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Fassin Didier, Defossez Anne-Claire, <i>L’Exil, toujours recommencé. Chronique de la frontière</i>
No full textInternational audienceRéférence : Fassin, Didier, Defossez, Anne-Claire, L’Exil, toujours recommencé. Chronique de la frontière. – Paris : Seuil, 2024. – 448 p. ISBN : 978-2-021-54969-0
Predicting prolonged dalbavancin exposure using machine learning: a validated strategy for individualized redosing
No full textInternational audienceABSTRACT Dalbavancin is a long-acting lipoglycopeptide increasingly used off-label for complex Gram-positive infections requiring prolonged therapy. Its extended half-life enables simplified regimens, but interindividual pharmacokinetic variability and pathogen MIC heterogeneity complicate dosing. We developed and externally validated machine learning (ML) models to predict whether dalbavancin plasma concentrations remain above predefined pharmacokinetic/pharmacodynamic targets after two standard 1,500 mg doses (day 1/day 8 or day 1/day 15). Predictions were binary (adequate vs subtherapeutic concentration), directly reflecting the clinical decision to readminister a 1,500 mg dose. Models were trained on simulated PK profiles from a published population PK (popPK) model and evaluated in three independent settings: (i) simulated validation data sets from two alternative published popPK models, (ii) a real-world cohort from Limoges University Hospital ( n = 31), and (iii) a secondary cohort from Nantes University Hospital ( n = 7). Input features included age, body weight, creatinine clearance, MIC, and a single plasma concentration obtained before the second dose. Support vector machine models achieved high accuracy (>88%) and sensitivity (>90%) across testing sets and clinical validation cohorts. In clinical data sets, no false negatives were observed (limited by sample size), with overall accuracy approaching 95%. Compared with maximum a posteriori Bayesian estimation, ML achieved higher accuracy and sensitivity across validation cohorts, particularly by reducing false negatives. Predictions remained reliable through week 8, the clinically relevant exposure window. This ML-based approach enables early individualized redosing decisions using minimal clinical inputs. By complementing Bayesian forecasting and reducing reliance on serial sampling, it represents a pragmatic strategy to support model-informed precision dosing of dalbavancin
Influence de la conscience morphologique sur la littératie et la réussite scolaire : une étude longitudinale auprès d’élèves de première année de cycle secondaire
No full textInternational audienceLa conscience morphologique joue un rôle central dans l’apprentissage du langage écrit. Toutefois, sa contribution aux différentes composantes de la littératie a été peu étudiée en français, en particulier au début du cycle secondaire. De plus, les relations spécifiques entre conscience morphologique, compétences en langage écrit et réussite scolaire demeurent encore peu explorées. La présente étude examine ces liens auprès de 60 élèves francophones scolarisés en première année de cycle secondaire (classe de 6e en France). La conscience morphologique a été mise en relation avec les compétences en orthographe, fluence en lecture, compréhension écrite, ainsi qu’avec la réussite scolaire. Les analyses de régression révèlent que, si la conscience morphologique ne prédit pas directement la réussite scolaire, elle explique une part significative de la variance des trois dimensions du langage écrit, dont le niveau orthographique, qui s’avère être un prédicteur important de la réussite en fin d’année. Ces résultats soulignent l’importance de la conscience morphologique dans les apprentissages au cycle secondaire. Ils montrent également l’intérêt de renforcer cette compétence chez les élèves afin de favoriser leur réussite
Investigation on the Influence of Operation and Injection Conditions on the Wave Dynamics of GH2 /GO2 Rotating Detonation Combustors
No full textInternational audienceThis study investigates experimentally an annular Rotating Detonation Combustor (RDC) using gaseous hydrogen and oxygen as propellants. The analysis explore the effects of the mass flow rate, the mixture ratio, the center-body geometry, the injector design, and a restriction area at the chamber outlet on the detonation regime. The results show a broad variety of regimes, some aligning with existing literature. Further analysis is needed to optimize stability.</div
Jean-Paul Sartre a-t-il fait une ontologie d’après la chute ? L’usage de Jean-Paul Sartre par Eugen Drewermann dans <i>Le Mal</i>
No full textInternational audienceIn Volume 3 of his work Le Mal (Evil), devoted to the exegesis of the Yahwist account of origins, Eugen Drewermann gives special attention to Sartre's philosophy. The author sees it as a fundamental tool for analyzing the logic that leads sinful man to evil, particularly in the convergences between the data in Genesis 2-11 and Sartre's analyses. What are the scope and limits of the use of Sartrean ontology and anthropology, both in themselves and in their articulation with the other sources of Sartrean thought invoked by Drewermann? How does the latter integrate Sartrean ontology into his own reflections? What does this integration mean? Is Sartre's ontology a theory of evil that is unaware of itself? And, ultimately, what can theology do for philosophy?Dans le tome 3 de son ouvrage Le Mal, consacré à l’exégèse du récit yavhiste des origines, Eugen Drewermann donne une place particulière à la philosophie de Sartre. L’auteur y voit un instrument fondamental pour analyser la logique conduisant au mal l’homme pécheur, notamment dans les convergences entre les données de Ge 2-11 et les analyses de Sartre. Quelle portée et des limites de l’usage de l’ontologie et de l’anthropologie sartrienne aussi bien en elle-même que dans leur articulation avec les autres sources de la pensée sartrienne convoquée par Drewermann . Comment ce dernier intègre-t-il l’ontologie sartrienne à ses réflexions propres ? Que veut dire cette intégration ? L’ontologie de Sartre est-elle une théorie du mal qui s’ignore ? Et, in fine, que peut faire la théologie à la philosophie
Apport de la génomique dans la prise en charge des cancers
No full textNational audienceThe contribution of genomics to cancer management is significant, thanks to the impact of next-generation sequencing (NGS) technologies on understanding and treating tumors. Identifying somatic and constitutional mutations allows for cancer classification and treatment guidance through a personalized approach. Tumorigenesis, clonal evolution, and tumor heterogeneity require techniques that examine an increasing number of genes and detect various types of alterations. Treatment resistance also justifies the use of genetic testing for monitoring and therapeutic adaptation. The current challenges in cancer genomics lie now in interpretation and access to treatments.L’apport de la génomique dans la prise en charge des cancers est significative grâce à l’impact des nouvelles technologies de séquençage de nouvelle génération (NGS) sur la compréhension et le traitement des tumeurs. L’identification des mutations somatiques et constitutionnelles permet de classifier les cancers et de guider les traitements via une approche personnalisée. La tumorigénèse, l’évolution clonale et l’hétérogénéité tumorale obligent à avoir des techniques avec de plus en plus de gènes examinés et avec la capacité de mettre en évidence différents types d’altération. La résistance aux traitements justifie aussi l’utilisation de tests génétiques pour le suivi et l’adaptation thérapeutique. Les défis de la génomique des cancers sont maintenant l’interprétation et l’accès aux traitements
Decomposition Analysis for Visualization of Noncovalent Interactions Based on the Fragment Molecular Orbital Method
No full textInternational audienceMany-body expansions of the electron density and Fock matrix in the fragment molecular orbital method (FMO) are used to reveal the role of polarization and charge transfer on noncovalent interactions (NCI). In addition to the physicochemical insight gained from these analyses, the use of FMO permits a rapid evaluation of electron densities to study NCI. The developed method is applied to a solvated sodium cation and a small polypeptide, validating the accuracy of the approach with respect to full calculations and revealing the role of polarization and charge transfer in NCI. In order to show the full potential of the approach, the FMO/NCI method is applied to a complex of the Trp-cage (PDB: 1L2Y) protein with a ligand, delivering fruitful insights into binding from both density and energy perspectives. NCI is shown to provide a comprehensive visual picture of interactions that might be missed without it, in particular, interactions between functional groups in a fragment
Evaluation of a pro-recovery training intervention (REFOCUS-RETAFORM) in specialist mental health services across France: stepped-wedge cluster randomised controlled trial protocol
No full textInternational audienceBackground: While recovery orientation is national policy in many countries, evidence remains limited for the effectiveness at a service level. This paper describes the protocol for implementing a pro-recovery training intervention (REFOCUS-RETAFORM) in specialist mental health services across France. The aim is to evaluate whether REFOCUS-RETAFORM plus usual care leads to improved outcomes for adolescent and adult mental health service users compared with usual care alone.Methods: A two-step stepped wedge cluster randomised controlled trial will be conducted, with a nested qualitative sub-study exploring stakeholders' views on changes in staff-user relationships and implementation influences. The REFOCUS-RETAFORM intervention is a training intervention for mental health staff, to develop recovery-promoting relationships and pro-recovery working practices. Clusters are services, which transition sequentially from control to intervention condition in a randomised order. Eight clusters are randomised to deliver REFOCUS-RETAFORM in year one and eight clusters in year two. Each cluster delivers REFOCUS-RETAFORM to two teams from their organisation (32 teams in total). Participants are a) service users aged 13-65 years attending services implementing REFOCUS-RETAFORM, and b) staff receiving the intervention. The primary outcome is the Questionnaire about the Process of Recovery. Secondary outcomes include perceived stigma and coercion, self-stigma and wellbeing for service users, and recovery-orientation for staff. Data will be collected from 540 service users (180 at baseline, 180 at month 12, 180 at month 24) and 220 staff. We will use multilevel mixed-effects models, adjusting for secular trends and thematic analysis for the qualitative interview data.Discussion: Findings will inform the continued transformation of French specialist mental health services toward a recovery orientation.Trial registration: Clinical Trials NCT05824234, registered 21 April 2023
