Prevalence of renal impairment and its association with cardiovascular risk factors in a general population: results of the Swiss SAPALDIA study

Background. Impaired renal function is evolving as an independent marker of the risk of cardiovascular morbidity and mortality. Little is known about the prevalence of impaired renal function and its relationship to cardiovascular risk factors in the Swiss general population. Methods. SAPALDIA comprises a random sample of the Swiss population established in 1991, originally to investigate the health effects of long-term exposure to air pollution. Participants were reassessed in 2002/3 and blood measurements were obtained (n = 6317). Renal function was estimated using the Cockcroft-Gault equation and the modified MDRD (four-component) equation incorporating age, race, gender and serum creatinine level. Results. The estimated prevalence of impaired renal function [estimated glomerular filtration rate <60 ml/min/1.73 m2] differed substantially between men and women, particularly at higher ages, and amounted to 13% [95% confidence interval (CI) 10-16%] and 36% (95% CI 32-40%) in men and women, respectively, of 65 years or older. Smoking, obesity, blood lipid levels, high systolic blood pressure and hyperuricaemia were all more common in men when compared with women. These cardiovascular risk factors were also associated independently with creatinine in both women and men. Women were less likely to receive cardiovascular drugs, in particular angiotensin-converting enzyme inhibitors and β-blockers, when compared with men of the same age. Conclusion. Moderate renal impairment seems to be prevalent in the general population, with an apparent excess in females which is not explained by conventional cardiovascular risk factors. The unexpected finding questions the validity of the prediction equations, in particular in female

Meta-analyses of the sensitivity and specificity of ante-mortem and post-mortem diagnostic tests for bovine tuberculosis in the UK and Ireland

Publication history: Accepted - 26 February 2017; Published online - 6th March 2017.Bovine Tuberculosis (bTB) in cattle is a global health problem and eradication of the disease requires accu-rate estimates of diagnostic test performance to optimize their efficiency. The objective of this study was,through statistical meta-analyses, to obtain estimates of sensitivity (Se) and specificity (Sp), for 14 differ-ent ante-mortem and post-mortem diagnostic tests for bTB in cattle. Using data from a systematic reviewof the scientific literature (published 1934–2009) diagnostic Se and Sp were estimated using Bayesianlogistic regression models adjusting for confounding factors. Random effect terms were used to accountfor unexplained heterogeneity. Parameters in the models were implemented using Markov Chain MonteCarlo (MCMC), and posterior distributions for the diagnostic parameters with adjustment for covariates(confounding factors) were obtained using the inverse logit function. Estimates for Se and/or Sp of thetuberculin skin tests and the IFN- blood test were compared with estimates published 2010–2015.Median Se for the single intradermal comparative cervical tuberculin skin (SICCT) test (standard inter-pretation) was 0.50 and Bayesian credible intervals (CrI) were wide (95% CrI 0.26, 0.78). Median Sp forthe SICCT test was 1.00 (95% CrI 0.99, 1.00). Estimates for the IFN- blood test Bovine Purified ProteinDerivative (PPD)-Avian PPD and Early Secreted Antigen target 6 and Culture Filtrate Protein 10 (ESAT-6/CFP10) ESAT6/CFP10 were 0.67 (95% CrI 0.49, 0.82) and 0.78 (95% CrI 0.60, 0.90) respectively for Se,and 0.98 (95% CrI 0.96, 0.99) and 0.99 (95% CrI 0.99, 1.00) for Sp. The study provides an overview of theaccuracy of a range of contemporary diagnostic tests for bTB in cattle. Better understanding of diagnostictest performance is essential for the design of effective control strategies and their evaluation.The SE3238 project “Meta-analysis of diagnostic tests and modelling to identify appropriate testing strategies to reduce M. bovis infection in GB herds” was funded by the UK Department for Envi-ronment, Food and Rural Affairs (Defra)

Evaluation of the methodological quality of studies of the performance of diagnostic tests for bovine tuberculosis using QUADAS

There has been little assessment of the methodological quality of studies measuring the performance (sensitivity and/or specificity) of diagnostic tests for animal diseases. In a systematic review, 190 studies of tests for bovine tuberculosis (bTB) in cattle (published 1934-2009) were assessed by at least one of 18 reviewers using the QUADAS (Quality Assessment of Diagnostic Accuracy Studies) checklist adapted for animal disease tests. VETQUADAS (VQ) included items measuring clarity in reporting (n = 3), internal validity (n = 9) and external validity (n = 2). A similar pattern for compliance was observed in studies of different diagnostic test types. Compliance significantly improved with year of publication for all items measuring clarity in reporting and external validity but only improved in four of the nine items measuring internal validity (p < 0.05). 107 references, of which 83 had performance data eligible for inclusion in a meta-analysis were reviewed by two reviewers. In these references, agreement between reviewers' responses was 71% for compliance, 32% for unsure and 29% for non-compliance. Mean compliance with reporting items was 2, 5.2 for internal validity and 1.5 for external validity. The index test result was described in sufficient detail in 80.1% of studies and was interpreted without knowledge of the reference standard test result in only 33.1%. Loss to follow-up was adequately explained in only 31.1% of studies. The prevalence of deficiencies observed may be due to inadequate reporting but may also reflect lack of attention to methodological issues that could bias the results of diagnostic test performance estimates. QUADAS was a useful tool for assessing and comparing the quality of studies measuring the performance of diagnostic tests but might be improved further by including explicit assessment of population sampling strategy.The SE3238 project “Meta-analysis of diagnostic tests and modelling to identify appropriate testing strategies to reduce M. bovis infection in GB herds” was funded by the UK Department for Environment, Food and Rural Affairs (Defra).http://www.elsevier.com/locate/prevetmedam2018Veterinary Tropical Disease

An assessment of risk compensation and spillover behavioural adaptions associated with the use of vaccines in animal disease management

This paper analyses farmers’ behavioural responses to Government attempts to reduce the risk of disease transmission from badgers to cattle through badger vaccination. Evidence for two opposing behavioural adaptions is examined in response to the vaccination of badgers to reduce the risk of transmission to farmed cattle. Risk compensation theory suggests that interventions that reduce risk, such as vaccination, are counterbalanced by negative behavioural adaptions. By contrast, the spillover effect suggests that interventions can prompt further positive behaviours. The paper uses data from a longitudinal mixed methods study of farmers’ attitudes to badger vaccination to prevent the spread of bovine tuberculosis, their reports of biosecurity practices, and cattle movement data in 5 areas of England, one of which experienced badger vaccination. Analysis finds limited evidence of spillover behaviours following vaccination. Lack of spillover is attributed to farmers’ beliefs in the effectiveness of biosecurity and the lack of similarity between badger vaccination and vaccination for other animal diseases. Risk compensation behaviours are associated with farmers’ beliefs as to who should manage animal disease. Rather than farmers’ belief in vaccine effectiveness, it is more likely that farmers’ low sense of being able to do anything to prevent disease influences their apparent risk compensation behaviours. These findings address the gap in the literature relating to farmers' behavioural adaptions to vaccine use in the management of animal disease

Evidence for genetic variance in resistance to tuberculosis in Great Britain and Irish Holstein-Friesian populations

peer-reviewedBackground: Here, we jointly summarise scientific evidence for genetic variation in resistance to infection with Mycobacterium bovis, the primary agent of bovine tuberculosis (TB), provided by two recent and separate studies of Holstein-Friesian dairy cow populations in Great Britain (GB) and Ireland. Methods: The studies quantified genetic variation within archived data from field and abattoir surveillance control programmes within each country. These data included results from the single intradermal comparative tuberculin test (SICTT), abattoir inspection for TB lesions and laboratory confirmation of disease status. Threshold animal models were used to estimate variance components for responsiveness to the SICTT and abattoir confirmed M. bovis infection. The link functions between the observed 0/1 scale and the liability scale were the complementary log-log in the GB, and logit link function in the Irish population. Results and discussion: The estimated heritability of susceptibility to TB, as judged by responsiveness to the SICTT, was 0.16 (0.012) and 0.14 (0.025) in the GB and Irish populations, respectively. For abattoir or laboratory confirmation of infection, estimates were 0.18 (0.044) and 0.18 (0.041) from the GB and the Irish populations, respectively. Conclusions: Estimates were all significantly different from zero and indicate that exploitable variation exists among GB and Irish Holstein Friesian dairy cows for resistance to TB. Epidemiological analysis suggests that factors such as variation in exposure or imperfect sensitivity and specificity would have resulted in underestimation of the true values

Ancient and Recent Adaptive Evolution of Primate Non-Homologous End Joining Genes

In human cells, DNA double-strand breaks are repaired primarily by the non-homologous end joining (NHEJ) pathway. Given their critical nature, we expected NHEJ proteins to be evolutionarily conserved, with relatively little sequence change over time. Here, we report that while critical domains of these proteins are conserved as expected, the sequence of NHEJ proteins has also been shaped by recurrent positive selection, leading to rapid sequence evolution in other protein domains. In order to characterize the molecular evolution of the human NHEJ pathway, we generated large simian primate sequence datasets for NHEJ genes. Codon-based models of gene evolution yielded statistical support for the recurrent positive selection of five NHEJ genes during primate evolution: XRCC4, NBS1, Artemis, POLλ, and CtIP. Analysis of human polymorphism data using the composite of multiple signals (CMS) test revealed that XRCC4 has also been subjected to positive selection in modern humans. Crystal structures are available for XRCC4, Nbs1, and Polλ; and residues under positive selection fall exclusively on the surfaces of these proteins. Despite the positive selection of such residues, biochemical experiments with variants of one positively selected site in Nbs1 confirm that functions necessary for DNA repair and checkpoint signaling have been conserved. However, many viruses interact with the proteins of the NHEJ pathway as part of their infectious lifecycle. We propose that an ongoing evolutionary arms race between viruses and NHEJ genes may be driving the surprisingly rapid evolution of these critical genes

Priorities for synthesis research in ecology and environmental science

ACKNOWLEDGMENTS We thank the National Science Foundation grant #1940692 for financial support for this workshop, and the National Center for Ecological Analysis and Synthesis (NCEAS) and its staff for logistical support.Peer reviewedPublisher PD

Priorities for synthesis research in ecology and environmental science

ACKNOWLEDGMENTS We thank the National Science Foundation grant #1940692 for financial support for this workshop, and the National Center for Ecological Analysis and Synthesis (NCEAS) and its staff for logistical support.Peer reviewedPublisher PD