Genetic loci on chromosome 5 are associated with circulating levels of interleukin-5 and eosinophil count in a European population with high risk for cardiovascular disease

IL-5 is a Th2 cytokine which activates eosinophils and is suggested to have an atheroprotective role. Genetic variants in the IL5 locus have been associated with increased risk of CAD and ischemic stroke. In this study we aimed to identify genetic variants associated with IL-5 concentrations and apply a Mendelian randomisation approach to assess IL-5 levels for causal effect on intima-media thickness in a European population at high risk of coronary artery disease. We analysed SNPs within robustly associated candidate loci for immune, inflammatory, metabolic and cardiovascular traits. We identified 2 genetic loci for IL-5 levels (chromosome 5, rs56183820, BETA = 0.11, P = 6.73E−5 and chromosome 14, rs4902762, BETA = 0.12, P = 5.76E−6) and one for eosinophil count (rs72797327, BETA = −0.10, P = 1.41E−6). Both chromosome 5 loci were in the vicinity of the IL5 gene, however the association with IL-5 levels failed to replicate in a meta-analysis of 2 independent cohorts (rs56183820, BETA = 0.04, P = 0.2763, I2 = 24, I2 − P = 0.2516). No significant associations were observed between SNPs associated with IL-5 levels or eosinophil count and IMT measures. Expression quantitative trait analyses indicate effects of the IL-5 and eosinophil-associated SNPs on RAD50 mRNA expression levels (rs12652920 (r2 = 0.93 with rs56183820) BETA = −0.10, P = 8.64E−6 and rs11739623 (r2 = 0.96 with rs72797327) BETA = −0.23, P = 1.74E−29, respectively). Our data do not support a role for IL-5 levels and eosinophil count in intima-media thickness, however SNPs associated with IL-5 and eosinophils might influence stability of the atherosclerotic plaque via modulation of RAD50 levels

Tetraspanin Tspan9 regulates platelet collagen receptor GPVI lateral diffusion and activation

The tetraspanins are a superfamily of four-transmembrane proteins, which regulate the trafficking, lateral diffusion and clustering of the transmembrane proteins with which they interact. We have previously shown that tetraspanin Tspan9 is expressed on platelets. Here we have characterised gene-trap mice lacking Tspan9. The mice were viable with normal platelet numbers and size. Tspan9-deficient platelets were specifically defective in aggregation and secretion induced by the platelet collagen receptor GPVI, despite normal surface GPVI expression levels. A GPVI activation defect was suggested by partially impaired GPVI-induced protein tyrosine phosphorylation. In mechanistic experiments, Tspan9 and GPVI co-immunoprecipitated and co-localised, but super-resolution imaging revealed no defects in collagen-induced GPVI clustering on Tspan9-deficient platelets. However, single particle tracking using total internal reflection fluorescence microscopy showed that GPVI lateral diffusion was reduced by approximately 50% in the absence of Tspan9. Therefore, Tspan9 plays a fine-tuning role in platelet activation by regulating GPVI membrane dynamics

Evaluating the role of quality assessment of primary studies in systematic reviews of cancer practice guidelines

BACKGROUND: The purpose of this study was to evaluate the role of study quality assessment of primary studies in cancer practice guidelines. METHODS: Reliable and valid study quality assessment scales were sought and applied to published reports of trials included in systematic reviews of cancer guidelines. Sensitivity analyses were performed to evaluate the relationship between quality scores and pooled odds ratios (OR) for mortality and need for blood transfusion. RESULTS: Results found that that whether trials were classified as high or low quality depended on the scale used to assess them. Although the results of the sensitivity analyses found some variation in the ORs observed, the confidence intervals (CIs) of the pooled effects from each of the analyses of high quality trials overlapped with the CI of the pooled odds of all trials. Quality score was not predictive of pooled ORs studied here. CONCLUSIONS: Had sensitivity analyses based on study quality been conducted prospectively, it is highly unlikely that different conclusions would have been found or that different clinical recommendations would have emerged in the guidelines

The state of the Martian climate

60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes

THE ISSUE. Traffic, Health, Environment; Intelligent Solutions Sustaining Urban Economies.

THE ISSUE is a project within the Regions of Knowledge scheme funded through the European Commission’s Seventh Framework Programme. THE ISSUE focuses on Traffic, Health and Environment to achieve Intelligent Solutions for Sustaining Urban Economies by bringing together innovative research-driven clusters to coordinate European research and technology development in six areas. These areas are Intelligent Transportation Systems; transport impacts on urban mobility; transport greening; intermodal regional transport; safety and security of citizens; and associated economic, health and environmental impacts. THE ISSUE project particularly addresses the use of space technologies from satellite remote sensing and navigation, as well as GIS and computer intelligence technologies in transport-related sectors. This paper looks into the general presentation of the project and the first results.EU FP7 Regions Of Knowledge projec

Intelligent Solutions Sustaining Urban Economies – Master Classes case study

This is an output from the FP7 Regions of Knowledge project THE-ISSUE. This project is developing an EU network in the field of Intelligent Transport Systems that deliver on multiple policy objectives, Transport Health & the Environment. More can be found at www.theissue.euTHE ISSUE is a project within the Regions of Knowledge scheme funded through the European Commission’s Seventh Framework Programme. THE ISSUE focuses on traffic, health and the environment to achieve intelligent solutions for sustaining urban economies by bringing together innovative research-driven clusters to coordinate European research and technology development in six areas. These comprise ITS; transport impacts on urban mobility; transport greening; intermodal regional transport; safety and security of citizens; and associated economic, health and environmental impacts. THE ISSUE project particularly addresses the use of space technologies from satellite remote sensing and navigation, as well as GIS and computer intelligence technologies in transport-related sectors. This paper specifically looks into the planned Master Classes program. THE ISSUE project comprises research clusters from the East Midlands Region in the UK, the Midi-Pyrenees and Aquitaine Regions in France, the Molise Region in Italy and the Mazovia Region in Poland. Each region has set up a three-way partnership between regional authorities, academic partners, and industry contributors working to draw together the industry and academic strengths in the regions and connect the research with the needs of managing traffic, transport, and air quality that the regional bodies are responsible for. The three-year project is supporting scientists, engineers and development agencies from the different regions to work together, using the latest space and information technologies, to develop more effective methods of easing road congestion and improving the urban environment. As part of THE ISSUE project "Master Class" knowledge exchange programmes will be developed using material from the earlier review of applicable technology and expertise within the THE ISSUE consortium. Two variants will be developed, one focussing on senior management and policy/strategy makers and the other with a focus on technical awareness and implementation. The "Master Classes" will be trailed and delivered through workshops for core partners and associates. The case studies, which will be part of the Master Classes, will present information on how cartography, GPS&GIS database applications, navigation and remote sensing are used in urban transport, health and air quality related data. The project is bringing together scientists, engineers, development agencies and bodies responsible for managing traffic, transport and air quality in four European regional clusters using advanced space and information technologies, to develop the most effective methods of easing urban congestion and improving the impact of transport on the local economy, urban environment, climate change and the health of citizens. These Master Classes materials will contribute for the exchange of knowledge and expertise in sustainable traffic solutions between academic, business and public sector partners within and across the five European regions.EU FP

The Death Throes of a Stripped Massive Star: An Eruptive Mass-Loss History Encoded in Pre-Explosion Emission, a Rapidly Rising Luminous Transient, and a Broad-Lined Ic Supernova SN2018gep

We present detailed observations of ZTF18abukavn (SN2018gep), discovered in high-cadence data from the Zwicky Transient Facility as a rapidly rising (1.3 mag/hr) and luminous (M_(g,peak) = −20 mag) transient. It is spectroscopically classified as a broad-lined stripped-envelope supernova (Ic-BL SN). The rapid rise to peak bolometric luminosity and blue colors at peak (t_(rise)∼0.5-3 days, L_(bol)≳3×10^(44) erg sec^(−1), g−r = −0.3) resemble the high-redshift Ic-BL iPTF16asu, as well as several other unclassified fast transients. The early discovery of SN2018gep (within an hour of shock breakout) enabled an intensive spectroscopic campaign, including the highest-temperature (T_(eff) ≳ 40,000K) spectra of a stripped-envelope SN. A retrospective search revealed luminous (M_g ∼ M_r ≈ −14mag) emission in the days to weeks before explosion, the first definitive detection of precursor emission for a Ic-BL. We find a limit on the isotropic gamma-ray energy release E_(γ,iso) < 4.9×10^(48) erg, a limit on X-ray emission L_X < 10^(40) erg sec^(−1), and a limit on radio emission νL_ν ≲ 10^(37) erg sec^(−1). Taken together, we find that the data are best explained by shock breakout in a massive shell of dense circumstellar material (0.02 M⊙) at large radii (3×10^(14)cm) that was ejected in eruptive pre-explosion mass-loss episodes