survey is collected every 3 months in each of the study households.

Findings

Data from the first year of study showed 93% of the households owned at least one form of livestock (55%, 19%, 41% and 88% own cattle, sheep, goats and chickens respectively). Digestive disorders, mainly diarrhea episodes, were the most common syndromes observed in cattle, goats and sheep, accounting for 56% of all livestock syndromes, followed by respiratory illnesses (18%). In humans, respiratory illnesses accounted for 54% of all illnesses reported, followed by acute febrile illnesses (40%) and diarrhea illnesses (5%). While controlling for household size, the incidence of human illness increased 1.31-fold for every 10 cases of animal illness or death observed (95% CI 1.16–1.49). Access and utilization of animal source foods such as milk and eggs were positively associated with the number of cattle and chickens owned by the household. Additionally, health care seeking was correlated with household incomes and wealth, which were in turn correlated with livestock herd size.

Conclusion

This study platform provides a unique longitudinal dataset that allows for the determination and quantification of linkages between human and animal health, including the impact of healthy animals on human disease averted, malnutrition, household educational attainment, and income levels.     

Where Do Poor Women in Developing Countries Give Birth? A Multi-Country Analysis of Demographic and Health Survey Data

Background

In 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 Findings

We 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.

Conclusions

In 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.     

Do Pollinators Contribute to Nutritional Health?

Despite suggestions that animal pollinators are crucial for human nutritional health, no studies have actually tested this claim. Here, we combined data on crop pollination requirements, food nutrient densities, and actual human diets to predict the effects of pollinator losses on the risk of nutrient deficiency. In four developing countries and across five nutrients, we found that 0 to 56% of populations would become newly at risk if pollinators were removed. Increases in risk were most pronounced for vitamin A in populations with moderate levels of total nutrient intake. Overall, the effects of pollinator decline varied widely among populations and nutrients. We conclude that the importance of pollinators to human nutrition depends critically on the composition of local diets, and cannot be reliably predicted from global commodity analyses. We identify conditions under which severe health effects of pollinator loss are most likely to occur.     

“One Health” or Three? Publication Silos Among the One Health Disciplines

The One Health initiative is a global effort fostering interdisciplinary collaborations to address challenges in human, animal, and environmental health. While One Health has received considerable press, its benefits remain unclear because its effects have not been quantitatively described. We systematically surveyed the published literature and used social network analysis to measure interdisciplinarity in One Health studies constructing dynamic pathogen transmission models. The number of publications fulfilling our search criteria increased by 14.6% per year, which is faster than growth rates for life sciences as a whole and for most biology subdisciplines. Surveyed publications clustered into three communities: one used by ecologists, one used by veterinarians, and a third diverse-authorship community used by population biologists, mathematicians, epidemiologists, and experts in human health. Overlap between these communities increased through time in terms of author number, diversity of co-author affiliations, and diversity of citations. However, communities continue to differ in the systems studied, questions asked, and methods employed. While the infectious disease research community has made significant progress toward integrating its participating disciplines, some segregation—especially along the veterinary/ecological research interface—remains.