The EU Center of Excellence for Exascale in Solid Earth (ChEESE): Implementation, results, and roadmap for the second phase

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The Changing Landscape for Stroke\ua0Prevention in AF: Findings From the GLORIA-AF Registry Phase 2

Background GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non\u2013vitamin K antagonist oral anticoagulant (NOAC), became available. Objectives This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase 1. Methods During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients\u2019 baseline characteristics. Atrial fibrillation disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Results Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age  6575 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score  652; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc = 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N = 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and antiplatelet drugs, respectively; 7.5% received no antithrombotic treatment. NOAC use was less common in Asia (27.7%), where 27.5% of patients received VKA, 25.0% antiplatelet drugs, and 19.8% no antithrombotic treatment. Conclusions The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in Asia and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701

SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a variety of tissues

Variability in SARS-CoV-2 susceptibility and COVID-19 disease severity between individuals is partly due to genetic factors. Here, we identify 4 genomic loci with suggestive associations for SARS-CoV-2 susceptibility and 19 for COVID-19 disease severity. Four of these 23 loci likely have an ethnicity-specific component. Genome-wide association study (GWAS) signals in 11 loci colocalize with expression quantitative trait loci (eQTLs) associated with the expression of 20 genes in 62 tissues/cell types (range: 1:43 tissues/gene), including lung, brain, heart, muscle, and skin as well as the digestive system and immune system. We perform genetic fine mapping to compute 99% credible SNP sets, which identify 10 GWAS loci that have eight or fewer SNPs in the credible set, including three loci with one single likely causal SNP. Our study suggests that the diverse symptoms and disease severity of COVID-19 observed between individuals is associated with variants across the genome, affecting gene expression levels in a wide variety of tissue types

A Solve-RD ClinVar-based reanalysis of 1522 index cases from ERN-ITHACA reveals common pitfalls and misinterpretations in exome sequencing

Purpose Within the Solve-RD project (https://solve-rd.eu/), the European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies aimed to investigate whether a reanalysis of exomes from unsolved cases based on ClinVar annotations could establish additional diagnoses. We present the results of the “ClinVar low-hanging fruit” reanalysis, reasons for the failure of previous analyses, and lessons learned. Methods Data from the first 3576 exomes (1522 probands and 2054 relatives) collected from European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies was reanalyzed by the Solve-RD consortium by evaluating for the presence of single-nucleotide variant, and small insertions and deletions already reported as (likely) pathogenic in ClinVar. Variants were filtered according to frequency, genotype, and mode of inheritance and reinterpreted. Results We identified causal variants in 59 cases (3.9%), 50 of them also raised by other approaches and 9 leading to new diagnoses, highlighting interpretation challenges: variants in genes not known to be involved in human disease at the time of the first analysis, misleading genotypes, or variants undetected by local pipelines (variants in off-target regions, low quality filters, low allelic balance, or high frequency). Conclusion The “ClinVar low-hanging fruit” analysis represents an effective, fast, and easy approach to recover causal variants from exome sequencing data, herewith contributing to the reduction of the diagnostic deadlock

A first update on mapping the human genetic architecture of COVID-19

peer reviewe

Des formations aux professions dans un secteur artisanal (la boulangerie)

Malgré la diminution du nombre de boulangeries artisanales, résultat de l industrialisation du secteur, la boulangerie artisanale reste encore l activité dominante. Ce maintien paradoxal résulte de l aide de groupes industriels de meunerie à l origine de marques de farines et d enseignes commerciales, et de la création de nouvelles formations au métier qui intègrent des personnes en reconversion compensant le manque de mains d œuvre et de repreneurs traditionnels ceci, dans un contexte français de valorisation de l artisanat comme créateur d emploi et garantie de qualité. L étude monographique de la boulangerie, à Rouen, principal siège de la formation à la boulangerie, et à Marseille, d où est parti le premier réseau d enseignes meunières, permet de mieux comprendre les divisions actuelles du monde de la boulangerie en France, les caractéristiques des boulangers, leurs manières d exercer cette activité, en couple ou non, et les répercussions de cette activité sur leur vie familialeIn spite of the reduction in the number of artisanal bakeries, result of the industrialization of the sector, artisanal bakery remains still the dominant activity. This paradoxical maintenance results from the assistance of industrial groups of flour-milling at the origin of marks from flours and commercial signs, and creation of new formations to the trade which integrate people in reconversion compensating for the lack of labour and transferees traditional - this, in a French context of valorisation of the craft industry as creator of use and guarantee of quality. The monographic study of bakery, in Rouen, principal seat of the formation to bakery, and Marseilles, from where the first network left signs millers, makes it possible to better include/understand current divisions of the world of bakery in France, the characteristics of the bakers, their manners of carrying on this activity, couples some or not, and the repercussions of this activity over their family lifeST DENIS-BU PARIS8 (930662101) / SudocSudocFranceF

Rupture dynamics along bimaterial interfaces: a parametric study of the shear-normal traction coupling

Earthquake ruptures often develop along faults separating materials with dissimilar elastic properties. Due to the broken symmetry, the propagation of the rupture along the bimaterial interface is driven by the coupling between interfacial sliding and normal traction pertur- bations. We numerically investigate in-plane rupture growth along a planar interface, under slip weakening friction, separating two dissimilar isotropic linearly elastic half-spaces, and we perform a parametric study of the classical Prakash–Clifton regularization, for different material contrasts. In particular the mesh-dependence and the regularization-dependence of the numerical solutions are analysed in this parameter space. When the regularization involves a slip-rate dependent relaxation time, a characteristic sliding distance is identified below which numerical solutions no longer depend on the regularization parameter, that is, they are phys- ically well-posed solutions. Such regularization provides an adaptive high-frequency filter of the slip-induced normal traction perturbations, following the dynamic shrinking of the dissi- pation zone during the acceleration phase. In contrast, a regularization involving a constant relaxation time leads to numerical solutions that always depend on the regularization parameter since it fails in adapting to the shrinking of the process zone. Dynamic regularization is further investigated using a non-local regularization based on a relaxation time that depends on the dynamic length of the dissipation zone. Such reformulation is shown to provide similar results as the dynamic timescale regularization proposed by Prakash–Clifton when the slip rate is replaced by the maximum slip rate along the sliding interface. This leads to the identification of a dissipative length scale associated with the coupling between interfacial sliding and nor- mal traction perturbations, together with a scaling law between the maximum slip rate and the dynamic size of the process zone during the rupture propagation. Dynamic timescale reg- ularization provides mesh-independent and physically well-posed numerical solutions during the acceleration phase towards an asymptotic speed. When generalized Rayleigh wave does not exist, numerical solutions are shown to tend towards an asymptotic velocity higher than the slowest shear wave speed. When the generalized Rayleigh wave speed exists, numerical solutions tend towards this velocity becoming noisier and noisier as the rupture progresses. In this regime regularization dependent, unstable finite-size pulses may be generated.Published48–672T. Sorgente SismicaJCR Journa