Biological and anthropogenic predictors of metal concentration in the Eurasian otter, a sentinel of freshwater ecosystems

Toxic metals have been linked to a range of adverse health effects in freshwater organisms. However, for higher vertebrates, there is little understanding of the large-scale drivers of exposure. We quantified toxic metal/semi-metal concentrations in a sentinel freshwater top predator, the Eurasian otter (Lutra lutra), across England and Wales, and determined how this varied with key natural and anthropogenic factors. We related liver concentrations in 278 otters that died between 2006 and 2017 to habitat biogeochemistry, proximity to point source contamination and to biological characteristics (length, sex, condition). Evidence for any positive association with putative anthropogenic sources (mining, human population, known discharges) was weak or lacking in nearly all cases, with the exception of a positive association between lead and human population density. Despite concerns that burgeoning use of nanosilver in consumer products might increase silver concentrations in waste waters, there was no increase over time. Spatial variation in soil/sediment pH, precipitation, and soil calcium oxide are indicated as significant predictors of metal concentrations in otters (higher cadmium and silver in areas with lower pH and higher rainfall, and higher chromium and lead in areas of lower calcium oxide). Liver chromium and nickel concentrations declined significantly over time (Cr 0.030 ± 1.2 to 0.015 ± 1.3 μg/g dry weight, Ni 0.0038 ± 1.2 to 0.00068 ± 1.5 μg/g, between 2006–2009 and 2014–2017), but other metals showed no temporal change. Biotic associations were important, with age related accumulation indicated for mercury and cadmium (as well as interactions with body condition). Our results suggest that larger-scale geochemical and hydrological processes are important in determining metal exposure in otters, and we provide an indication of risk factors that may be of relevance for freshwater vertebrates in other countries with well-developed water pollution management

Systematic review of studies generating individual participant data on the efficacy of drugs for treating soil-transmitted helminthiases and the case for data-sharing

Preventive chemotherapy and transmission control (PCT) by mass drug administration is the cornerstone of the World Health Organization (WHO)’s policy to control soil-transmitted helminthiases (STHs) caused by Ascaris lumbricoides (roundworm), Trichuris trichiura (whipworm) and hookworm species (Necator americanus and Ancylostama duodenale) which affect over 1 billion people globally. Despite consensus that drug efficacies should be monitored for signs of decline that could jeopardise the effectiveness of PCT, systematic monitoring and evaluation is seldom implemented. Drug trials mostly report aggregate efficacies in groups of participants, but heterogeneities in design complicate classical meta-analyses of these data. Individual participant data (IPD) permit more detailed analysis of drug efficacies, offering increased sensitivity to identify atypical responses potentially caused by emerging drug resistance

A 2.3-Day Periodic Variability in the Apparently Single Wolf-Rayet Star WR 134: Collapsed Companion or Rotational Modulation?

We present the results of an intensive campaign of spectroscopic and photometric monitoring of the peculiar Wolf-Rayet star WR 134 from 1989 to 1997. This unprecedentedly large data set allows us to confirm unambiguously the existence of a coherent 2.25 +/- 0.05 day periodicity in the line-profile changes of He II 4686, although the global pattern of variability is different from one epoch to another. This period is only marginally detected in the photometric data set. Assuming the 2.25 day periodic variability to be induced by orbital motion of a collapsed companion, we develop a simple model aiming at investigating (i) the effect of this strongly ionizing, accreting companion on the Wolf-Rayet wind structure, and (ii) the expected emergent X-ray luminosity. We argue that the predicted and observed X-ray fluxes can only be matched if the accretion on the collapsed star is significantly inhibited. Additionally, we performed simulations of line-profile variations caused by the orbital revolution of a localized, strongly ionized wind cavity surrounding the X-ray source. A reasonable fit is achieved between the observed and modeled phase-dependent line profiles of He II 4686. However, the derived size of the photoionized zone substantially exceeds our expectations, given the observed low-level X-ray flux. Alternatively, we explore rotational modulation of a persistent, largely anisotropic outflow as the origin of the observed cyclical variability. Although qualitative, this hypothesis leads to greater consistency with the observations.Comment: 34 pages, 16 figures. Accepted by the Astrophysical Journa

The genetics of feto-placental development: A study of acid phosphatase locus 1 and adenosine deaminase polymorphisms in a consecutive series of newborn infants

<p>Abstract</p> <p>Background</p> <p>Acid phosphatase locus 1 and adenosine deaminase locus 1 polymorphisms show cooperative effects on glucose metabolism and immunological functions. The recent observation of cooperation between the two systems on susceptibility to repeated spontaneous miscarriage prompted us to search for possible interactional effects between these genes and the correlation between birth weight and placental weight. Deviation from a balanced development of the feto-placental unit has been found to be associated with perinatal morbidity and mortality and with cardiovascular diseases in adulthood.</p> <p>Methods</p> <p>We examined 400 consecutive newborns from the Caucasian population of Rome. Birth weight, placental weight, and gestational length were registered. Acid phosphatase locus 1 and adenosine deaminase locus 1 phenotypes were determined by starch gel electrophoresis and correlation analysis was performed by SPSS programs. Informed verbal consent to participate in the study was obtained from the mothers.</p> <p>Results</p> <p>Highly significant differences in birth weight-placental weight correlations were observed among acid phosphatase locus 1 phenotypes (p = 0.005). The correlation between birth weight and placental weight was markedly elevated in subjects carrying acid phosphatase locus 1 phenotypes with medium-low F isoform concentration (A, CA and CB phenotypes) compared to those carrying acid phosphatase locus 1 phenotypes with medium-high F isoform concentration (BA and B phenotypes) (p = 0.002). Environmental and developmental variables were found to exert a significant effect on birth weight-placental weight correlation in subjects with medium-high F isoform concentrations, but only a marginal effect was observed in those with medium-low F isoform concentrations. The correlation between birth weight and placental weight is higher among carriers of the adenosine deaminase locus 1 allele*2, which is associated with low activity, than in homozygous adenosine deaminase locus 1 phenotype 1 carriers (p = 0.04). The two systems show a cooperative effect on the correlation between birth weight and placental weight: the highest value is observed in newborns carrying adenosine deaminase locus 1 allele*2 and acid phosphatase locus 1 phenotypes with medium-low F isoform concentration (p = 0.005).</p> <p>Conclusion</p> <p>These data suggest that zygotes with low adenosine deaminase locus 1 activity and low F activity may experience the most favourable intrauterine conditions for a balanced development of the feto-placental unit.</p

Height and timing of growth spurt during puberty in young people living with vertically acquired HIV in Europe and Thailand.

OBJECTIVE: The aim of this study was to describe growth during puberty in young people with vertically acquired HIV. DESIGN: Pooled data from 12 paediatric HIV cohorts in Europe and Thailand. METHODS: One thousand and ninety-four children initiating a nonnucleoside reverse transcriptase inhibitor or boosted protease inhibitor based regimen aged 1-10 years were included. Super Imposition by Translation And Rotation (SITAR) models described growth from age 8 years using three parameters (average height, timing and shape of the growth spurt), dependent on age and height-for-age z-score (HAZ) (WHO references) at antiretroviral therapy (ART) initiation. Multivariate regression explored characteristics associated with these three parameters. RESULTS: At ART initiation, median age and HAZ was 6.4 [interquartile range (IQR): 2.8, 9.0] years and -1.2 (IQR: -2.3 to -0.2), respectively. Median follow-up was 9.1 (IQR: 6.9, 11.4) years. In girls, older age and lower HAZ at ART initiation were independently associated with a growth spurt which occurred 0.41 (95% confidence interval 0.20-0.62) years later in children starting ART age 6 to 10 years compared with 1 to 2 years and 1.50 (1.21-1.78) years later in those starting with HAZ less than -3 compared with HAZ at least -1. Later growth spurts in girls resulted in continued height growth into later adolescence. In boys starting ART with HAZ less than -1, growth spurts were later in children starting ART in the oldest age group, but for HAZ at least -1, there was no association with age. Girls and boys who initiated ART with HAZ at least -1 maintained a similar height to the WHO reference mean. CONCLUSION: Stunting at ART initiation was associated with later growth spurts in girls. Children with HAZ at least -1 at ART initiation grew in height at the level expected in HIV negative children of a comparable age

Observed Reductions in Schistosoma mansoni Transmission from Large-Scale Administration of Praziquantel in Uganda: A Mathematical Modelling Study

To date schistosomiasis control programmes based on chemotherapy have largely aimed at controlling morbidity in treated individuals rather than at suppressing transmission. In this study, a mathematical modelling approach was used to estimate reductions in the rate of Schistosoma mansoni reinfection following annual mass drug administration (MDA) with praziquantel in Uganda over four years (2003-2006). In doing this we aim to elucidate the benefits of MDA in reducing community transmission.Age-structured models were fitted to a longitudinal cohort followed up across successive rounds of annual treatment for four years (Baseline: 2003, TREATMENT: 2004-2006; n = 1,764). Instead of modelling contamination, infection and immunity processes separately, these functions were combined in order to estimate a composite force of infection (FOI), i.e., the rate of parasite acquisition by hosts.MDA achieved substantial and statistically significant reductions in the FOI following one round of treatment in areas of low baseline infection intensity, and following two rounds in areas with high and medium intensities. In all areas, the FOI remained suppressed following a third round of treatment.This study represents one of the first attempts to monitor reductions in the FOI within a large-scale MDA schistosomiasis morbidity control programme in sub-Saharan Africa. The results indicate that the Schistosomiasis Control Initiative, as a model for other MDA programmes, is likely exerting a significant ancillary impact on reducing transmission within the community, and may provide health benefits to those who do not receive treatment. The results obtained will have implications for evaluating the cost-effectiveness of schistosomiasis control programmes and the design of monitoring and evaluation approaches in general

A systematic review of measures used in studies of human papillomavirus (HPV) vaccine acceptability

The recent proliferation of studies describing factors associated with HPV vaccine acceptability could inform health care providers in improving vaccine coverage and support future research. This review examined measures of HPV and HPV-vaccine knowledge, attitudes, beliefs and acceptability, described psychometric characteristics, and provided recommendations about their use

Age-dependent impact of two exercise training regimens on genomic and metabolic remodeling in skeletal muscle and liver of male mice

Skeletal muscle adapts to different exercise training modalities with age; however, the impact of both variables at the systemic and tissue levels is not fully understood. Here, adult and old C57BL/6 male mice were assigned to one of three groups: sedentary, daily high-intensity intermittent training (HIIT), or moderate intensity continuous training (MICT) for 4 weeks, compatible with the older group’s exercise capacity. Improvements in body composition, fasting blood glucose, and muscle strength were mostly observed in the MICT old group, while effects of HIIT training in adult and old animals was less clear. Skeletal muscle exhibited structural and functional adaptations to exercise training, as revealed by electron microscopy, OXPHOS assays, respirometry, and muscle protein biomarkers. Transcriptomics analysis of gastrocnemius muscle combined with liver and serum metabolomics unveiled an age-dependent metabolic remodeling in response to exercise training. These results support a tailored exercise prescription approach aimed at improving health and ameliorating age-associated loss of muscle strength and function in the elderly.This work was supported by funding from the Intramural Research Program of the National Institute on Aging/NIH. Work in JMV laboratory was supported by the Spanish Ministerio de Economía y Competitividad (MINECO) grant BFU2015-64630-R, Ministerio de Ciencia, Innovación y Universidades (MICIU) grant RTI2018-100695-B-I00, Spanish Junta de Andalucía grants P18-RT-4264, 1263735-R and BIO-276, the FEDER Funding Program from the European Union, and Universidad de Córdoba. MCR was supported by a FPU fellowship from the Spanish Ministerio de Educación, Cultura y Deporte (reference FPU14/06308). SRL held a FPI predoctoral contract funded by MINECO (reference BES-2016-078229).Peer reviewe

Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead.

Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety 'Mode of Action' framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology