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Therapeutic Management During Pregnancy and Relapse Risk in Women With Multiple Sclerosis
No full textInternational audienceImportance: In women with multiple sclerosis (MS), disease-modifying therapy (DMT) management during pregnancy might impact relapse risk.Objective: To estimate the effect of DMT management during pregnancy on MS relapse rate and compare different therapeutic strategies.Design, setting, and participants: This was a multicenter retrospective cohort study using data from January 1990 to December 2023. Data were extracted in December 2023 from the French MS registry. Among 52 955 women in the registry, we included pregnancies identified through childbirths in patients with relapsing-onset MS who were monitored for at least 18 months before delivery and 9 months after. Pregnancies occurring less than 18 months apart or with missing month of birth were excluded.Exposures: Mediation analysis was used to estimate the total, direct, and indirect (mediated by DMT management) effects of pregnancy. Different therapeutic strategies were compared: DMT interruption, switching to or maintaining interferon β or glatiramer acetate, switching to or maintaining natalizumab until the third trimester, and switching to or maintaining intravenous anti-CD20 and interrupting it 3 months before conception.Main outcomes and measures: The primary outcome was the annualized relapse rate (ARR) during the preconception, gestation, and postpartum periods. Within a causal inference framework, counterfactual ARRs were estimated using longitudinal g-computation, combining a random forest algorithm for predicting DMTs, and a mixed-effects Poisson model for relapses.Results: We included 6341 pregnancies occurring in 4998 women (mean [SD] age at conception, 31.5 [4.5] years). DMT management during pregnancy significantly increased ARR during gestation (causal rate ratio [cRR], 1.13; 95% CI, 1.06-1.22) and postpartum (cRR, 1.08; 95% CI, 1.01-1.16) periods. This led to a deleterious total effect of pregnancy on ARR, particularly in women receiving natalizumab before pregnancy with prolonged interruption (ie, interruption before the second trimester or resumption more than 3 months after delivery; cRR, 2.18; 95% CI, 1.76-2.69), and in women receiving fingolimod (cRR, 2.15; 95% CI, 1.60-2.93). Compared to DMT interruption, anti-CD20 strategy was the most effective (cRR, 0.38; 95% CI, 0.25-0.52), followed by the natalizumab strategy with short interruption (cRR, 0.80; 95% CI, 0.71-0.90), whereas interferon β (cRR, 0.93; 95% CI, 0.86-0.99) and glatiramer acetate strategies (cRR, 0.91; 95% CI, 0.84-0.99) were less effective.Conclusion: In this study, DMT management during pregnancy significantly increased relapse risk, particularly in patients receiving natalizumab with prolonged interruption or fingolimod. The strategy based on the use of anti-CD20 before pregnancy was the most effective to mitigate this risk
Four functional profiles for fibre and mucin metabolism in the human gut microbiome
No full textInternational audienceDeciphering the complex interactions between the gut microbiome and the host health require evolved analysis methods focusing on the microbial ecosystem functions. We broke down gut microbiota metabolism into 101 functional traits representative of fibre and mucin degradation and we used nonnegative matrix factorization to mine metagenomic datasets. We identified four distinct metabolic profiles that can be used to characterize the microbiota during dysbiosis, Crohn disease or high fiber diet
Les encadrements de la paternité
No full textLe troisième numéro de 2025 de la Revue française des affaires sociales est dédié aux encadrements de la paternité, c'est-à-dire à la manière dont l'investissement paternel dans les tâches parentales est influencé par des professionnels, des organisations ou des dispositifs institutionnels
Apprendre à décider : une perspective neurocognitive chez le Rat : le rôle de la noradrénaline préfrontale chez le rat dans le comportement adaptatif
No full textEvery day, organisms adapt their choices to a changing environment, relying on the ability to learn which actions lead to valuable outcomes and to revise these predictions when circumstances shift. Such adaptive decision-making is central to survival and is thought to depend on prefrontal circuits and their modulation by neuromodulators such as dopamine, noradrenaline or serotonin. Yet, the precise role of noradrenergic transmission in prefrontal subregions remains unclear. This thesis combines behavioural paradigms, circuit manipulations, fiber photometry recordings, and computational modelling to investigate how noradrenergic inputs to the medial prefrontal cortex (mPFC) and the orbitofrontal cortex (OFC) shape flexible learning.In the first set of experiments, we used a Pavlovian contingency degradation paradigm to probe stimulus–outcome updating. We show that noradrenergic transmission in the mPFC is necessary for adapting to changes in predictive contingencies, complementing its well-established involvement in instrumental contingency degradation that underpins goal-directed behaviour. In a second line of work, we used a reversal learning paradigm, where outdated associations must be abandoned and replaced with new ones. Here, we demonstrate that stronger noradrenaline responses in the OFC predict better individual performance, and we confirmed the causal role of this signal by showing that chemogenetic and optogenetic silencing of LC→OFC projections slowed reversal learning. Finally, using a probabilistic reversal learning task, we combined computational modeling, photometry recordings, and chemogenetic manipulations. We show that rat behavior is best explained by a meta-reinforcement learning model with volatility-dependent learning rates, that orbitofrontal noradrenaline seems to track these volatility estimates, and that silencing LC→OFC projections selectively slows adaptive adjustments, mimicking model lesions of volatility signaling.Taken together, these findings provide converging evidence that noradrenaline contributes in anatomically specific ways to flexible behavior. While NA in the mPFC is required for detecting and adapting to changes in the causal relationship between stimuli and their outcomes, NA in the OFC enables reversal and volatility-dependent adjustments of learning. This work highlights the complementary functions of prefrontal noradrenaline in ensuring that behavior remains both stable and adaptable in uncertain environments.Chaque jour, les organismes adaptent leurs choix à un environnement changeant, en s’appuyant sur leur capacité à apprendre quelles actions conduisent à des conséquences bénéfiques et à réviser ces prédictions lorsque les circonstances évoluent. Une telle prise de décision adaptative est essentielle à la survie et dépendrait des circuits préfrontaux et de leur modulation par des neuromodulateurs tels que la dopamine, la noradrénaline ou la sérotonine. Pourtant, le rôle précis de la transmission noradrénergique dans les sous-régions préfrontales reste mal compris. Cette thèse combine paradigmes comportementaux, manipulations de circuits, photométrie par fibre optique et modélisation computationnelle afin d’examiner comment les afférences noradrénergiques au cortex préfrontal médian (mPFC) et au cortex orbitofrontal (OFC) façonnent l’apprentissage flexible.Dans un premier ensemble d’expériences, nous avons utilisé la dégradation de contingence pavlovienne pour sonder la mise à jour des associations stimulus–conséquences. Nous montrons que la transmission noradrénergique dans le mPFC est nécessaire pour s’adapter aux changements de contingences prédictives, étendant ainsi la contribution connue de cette région dans la dégradation de contingence instrumentale qui sous-tend le comportement dirigé vers un but. Dans une seconde série de travaux, nous avons examiné l’apprentissage par inversement, où les associations obsolètes doivent être abandonnées et remplacées par de nouvelles. Nous démontrons ici que des réponses noradrénergiques plus fortes dans l’OFC prédisent de meilleures performances individuelles, et nous confirmons le rôle causal de ce signal en montrant que l’inhibition chémogénétique et optogénétique des projections LC→OFC ralentit l’apprentissage par inversement. Enfin, dans une tâche de renversement probabiliste, nous avons combiné modélisation computationnelle, photométrie et manipulations chémo-génétiques. Nous montrons que le comportement des rats est mieux expliqué par un modèle de méta-apprentissage par renforcement, dans lequel le taux d’apprentissage dépend de la volatilité ; que la noradrénaline orbitofrontale semble refléter ces estimations de volatilité ; et que l’inhibition des projections LC→OFC ralentit sélectivement les ajustements adaptatifs, mimant les lésions de la modulation de la volatilité dans le modèle.Pris ensemble, ces résultats fournissent des preuves convergentes que la noradrénaline contribue de manière anatomiquement spécifique au comportement flexible. Alors que la NA dans le mPFC est requise pour détecter et s’adapter aux changements dans la relation causale entre les stimuli et leurs conséquences, la NA dans l’OFC permet de s’adapter à l’inversement des contingences et les ajustements du taux d’apprentissage guidés par la volatilité. Ce travail met en lumière les fonctions complémentaires de la noradrénaline préfrontale pour garantir que le comportement reste à la fois stable et adaptable dans des environnements incertains
Pneumocystis pneumonia in older non-HIV-infected patients: a French, multicentre, retrospective, cohort study
No full textInternational audienceBackground: Pneumocystis pneumonia (PCP) is well-described in younger and HIV-infected populations, but limited data are available for older non-HIV-infected patients. The aim was to describe the clinical characteristics, management and outcomes of PCP in older non-HIV-infected patients and to identify factors associated with in-hospital mortality.Methods: This multicentre, retrospective, cohort study included patients aged ≥ 75 years, hospitalised for non-HIV-related PCP in 12 French university hospitals between January, 2010 and December, 2021. PCP diagnosis was confirmed by PCR or microscopy. Data on demographics, comorbidities, clinical features, management and outcomes were collected. Factors associated with in-hospital mortality were identified by univariate and multivariate analysis.Results: A total of 175 patients were screened and 162 were included (median age: 79 years, 57.4% male). Most patients had haematological malignancies (35.8%) or solid tumours (34.5%) and were treated with long-term corticosteroids (60%). Respiratory symptoms (87.6%) and bilateral interstitial lung involvement were common. Diagnosis was based on PCR of bronchoalveolar lavage (66.4%) or sputum samples (32.3%). In-hospital mortality was 27.8%. CRP level > 110 mg/L (HR = 2.55 [95%CI: 1.35–4.83], p = 0.004) and initiation of corticosteroids for PCP treatment (HR = 1.89 [95%CI: 1.03–3.44], p = 0.039) were associated with mortality. Patients with higher oxygen saturation at admission (HR = 0.94 [95%CI: 0.91–0.97], p < 0.001) had a lower risk of death.Conclusion: PCP in older non-HIV-infected patients has a high mortality rate, particularly in the presence of elevated CRP, hypoxaemia or corticosteroid use. Future research should focus on identifying subgroups potentially benefiting from corticosteroids and exploring safe therapeutic options for this vulnerable populatio
Les nombres écologiques. Ou ce que devient l’environnement mis en nombre: Introduction aux numéros 2025-2 et 2025-3
No full textInternational audienceThis text introduces the 2025-2 and 2025-3 issues of the journal Statistique et Societé, which are dedicated to the “Ecological Numbers” special feature. It provides an opportunity to think about the specific nature of these numbers, four characteristics of which are highlighted: their heterogeneity and complexity, the spatial and temporal scales they confront, and finally, the circulation and visibility that accompany them. These characteristics run through the articles that make up the two issues: the first is entitled “Ecological Numbers (I). Climate, Greenhouse Gases,” and the second “Ecological Numbers (II). Environments, Spaces, Species.Ce texte introduit les deux numéros 2025-2 et 2025-3 que la revue Statistique et société consacre au dossier « Nombres écologiques ». Il fournit l’occasion de réfléchir à la spécificité de ces nombres, dont quatre traits sont dégagés : l’hétérogénéité et la complexité qui les caractérisent, les échelles d’espace mais aussi de temps auxquelles ils confrontent, les circulations et mises en visibilités, enfin, qui les accompagnent. Ces traits traversent les articles qui composent les deux numéros : le premier est intitulé « Les nombres écologiques (I). Climat, gaz à effets de serre », le second « Les nombres écologiques (II). Milieux, espaces, espèces »
TRAKJAK: a complete blood count-based prediction of polycythemia vera at initial erythrocytosis workup to reduce financial and ecological costs
No full textInternational audienceBackground: Erythrocytosis is common in daily clinical practice, and polycythemia vera (PV), a myeloproliferative neoplasm associated with JAK2 mutations, should be systematically considered in clinical reasoning process. Financial constraints and environmental burden of extensive testing prompted us to develop a predictive score for PV to guide decision to screen for JAK2 mutations.Methods: We retrospectively collected clinical and biological data from patients with PV and non-PV erythrocytosis who had low erythropoietin levels in 2024 at our hospital (derivation cohort). Data were analysed using univariable and multivariable methods to develop the TRAKJAK score, which was then validated in a separate cohort of patients referred to our centre in 2025 for erythrocytosis.Results: We included 134 patients in derivation cohort (96 [72%] with PV and 38 [28%] without) and 65 in validation cohort (33 [51%] with PV and 32 [49%] without). The TRAKJAK score required at least one positive parameter among RBC count ≥ 6.57 × 1012/L, basophil count ≥ 0.1 × 109/L, and platelet count ≥300 × 109/L. In validation cohort, negative predictive value (NPV) was 96%, sensitivity was 97%, positive predictive value (PPV) was 82%, and specificity was 78%. In global cohort, sensitivity was 98%, specificity was 89%, PPV was 94%, and NPV was 95%, with a false negative rate of 1.5% and a false positive rate of 4.0%.Conclusion: Use of TRAKJAK could have prevented unnecessary JAK2 mutation screening in 62/70 patients (88%) who ultimately did not have PV. Like all clinical prediction tools, TRAKJAK is an aid to reduce over-investigation and must not replace clinical judgement
Les fausses élévations de la protéine C-réactive : quand y penser ?
No full textInternational audienceIntroduction: C-reactive protein (CRP) is the key biomarker for diagnosing and monitoring inflammatory conditions. However, challenges arise when patients exhibit elevated CRP levels without an evident inflammatory cause. Despite the performance of CRP assays using immunoturbidimetry, this method remains sensitive to interferences that may result in false positive results.Case reports: Drawing from three case studies illustrating analytical interferences in CRP measurements, we propose a comprehensive review of the literature on this subject. The most common cause of analytical interference in CRP measurement is the binding of rheumatoid factor to capture antibodies, generating a signal detected by immunoturbidimetry despite the absence of CRP in the sample. To identify such interferences, various antibody neutralization techniques and alternative assay methods can be employed. Reporting falsely elevated CRP levels may lead to unnecessary and potentially invasive diagnostic procedures, causing undue patient anxiety. Moreover, erroneous laboratory results can result in diagnostic errors or the initiation of inappropriate therapies, contributing to patient harm and additional healthcare costs.Conclusion: Unexplained and persistent elevation of CRP levels, particularly in the absence of other inflammatory markers and clinical evidence, should raise suspicion of analytical interference and prompt immediate discussion between clinicians and medical biologists to clarify the situation
L’intercomprensione in classe per l’apprendimento delle lingue vicine: strumenti pedagogici e aspetti teorici
No full textInternational audienceQuesta proposta di atelier riguarda l’intercomprensione tra lingue romanze in classe (Caddéo & Jamet, 2023) e i modi in cui usare questo approccio per l’insegnamento e l’apprendimento, da parte di due ricercatori lavorando su questo tema da anni all’interno di diversi contesti (scolastico, universitario, centro linguistico...). Avrà per obiettivo di dare qualche punti di riferimento teorici e proporre diversi esempi di risorse e attività didattiche per l’uso dell’intercomprensione in classe di lingue “straniere” o piuttosto vicine.La proposta si rivolge quindi a tutti e tutte gli insegnanti di lingue straniere in Ticino, e in particolare di lingue vicine (francese, spagnolo...) a qualsiasi livelli (scolastico, universitario...) interessati/e agli approcci contrastivi per la classe. Questo atelier mira in particolare a sensibilizzare gli insegnanti sull’appoggio che rappresentano le somiglianze tra lingue vicine per la didattica per poter sviluppare delle competenze ricettive più velocemente, e concentrarsi quindi di più sulle abilità di produzione.Ci appoggeremmo su diversi metodi (Meissner et al., 2004; Pandolfi, Christopher & Somenzi, 2014; Benavente Ferrera et al., 2022), siccome su progetti personali dei due autori nei loro contesti di insegnamento e ricerca (Francia, Italia, Svizzera Italiana, Brasile) per l’elaborazione di materiale pedagogico contestualizzato. Presenteremo anche alcuni spunti per collegare gli apprendimenti linguistici tra di loro (Candelier & Manno, dir., 2023) e di usare l’intercomprensione in classe non solo per i corsi di lingua ma anche i corsi di materie scolastiche per promotore il loro apprendimento in un ambito plurilingue (Escudé, dir., 2008). Per questo, l’atelier si orienterà intorno a tre principale tematiche:1. Intercomprensione e attività ludiche: riflessioni e presentazione di risorse per usare l’intercomprensione di maniera ludica in classe, soprattutto per l’apprendimento del lessico.2. Intercomprensione e variazione linguistica: riflessioni e presentazione di risorse per usare l’intercomprensione come punto di partenza per una sensibilizzazione alle variazioni regionali delle lingue romanze (francese della Svizzera romanda, italiano del Ticino..).3. Intercomprensione e abilità produttive: riflessione sulla creazione di percorsi pedagogici mirati tra due lingue vicine in cui l'uso dell’intercomprensione può servire come base per lo sviluppo delle abilità produttive
Systematic evaluation of Li3PO4 coatings on LNMO for enhanced cycling stability using NMR-based interfacial probes
No full textInternational audienceHigh-voltage cathodes such as LiMn1.5Ni0.5O4 (LNMO) offer promising energy density but suffer from interfacial degradation accelerated at elevated voltages and temperatures. Here, we present a comprehensive comparative study of three Li3PO4 coating methods (precipitation, sol–gel, and dry sol–gel routes) applied to commercial LNMO powders. Coating quality and intimacy are systematically assessed using a correlative, multitechnique approach including 7Li and 31P solid-state NMR, X-ray diffraction, and electrochemical testing. A key insight from this study is the use of ssNMR relaxation behavior as a sensitive probe of coating intimacy to the active phase. The methodology is validated on commercial LNMO and reproduced in a lab-synthesized LNMO to demonstrate reproducibility across particle morphologies. Among all methods, the sol–gel route produced a uniform ∼20 nm coating with optimal surface contact, translating to improved rate capability and outstanding high-temperature cycling stability (87% retention after 100 cycles at 50 °C compared to 29% for the non-coated LNMO), while retaining rate capability. These findings establish a practical framework for designing robust interfacial coatings in high-voltage lithium-ion battery materials