Mechanisms of Psychological Distress following War in the Former Yugoslavia: The Role of Interpersonal Sensitivity

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.This study was funded by a grant from the European Commission, contract number INCO-CT-2004-509176. AN was supported by a Clinical Early Career Research Fellowship (113295) and a Project Grant (104288

Decoration supplementation and male–male competition in the great bowerbird (Ptilonorhynchus nuchalis): a test of the social control hypothesis

Many animals use signals to communicate their social status to conspecifics, and the social control hypothesis suggests that social interactions maintain the evolutionary stability of status signals: low-quality individuals signal at a low level to prevent high-quality individuals from “punishing” them. I examined whether the numbers of decorations at bowers are socially controlled in the great bowerbird (Ptilonorhynchus nuchalis). In two populations, I supplemented males with decorations to determine whether they (a) rejected supplemental decorations and (b) experienced increased bower destruction from rivals. In contrast to the social control hypothesis, males in both populations accepted most supplemental decorations. Though the mean destruction rate did not increase during supplementation in either population, one of the study populations (Townsville) exhibited a negative correlation between the numbers of decorations naturally displayed at bowers and the change in destruction rate during the experiment. Townsville males that naturally had few decorations at their bowers also had more decorations stolen by other males during supplementation than males that naturally had many decorations. These results suggest that the numbers of decorations at bowers are an honest signal of the male's ability to defend his display site from rivals in at least one population of the great bowerbird (Townsville), but they do not support the social control hypothesis because males at both sites failed to limit signal expression. I discuss how the external nature of bower decorations and their availability in the environment may influence the costs and benefits of decoration theft and social control

Progression of conventional cardiovascular risk factors and vascular disease risk in individuals: insights from the PROG-IMT consortium

Aims Averaged measurements, but not the progression based on multiple assessments of carotid intima-media thickness, (cIMT) are predictive of cardiovascular disease (CVD) events in individuals. Whether this is true for conventional risk factors is unclear. Methods and results An individual participant meta-analysis was used to associate the annualised progression of systolic blood pressure, total cholesterol, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol with future cardiovascular disease risk in 13 prospective cohort studies of the PROG-IMT collaboration (n = 34,072). Follow-up data included information on a combined cardiovascular disease endpoint of myocardial infarction, stroke, or vascular death. In secondary analyses, annualised progression was replaced with average. Log hazard ratios per standard deviation difference were pooled across studies by a random effects meta-analysis. In primary analysis, the annualised progression of total cholesterol was marginally related to a higher cardiovascular disease risk (hazard ratio (HR) 1.04, 95% confidence interval (CI) 1.00 to 1.07). The annualised progression of systolic blood pressure, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol was not associated with future cardiovascular disease risk. In secondary analysis, average systolic blood pressure (HR 1.20 95% CI 1.11 to 1.29) and low-density lipoprotein cholesterol (HR 1.09, 95% CI 1.02 to 1.16) were related to a greater, while high-density lipoprotein cholesterol (HR 0.92, 95% CI 0.88 to 0.97) was related to a lower risk of future cardiovascular disease events. Conclusion Averaged measurements of systolic blood pressure, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol displayed significant linear relationships with the risk of future cardiovascular disease events. However, there was no clear association between the annualised progression of these conventional risk factors in individuals with the risk of future clinical endpoints

Genetic Determinants of Electrocardiographic P-Wave Duration and Relation to Atrial Fibrillation

Background: The P-wave duration (PWD) is an electrocardiographic measurement that represents cardiac conduction in the atria. Shortened or prolonged PWD is associated with atrial fibrillation (AF). We used exome-chip data to examine the associations between common and rare variants with PWD. / Methods: Fifteen studies comprising 64 440 individuals (56 943 European, 5681 African, 1186 Hispanic, 630 Asian) and ≈230 000 variants were used to examine associations with maximum PWD across the 12-lead ECG. Meta-analyses summarized association results for common variants; gene-based burden and sequence kernel association tests examined low-frequency variant-PWD associations. Additionally, we examined the associations between PWD loci and AF using previous AF genome-wide association studies. / Results: We identified 21 common and low-frequency genetic loci (14 novel) associated with maximum PWD, including several AF loci (TTN, CAND2, SCN10A, PITX2, CAV1, SYNPO2L, SOX5, TBX5, MYH6, RPL3L). The top variants at known sarcomere genes (TTN, MYH6) were associated with longer PWD and increased AF risk. However, top variants at other loci (eg, PITX2 and SCN10A) were associated with longer PWD but lower AF risk. / Conclusions: Our results highlight multiple novel genetic loci associated with PWD, and underscore the shared mechanisms of atrial conduction and AF. Prolonged PWD may be an endophenotype for several different genetic mechanisms of AF

Bypassing cellular EGF receptor dependence through epithelial-to-mesenchymal-like transitions

Over 90% of all cancers are carcinomas, malignancies derived from cells of epithelial origin. As carcinomas progress, these tumors may lose epithelial morphology and acquire mesenchymal characteristics which contribute to metastatic potential. An epithelial-to-mesenchymal transition (EMT) similar to the process critical for embryonic development is thought to be an important mechanism for promoting cancer invasion and metastasis. Epithelial-to-mesenchymal transitions have been induced in vitro by transient or unregulated activation of receptor tyrosine kinase signaling pathways, oncogene signaling and disruption of homotypic cell adhesion. These cellular models attempt to mimic the complexity of human carcinomas which respond to autocrine and paracrine signals from both the tumor and its microenvironment. Activation of the epidermal growth factor receptor (EGFR) has been implicated in the neoplastic transformation of solid tumors and overexpression of EGFR has been shown to correlate with poor survival. Notably, epithelial tumor cells have been shown to be significantly more sensitive to EGFR inhibitors than tumor cells which have undergone an EMT-like transition and acquired mesenchymal characteristics, including non-small cell lung (NSCLC), head and neck (HN), bladder, colorectal, pancreas and breast carcinomas. EGFR blockade has also been shown to inhibit cellular migration, suggesting a role for EGFR inhibitors in the control of metastasis. The interaction between EGFR and the multiple signaling nodes which regulate EMT suggest that the combination of an EGFR inhibitor and other molecular targeted agents may offer a novel approach to controlling metastasis

The genomics of heart failure: design and rationale of the HERMES consortium

AIMS: The HERMES (HEart failure Molecular Epidemiology for Therapeutic targetS) consortium aims to identify the genomic and molecular basis of heart failure. METHODS AND RESULTS: The consortium currently includes 51 studies from 11 countries, including 68 157 heart failure cases and 949 888 controls, with data on heart failure events and prognosis. All studies collected biological samples and performed genome-wide genotyping of common genetic variants. The enrolment of subjects into participating studies ranged from 1948 to the present day, and the median follow-up following heart failure diagnosis ranged from 2 to 116 months. Forty-nine of 51 individual studies enrolled participants of both sexes; in these studies, participants with heart failure were predominantly male (34–90%). The mean age at diagnosis or ascertainment across all studies ranged from 54 to 84 years. Based on the aggregate sample, we estimated 80% power to genetic variant associations with risk of heart failure with an odds ratio of ≥1.10 for common variants (allele frequency ≥ 0.05) and ≥1.20 for low-frequency variants (allele frequency 0.01–0.05) at P < 5 × 10^{-8} under an additive genetic model. CONCLUSIONS: HERMES is a global collaboration aiming to (i) identify the genetic determinants of heart failure; (ii) generate insights into the causal pathways leading to heart failure and enable genetic approaches to target prioritization; and (iii) develop genomic tools for disease stratification and risk prediction

One consensual depression diagnosis tool to serve many countries: a challenge! A RAND/UCLA methodology

Objective From a systematic literature review (SLR), it became clear that a consensually validated tool was needed by European General Practitioner (GP) researchers in order to allow multi-centred collaborative research, in daily practice, throughout Europe. Which diagnostic tool for depression, validated against psychiatric examination according to the DSM, would GPs select as the best for use in clinical research, taking into account the combination of effectiveness, reliability and ergonomics? A RAND/UCLA, which combines the qualities of the Delphi process and of the nominal group, was used. GP researchers from different European countries were selected. The SLR extracted tools were validated against the DSM. The Youden index was used as an effectiveness criterion and Cronbach’s alpha as a reliability criterion. Ergonomics data were extracted from the literature. Ergonomics were tested face-to-face. Results The SLR extracted 7 tools. Two instruments were considered sufficiently effective and reliable for use: the Hospital Anxiety and Depression Scale and the Hopkins Symptoms Checklist-25 (HSCL-25). After testing face-to-face, HSCL-25 was selected. A multicultural consensus on one diagnostic tool for depression was obtained for the HSCL-25. This tool will provide the opportunity to select homogeneous populations for European collaborative research in daily practice

Reassessment of pre-industrial fire emissions strongly affects anthropogenic aerosol forcing

Uncertainty in pre-industrial natural aerosol emissions is a major component of the overall uncertainty in the radiative forcing of climate. Improved characterisation of natural emissions and their radiative effects can therefore increase the accuracy of global climate model projections. Here we show that revised assumptions about pre-industrial fire activity result in significantly increased aerosol concentrations in the pre-industrial atmosphere. Revised global model simulations predict a 35% reduction in the calculated global mean cloud albedo forcing over the Industrial Era (1750–2000 CE) compared to estimates using emissions data from the Sixth Coupled Model Intercomparison Project. An estimated upper limit to pre-industrial fire emissions results in a much greater (91%) reduction in forcing. When compared to 26 other uncertain parameters or inputs in our model, pre-industrial fire emissions are by far the single largest source of uncertainty in pre-industrial aerosol concentrations, and hence in our understanding of the magnitude of the historical radiative forcing due to anthropogenic aerosol emissions

The genomics of heart failure: design and rationale of the HERMES consortium

Aims The HERMES (HEart failure Molecular Epidemiology for Therapeutic targets) consortium aims to identify the genomic and molecular basis of heart failure.Methods and results The consortium currently includes 51 studies from 11 countries, including 68 157 heart failure cases and 949 888 controls, with data on heart failure events and prognosis. All studies collected biological samples and performed genome-wide genotyping of common genetic variants. The enrolment of subjects into participating studies ranged from 1948 to the present day, and the median follow-up following heart failure diagnosis ranged from 2 to 116 months. Forty-nine of 51 individual studies enrolled participants of both sexes; in these studies, participants with heart failure were predominantly male (34-90%). The mean age at diagnosis or ascertainment across all studies ranged from 54 to 84 years. Based on the aggregate sample, we estimated 80% power to genetic variant associations with risk of heart failure with an odds ratio of >1.10 for common variants (allele frequency > 0.05) and >1.20 for low-frequency variants (allele frequency 0.01-0.05) at P < 5 x 10(-8) under an additive genetic model.Conclusions HERMES is a global collaboration aiming to (i) identify the genetic determinants of heart failure; (ii) generate insights into the causal pathways leading to heart failure and enable genetic approaches to target prioritization; and (iii) develop genomic tools for disease stratification and risk prediction.Cardiolog