Eave tubes for malaria control in Africa: a modelling assessment of potential impact on transmission.

BACKGROUND: Novel interventions for malaria control are necessary in the face of problems such as increasing insecticide resistance and residual malaria transmission. One way to assess performance prior to deployment in the field is through mathematical modelling. Modelled here are a range of potential outcomes for eave tubes, a novel mosquito control tool combining house screening and targeted use of insecticides to provide both physical protection and turn the house into a lethal mosquito killing device. METHODS: The effect of eave tubes was modelled by estimating the reduction of infectious mosquito bites relative to no intervention (a transmission metric defined as relative transmission potential, RTP). The model was used to assess how RTP varied with coverage when eave tubes were used as a stand-alone intervention, or in combination with either bed nets (LLINs) or indoor residual spraying (IRS). RESULTS: The model indicated the impact of eave tubes on transmission increases non-linearly as coverage increases, suggesting a community level benefit. For example, based on realistic assumptions, just 30 % coverage resulted in around 70 % reduction in overall RTP (i.e. there was a benefit for those houses without eave tubes). Increasing coverage to around 70 % reduced overall RTP by >90 %. Eave tubes exhibited some redundancy with existing interventions, such that combining interventions within properties did not give reductions in RTP equal to the sum of those provided by deploying each intervention singly. However, combining eave tubes and either LLINs or IRS could be extremely effective if the technologies were deployed in a non-overlapping way. CONCLUSION: Using predictive models to assess the benefit of new technologies has great value, and is especially pertinent prior to conducting expensive, large scale, randomized controlled trials. The current modelling study indicates eave tubes have considerable potential to impact malaria transmission if deployed at scale and can be used effectively with existing tools, especially if they are combined strategically with, for example, IRS and eave tubes targeting different houses.This work was supported by European Union Seventh Framework Programme Grant 306105, FP7-HEALTH-2012-INNOVATION-1

A solar powered handheld plasma source for microbial decontamination applications

A fully portable atmospheric pressure air plasma system is reported to be suitable for the microbial decontamination of both surfaces and liquids. The device operates in quiescent air, and includes an integrated battery which is charged from a solar cell and weighs less than 750 g, making it highly amenable for a wide variety of applications beyond the laboratory. Using particle imaging velocimetry to visualise air flows around the device, the geometric configuration of the plasma generating electrodes was enhanced to induce a gas flow on the order of 0.5 m s-1 directed towards a sample placed downstream, thus improving the transport of plasma generated reactive species to the sample. The microbial decontamination efficiency of the system was assessed using potable water samples inoculated with common waterborne organisms Escherichia coli and Pseudomonas fluorescens. The reduction in the number of microorganisms was found to be in the range of 2-8 log and was strongly dependent on the plasma generation conditions

Social genetic and social environment effects on parental and helper care in a cooperatively breeding bird

Phenotypes expressed in a social context are not only a function of the individual, but can also be shaped by the phenotypes of social partners. These social effects may play a major role in the evolution of cooperative breeding if social partners differ in the quality of care they provide and if individual carers adjust their effort in relation to that of other carers. When applying social effects models to wild study systems, it is also important to explore sources of individual plasticity that could masquerade as social effects. We studied offspring provisioning rates of parents and helpers in a wild population of long-tailed tits Aegithalos caudatus using a quantitative genetic framework to identify these social effects and partition them into genetic, permanent environment and current environment components. Controlling for other effects, individuals were consistent in their provisioning effort at a given nest, but adjusted their effort based on who was in their social group, indicating the presence of social effects. However, these social effects differed between years and social contexts, indicating a current environment effect, rather than indicating a genetic or permanent environment effect. While this study reveals the importance of examining environmental and genetic sources of social effects, the framework we present is entirely general, enabling a greater understanding of potentially important social effects within any ecological population

Does more education cause lower BMI, or do lower-BMI individuals become more educated? Evidence from the National Longitudinal Survey of Youth 1979

More educated adults have lower average body mass index (BMI). This may be due to selection, if adolescents with lower BMI attain higher levels of education, or it may be due to causation, if higher educational attainment reduces BMI gain in adulthood. We test for selection and causation in the National Longitudinal Survey of Youth 1979, which has followed a representative US cohort from age 14–22 in 1979 through age 47–55 in 2012. Using ordinal logistic regression, we test the selection hypothesis that overweight and obese adolescents were less likely to earn high school diplomas and bachelor's degrees. Then, controlling for selection with individual fixed effects, we estimate the causal effect of degree completion on BMI and obesity status. Among 18-year-old women, but not among men, being overweight or obese predicts lower odds of attaining higher levels of education. At age 47–48, higher education is associated with lower BMI, but 70–90% of the association is due to selection. Net of selection, a bachelor's degree predicts less than a 1 kg reduction in body weight, and a high school credential does not reduce BMI

Differential binding affinity of mutated peptides for MHC class I is a predictor of survival in advanced lung cancer and melanoma

Background: Cancer mutations generate novel (neo-)peptides recognised by T cells, but the determinants of recognition are not well characterised. The difference in predicted class I major histocompatibility complex (MHC-I) binding affinity between wild-type and corresponding mutant peptides (differential agretopicity index; DAI) may reflect clinically relevant cancer peptide immunogenicity. Our aim was to explore the relationship between DAI, measures of immune infiltration and patient outcomes in advanced cancer. Patients and methods: Cohorts of patients with advanced non-small-cell lung cancer (NSCLC; LUAD, n = 66) and melanoma (SKCM, n = 72) were obtained from The Cancer Genome Atlas. Three additional cohorts of immunotherapy treated patients with advanced melanoma (total n = 131) and NSCLC (n = 31) were analysed. Neopeptides and their clonal status were defined using genomic data. MHC-I binding affinity was predicted for each neopeptide and DAI values summarised as the sample mean DAI. Correlations between mean DAI and markers of immune activity were evaluated using measures of lymphocyte infiltration and immune gene expression. Results: In univariate and multivariate analyses, mean DAI significantly correlated with overall survival in 3/5 cohorts, with evidence of superiority over nonsynonymous mutational and neoantigen burden. In these cohorts, the effect was seen for mean DAI of clonal but not subclonal peptides. In SKCM, the association between mean DAI and survival bordered significance (P = 0.068), reaching significance in an immunotherapy-treated melanoma cohort (P = 0.003). Mean DAI but not mutational nor neoantigen burden was positively correlated with independently derived markers of immune infiltration in both SKCM (P = 0.027) and LUAD (P = 0.024). Conclusions: The association between mean DAI, survival and measures of immune activity support the hypothesis that DAI is a determinant of cancer peptide immunogenicity. Investigation of DAI as a marker of immunologically relevant peptides in further datasets and future clinical studies of neoantigen based immunotherapies is warranted

Estimation of Dietary Iron Bioavailability from Food Iron Intake and Iron Status

Currently there are no satisfactory methods for estimating dietary iron absorption (bioavailability) at a population level, but this is essential for deriving dietary reference values using the factorial approach. The aim of this work was to develop a novel approach for estimating dietary iron absorption using a population sample from a sub-section of the UK National Diet and Nutrition Survey (NDNS). Data were analyzed in 873 subjects from the 2000–2001 adult cohort of the NDNS, for whom both dietary intake data and hematological measures (hemoglobin and serum ferritin (SF) concentrations) were available. There were 495 men aged 19–64 y (mean age 42.7±12.1 y) and 378 pre-menopausal women (mean age 35.7±8.2 y). Individual dietary iron requirements were estimated using the Institute of Medicine calculations. A full probability approach was then applied to estimate the prevalence of dietary intakes that were insufficient to meet the needs of the men and women separately, based on their estimated daily iron intake and a series of absorption values ranging from 1–40%. The prevalence of SF concentrations below selected cut-off values (indicating that absorption was not high enough to maintain iron stores) was derived from individual SF concentrations. An estimate of dietary iron absorption required to maintain specified SF values was then calculated by matching the observed prevalence of insufficiency with the prevalence predicted for the series of absorption estimates. Mean daily dietary iron intakes were 13.5 mg for men and 9.8 mg for women. Mean calculated dietary absorption was 8% in men (50th percentile for SF 85 µg/L) and 17% in women (50th percentile for SF 38 µg/L). At a ferritin level of 45 µg/L estimated absorption was similar in men (14%) and women (13%). This new method can be used to calculate dietary iron absorption at a population level using data describing total iron intake and SF concentration

Fluctuating selection models and Mcdonald-Kreitman type analyses

It is likely that the strength of selection acting upon a mutation varies through time due to changes in the environment. However, most population genetic theory assumes that the strength of selection remains constant. Here we investigate the consequences of fluctuating selection pressures on the quantification of adaptive evolution using McDonald-Kreitman (MK) style approaches. In agreement with previous work, we show that fluctuating selection can generate evidence of adaptive evolution even when the expected strength of selection on a mutation is zero. However, we also find that the mutations, which contribute to both polymorphism and divergence tend, on average, to be positively selected during their lifetime, under fluctuating selection models. This is because mutations that fluctuate, by chance, to positive selected values, tend to reach higher frequencies in the population than those that fluctuate towards negative values. Hence the evidence of positive adaptive evolution detected under a fluctuating selection model by MK type approaches is genuine since fixed mutations tend to be advantageous on average during their lifetime. Never-the-less we show that methods tend to underestimate the rate of adaptive evolution when selection fluctuates

Methodological considerations in the analysis of fecal glucocorticoid metabolites in tufted capuchins (Cebus apella)

Analysis of fecal glucocorticoid (GC) metabolites has recently become the standard method to monitor adrenocortical activity in primates noninvasively. However, given variation in the production, metabolism, and excretion of GCs across species and even between sexes, there are no standard methods that are universally applicable. In particular, it is important to validate assays intended to measure GC production, test extraction and storage procedures, and consider the time course of GC metabolite excretion relative to the production and circulation of the native hormones. This study examines these four methodological aspects of fecal GC metabolite analysis in tufted capuchins (Cebus apella). Specifically, we conducted an adrenocorticotrophic hormone (ACTH) challenge on one male and one female capuchin to test the validity of four GC enzyme immunoassays (EIAs) and document the time course characterizing GC me- tabolite excretion in this species. In addition, we compare a common field-friendly technique for extracting fecal GC metabolites to an established laboratory extraction methodology and test for effects of storing “field extracts” for up to 1 yr. Results suggest that a corticosterone EIA is most sensitive to changes in GC production, provides reliable measures when extracted according to the field method, and measures GC metabolites which remain highly stable after even 12 mo of storage. Further, the time course of GC metabolite excretion is shorter than that described yet for any primate taxa. These results provide guidelines for studies of GCs in tufted capuchins, and underscore the importance of validating methods for fecal hormone analysis for each species of interest