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Exploring a Rigid Macrocyclic Ligand Bearing Malonate Pendants for Gd(III) Complexation: the Coordination Chemistry of [Gd(OPDMA)]<sup>−</sup>
No full textInternational audienceThe emergence of nephrogenic systemic fibrosis, clearly linked to the in vivo dissociation of Gd(III)-based MRI contrast agents (CA), has promoted intensive research to identify safe CA candidates. Towards this goal, we have designed the novel ligand H4OPDMA, which combines a rigidified macrocycle, low total ligand basicity, and malonate pendant arms to increase the number of donor atoms. Thanks to these design elements, H4OPDMA is capable of forming a Gd(III) chelate with high thermodynamic stability and kinetic inertness. Indeed, the conditional stability of [Gd(OPDMA)]− (pGd = 14.8; pH 7.4, cGdL = 10–5 M) calculated for physiological conditions is comparable to that of [Gd(DTPA)]2− (pGd = 15.6), and its dissociation half-life is estimated to be 3.2 years at 37 °C and pH 7.4, making it an exceptionally inert chelate. Moreover, the water proton relaxation enhancement efficacy of [Gd(OPDMA)]− (r1 = 4.5 mM–1 s–1, 25°C, 20 MHz) is similar to that of clinical MRI contrast agents. Luminescence lifetime measurements and 17O NMR data confirmed the presence of one water molecule in the inner sphere of the metal ion (q = 1), which undergoes relatively fast exchange (k = (73 ± 12) × 106 s–1). The fast water exchange can likely be related to an associatively activated mechanism, as suggested by the negative activation entropy, ΔS⧧ = −(7 ± 1) J mol–1 K–1. In accordance with this, DFT calculations indicate an eight-coordinated structure for the Gd(III) ion, involving one water molecule and seven donor atoms of the OPDMA4–, while one carboxylate group remains uncoordinated
ECOSBot: a multicenter validation pilot study of a generative AI tool for OSCE-based nephrology training
No full textInternational audienceBackgroundDeveloping diagnostic reasoning in nephrology is particularly challenging due to its pathophysiological complexity and reliance on abstract clinical data. Objective Structured Clinical Examinations (OSCEs) are pivotal for nephrology training but remain resource-intensive and difficult to scale. Generative artificial intelligence (AI) offers a promising alternative, yet its capacity to emulate nephrology-specific OSCEs has not been formally assessed.MethodsWe developed ECOSBot, a web-based tool powered by GPT-4o, to simulate both standardized patients and examiners for nephrology-focused OSCEs. In this multicenter prospective study, undergraduate medical students from five French medical schools interacted with ECOSBot across four clinical stations. All interactions were double-rated by nephrology faculty members to establish a gold standard. ECOSBot’s performance was evaluated against this standard using four criteria (script coverage, authenticity, correctness and relevance) for patient simulation, and via checklists and competency-based ratings for examiner scoring. Usability was assessed using the Chatbot Usability Questionnaire (CUQ), adapted to include six items on feedback quality.ResultsNinety-one students generated 2939 prompts across 184 OSCE sessions. ECOSBot demonstrated high fidelity in patient simulation: authenticity 98.6% [95% confidence interval (CI) 98.2–99.0], correctness 98.3% (95% CI 97.9–98.7) and relevance 99.2% (95% CI 98.9–99.5), including during exchanges not explicitly covered by the pre-specified scenario. As an examiner, ECOSBot showed strong agreement with human raters on global scores [intraclass correlation coefficient (ICC) = 0.94, 95% CI 0.91–0.96], consistent across case formats, training levels and institutions. However, scoring of attitude and communication skills was less reliable (ICC = 0.44, 95% CI 0.28–0.58). Median CUQ score was 69.7/100, with 91.7% of students finding the tool highly useful for OSCE preparation in nephrology.ConclusionsECOSBot reliably simulated both roles in nephrology OSCEs with high fidelity and strong alignment with expert rating. While challenges remain for subjective skill assessment, this tool offers a scalable and autonomous solution to enhance nephrology education
Quand une crise sanitaire mondiale percute l’expérience parentale du cancer pédiatrique
No full textInternational audienceThis chapter explores the repercussions of the Covid-19 health crisis on the experience of families with children suffering from pediatric cancer. While the sociology of health has largely studied the management of chronic and serious illnesses, this work questions the way in which a global health crisis impacts and redefines the frameworks of this management, already marked by multiple uncertainties and constraints. Based on a qualitative survey of parents of children treated in oncopediatrics, the article analyzes the juxtaposition of two crises - the child's illness and the pandemic - and looks at how families adjust their daily practices, their perceptions of risk and their relationships with caregivers. Drawing on concepts from the sociology of public action and experiential knowledge, the authors question the tensions between parental and medical knowledge in a context of risk management on both an individual and collective scale.Ce chapitre explore les répercussions de la crise sanitaire du Covid-19 sur l'expérience des familles dont un enfant est atteint de cancer pédiatrique. Alors que la sociologie de la santé a largement étudié la gestion des maladies chroniques et graves, ce travail interroge la manière dont une crise sanitaire mondiale vient percuter et redéfinir les cadres de cette gestion, déjà marquée par des incertitudes et des contraintes multiples. À partir d'une enquête qualitative menée auprès de parents d'enfants suivis en oncopédiatrie, l'article analyse la juxtaposition de deux crises — la maladie de l'enfant et la pandémie — et s’intéresse à la manière dont les familles ajustent leurs pratiques quotidiennes, leurs perceptions du risque et leurs relations avec les soignants. En mobilisant des concepts issus de la sociologie de l’action publique et des savoirs expérientiels, les autrices questionnent les tensions entre savoirs parentaux et savoirs médicaux dans un contexte de gestion du risque à double échelle, individuelle et collective
« Le modèle académique des premières sociétés de Concert (France, 1707–1770) »
No full textInternational audienceLes premières « Académies de musique » ou « Concerts » apparaissent dans les provinces de France dans les années 1710, et se développent de façon considérable entre 1720 et 1750. Leur rapide dissémination au sein du maillage urbain constitue un phénomène majeur de la vie musicale, celui des premiers concerts en société. À la croisée entre sociétés savantes et entreprises de spectacle, ces institutions, actives dans plus de 60 villes françaises, opèrent un bouleversement sans précédent du paysage culturel, qui s’accompagne d’une profonde mutation des espaces, des publics et des répertoires. Elles inspireront notamment la création du Concert spirituel parisien, des Concerts d’amateurs (auxquelles elles céderont la place à la fin du XVIIIe siècle) et jusqu’aux sociétés philharmoniques du XIXe siècle.Débuté il y a 3 ans, le chantier de collecte de sources du projet AcadéC a permis de rassembler un vaste corpus d’archives documentant la structure, la gestion administrative, les modalités de production des concerts hebdomadaires et les pratiques musicales de ces académies de musique. Dès leur fondation, celles-ci se réclament d’un modèle commun et original, tout en faisant apparaître des particularités locales. Les sources, en particulier les règlements, permettent d’interroger le processus de création de ces organisations collectives, et notamment le choix du nom et des attributs, les permissions et autorisations des autorités locales ou royales, la hiérarchisation interne de leurs membres, l’organisation administrative ou encore la gestion financière et artistique.Sources proposées à l’étude :1721, Orléans, statuts1758, Orléans : projet d’abonnement1775, Narbonne, règlements de l’orchestr
Évaluer les unités spatiales et analyser la formation des ensembles archéologiques à partir des remontages : l’application archeofrag.gui, une chaîne opératoire intégrée
No full textNational audienceL'identification d'unités spatiales distinctes est au fondement de l'investigation archéologique, qu'il s'agisse de couches stratigraphiques ou de tout autre sorte d'entité spatiale dont la définition constitue le préalable aux étapes ultérieures d'un raisonnement archéologique. De nombreuses méthodes ont été publiées depuis la fin du XIXe siècle. Aucune, néanmoins, n'avait encore été intégrée dans des outils logiciels en facilitant la diffusion et l'usage, jusqu'à la publication de la méthode TSAR (Topological Study of Archaeological Refitting). Le package R 'archeofrag' implémente cette méthode. Cependant, la connaissance du langage R constituant une barrière importante pour l'utilisation de cet outil, une application à interface graphique, 'archeofrag.gui', a été développée pour en faciliter l’usage
L'opéra-comique et la Révolution française: Effervescence et création musicale entre les Lumières et le Romantisme
No full textInternational audienceDepuis le Bicentenaire de la Révolution, la recherche en musicologie n’a cessé de s’intéresser à cette période tant du point de vue de la vie musicale en général, que de celui des théâtres en province ou des principaux genres et institutions musicales parisiennes. Néanmoins, alors que l’opéra-comique constitue le genre de théâtre lyrique français le plus important et le plus influent en France et en Europe à la fin du XVIIIe siècle, ce genre mêlant épisodes parlés et chantés a, paradoxalement, reçu peu d’attention.En s’appuyant sur des recherches récentes, des outils numériques nouvellement développés et des sources parfois inédites, cet ouvrage a pour but de s’intéresser aux évolutions esthétiques de l’opéra-comique entre le début de la Révolution et la réunion des théâtres Favart et Feydeau en 1801 et d’attirer l’attention sur des ouvrages qui ont servi de base esthétique au théâtre lyrique français et Européen au XIXe siècle. En analysant le répertoire des théâtres et les processus d’hybridation du genre sous l’impulsion de différents facteurs liés, pour partie, aux circonstances révolutionnaires, cette étude attire l’attention sur les processus artistiques et musicaux qui sont en jeu au cours d’une période fondatrice tant pour les institutions musicales françaises que pour les genres musicaux et tente de proposer un changement de perspective sur la naissance du romantisme
Should I Wait or Should I Pay? The Dynamics of Private and Public Healthcare
No full textIn many countries, a private health system coexists with the public one. Recently, however, it seems that the latter is subjected to budgetary cuts and no longer able to meet the needs of citizens. Within an OLG model with production and in which young agents invest in preventive medicine and consume private healthcare beside public one, we prove that access to public health system is rationed by increasing waiting times, entailing costs in terms of treatment e!ectiveness and psychological order. Considering a fiscal policy aimed at providing health services, we prove that there emerge two dynamic regimes, the first prevailing for low GDP levels, the other for larger ones, where waiting times are countercyclical. We find two stationary capital levels, the lower one being globally unstable while the higher one globally stable. We also study the set of optimal allocations and prove that stationary GDP is increasing in the social discount factor. Finally, we show that it is possible to decentralize any optimal allocation by fixing opportunely the debt-to-GDP ratio and government spending in healthcare
Intégration visuo-haptique ambiguë dans un environnement de téléopération
No full textInternational audienceHuman agents have been shown to integrate visual and haptic information in a statistically-optimal fashion, by weighting each information by its reliability. So far, previous experiments had always added noise to the visual cues, in order to equalize visual reliability (high) with haptic (low) reliability. The present study aims to further characterize the rules of multisensory integration, by varying visual and haptic reliabilities. To that aim, we will ask healthy adults (target n = 10) to perform a psychometric size-discrimination task. Visual, haptic, and visuo-haptic objects (rectangular 3D shapes) will be presented by means of a simulated visual environment (computer screen) and a haptic interface (Omega 7.0). Participants will be presented two successive objects, a standard stimulus (width: 64 mm) and a comparison stimulus (width: standard ± 1, 2, 3, 5, 8 mm), and will be asked to estimate which object is the largest. Cue reliabilities will be manipulated using visual sharpness (normal vs blurred) and haptic stiffness (“hard” [3000 N/m] vs. “soft” [1000 N/m]), respectively. Visuo-haptic conflicts (-2, 0, +2 mm) will be used to induce sensory reweighting. According to pilot observations, visuo-haptic noises tend to increase the JND measurements. Data collection will take place in March-April. The main experiment will test whether visuo-haptic integration is optimal for the different combinations of noisy and non-noisy unimodal cues
A consortium of seven commensal bacteria promotes gut microbiota recovery and strengthens ecological barrier against vancomycin-resistant enterococci
No full textInternational audienceVancomycin-resistant enterococci (VRE) often originate from the gastrointestinal tract, where their proliferation precedes dissemination into the bloodstream, and can lead to systemic infection. Uncovering the actors and mechanisms reducing the intestinal colonisation by VRE is essential to control infection. We aimed to identify commensal bacteria that interfere with VRE gut colonisation or act as an ecological barrier.ResultsWe performed a 3-week longitudinal analysis of the gut microbiota composition and VRE carriage levels during microbiota recovery in mice colonised with VRE after antibiotic-induced dysbiosis. By combining biological data and mathematical modelling, we identified 15 molecular species (OTUs) that negatively correlated with VRE overgrowth. Six strains representative of these OTUs were collected, cultivated and used in mixture with a seventh strain (Mix7) in two different mouse lines challenged with VRE. Of the seven strains, three belonged to Lachnospiraceae, one to Muribaculaceae, one to Ruminococcaceae and two to Lactobacillaceae. We found that Mix7 led to a better recovery of the gut microbiota composition and reduced VRE carriage. Differences in the effect of Mix7 were observed between responder and non-responder mice. These differences were associated with variations in the composition of the initial microbiota and during recovery and represent potential biomarkers for predicting response to Mix7. In a mouse model of alternative stable state of dysbiosis, response to Mix7 was associated with higher concentrations of short-chain fatty acids (acetate, propionate, butyrate) and a range of metabolites including bile acids, reflecting the recovery of the microbiota back to initial state. Furthermore, Muribaculum intestinale strain was required to obtain the Mix7 effect on VRE reduction in vivo, but the presence of at least one of the other six strains was needed. None of the supernatant of the seven strains, alone or in combination, inhibited VRE growth in vitro. Interestingly, five strains belong to species shared among humans and mice, and the other two have human functional equivalents.ConclusionsAn innovative approach based on mathematical modelling of the microbiota composition permitted to identify a mixture of commensal bacterial strains, which improves the ecological barrier effect against VRE. The mechanisms are dependent on the recovery and initial composition of the microbiota. Ultimately, this work will enable a move towards a personalised medicine by targeting predisposed patients presenting a risk of infection, such as neutropenic or bone-marrow transplant patients, and likely to respond to supplementation with commensal strains, providing new live biotherapeutic products and biomarkers to predict response to supplementation.--QgEhBLB8UrKv1oYceiTBVideo AbstractConclusionsAn innovative approach based on mathematical modelling of the microbiota composition permitted to identify a mixture of commensal bacterial strains, which improves the ecological barrier effect against VRE. The mechanisms are dependent on the recovery and initial composition of the microbiota. Ultimately, this work will enable a move towards a personalised medicine by targeting predisposed patients presenting a risk of infection, such as neutropenic or bone-marrow transplant patients, and likely to respond to supplementation with commensal strains, providing new live biotherapeutic products and biomarkers to predict response to supplementation
VISION TRANSFORMERS FOR X-RAY DIFFRACTION PATTERNS ANALYSIS
No full textInternational audienceUnderstanding materials properties depends largely on the ability to determine its components, and in particular its mineral phases. Powder X-ray diffraction (XRD) is a powerful tool for such purposes. This paper presents a Transformerbased vision model (ViT) for mineral phase identification, and proportion inference to quantify the mineral phases present in a material. Our analysis shows that the tokenization strategy is a critical step for XRD pattern analysis. The results obtained for both tasks are excellent and more robust than those obtained with a CNN. The proposed approach also makes it possible to introduce visualization tools for signal analysis, to better understand how information flows through the model and how data is classified or quantified