Several studies have reported that the cholesteryl ester transfer protein (CETP) TaqIB gene polymorphism is associated with HDL cholesterol (HDL-C) levels and the risk of coronary artery disease ...(CAD), but the results are inconsistent. In addition, an interaction has been implicated between this genetic variant and pravastatin treatment, but this has not been confirmed.
A meta-analysis was performed on individual patient data from 7 large, population-based studies (each >500 individuals) and 3 randomized, placebo-controlled, pravastatin trials. Linear and logistic regression models were used to assess the relation between TaqIB genotype and HDL-C levels and CAD risk. After adjustment for study, age, sex, smoking, body mass index (BMI), diabetes, LDL-C, use of alcohol, and prevalence of CAD, TaqIB genotype exhibited a highly significant association with HDL-C levels, such that B2B2 individuals had 0.11 mmol/L (0.10 to 0.12, P<0.0001) higher HDL-C levels than did B1B1 individuals. Second, after adjustment for study, sex, age, smoking, BMI, diabetes, systolic blood pressure, LDL-C, and use of alcohol, TaqIB genotype was significantly associated with the risk of CAD (odds ratio=0.78 0.66 to 0.93) in B2B2 individuals compared with B1B1 individuals (P for linearity=0.008). Additional adjustment for HDL-C levels rendered a loss of statistical significance (P=0.4). Last, no pharmacogenetic interaction between TaqIB genotype and pravastatin treatment could be demonstrated.
The CETP TaqIB variant is firmly associated with HDL-C plasma levels and as a result, with the risk of CAD. Importantly, this CETP variant does not influence the response to pravastatin therapy.
Two recent reports have highlighted ANK3 as a susceptibility gene for bipolar disorder (BD). We first reported association between BD and the ANK3 marker rs9804190 in a genome-wide association study ...(GWAS) of two independent samples (Baum et al., 2008). Subsequently, a meta-analysis of GWAS data based on samples from the US and the UK reported association with a different ANK3 marker, rs10994336 (Ferreira et al., 2008). The markers lie about 340 kb apart in the gene. Here, we test both markers in additional samples and characterize the contribution of each marker to BD risk. Our previously reported findings at rs9804190, which had been based on DNA pooling, were confirmed by individual genotyping in the National Institute of Mental Health (NIMH) waves 1-4 (P=0.05; odds ratio (OR)=1.24) and German (P=0.0006; OR=1.34) samples. This association was replicated in an independent US sample known as NIMH wave 5 (466 cases, 212 controls; P=0.017; OR=1.38). A random-effects meta-analysis of all three samples was significant (P=3 x 10(-6); OR=1.32), with no heterogeneity. Individual genotyping of rs10994336 revealed a significant association in the German sample (P=0.0001; OR=1.70), and similar ORs in the NIMH 1-4 and NIMH 5 samples that were not significant at the P<0.05 level. Meta-analysis of all three samples supported an association with rs10994336 (P=1.7 x 10(-5); OR=1.54), again with no heterogeneity. There was little linkage disequilibrium between the two markers. Further analysis suggested that each marker contributed independently to BD, with no significant marker x marker interaction. Our findings strongly support ANK3 as a BD susceptibility gene and suggest true allelic heterogeneity.
The Large Binocular Telescope Interferometer (LBTI) enables nulling interferometric observations across the N band (8 to 13 m) to suppress a star's bright light and probe for faint circumstellar ...emission. We present and statistically analyze the results from the LBTI/Hunt for Observable Signatures of Terrestrial Systems survey for exozodiacal dust. By comparing our measurements to model predictions based on the solar zodiacal dust in the N band, we estimate a 1 median sensitivity of 23 zodis times the solar system dust surface density in its habitable zone (HZ; 23 zodis) for early-type stars and 48 zodis for Sun-like stars, where 1 zodi is the surface density of HZ dust in the solar system. Of the 38 stars observed, 10 show significant excess. A clear correlation of our detections with the presence of cold dust in the systems was found, but none with the stellar spectral type or age. The majority of Sun-like stars have relatively low HZ dust levels (best-fit median: 3 zodis, 1 upper limit: 9 zodis, 95% confidence: 27 zodis based on our N band measurements), while ∼20% are significantly more dusty. The solar system's HZ dust content is consistent with being typical. Our median HZ dust level would not be a major limitation to the direct imaging search for Earth-like exoplanets, but more precise constraints are still required, in particular to evaluate the impact of exozodiacal dust for the spectroscopic characterization of imaged exo-Earth candidates.
We report a B-mode power spectrum measurement from the cosmic microwave background (CMB) polarization anisotropy observations made using the SPTpol instrument on the South Pole Telescope. This work ...uses 500 deg2 of SPTpol data, a five-fold increase over the last SPTpol B-mode release. As a result, the bandpower uncertainties have been reduced by more than a factor of two, and the measurement extends to lower multipoles: 52 < ℓ < 2301 . Data from both 95 and 150 GHz are used, allowing for three cross-spectra: 95 GHz × 95 GHz , 95 GHz × 150 GHz , and 150 GHz × 150 GHz . B -mode power is detected at very high significance; we find P ( B B < 0 ) = 5.8 × 10−71, corresponding to a 18.1σ detection of power. With a prior on the galactic dust from Planck, WMAP and BICEP2/Keck observations, the SPTpol B-mode data can be used to set an upper limit on the tensor-to-scalar ratio, r < 0.44 at 95% confidence (the expected 1σ constraint on r given the measurement uncertainties is 0.22). We find the measured B-mode power is consistent with the Planck best-fit Λ CDM model predictions. Scaling the predicted lensing B-mode power in this model by a factor Alens, the data prefer Alens = 1.17 ± 0.13 . These data are currently the most precise measurements of B-mode power at ℓ > 320.
We present a catalog of emissive point sources detected in the SPT-SZ survey, a contiguous 2530 square degree area surveyed with the South Pole Telescope (SPT) from 2008-2011 in three bands centered ...at 95, 150, and 220 GHz. The catalog contains 4845 sources measured at a significance of 4.5 or greater in at least one band, corresponding to detections above approximately 9.8, 5.8, and 20.4 mJy in 95, 150, and 220 GHz, respectively. The spectral behavior in the SPT bands is used for source classification into two populations based on the underlying physical mechanisms of compact, emissive sources that are bright at millimeter wavelengths: synchrotron radiation from active galactic nuclei and thermal emission from dust. The latter population includes a component of high-redshift sources often referred to as submillimeter galaxies (SMGs). In the relatively bright flux ranges probed by the survey, these sources are expected to be magnified by strong gravitational lensing. The survey also contains sources consistent with protoclusters, groups of dusty galaxies at high redshift undergoing collapse. We cross-match the SPT-SZ catalog with external catalogs at radio, infrared, and X-ray wavelengths and identify available redshift information. The catalog splits into 3980 synchrotron-dominated and 865 dust-dominated sources, and we determine a list of 506 SMGs. Ten sources in the catalog are identified as stars. We calculate number counts for the full catalog, and synchrotron and dusty components, using a bootstrap method and compare our measured counts with models. This paper represents the third and final catalog of point sources in the SPT-SZ survey.
We compare the properties of a number of encapsulant and soft backsheet materials that are important for photovoltaic (PV) module packaging. These properties include moisture transport and ...interfacial adhesion as a function of accelerated exposure to damp heat. Various cleaning and priming methods were studied for improving adhesion to glass and polymer surfaces. Barrier coatings prepared by industry and at NREL have been found to promote adhesion and provide varying levels of moisture-ingress protection. Plasma pre-etch of polyethylene terephthalate (PET) before barrier deposition reduces adhesion strength and moisture barrier properties. Resistance to cracking during lamination and peeling during test are investigated. The relative effectiveness of various combined packaging strategies to protect PV devices has been studied using 80-nm-thick aluminum films deposited onto 10
cm×10
cm glass substrates. Glass/ethylene vinyl acetate (EVA)/aluminized-glass laminate constructions were found to trap harmful compounds that catalyzed moisture-driven corrosion of Al. Constructions with breathable backsheets allow higher rates of moisture ingress, but also allow egress of deleterious substances, thereby reducing corrosion.
Strong-gravitational lens systems with quadruply imaged quasars (quads) are unique probes to address several fundamental problems in cosmology and astrophysics. Although they are intrinsically very ...rare, ongoing and planned wide-field deep-sky surveys are set to discover thousands of such systems in the next decade. It is thus paramount to devise a general framework to model strong-lens systems to cope with this large influx without being limited by expert investigator time. We propose such a general modelling framework (implemented with the publicly available software lenstronomy) and apply it to uniformly model three-band Hubble Space Telescope Wide Field Camera 3 images of 13 quads. This is the largest uniformly modelled sample of quads to date and paves the way for a variety of studies. To illustrate the scientific content of the sample, we investigate the alignment between the mass and light distribution in the deflectors. The position angles of these distributions are well-aligned, except when there is strong external shear. However, we find no correlation between the ellipticity of the light and mass distributions. We also show that the observed flux-ratios between the images depart significantly from the predictions of simple smooth models. The departures are strongest in the bluest band, consistent with microlensing being the dominant cause in addition to millilensing. Future papers will exploit this rich data set in combination with ground-based spectroscopy and time delays to determine quantities such as the Hubble constant, the free streaming length of dark matter, and the normalization of the initial stellar mass function.
Given that cardiovascular safety liabilities remain a major cause of drug attrition during preclinical and clinical development, adverse drug reactions, and post‐approval withdrawal of medicines, the ...Medical Research Council Centre for Drug Safety Science hosted a workshop to discuss current challenges in determining, understanding and addressing ‘Cardiovascular Toxicity of Medicines’. This article summarizes the key discussions from the workshop that aimed to address three major questions: (i) what are the key cardiovascular safety liabilities in drug discovery, drug development and clinical practice? (ii) how good are preclinical and clinical strategies for detecting cardiovascular liabilities? and (iii) do we have a mechanistic understanding of these liabilities? It was concluded that in order to understand, address and ultimately reduce cardiovascular safety liabilities of new therapeutic agents there is an urgent need to:
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Fully characterize the incidence, prevalence and impact of drug‐induced cardiovascular issues at all stages of the drug development process.
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Ascertain the predictive value of existing non‐clinical models and assays towards the clinical outcome.
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Understand the mechanistic basis of cardiovascular liabilities; by addressing areas where it is currently not possible to predict clinical outcome based on preclinical safety data.
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Provide scientists in all disciplines with additional skills to enable them to better integrate preclinical and clinical data and to better understand the biological and clinical significance of observed changes.
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Develop more appropriate, highly relevant and predictive tools and assays to identify and wherever feasible to eliminate cardiovascular safety liabilities from molecules and wherever appropriate to develop clinically relevant and reliable safety biomarkers.
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