The US President’s Malaria Initiative and under-five child mortality in Sub-Saharan Africa: A difference-in-differences analysis

Background Despite substantial financial contributions by the United States President’s Malaria Initiative (PMI) since 2006, no studies have carefully assessed how this program may have affected important population-level health outcomes. We utilized multiple publicly available data sources to evaluate the association between introduction of PMI and child mortality rates in sub-Saharan Africa (SSA). Methods and findings We used difference-in-differences analyses to compare trends in the primary outcome of under-5 mortality rates and secondary outcomes reflecting population coverage of malaria interventions in 19 PMI-recipient and 13 non-recipient countries between 1995 and 2014. The analyses controlled for presence and intensity of other large funding sources, individual and household characteristics, and country and year fixed effects. PMI program implementation was associated with a significant reduction in the annual risk of under-5 child mortality (adjusted risk ratio [RR] 0.84, 95% CI 0.74–0.96). Each dollar of per-capita PMI expenditures in a country, a measure of PMI intensity, was also associated with a reduction in child mortality (RR 0.86, 95% CI 0.78–0.93). We estimated that the under-5 mortality rate in PMI countries was reduced from 28.9 to 24.3 per 1,000 personyears. Population coverage of insecticide-treated nets increased by 8.34 percentage points (95% CI 0.86–15.83) and coverage of indoor residual spraying increased by 6.63 percentage points (95% CI 0.79–12.47) after PMI implementation. Per-capita PMI spending was also associated with a modest increase in artemisinin-based combination therapy coverage (3.56 percentage point increase, 95% CI −0.07–7.19), though this association was only marginally significant (p = 0.054). Our results were robust to several sensitivity analyses. Because our study design leaves open the possibility of unmeasured confounding, we cannot definitively interpret these results as causal. Conclusions PMI may have significantly contributed to reducing the burden of malaria in SSA and reducing the number of child deaths in the region. Introduction of PMI was associated with increased coverage of malaria prevention technologies, which are important mechanisms through which child mortality can be reduced. To our knowledge, this study is the first to assess the association between PMI and all-cause child mortality in SSA with the use of appropriate comparison groups and adjustments for regional trends in child mortality

An energy budget agent-based model of earthworm populations and its application to study the effects of pesticides

Earthworms are important organisms in soil communities and so are used as model organisms in environ-mental risk assessments of chemicals. However current risk assessments of soil invertebrates are based on short-term laboratory studies, of limited ecological relevance, supplemented if necessary by site-specific field trials, which sometimes are challenging to apply across the whole agricultural landscape. Here, we investigate whether population responses to environmental stressors and pesticide exposure can be accurately predicted by combining energy budget and agent-based models (ABMs), based on knowledge of how individuals respond to their local circumstances. A simple energy budget model was implemented within each earthworm Eisenia fetida in the ABM, based on a priori parameter estimates .From broadly accepted physiological principles, simple algorithms specify how energy acquisition and expenditure drive life cycle processes. Each individual allocates energy between maintenance, growth and/or reproduction under varying conditions of food density, soil temperature and soil moisture. When simulating published experiments, good model fits were obtained to experimental data on individual growth, reproduction and starvation. Using the energy budget model as a platform we developed methods to identify which of the physiological parameters in the energy budget model (rates of ingestion, maintenance, growth or reproduction) are primarily affected by pesticide applications, producing four hypotheses about how toxicity acts. We tested these hypotheses by comparing model outputs with published toxicity data on the effects of copper oxychloride and chlorpyrifos on E. fetida. Both growth and reproduction were directly affected in experiments in which sufficient food was provided, whilst maintenance was targeted under food limitation. Although we only incorporate toxic effects at the individual level we show how ABMs can readily extrapolate to larger scales by providing good model fits to field population data. The ability of the presented model to fit the available field and laboratory data for E.fetida demonstrates the promise of the agent-based approach in ecology, by showing how biological knowledge can be used to make ecological inferences. Further work is required to extend the approach to populations of more ecologically relevant species studied at the field scale. Such a model could help extrapolate from laboratory to field conditions and from one set of field conditions to another or from species to species

Caloric estimation bias of realistic meal and beverage preparations

This study was undertaken to characterize caloric estimation bias in realistic meal and beverage preparations of varied size and nutritional value. Differences in the estimation bias of meals and beverages were determined in relation to sex and weight status (body mass index and percent body fat). In general, most subjects were inaccurate in caloric estimation. Subjects were more accurate when estimating larger versus smaller, and unhealthy versus healthy realistic, home-style food items. Accurate prediction of solid foods was not related to accurate beverage prediction. In addition to the size of food items, the healthfulness and form of calories are predictors of caloric estimation accuracy

Implications of Components of Income Excluded from Pro Forma Earnings for Future Profitability and Equity Valuation

This study addresses three research questions relating to total exclusions, special items, and other exclusions. Are each of these pro forma exclusion components forecasting irrelevant? Are each of the exclusion components value irrelevant? Are the valuation multiples on the exclusion components justified by their ability to forecast future profitability as predicted by the Ohlson (1999) model? Findings are generally consistent with the market-inefficiency results presented in Doyle et al. (2003) . Total exclusions are valued negatively by the market despite the prediction that total exclusions will be valued positively. Valuation results also suggest that stocks with positive other exclusions are overpriced. Copyright 2007 The Authors Journal compilation (c) 2007 Blackwell Publishing Ltd.

MMP Inhibition in Prostate Cancer

Matrix metalloproteinases (MMPs) play a significant role during the development and metastasis of prostate cancer (CaP). CaP cells secrete high levels of MMPs and low levels of endogenous MMP inhibitors (TIMPs), thus creating an excess balance of MMPs. Established CaP cell lines that express high levels of MMPs frequently metastasize to the bone and the lungs. Drugs such as Taxol and alendronate that reduce cell motility and calcium metabolism reduce bony metastasis of xenografted CaP tumors. We tested several synthetic, nontoxic inhibitors of MMPs that can be administered orally, including doxycycline (DC) and chemically modified tetracyclines (CMTs) on CaP cells in vitro and on a rat CaP model in vivo. Among several anti‐MMP agents tested, CMT‐3 (6‐deoxy, 6‐demethyl,4‐de‐dimethylamino tetracycline) showed highest activity against CaP cell invasion and cell proliferation. Micromolar concentration of CMT‐3 and DC inhibited both the secretion and activity of MMPs by CaP cells. When tested for in vivo efficacy in the Dunning rat CaP model by daily oral gavage, CMT‐3 and DC both reduced the lung metastases (> 50%). CMT‐3, but not DC, inhibited tumor incidence (55 ± 9%) and also reduced the tumor growth rate (27 ± 9.3%). More significantly, the drugs showed minimum systemic toxicity. Ongoing studies indicate that CMT‐3 may inhibit the skeletal metastases of CaP cells and delay the onset of paraplegia due to lumbar metastases. These preclinical studies provide the basis for clinical trials of CMT‐3 for the treatment of metastatic disease