FSI simulations for explosions very near reinforced concrete structures

The analysis of explosives in contact or very near to reinforced concrete (RC) structures is an important aspect in the design of protective structures and vulnerability assessments. Although this remains a topic of high importance for defence, a more widespread interest has developed as civilian structures become the targets of terrorism. This type of assessment requires a robust simulation method for coupled fluid-structural interactions (FSI) which can handle the explosive detonation, air blast propagation, structural deformation, and damage evolution. This paper describes the application of a loose-coupling method which combines the FEFLO CFD code and SAIC’s CSD code for 3D numerical simulations of unconfined and semi-confined explosions near RC structures. This approach takes advantage of the unstructured tetrahedral mesh for the CFD and an embedded method for CSD structures inside the fluid domain. Comparisons of simulations with experiment provide validation, but also reveal some weaknesses of the method. A good agreement between simulation and experiment is found with moderate explosive loading. However, a severe explosive loading with confinement results in extensive damage to the structure which is difficult to reproduce in simulations

Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus

A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10-20), ER-negative BC (P=1.1 × 10-13), BRCA1-associated BC (P=7.7 × 10-16) and triple negative BC (P-diff=2 × 10-5). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10-3) and ABHD8 (P<2 × 10-3). Chromosome conformation capture identifies interactions between four candidate SNPs and ABHD8, and luciferase assays indicate six risk alleles increased transactivation of the ADHD8 promoter. Targeted deletion of a region containing risk SNP rs56069439 in a putative enhancer induces ANKLE1 downregulation; and mRNA stability assays indicate functional effects for an ANKLE1 3′-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

A new polygenic score for refractive error improves detection of children at risk of high myopia but not the prediction of those at risk of myopic macular degeneration

Background High myopia (HM), defined as a spherical equivalent refractive error (SER) ≤ −6.00 diopters (D), is a leading cause of sight impairment, through myopic macular degeneration (MMD). We aimed to derive an improved polygenic score (PGS) for predicting children at risk of HM and to test if a PGS is predictive of MMD after accounting for SER. Methods The PGS was derived from genome-wide association studies in participants of UK Biobank, CREAM Consortium, and Genetic Epidemiology Research on Adult Health and Aging. MMD severity was quantified by a deep learning algorithm. Prediction of HM was quantified as the area under the receiver operating curve (AUROC). Prediction of severe MMD was assessed by logistic regression. Findings In independent samples of European, African, South Asian and East Asian ancestry, the PGS explained 19% (95% confidence interval 17–21%), 2% (1–3%), 8% (7–10%) and 6% (3–9%) of the variation in SER, respectively. The AUROC for HM in these samples was 0.78 (0.75–0.81), 0.58 (0.53–0.64), 0.71 (0.69–0.74) and 0.67 (0.62–0.72), respectively. The PGS was not associated with the risk of MMD after accounting for SER: OR = 1.07 (0.92–1.24). Interpretation Performance of the PGS approached the level required for clinical utility in Europeans but not in other ancestries. A PGS for refractive error was not predictive of MMD risk once SER was accounted fo

Modeling Atmospheric Lines by the Exoplanet Community (MALBEC) Version 1.0: A CUISINES Radiative Transfer Intercomparison Project

Radiative transfer (RT) models are critical in the interpretation of exoplanetary spectra, in simulating exoplanet climates, and when designing the specifications of future flagship observatories. However, most models differ in methodologies and input data, which can lead to significantly different spectra. In this paper, we present the experimental protocol of the Modeling Atmospheric Lines By the Exoplanet Community (MALBEC) project. MALBEC is an exoplanet model intercomparison project that belongs to the Climates Using Interactive Suites of Intercomparisons Nested for Exoplanet Studies framework, which aims to provide the exoplanet community with a large and diverse set of comparison and validation of models. The proposed protocol tests include a large set of initial participating RT models, a broad range of atmospheres (from hot Jupiters to temperate terrestrials), and several observation geometries, which would allow us to quantify and compare the differences between different RT models used by the exoplanetary community. Two types of tests are proposed: transit spectroscopy and direct imaging modeling, with results from the proposed tests to be published in dedicated follow-up papers. To encourage the community to join this comparison effort and as an example, we present simulation results for one specific transit case (GJ-1214 b), in which we find notable differences in how the various codes handle the discretization of the atmospheres (e.g., sub-layering), the treatment of molecular opacities (e.g., correlated-k, line-by-line) and the default spectroscopic repositories generally used by each model (e.g., HITRAN, HITEMP, ExoMol).ISSN:2632-333

Modeling Atmospheric Lines by the Exoplanet Community (MALBEC) Version 1.0:A CUISINES Radiative Transfer Intercomparison Project

Radiative transfer (RT) models are critical in the interpretation of exoplanetary spectra, in simulating exoplanet climates, and when designing the specifications of future flagship observatories. However, most models differ in methodologies and input data, which can lead to significantly different spectra. In this paper, we present the experimental protocol of the Modeling Atmospheric Lines By the Exoplanet Community (MALBEC) project. MALBEC is an exoplanet model intercomparison project that belongs to the Climates Using Interactive Suites of Intercomparisons Nested for Exoplanet Studies framework, which aims to provide the exoplanet community with a large and diverse set of comparison and validation of models. The proposed protocol tests include a large set of initial participating RT models, a broad range of atmospheres (from hot Jupiters to temperate terrestrials), and several observation geometries, which would allow us to quantify and compare the differences between different RT models used by the exoplanetary community. Two types of tests are proposed: transit spectroscopy and direct imaging modeling, with results from the proposed tests to be published in dedicated follow-up papers. To encourage the community to join this comparison effort and as an example, we present simulation results for one specific transit case (GJ-1214 b), in which we find notable differences in how the various codes handle the discretization of the atmospheres (e.g., sub-layering), the treatment of molecular opacities (e.g., correlated-k, line-by-line) and the default spectroscopic repositories generally used by each model (e.g., HITRAN, HITEMP, ExoMol).</p