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

Letter chunking in handwriting : motor and language influences : study of capital letter writing in the adult subject

L’écriture est une habileté motrice au service du langage. Écrire nécessite donc la prise en compte de contraintes motrices (périphériques) et linguistiques (centrales). Dans ce travail, nous nous sommes intéressés aux influences linguistiques qui s’exercent sur la sortie graphique, et à leur impact éventuel sur notre façon d’écrire. En parallèle, nous avons recherché les contraintes motrices qui règlent localement l’organisation de la sortie graphique. Ces différents niveaux d’organisation du langage écrit doivent interagir.Nous avons analysé l’écriture des majuscules chez l’adulte, en examinant les indices temporels et cinématiques de l’intervalle inter-lettres. La 1ere expérience était destinée à mettre en évidence des regroupements syllabiques de lettres dans les mots. Les résultats préliminaires nous ont orienté vers l’étude d’autres contraintes, motrices, d’organisation de l’écriture. Des regroupements de lettres peuvent en effet se produire aussi sur la base de critères moteurs. Il pourrait exister une certaine ‘compatibilité motrice’ entre les lettres qui serait susceptible de moduler l’expression des effets linguistiques. Dans l’expérience 2, nous avons mis en évidence une compatibilité subjective entre certaines lettres. Nous avons ensuite proposé des règles d’associations motrices des lettres que nous avons testées dans les expériences 3A et 3B. Au cours de l’expérience 3A, nous avons étendu la compatibilité motrice à d’autres caractères graphiques, tels que les chiffres. Dans l’expérience 3B, nous avons vérifié avec des gauchers que les règles de compatibilité dépendent de la façon d’écrire les lettres et, dans une certaine mesure, de leur fréquence dans la langue.Ces résultats suggèrent que la direction et l’amplitude du mouvement nécessaire pour enchainer certaines lettres majuscules peut les rendre moins aisées à écrire. D’autres expériences doivent confirmer et préciser ces règles de compatibilité. Finalement, nous envisageons les conséquences théoriques de nos résultats sur les modèles de traitement du langage écrit.Hand-writing is a motor activity which is at the service of language. The act of writing therefore entails both motor (peripheral) and linguistic (central) constraints. In this study, we have focused on the linguistic influences upon graphical output, and on their potential impact upon our way of writing. At the same time, we have studied the immediate motor constraints which determine how graphical output is produced. These different layers are bound to interact in the production of written language.We analyzed adult hand-written capital letters, by examining evidence of the interval, in time and in movement, between the formation of consecutive letters. The first experiment was designed to highlight syllabic groupings of letters within words. Our preliminary findings directed us towards the study of other, motor, constraints upon the production of hand-writing. In effect, letter groupings can also be created on the basis of motor criteria. A certain "motor compatibility" between letters could exist, which would be capable of modulating what is produced by linguistic factors. In the second experiment, we focused on subjective compatibility between certain letters. We then proposed rules for motor associations of letters which we tested in experiments 3A and 3B. In the course of experiment 3A, we extended motor compatibility to other graphical symbols, such as numbers. In experiment 3B, we ascertained with left­ handed subjects, that the rules for compatibility depend upon the way letters are writ ten and to a certain extent, on their recurrence in the language.These findings suggest that the direction and range of movement required to produce certain capital letters can make them less easy to write. Other experiments should confirm and refine these compatibility rules. Finally, we anticipate the theoretical consequences of our findings for existing models of understanding written language

Figures et présence de la détresse psychique

PARIS7-Bibliothèque centrale (751132105) / SudocSudocFranceF

ERP evidence of fast learning of a second language vocabulary: New labels and existing concepts

What does it take to acquire a semantic network in a second language? The present ERP study shows extremely rapid instantiation of both learned words and related concepts, via computerized games. Participants served as their own control. Electrical activity of the brain, recorded at the scalp, was examined prior to exposure with the second language and 8 days later, following a 6 day training session (preceded and followed by orientation and consolidation, respectively). Participants learned 12 words per day (nouns and verbs), for a total of 72 words over 6 consecutive days. Results show rapid changes in cortical activity, associated with learning. Prior to exposure, no modulation of the N400 component was found as a function of the correct match vs. mismatch of audio presentation of words and their associated images. Post training, a large N400 effect was found for mismatch trials compared to correctly matched audio-visual trials. More importantly, images that were semantically related to learned words (eg. for the learned word “horse” the image of a saddle was presented), produced a reduction of the N400 compared to mismatched pairs (eg. the image of a building followed by the auditory presentation of the same learned word “horse”). Our results attest to the plasticity of adult learners' brains and provide evidence for rapid onset of a semantic network in a late learned language

L'IA pour mieux apprendre et apprehender L'IA

National audienceL'IA en éducation peut être abordée depuis trois perspectives parallèles. D'abord, elle peut servir à adapter l'expérience d'apprentissage par la conception d'outils prenant en compte différentes caractéristiques des apprenants ou des traces numériques issues de leur interaction avec des systèmes. Bien utilisés, de tels systèmes pourraient décharger les enseignants de tâches relatives à la transmission des contenus et leur permettre d'intervenir sur des aspects plus complexes de l'apprentissage des élèves. Ensuite, l'IA peut être utilisée comme outil scientifique pour mieux comprendre les phénomènes d'apprentissage humain, par la modélisation de l'apprenant. Finalement, l'IA peut être envisagée depuis la perspective de l'éducation critique à l'IA. Ce chapitre présente succinctement ces trois perspectives qui ne s'excluent pas les unes des autres, mais qui se complètent pour mieux cerner les enjeux de l'IA. Les dernières recherches associant les sciences de l'éducation et les sciences du numérique permettent de comprendre les liens entre l'intelligence artificielle (IA) et l'éducation, y compris leurs limites. Ces recherches nous montrent comment l'IA peut être pensée pour mieux apprendre et développer son esprit critique (Roux et al. 2020 ; Viéville, 2018), pour comprendre l'apprentissage humain lui-même, et enfin comme objet d'enseignement, pour maîtriser de manière éclairée ces outils devenus quotidiens (Viéville et Guitton, 2020)

Automatic Generation of Questions from DBpedia

International audienceThe production of Educational quizzes is a time-consuming task that can be automated by taking advantage of existing knowledge bases available on the Web of Linked Open Data (LOD) such as DBpedia. For these quizzes to be useful to learners, their questions must be generated in compliance with the knowledge and skills necessary to master for each subject and school year according to the official educational standards. We present an approach that exploits structured knowledge bases that contain the knowledge and skills, from which it selects a set of DBpedia resources relevant to a specific school subject and year. This set of resources is enriched with additional related resources, through the NEFCE heuristic. Finally, question generation strategies are applied to the graph generated with this set of resulting resources. Likewise, we provide an evaluation of two knowledge bases and of the proposed NEFCE heuristics

Un MOOC pour initier a l'IA : « Intelligence Artificielle avec Intelligence »

National audiencePour appréhender l'IA au quotidien, il faut former les citoyens dès la fin du primaire et tout au long de la vie à la compréhension de ses fondamentaux. Le MOOC « Intelligence artificielle avec intelligence » (IAI) est une formation hybride et participative permettant à des citoyens de s'initier à l'IA de manière à la fois théorique et expérimentale, par l'essai de différentes technologies comme la reconnaissance d'images. La formation permet de mieux comprendre, pour mieux appréhender cette IA désormais présente au quotidien

Does writing help alphabetic readers accommodate for an ideographic system? Evidence from fMRI

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Quantitative proteome profiling of dystrophic dog skeletal muscle reveals a stabilized muscular architecture and protection against oxidative stress after systemic delivery of MuStem cells.

International audienceProteomic profiling plays a decisive role in the elucidation of molecular signatures representative of a specific clinical context. MuStem cell-based therapy represents a promising approach for clinical applications to cure Duchenne Muscular Dystrophy (DMD). To expand our previous studies collected in the clinically relevant DMD animal model, we decided to investigate the skeletal muscle proteome four months after systemic delivery of allogenic MuStem cells. Quantitative proteomics with isotope-coded protein labelling (ICPL) was used to compile quantitative changes in the protein expression profiles of muscle in transplanted Golden Retriever Muscular Dystrophy (GRMD) dogs as compared to GRMD dogs. A total of 492 proteins were quantified, including 25 that were overrepresented and 46 that were underrepresented after MuStem cell transplantation. Interestingly, this study demonstrates that somatic stem cell therapy impacts on the structural integrity of the muscle fascicle by acting on fibres and its connections with the extracellular matrix. We also show that cell infusion promotes protective mechanisms against oxidative stress and favours the initial phase of muscle repair. This study allows us to identify putative candidates for tissue markers that might be of great value in objectively exploring the clinical benefits resulting from our cell-based therapy for DMD. This article is protected by copyright. All rights reserved

The neural network of reading: Does writing help the brain accommodate for linguistic diversity?

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