Simulations magnétohydrodynamiques en régime idéal

Cette thèse s’intéresse à la modélisation magnétohydrodynamique des écoulements de fluides conducteurs d’électricité multi-échelles en mettant l’emphase sur deux applications particulières de la physique solaire: la modélisation des mécanismes des variations de l’irradiance via la simulation de la dynamo globale et la reconnexion magnétique. Les variations de l’irradiance sur les périodes des jours, des mois et du cycle solaire de 11 ans sont très bien expliquées par le passage des régions actives à la surface du Soleil. Cependant, l’origine ultime des variations se déroulant sur les périodes décadales et multi-décadales demeure un sujet controversé. En particulier, une certaine école de pensée affirme qu’une partie de ces variations à long-terme doit provenir d’une modulation de la structure thermodynamique globale de l’étoile, et que les seuls effets de surface sont incapables d’expliquer la totalité des fluctuations. Nous présentons une simulation globale de la convection solaire produisant un cycle magnétique similaire en plusieurs aspects à celui du Soleil, dans laquelle le flux thermique convectif varie en phase avec l’ ́energie magnétique. La corrélation positive entre le flux convectif et l’énergie magnétique supporte donc l’idée qu’une modulation de la structure thermodynamique puisse contribuer aux variations à long-terme de l’irradiance. Nous analysons cette simulation dans le but d’identifier le mécanisme physique responsable de la corrélation en question et pour prédire de potentiels effets observationnels résultant de la modulation structurelle. La reconnexion magnétique est au coeur du mécanisme de plusieurs phénomènes de la physique solaire dont les éruptions et les éjections de masse, et pourrait expliquer les températures extrêmes caractérisant la couronne. Une correction aux trajectoires du schéma semi-Lagrangien classique est présentée, qui est basée sur la solution à une équation aux dérivées partielles nonlinéaire du second ordre: l’équation de Monge-Ampère. Celle-ci prévient l’intersection des trajectoires et assure la stabilité numérique des simulations de reconnexion magnétique pour un cas de magnéto-fluide relaxant vers un état d’équilibre.This thesis concentrates on magnetohydrodynamical modeling of multiscale conducting fluids with emphasis on two particular applications of solar physics: the modeling of solar irradiance mechanisms via the numerical simulation of the global dynamo and of magnetic reconnection. Irradiance variations on the time scales of days, months, and of the 11 yr solar cycle are very well described by changes in the surface coverage by active regions. However, the ultimate origin of the long-term decadal and multi-decadal variations is still a matter of debate. In particular, one school of thought argues that a global modulation of the solar thermodynamic structure by magnetic activity is required to account for part of the long-term variations, in addition to pure surface effects. We hereby present a global simulation of solar convection producing solar-like magnetic cycles, in which the convective heat flux varies in phase with magnetic energy. We analyze the simulation to uncover the physical mechanism causing the positive correlation and to predict potential observational signatures resulting from the flux modulation. Magnetic reconnection is central to many solar physics phenomena including flares and coronal mass ejections, and could also provide an explanation for the extreme temperatures (T ∼ 106K) that charaterize the coronna. A trajectory correction to the classical semi-Lagrangian scheme is presented, which is based on the solution to a second-order nonlinear partial differential equation: the Monge-Amp`ere equation. Using the correction prevents the intersection of fluid trajectories and assures the physical realizability of magnetic reconnection simulations for the case of a magneto- fluid relaxing toward an equilibrium state

Pharmacogenomics of the efficacy and safety of Colchicine in COLCOT

© 2021 The Authors. Circulation: Genomic and Precision Medicine is published on behalf of the American Heart Association, Inc., by Wolters Kluwer Health, Inc. This is an open access article under the terms of the Creative Commons Attribution Non-Commercial License, which permits use, distribution, and reproduction in any medium, provided that the original work is properly cited and is not used for commercial purposes.Background: The randomized, placebo-controlled COLCOT (Colchicine Cardiovascular Outcomes Trial) has shown the benefits of colchicine 0.5 mg daily to lower the rate of ischemic cardiovascular events in patients with a recent myocardial infarction. Here, we conducted a post hoc pharmacogenomic study of COLCOT with the aim to identify genetic predictors of the efficacy and safety of treatment with colchicine. Methods: There were 1522 participants of European ancestry from the COLCOT trial available for the pharmacogenomic study of COLCOT trial. The pharmacogenomic study's primary cardiovascular end point was defined as for the main trial, as time to first occurrence of cardiovascular death, resuscitated cardiac arrest, myocardial infarction, stroke, or urgent hospitalization for angina requiring coronary revascularization. The safety end point was time to the first report of gastrointestinal events. Patients' DNA was genotyped using the Illumina Global Screening array followed by imputation. We performed a genome-wide association study in colchicine-treated patients. Results: None of the genetic variants passed the genome-wide association study significance threshold for the primary cardiovascular end point conducted in 702 patients in the colchicine arm who were compliant to medication. The genome-wide association study for gastrointestinal events was conducted in all 767 patients in the colchicine arm and found 2 significant association signals, one with lead variant rs6916345 (hazard ratio, 1.89 [95% CI, 1.52-2.35], P=7.41×10-9) in a locus which colocalizes with Crohn disease, and one with lead variant rs74795203 (hazard ratio, 2.51 [95% CI, 1.82-3.47]; P=2.70×10-8), an intronic variant in gene SEPHS1. The interaction terms between the genetic variants and treatment with colchicine versus placebo were significant. Conclusions: We found 2 genomic regions associated with gastrointestinal events in patients treated with colchicine. Those findings will benefit from replication to confirm that some patients may have genetic predispositions to lower tolerability of treatment with colchicine.info:eu-repo/semantics/publishedVersio

Analysis of shared common genetic risk between amyotrophic lateral sclerosis and epilepsy

Because hyper-excitability has been shown to be a shared pathophysiological mechanism, we used the latest and largest genome-wide studies in amyotrophic lateral sclerosis (n = 36,052) and epilepsy (n = 38,349) to determine genetic overlap between these conditions. First, we showed no significant genetic correlation, also when binned on minor allele frequency. Second, we confirmed the absence of polygenic overlap using genomic risk score analysis. Finally, we did not identify pleiotropic variants in meta-analyses of the 2 diseases. Our findings indicate that amyotrophic lateral sclerosis and epilepsy do not share common genetic risk, showing that hyper-excitability in both disorders has distinct origins

Analysis of shared heritability in common disorders of the brain

ience, this issue p. eaap8757 Structured Abstract INTRODUCTION Brain disorders may exhibit shared symptoms and substantial epidemiological comorbidity, inciting debate about their etiologic overlap. However, detailed study of phenotypes with different ages of onset, severity, and presentation poses a considerable challenge. Recently developed heritability methods allow us to accurately measure correlation of genome-wide common variant risk between two phenotypes from pools of different individuals and assess how connected they, or at least their genetic risks, are on the genomic level. We used genome-wide association data for 265,218 patients and 784,643 control participants, as well as 17 phenotypes from a total of 1,191,588 individuals, to quantify the degree of overlap for genetic risk factors of 25 common brain disorders. RATIONALE Over the past century, the classification of brain disorders has evolved to reflect the medical and scientific communities' assessments of the presumed root causes of clinical phenomena such as behavioral change, loss of motor function, or alterations of consciousness. Directly observable phenomena (such as the presence of emboli, protein tangles, or unusual electrical activity patterns) generally define and separate neurological disorders from psychiatric disorders. Understanding the genetic underpinnings and categorical distinctions for brain disorders and related phenotypes may inform the search for their biological mechanisms. RESULTS Common variant risk for psychiatric disorders was shown to correlate significantly, especially among attention deficit hyperactivity disorder (ADHD), bipolar disorder, major depressive disorder (MDD), and schizophrenia. By contrast, neurological disorders appear more distinct from one another and from the psychiatric disorders, except for migraine, which was significantly correlated to ADHD, MDD, and Tourette syndrome. We demonstrate that, in the general population, the personality trait neuroticism is significantly correlated with almost every psychiatric disorder and migraine. We also identify significant genetic sharing between disorders and early life cognitive measures (e.g., years of education and college attainment) in the general population, demonstrating positive correlation with several psychiatric disorders (e.g., anorexia nervosa and bipolar disorder) and negative correlation with several neurological phenotypes (e.g., Alzheimer's disease and ischemic stroke), even though the latter are considered to result from specific processes that occur later in life. Extensive simulations were also performed to inform how statistical power, diagnostic misclassification, and phenotypic heterogeneity influence genetic correlations. CONCLUSION The high degree of genetic correlation among many of the psychiatric disorders adds further evidence that their current clinical boundaries do not reflect distinct underlying pathogenic processes, at least on the genetic level. This suggests a deeply interconnected nature for psychiatric disorders, in contrast to neurological disorders, and underscores the need to refine psychiatric diagnostics. Genetically informed analyses may provide important "scaffolding" to support such restructuring of psychiatric nosology, which likely requires incorporating many levels of information. By contrast, we find limited evidence for widespread common genetic risk sharing among neurological disorders or across neurological and psychiatric disorders. We show that both psychiatric and neurological disorders have robust correlations with cognitive and personality measures. Further study is needed to evaluate whether overlapping genetic contributions to psychiatric pathology may influence treatment choices. Ultimately, such developments may pave the way toward reduced heterogeneity and improved diagnosis and treatment of psychiatric disorders

Impact d’un guide d’antibioprophylaxie chirurgicale pour les cholécystectomies et les hystérectomies en établissement de santé

Résumé Il s’agit d’une étude quasi expérimentale de type pré et post qui évalue l’impact de l’implantation d’un nouveau guide d’utilisation des antibiotiques en prophylaxie pour l’hystérectomie et la cholécystectomie. L’étude a permis de recruter 663 sujets, dont 601 ont été inclus dans notre analyse. On observe que le recours à l’antibioprophylaxie, selon les recommandations proposées, est conforme dans 54 % des cas dans le groupe préintervention contre 66 % dans le groupe postintervention, une différence statistiquement significative (p = 0,003). Parmi les patients ayant reçu des antibiotiques (n = 270), on note que la conformité globale (c’est-à-dire pour les quatre critères combinés, soit le choix, la dose, le délai et le lieu) passe de 31 % avant l’implantation du guide à 39 % après (p = 0,15). De même, aucune différence significative n’est observée entre les taux de conformité pour chacun des critères entre le groupe pré et le groupe post. Le taux de conformité global est plus élevé pour les cholécystectomies (59 %) que pour les hystérectomies (27 %) (p < 0,001). Au niveau des coûts, on observe une réduction significative de la moyenne des coûts pour l’ensemble des patients inclus dans l’étude entre le groupe contrôle (n = 301 – coût moyen 3,03 $± 2,16) et le groupe expérimental (2,56$ ± 2,18) (p = 0,01, test de t). La différence n’est toutefois plus significative quand on considère uniquement les patients ayant reçu une antibioprophylaxie entre le groupe contrôle (n = 121 – coût moyen 3,75 $± 6,22) et le groupe expérimental (n = 149 – 2,63$ ± 3,32) (p = 0,06, test de t). Bien que l’utilisation d’antibiotiques en prophylaxie chirurgicale ait été largement étudiée, on observe un taux de conformité limité par rapport aux lignes directrices publiées. Même si nous n’avons pas observé de différences quant à tous les paramètres de conformité à la suite de l’implantation du protocole, une intervention ponctuelle des pharmaciens peut contribuer à améliorer globalement la conformité de l’antibioprophylaxie en établissement de santé. Abstract This pre-post quasi-experimental study assesses the impact of the implementation of a new guide on prophylactic antibiotics use for hysterectomy and cholecystectomy. 663 subjects have been recruited, from which 601 have been included in our analysis. Antibioprophylaxis is used in accordance with the suggested guidelines in 54% of cases in the preintervention group, compared to 66% in the postintervention group, a statistically significant difference (p = 0.003). Among patients that have been treated with antibiotics (n = 270), global conformity (combination of the four criteria: choice, dose, administration time and place) goes from 31% before implementation of the guide to 39% afterwards (p = 0.15). Likewise, among pre and post groups, no statistically significant difference was noted between conformity rates for each of the criteria. Global conformity rate is higher for cholecystectomies (59%) than for hysterectomies (27%) (p < 0.001). As for costs, we note a significant decrease of the average cost as a whole between the control group (n = 301 – average cost $3.03 ± 2.16) and the experimental group ($2.56 ± 2.18) (p = 0.01, t-test). However, this difference is no longer significant if we only take into account patients who have received antibioprophylaxis, between the control group (n = 121 – average cost $3.75 ± 6.22) and the experimental group (n = 149 – average cost$2.63 ± 3.32) (p = 0.06, t-test). Although the use of antibiotics in surgical prophylaxis has been widely studied, we observe a limited conformity rate in relation to published guidelines. Despite the fact that we have not noticed any difference as to all conformity parameters following protocol implementation, a punctual intervention by the pharmacists may contribute to improve global conformity to antibioprophylaxis in healthcare facilities

Inferring depth-dependent plasma motions from surface observations using the DeepVel neural network

Coverage of plasma motions is limited to the line-of-sight component at the Sun’s surface. Multiple tracking and inversion methods were developed to infer the transverse motions from observational data. Recently, the DeepVel neural network was trained with computations performed by numerical simulations of the solar photosphere to recover the missing transverse component at the surface and at two additional optical depths simultaneously from the surface white light intensity in the Quiet Sun. We argue that deep learning could provide additional spatial coverage to existing observations in the form of depth-dependent synthetic observations, i.e. estimates generated through the emulation of numerical simulations. We trained different versions of DeepVel using slices from numerical simulations of both the Quiet Sun and Active Region at various optical and geometrical depths in the solar atmosphere, photosphere and upper convection zone to establish the upper and lower limits at which the neural network can generate reliable synthetic observations of plasma motions from surface intensitygrams. Flow fields inferred in the photosphere and low chromosphere τ ∈ [0.1, 1) are comparable to inversions performed at the surface (τ ≈ 1) and are deemed to be suitable for use as synthetic estimates in data assimilation processes and data-driven simulations. This upper limit extends closer to the transition region (τ ≈ 0.01) in the Quiet Sun, but not for Active Regions. Subsurface flows inferred from surface intensitygrams fail to capture the small-scale features of turbulent convective motions as depth crosses a few hundred kilometers. We suggest that these reconstructions could be used as first estimates of a model’s velocity vector in data assimilation processes to nowcast and forecast short term solar activity and space weather

L'autre transparence : Oeuvres holographiques, 6 artistes du Québec : Boissonnet, Cantin, Cossette, Dyens, Evergon, Mathieu

For the presentation of holograms by six Québec artists, Boissonnet and Fischer give evidence of the evolution of holography as an artistic form. Brief artists' statements. Biographical notes