Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome associated with COVID-19: An Emulated Target Trial Analysis.

RATIONALE: Whether COVID patients may benefit from extracorporeal membrane oxygenation (ECMO) compared with conventional invasive mechanical ventilation (IMV) remains unknown. OBJECTIVES: To estimate the effect of ECMO on 90-Day mortality vs IMV only Methods: Among 4,244 critically ill adult patients with COVID-19 included in a multicenter cohort study, we emulated a target trial comparing the treatment strategies of initiating ECMO vs. no ECMO within 7 days of IMV in patients with severe acute respiratory distress syndrome (PaO2/FiO2 <80 or PaCO2 ≥60 mmHg). We controlled for confounding using a multivariable Cox model based on predefined variables. MAIN RESULTS: 1,235 patients met the full eligibility criteria for the emulated trial, among whom 164 patients initiated ECMO. The ECMO strategy had a higher survival probability at Day-7 from the onset of eligibility criteria (87% vs 83%, risk difference: 4%, 95% CI 0;9%) which decreased during follow-up (survival at Day-90: 63% vs 65%, risk difference: -2%, 95% CI -10;5%). However, ECMO was associated with higher survival when performed in high-volume ECMO centers or in regions where a specific ECMO network organization was set up to handle high demand, and when initiated within the first 4 days of MV and in profoundly hypoxemic patients. CONCLUSIONS: In an emulated trial based on a nationwide COVID-19 cohort, we found differential survival over time of an ECMO compared with a no-ECMO strategy. However, ECMO was consistently associated with better outcomes when performed in high-volume centers and in regions with ECMO capacities specifically organized to handle high demand. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Optimisation d'un procédé d'assemblage de préformes composites par modélisation éléments finis avec application à la réalisation industrielle d'éléments profilés T ou H

Cette thèse industrielle porte sur l optimisation du renforcement d une jonction de préformes dans une structure RTM. L étude couvre à la fois l analyse par éléments finis et des validations expérimentales. Le modèle de structure à la base des recherches est un profilé composite carbone/époxy en Té dont la jonction est renforcée grâce au procédé de piquage O3S® (one single side stitching) breveté par EADS. Le comportement de ce profilé est étudié sous un chargement mécanique élémentaire de traction (ou arrachement ) et de cisaillement. Le problème a été modélisé de façon macroscopique à l aide de la méthode des éléments finis sous des hypothèses de linéarité, d isotropie ou d orthotropie, et de déformation plane. Un critère de rupture a été associé afin de prévoir le premier délaminage dans la structure. Des essais mécaniques ont permis de quantifier la tenue mécanique des structures RTM et de l optimiser par la modélisation. L étude s est déroulée en trois étapes : Caractérisation des moyens de fabrication développés spécialement pour les recherches ainsi que de l influence des paramètres de renforcement de la jonction ; Étude comparative de trois arrangements des préformes constitutives du Té (dits drapages ) et proposition d amélioration du motif de piquage. Un concept de drapage optimal et une amélioration du motif de piquage sont identifiés ; La jonction optimale (choix du drapage et du motif de piquage) est optimisée par modélisation puis validée par essais mécaniques. Ces travaux ont conduit à une amélioration significative de la tenue mécanique par rapport à l état de l art tout en conservant un coût de production sensiblement équivalentThis thesis is dedicated to the optimization of RTM preforms junction reinforcement. The study deals with both finite element analysis (FEA) and experimentation. The basis for this research is a carbon/epoxy Tee-profile with a junction reinforced by the O3S® stitching process (one single side stitching), patented by EADS. The behaviour of such a Tee-beam was studied under elementary tensile and shear loadings. The problem was idealized macroscopically by the finite element method under linear and plane strain conditions, with isotropic or orthotropic behavior. An Interlaminar failure criterion was used in order to predict the first delamination in the structure. Mechanical tests were carried out to quantify the mechanical resistance of the RTM structures while FEA was used to optimize it. The study was organized in three steps : Characterization of the manufacturing process and tool developed specifically for this research project as well as the parameters influencing the strength of the assembly ; Comparative study of three different stacking sequences for the Tee preforms (or draping ) and stitching pattern enhancement proposals. An optimal preform configuration and an improvement of the stitching pattern were identified ; Optimization of the identified concept by FEA and validation by mechanical experimentations. Compared to the state of art, this study lead to a significant improvement of the mechanical strength of preforms assembly for an equivalent production costVALENCIENNES-BU Sciences Lettres (596062101) / SudocSudocFranceF

Combined networks regulating seed maturation

International audienceSeed maturation is an important phase of seed development during which embryo growth ceases, storage products accumulate, the protective tegument differentiates and tolerance to desiccation develops, leading to seed dormancy. The spatial and temporal regulation of all these processes requires the concerted action of several signaling pathways that integrate information from genetic programs, and both hormonal and metabolic signals. Recent genetic studies have identified some of the interactions that occur between four master regulators in Arabidopsis, increasing our knowledge of the control of the transcriptional program involved in seed maturation. Moreover, several recent breakthroughs have led to a better understanding of the role of abscisic acid signal modulation and the importance of metabolic regulation in the maternal to filial switch leading to the maturation phase

Identification of flow classes in the wake of a simplified truck model depending on the underbody velocity

International audienceno abstrac

Contrôle du sillage par jets pulsés d'un corps bidimensionnel en interaction avec le sol

Cette étude expérimentale a pour but d'étudier l'écoulement de proche sillage derrière un corps non profilé bidimensionnel par contrôle actif en boucle ouverte. Le rapport λ entre la vitesse sous l'obstacle Us et la vitesse incidente U∞ est ajustable; dans les cas non contrôlés, la dissymétrie du sillage se traduit par différentes structurations de la zone de recirculation, avec ou sans zones décollées en contact avec le sol. Le contrôle est effectué par l'utilisation combinée d'un petit volet déflecteur et d'un jet pulsé; une variation de la fréquence réduite d'actionnement StH construite sur la hauteur H de l'obstacle permet de quantifier le coefficient de pression Cp sur la face arrière de l'obstacle et d'identifier différents régimes d'écoulement suivant les valeurs de λ et StH: (i) pour λ=1, légère diminution de Cp pour toutes les fréquences d'actionnement, et identification de fréquences discrètes entraînant une dégradation accrue du coefficient de pression - (ii) pour λ=0.22, diminution de Cp à basse fréquence, mais augmentation du coefficient de pression avec un mécanisme de saturation à fréquence élevée. Pour λ=0.22, l'écoulement naturel non contrôlé, est attaché au volet. On montre alors que l'augmentation de Cp pour l'écoulement contrôlé à haute fréquence s'accompagne d'une diminution du taux de croissance de l'épaisseur de la couche de cisaillement et d'une diminution des différentes tensions de Reynolds. Ces derniers résultats sont mis en regard avec des travaux récents effectués pour la diminution de traînée de corps 3D non profilés à culot droit

AtbHLH68 transcription factor contributes to the regulation of ABA homeostasis and drought stress tolerance in Arabidopsis thaliana

Basic helix-loop-helix (bHLH) transcription factors are involved in a wide range of developmental processes and in response to biotic and abiotic stresses. They represent one of the biggest families of transcription factors but only few of them have been functionally characterized. Here we report the characterization of AtbHLH68 and show that, although the knock out mutant did not have an obvious development phenotype, it was slightly more sensitive to drought stress than the Col-0, and AtbHLH68 overexpressing lines displayed defects in lateral root (LR) formation and a significant increased tolerance to drought stress, likely related to an enhanced sensitivity to abscisic acid (ABA) and/or increased ABA content. AtbHLH68 was expressed in the vascular system of Arabidopsis and its expression was modulated by exogenously applied ABA in an organ-specific manner. We showed that the expression of genes involved in ABA metabolism [AtAAO3 (AtALDEHYDE OXIDASE 3) and AtCYP707A3 (AtABSCISIC ACID 8′HYDROXYLASE 3)], in ABA-related response to drought-stress (AtMYC2, AtbHLH122 and AtRD29A) or during LRs development (AtMYC2 and AtABI3) was de-regulated in the overexpressing lines. We propose that AtbHLH68 has a function in the regulation of LR elongation, and in the response to drought stress, likely through an ABA-dependent pathway by regulating directly or indirectly components of ABA signaling and/or metabolism