Identification of a novel proinsulin-associated SNP and demonstration that proinsulin is unlikely to be a causal factor in subclinical vascular remodelling using Mendelian randomisation

Background and aims Increased proinsulin relative to insulin levels have been associated with subclinical atherosclerosis (measured by carotid intima-media thickness (cIMT)) and are predictive of future cardiovascular disease (CVD), independently of established risk factors. The mechanisms linking proinsulin to atherosclerosis and CVD are unclear. A genome-wide meta-analysis has identified nine loci associated with circulating proinsulin levels. Using proinsulin-associated SNPs, we set out to use a Mendelian randomisation approach to test the hypothesis that proinsulin plays a causal role in subclinical vascular remodelling. Methods We studied the high CVD-risk IMPROVE cohort (n = 3345), which has detailed biochemical phenotyping and repeated, state-of-the-art, high-resolution carotid ultrasound examinations. Genotyping was performed using Illumina Cardio-Metabo and Immuno arrays, which include reported proinsulin-associated loci. Participants with type 2 diabetes (n = 904) were omitted from the analysis. Linear regression was used to identify proinsulin-associated genetic variants. Results We identified a proinsulin locus on chromosome 15 (rs8029765) and replicated it in data from 20,003 additional individuals. An 11-SNP score, including the previously identified and the chromosome 15 proinsulin-associated loci, was significantly and negatively associated with baseline IMTmean and IMTmax (the primary cIMT phenotypes) but not with progression measures. However, MR-Eggers refuted any significant effect of the proinsulin-associated 11-SNP score, and a non-pleiotropic SNP score of three variants (including rs8029765) demonstrated no effect on baseline or progression cIMT measures. Conclusions We identified a novel proinsulin-associated locus and demonstrated that whilst proinsulin levels are associated with cIMT measures, proinsulin per se is unlikely to have a causative effect on cIMT

Síndrome da medula presa: registro de dois casos

Registro de dois casos da síndrome de medula presa nos quais o estabelecimento correto do diagnóstico permitiu adotar conduta terapêutica adequada. Esta consiste na ressecção cirúrgica do filum terminale. São comentados aspectos embriológicos e fisiopatogênicos de interesse à síndrome, bem como são analisadas suas manifestações clínicas principais, os exames complementares que possibilitam o diagnóstico, particularmente a mielografia, e aspectos da terapêutica cirúrgica

Bayesian distances and extinctions for giants observed by Kepler and APOGEE

We present a first determination of distances and extinctions for individual stars in the first release of the APOKASC catalogue, built from the joint efforts of the Apache Point Observatory Galactic Evolution Experiment (APOGEE) and the Kepler Asteroseismic Science Consortium (KASC). Our method takes into account the spectroscopic constraints derived from the APOGEE Stellar Parameters and Chemical Abundances Pipeline, together with the asteroseismic parameters from KASC. These parameters are then employed to estimate intrinsic stellar properties, including absolute magnitudes, using the Bayesian tool PARAM. We then find the distance and extinction that best fit the observed photometry in Sloan Digital Sky Survey (SDSS), 2MASS, and WISE passbands. The first 1989 giants targetted by APOKASC are found at typical distances between 0.5 and 5 kpc, with individual uncertainties of just ∼1.8 per cent. Our extinction estimates are systematically smaller than provided in the Kepler Input Catalogue and by the Schlegel et al. maps. Distances to individual stars in the NGC 6791 and NGC 6819 star clusters agree to within their credible intervals. Comparison with the APOGEE red clump and SAGA catalogues provide another useful check, exhibiting agreement with our measurements to within a few per cent. Overall, present methods seem to provide excellent distance and extinction determinations for the bulk of the APOKASC sample. Approximately one third of the stars present broad or multiple-peaked probability density functions and hence increased uncertainties. Uncertainties are expected to be reduced in future releases of the catalogue, when a larger fraction of the stars will have seismically determined evolutionary status classifications

SDSS-III : massive spectroscopic surveys of the distant universe, the Milk Way, and extra-solar planetary systems

Building on the legacy of the Sloan Digital Sky Survey (SDSS-I and II), SDSS-III is a program of four spectroscopic surveys on three scientific themes: dark energy and cosmological parameters, the history and structure of the Milky Way, and the population of giant planets around other stars. In keeping with SDSS tradition, SDSS-III will provide regular public releases of all its data, beginning with SDSS Data Release 8 (DR8), which was made public in 2011 January and includes SDSS-I and SDSS-II images and spectra reprocessed with the latest pipelines and calibrations produced for the SDSS-III investigations. This paper presents an overview of the four surveys that comprise SDSS-III. The Baryon Oscillation Spectroscopic Survey will measure redshifts of 1.5 million massive galaxies and Lyα forest spectra of 150,000 quasars, using the baryon acoustic oscillation feature of large-scale structure to obtain percent-level determinations of the distance scale and Hubble expansion rate at z < 0.7 and at z ≈ 2.5. SEGUE- 2, an already completed SDSS-III survey that is the continuation of the SDSS-II Sloan Extension for Galactic Understanding and Exploration (SEGUE), measured medium-resolution (R = λ/Δλ ≈ 1800) optical spectra of 118,000 stars in a variety of target categories, probing chemical evolution, stellar kinematics and substructure, and the mass profile of the dark matter halo from the solar neighborhood to distances of 100 kpc. APOGEE, the Apache Point Observatory Galactic Evolution Experiment, will obtain high-resolution (R ≈ 30,000), high signal-to-noise ratio (S/N 100 per resolution element), H-band (1.51μm < λ < 1.70μm) spectra of 105 evolved, late-type stars, measuring separate abundances for ∼15 elements per star and creating the first high-precision spectroscopic survey of all Galactic stellar populations (bulge, bar, disks, halo) with a uniform set of stellar tracers and spectral diagnostics. The Multi-object APO Radial Velocity Exoplanet Large-area Survey (MARVELS) will monitor radial velocities of more than 8000 FGK stars with the sensitivity and cadence (10–40ms−1, ∼24 visits per star) needed to detect giant planets with periods up to two years, providing an unprecedented data set for understanding the formation and dynamical evolution of giant planet systems. As of 2011 January, SDSS-III has obtained spectra of more than 240,000 galaxies, 29,000 z 2.2 quasars, and 140,000 stars, including 74,000 velocity measurements of 2580 stars for MARVELS