Emergence of heat extremes attributable to anthropogenic influences

Climate scientists have demonstrated that a substantial fraction of the probability of numerous recent extreme events may be attributed to human-induced climate change. However, it is likely that for temperature extremes occurring over previous decades a fraction of their probability was attributable to anthropogenic influences. We identify the first record-breaking warm summers and years for which a discernible contribution can be attributed to human influence. We find a significant human contribution to the probability of record-breaking global temperature events as early as the 1930s. Since then, all the last 16 record-breaking hot years globally had an anthropogenic contribution to their probability of occurrence. Aerosol-induced cooling delays the timing of a significant human contribution to record-breaking events in some regions. Without human-induced climate change recent hot summers and years would be very unlikely to have occurred.111411Ysciescopu

A feasibility trial to examine the social norms approach for the prevention and reduction of licit and illicit drug use in European University and college students.

Background: Incorrect perceptions of high rates of peer alcohol and tobacco use are predictive of increased personal use in student populations. Correcting misperceptions by providing feedback has been shown to be an effective intervention for reducing licit drug use. It is currently unknown if social norms interventions are effective in preventing and reducing illicit drug use in European students. The purpose of this paper is to describe the design of a multi-site cluster controlled trial of a web-based social norms intervention aimed at reducing licit and preventing illicit drug use in European university students. Methods/Design: An online questionnaire to assess rates of drug use will be developed and translated based on existing social norms surveys. Students from sixteen universities in seven participating European countries will be invited to complete the questionnaire. Both intervention and control sites will be chosen by convenience. In each country, the intervention site will be the university that the local principal investigator is affiliated with. We aim to recruit 1000 students per site (baseline assessment). All participants will complete the online questionnaire at baseline. Baseline data will be used to develop social norms messages that will be included in a web-based intervention. The intervention group will receive individualized social norms feedback. The website will remain online during the following 5 months. After five months, a second survey will be conducted and effects of the intervention on social norms and drug use will be measured in comparison to the control site. Discussion: This project is the first cross-national European collaboration to investigate the feasibility of a social norms intervention to reduce licit and prevent illicit drug use among European university students. Final trial registration number DRKS00004375 on the ‘German Clinical Trials Register’.This study is funded by the European Commission, Directorate General Justice, Freedom and Security (JLS/2009-2010/DPIP/AG

The solution structure of the human IgG2 subclass is distinct from those for human IgG1 and IgG4 providing an explanation for their discrete functions

Human IgG2 antibody displays distinct therapeutically-useful properties compared with the IgG1, IgG3 and IgG4 antibody subclasses. IgG2 is the second most abundant IgG subclass, being able to bind human FcγRII/FcγRIII, but not to FcγRI or complement C1q. Structural information on IgG2 is limited by the absence of a full-length crystal structure for this. To this end, we determined the solution structure of human myeloma IgG2 by atomistic X-ray and neutron scattering modelling. Analytical ultracentrifugation disclosed that IgG2 is monomeric with a sedimentation coefficient s020,w of 7.2 S. IgG2 dimer formation was ≤ 5% and independent of the buffer conditions. Small-angle X-ray scattering in a range of NaCl concentrations and in light and heavy water revealed that the X-ray radius of gyration Rg is 5.2-5.4 nm, after allowing for radiation damage at higher concentrations, and that the neutron Rg value of 5.0 nm remained unchanged in all conditions. The X-ray and neutron distance distribution curves P(r) revealed two peaks, M1 and M2, that were unchanged in different buffers. The creation of ˃123,000 physically-realistic atomistic models by Monte Carlo simulations for joint X-ray and neutron-scattering curve fits, constrained by the requirement of correct disulfide bridges in the hinge, resulted in the determination of symmetric Y-shaped IgG2 structures. These molecular structures were distinct from those for asymmetric IgG1 and asymmetric and symmetric IgG4, and were attributable to the four hinge disulfides. Our IgG2 structures rationalize the existence of the human IgG1, IgG2, and IgG4 subclasses, and explain the receptor binding functions of IgG2

Threshold selection in gene co-expression networks using spectral graph theory techniques

Abstract Background Gene co-expression networks are often constructed by computing some measure of similarity between expression levels of gene transcripts and subsequently applying a high-pass filter to remove all but the most likely biologically-significant relationships. The selection of this expression threshold necessarily has a significant effect on any conclusions derived from the resulting network. Many approaches have been taken to choose an appropriate threshold, among them computing levels of statistical significance, accepting only the top one percent of relationships, and selecting an arbitrary expression cutoff. Results We apply spectral graph theory methods to develop a systematic method for threshold selection. Eigenvalues and eigenvectors are computed for a transformation of the adjacency matrix of the network constructed at various threshold values. From these, we use a basic spectral clustering method to examine the set of gene-gene relationships and select a threshold dependent upon the community structure of the data. This approach is applied to two well-studied microarray data sets from Homo sapiens and Saccharomyces cerevisiae. Conclusion This method presents a systematic, data-based alternative to using more artificial cutoff values and results in a more conservative approach to threshold selection than some other popular techniques such as retaining only statistically-significant relationships or setting a cutoff to include a percentage of the highest correlations

Differential effects of nicotine on alcohol consumption in men and women

Nicotine and alcohol are frequently co-used, suggesting that use of one drug may facilitate use of the other. Furthermore, because men and women differ in their responses to both drugs, it is possible that men and women also differ in their responses to the combination of nicotine and alcohol.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46375/1/213_2006_Article_338.pd

Peer substance use overestimation among French university students: a cross-sectional survey

<p>Abstract</p> <p>Background</p> <p>Normative misperceptions have been widely documented for alcohol use among U.S. college students. There is less research on other substances or European cultural contexts. This study explores which factors are associated with alcohol, tobacco and cannabis use misperceptions among French college students, focusing on substance use.</p> <p>Methods</p> <p>12 classes of second-year college students (n = 731) in sociology, medicine, nursing or foreign language estimated the proportion of tobacco, cannabis, alcohol use and heavy episodic drinking among their peers and reported their own use.</p> <p>Results</p> <p>Peer substance use overestimation frequency was 84% for tobacco, 55% for cannabis, 37% for alcohol and 56% for heavy episodic drinking. Cannabis users (p = 0.006), alcohol (p = 0.003) and heavy episodic drinkers (p = 0.002), are more likely to overestimate the prevalence of use of these consumptions. Tobacco users are less likely to overestimate peer prevalence of smoking (p = 0.044). Women are more likely to overestimate tobacco (p < 0.001) and heavy episodic drinking (p = 0.007) prevalence. Students having already completed another substance use questionnaire were more likely to overestimate alcohol use prevalence (p = 0.012). Students exposed to cannabis prevention campaigns were more likely to overestimate cannabis (p = 0.018) and tobacco use (p = 0.022) prevalence. Other identified factors are class-level use prevalences and academic discipline.</p> <p>Conclusions</p> <p>Local interventions that focus on creating realistic perceptions of substance use prevalence could be considered for cannabis and alcohol prevention in French campuses.</p

Rapid and Accurate Detection of Mycobacterium tuberculosis in Sputum Samples by Cepheid Xpert MTB/RIF Assay-A Clinical Validation Study

Background: A crucial impediment to global tuberculosis control is the lack of an accurate, rapid diagnostic test for detection of patients with active TB. A new, rapid diagnostic method, (Cepheid) Xpert MTB/RIF Assay, is an automated sample preparation and real-time PCR instrument, which was shown to have good potential as an alternative to current reference standard sputum microscopy and culture.Methods: We performed a clinical validation study on diagnostic accuracy of the Xpert MTB/RIF Assay in a TB and HIV endemic setting. Sputum samples from 292 consecutively enrolled adults from Mbeya, Tanzania, with suspected TB were subject to analysis by the Xpert MTB/RIF Assay. The diagnostic performance of Xpert MTB/RIF Assay was compared to standard sputum smear microscopy and culture. Confirmed Mycobacterium tuberculosis in a positive culture was used as a reference standard for TB diagnosis.Results: Xpert MTB/RIF Assay achieved 88.4% (95% CI = 78.4% to 94.9%) sensitivity among patients with a positive culture and 99% (95% CI = 94.7% to 100.0%) specificity in patients who had no TB. HIV status did not affect test performance in 172 HIV-infected patients (58.9% of all participants). Seven additional cases (9.1% of 77) were detected by Xpert MTB/RIF Assay among the group of patients with clinical TB who were culture negative. Within 45 sputum samples which grew non-tuberculous mycobacteria the assay's specificity was 97.8% (95% CI = 88.2% to 99.9%).Conclusions: The Xpert MTB/RIF Assay is a highly sensitive, specific and rapid method for diagnosing TB which has potential to complement the current reference standard of TB diagnostics and increase its overall sensitivity. Its usefulness in detecting sputum smear and culture negative patients needs further study. Further evaluation in high burden TB and HIV areas under programmatic health care settings to ascertain applicability, cost-effectiveness, robustness and local acceptance are required