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Unveiling the molecular identity of plant autophagic compartments: A proteo-lipidomic study in <i>Arabidopsis thaliana</i>
No full textAbstract Autophagy is an intracellular catabolic and recycling process critical for plant stress tolerance. Upon autophagy induction, a unique and very specialized membrane named phagophore nucleates, shapes, expands and fuses to yield a double membrane vesicle sequestering and trafficking cargo for degradation. To better understand how this intense series of membrane remodeling events is orchestrated and identify the underlying actors, we aimed at establishing the molecular footprint of the phagophore. In this study, we first report on a method to purify autophagic compartments in Arabidopsis, by combining cell fractionation and immuno-isolation in native conditions. Second, proteomic analyses of ATG-isolated membranes allowed us to establish a list of candidate proteins involved in autophagy, membrane remodeling, vesicular trafficking and lipid metabolism and colocalizing with autophagic compartments after transient expression in Nicotiana benthamiana . Third, lipidomic analyses revealed that ATG-isolated membranes are mostly composed of glycerophospholipids-with a minor contribution of sterols and sphingolipids-, including a large proportion of phosphatidylcholine and phosphatidylglycerol. Together, our study unravels the singular composition of the plant phagophore and provides key protein and lipid candidates to explore how lipid and membrane dynamics instruct the autophagy pathway
Évaluation des événements indésirables associés à la sédation procédurale extrahospitalière : une étude observationnelle prospective multicentrique - Étude Procédol
No full textIntroduction: managing acute pain during procedures is a priority in emergency medicine. Procedural sedation is an alternative to general anesthesia that ensures patient comfort while maintaining respiratory and hemodynamic safety. These procedures carry significant risks. Many studies have been conducted in the hospital setting about adverse events, but very few have focused on the prehospital context. Objective: the main objective of this study was to describe the adverse events associated with procedural sedation performed in out-of-hospital emergency medicine. Methods: this was a prospective obervational, national multicenter study including adults who underwent procedural sedation in the prehospital setting between june 1st, 2023, and june 7th, 2025. The primary outcome was the occurrence of one or more adverse events during out-of-hospital procedural sedation. Main results: Adverse events occurred in 95 patients out of 400 included, corresponding to a rate of 23.8%. The main events were respiratory and psychodysleptic. Adverse events occurred in nearly one quarter of cases, but were mostly minimal or minor, and no sentinel events requiring invasive action were reported. Conclusion: adverse events related to out-of-hospital procedural sedation are not uncommon, but are usually mild. future randomized interventional studies could help develop standardized protocols to harmonize practice.Introduction : la prise en charge de la douleur aiguë associée à des gestes constitue une priorité en médecine d’urgence. La sédation procédurale est une alternative à l’anesthésie générale qui permet d’assurer le confort du patient tout en garantissant la sécurité respiratoire et hémodynamique. Ces procédures présentent des risques non négligeables. De nombreuses études ont été menées à ce sujet en contexte hospitalier, mais très peu se sont intéressées au contexte préhospitalier. Objectif : l’objectif principal de ce travail était de décrire les événements indésirables associés à la réalisation d’une sédation procédurale en médecine d’urgence extrahospitalière. Méthode : il s’agissait d’une étude observationnelle prospective multicentrique nationale, concernant les adultes ayant bénéficié d’une sédation procédurale en préhospitalier entre le 1er juin 2023 et le 7 juin 2025. Le critère de jugement principal était la survenue d’un ou de plusieurs événements indésirables lors de la réalisation d’une sédation procédurale extrahospitalière. Résultats principaux : des événements indésirables sont survenus chez 95 patients sur 400 inclusions, soit un taux de 23,8 %. Les événements principaux étaient respiratoires et psychodysleptiques. Ils survenaient donc dans presque un quart des cas, mais principalement minimes ou mineurs, et aucun événement sentinelle nécessitant une action invasive n’a été rapporté. Conclusion : les événements indésirables liés à la sédation procédurale extrahospitalière ne sont pas rares, mais sont le plus souvent bénins. La réalisation d’études interventionnelles randomisées pourrait permettre la réalisation de protocoles ultérieurs afin d’homogénéiser les pratiques
Innovative clinical trial approach for evaluating digital medical devices under European HTA fast-Track frameworks
No full textInternational audienceBackground / Introduction: Recently, several health technology assessment bodies across European Union countries have begun incorporating users' demands for quicker access to digital medical devices (DMDs). Introducing a conditional fast-track pathway that enables early access and reimbursement presents an attractive solution for patients, healthcare professionals, and the medical device industry. However, regulators must ensure they have enough data to justify provisional reimbursement and user access, even if complete clinical evidence is not yet available. By the time manufacturers complete the clinical study, they will have also gathered real-world data (RWD) from the DMD's use in the population. This dual source of information—clinical trial data and RWD—provides regulators with a richer evidence base for final decision-making, a significant improvement over the traditional reliance solely on clinical trial data. We propose a statistical framework that integrates clinical trial data and RWD, allowing a more rigorous evaluation of DMDs in compliance with European fast-track regulatory requirements.Methods: Our framework includes three stages: (1) an interim analysis of clinical trial data to support temporary regulatory authorization and enable the collection of RWD; (2) a final analysis of the clinical trial data; and (3) a meta-analysis that integrates RWD with clinical trial data, provided temporary authorization was be granted. Various metrics are introduced to optimize the timing of the interim analysis and the application for temporary authorization. The framework was evaluated using a simulation study.Results: Using a significance level α=0.025 and a power 1-β=0.9 for a one-sided two-sample test for proportions, Π_I^trial=0.7 and Π_C^trial=0.4 as the true response rates for the intervention and control arms in the clinical trial population, c^*=0.8 as the threshold for the conditional power (CP), the timing of the interim analysis is deduced as t=0.5 and the CP is greater than c^* in 70% of cases. In these situations, the temporary regulatory authorization is obtained, and therefore RWD can be collected in parallel with the second part of the clinical trial. Then, integrating RWD into the final analysis allows a gain in effective sample size compared to the traditional approach.Conclusion: This framework should include a post-market evaluation of the DMD after its widespread adoption, in line with the principles of phase IV studies. While the primary purpose of the final augmented analysis is to refine the findings of clinical trials, it can also serve as an initial assessment of the generalizability of those results in real-world settings
Création d’un outil de sensibilisation à la prise en charge orthophonique auprès d’adultes porteurs de trisomie 21 et de leurs aidants
No full textDown syndrome is a genetic syndrome affecting around 1/1000 births per year worldwide. This syndrome can cause cognitive, language and communication difficulties which can remain at adulthood. Although it is beneficial for them, speech therapy for adults with Down syndrome is not generalized. A caregiver is sometimes necessary in helping adults with Down syndrome to understand information and make decisions. In order to inform adults with Down syndrome and their carers about the benefits of a speech therapy and to give them useful advice, we chose to create an awareness-raising tool that consists of two targeted brochures. The first one is for adults with Down syndrome and the second one is for caregivers. We met 18 adults with Down syndrome and 20 caregivers. These meetings aimed at assessing their understanding of the tool and its relevance. The results showed that the form and content of the brochure for caregivers were appropriate. The form of the brochure for adults with Down syndrome was adequate. However, its content would require some adjustments. Creating two separate brochures was relevant. A majority of interviewed people explained that the tool motivated them to have a speech therapy. Thanks to the interviews, we collected tips in order to adapt the tool for target users.La trisomie 21 est un syndrome génétique touchant environ 1/1000 naissances par an dans le monde. Ce syndrome engendre parfois des difficultés cognitives, langagières et communicationnelles qui peuvent persister à l’âge adulte. La prise en charge orthophonique auprès des adultes porteurs de trisomie 21, bien que bénéfique, n'est pas généralisée. L’aidant joue un rôle essentiel dans la compréhension des informations et dans les prises de décision de l’adulte porteur de trisomie 21. Afin d’informer ce dernier et son aidant de l’intérêt d’une prise en charge orthophonique et de leur fournir des conseils utiles, nous avons choisi d’élaborer un outil de sensibilisation sous forme de deux brochures ciblées. La première brochure est à destination des adultes porteurs de trisomie 21 et la seconde, à destination de leurs aidants. 18 adultes porteurs de trisomie 21 et 20 aidants ont été rencontrés. Ces entretiens avaient pour but d’analyser la compréhension de l’outil et sa pertinence. Notre étude a mis en évidence que la forme et le contenu de la brochure destinée aux aidants étaient adaptés. Cependant, nous avons relevé que la forme de la brochure à destination des adultes porteurs de trisomie 21 était appropriée mais que son contenu nécessitait quelques modifications. Par ailleurs, élaborer deux brochures distinctes était judicieux et une majorité des individus interrogés ont exprimé que l’outil motivait à initier ou à poursuivre le suivi orthophonique. Les entretiens nous ont permis de recueillir des conseils pour améliorer l’outil et le rendre davantage adapté au public concerné
Shapley Value Computation in Ontology-Mediated Query Answering (Extended Abstract): Extended Abstract for "Best Papers from Sister Conferences Track"
No full textInvited to be presented on IJCAI 2025 "Sister Conferences Best Paper Track" based on the paper with same title which appeared in KR 2024.International audienceIn this work, we explore the use of the Shapley value in ontology-mediated query answering (OMQA) and provide a detailed complexity analysis of Shapley value computation (SVC) in the OMQA setting. In particular, we establish a FP/#P-hard dichotomy for SVC for ontology-mediated queries (T,q) composed of an ontology T formulated in the description logic ELHI-bot and a connected constant-free homomorphism-closed query q. We further strengthen the #P-hardness side of the dichotomy to cover possibly disconnected queries with constants. Our results exploit recently discovered connections between SVC and probabilistic query evaluation and allow us to generalize existing results on probabilistic OMQA
Justice sans audience: Étude d'impact sur les justiciables et les professionnels du droit
No full textCette recherche est issue de l’appel à projet lancé en 2021 sur le thème : Justice sans audienceAlthough its functions differ according to the written or oral nature of the procedure, the hearing is historically and ontologically associated with the trial and with everything that symbolises Justice. Despite this anchoring, the hearing is no longer a sacred time-space, since its abolition is now accepted in favour of entirely written civil or criminal proceedings, giving rise to a judgment on the record and therefore without a hearing. While much work has already been done on the weakening of the role of the hearing and the transformation of its physiognomy, the aim of this research is to examine more radically whether it is being maintained or disappearing in the handling of certain types of litigation. The advent of justice without a hearing is therefore a reality whose scope has been significantly amplified by the health crisis. Taking note of this new paradigm, this research conducted by a multidisciplinary team of researchers in law and political science, and sociologists, designed as an impact study, assesses the consequences of eliminating the hearing phase for all parties involved in the trial. It focuses on two complementary areas: the first looks at litigants, questioning the usefulness of hearings, the social acceptability of their abolition and the compatibility of this abolition with the fundamental rights of the trial; the second focuses on the perception of justice without hearings by legal professionals and the impact of these procedures on the organisation of their work and the meaning of their missions. Based on an empirical analysis combining various qualitative and quantitative survey methods, it appears that the decline in court hearings is viewed with mixed feelings by those involved in the justice system. Firstly, despite observing a real decline in court hearings in judicial practice, professionals remain relatively attached to them. Indeed, even if hearings are in some cases seen as a waste of time, the majority of them consider that it would in fact be difficult to do without hearings, as they are such an important organisational marker and stage in the decision-making process. Litigants, meanwhile, express their attachment to hearings through a generally more positive view of proceedings with hearings than without, as the latter seem to undermine their sense of being heard and of having their procedural rights respected. The findings highlighted the effective reduction in the number of hearings in legal proceedings, made possible by the absence of any fundamental incompatibility between a judgment without a hearing and the fundamental principles of procedure. Despite this observation, the lukewarm reception given to the abolition of hearing time by justice professionals, and the difficulty of envisioning the development of justice without a hearing, actually point to the need to rethink the hearing.Bien que ses fonctions diffèrent selon la nature écrite ou orale de la procédure, l’audience est historiquement et ontologiquement associée au procès et à tout ce qui symbolise la Justice. Cependant, malgré cet ancrage, l’audience n’est plus un espace-temps sacré puisque sa suppression est désormais admise à la faveur de procédures civiles ou pénales entièrement écrites, donnant lieu à un jugement sur dossier et donc sans audience. Prenant acte de ce nouveau paradigme, le rapport montre que le recul de l’audience est apprécié de façon très mitigée par les acteurs de la justice. L’attachement des professionnels à l’audience reste relativement fort. Si dans certains cas, ils vivent l’audience comme une perte de temps, la majorité d’entre eux considèrent qu’il serait en réalité difficile de s’en passer, tant elle est un marqueur organisationnel et une étape du processus décisionnel. Les justiciables s’expriment, quant à eux, à travers une vision globalement plus positive des procédures avec audience que sans audience, ces dernières semblant heurter leur sentiment d’être entendus et de voir leurs droits procéduraux respectés. Ainsi, si le rapport permet de mettre en lumière le recul effectif de l’audience dans les procédures judiciaires rendu possible par une absence d’incompatibilité fondamentale entre jugement sans audience et principes fondamentaux de la procédure, il conclut à la nécessité de repenser autrement l’audience
Wavefront Shaping of Scattering Forces Enhances Optical Trapping of Levitated Nanoparticles
No full textOptically-levitated nanoparticles in vacuum offer a pristine platform for high-quality mechanical oscillators, enabling a wide range of precision measurements and quantum technologies. A key performance metric in such systems is the stiffness of the optical trap, which is typically enhanced by increasing laser power-at the cost of unwanted heating, reduced coherence, and enhanced quantum backaction. Here, we demonstrate a fundamentally new route to increasing trap stiffness: wavefront shaping of the optical field. By tailoring the spatial phase profile of the trapping beam, we significantly boost the mechanical confinement of subwavelength particles without raising the optical intensity. Remarkably, this enhancement arises from a selective reduction of non-conservative optical forces, while preserving the conservative restoring forces that define trap stiffness. As a result, mechanical nonlinearities are also reduced, improving stability at low pressures. Our findings challenge the long-standing assumption that diffraction-limited focusing is optimal for dipolar Rayleigh particles, and establish wavefront shaping as a powerful, readily applicable tool to control optomechanical forces in levitation experiments. This opens new avenues for minimizing backaction, reducing thermal decoherence, and expanding the range of materials that can be stably levitated
Modèle de maturité pour la fabrication additive métallique : AMRL
No full textInternational audienceDespite many promises, metal additive manufacturing (MAM) adoption is still limited within the industry. To effectively and successfully implement MAM, companies need to assess their maturity status quo, combined with the MAM technology maturity, at both organisational and operational levels. However, existing maturity models (MMs) are either only dedicated to just one of these levels or are not adapted to MAM. Thus, this paper proposes an original and tailored MM: the Additive Manufacturing Readiness Levels (AMRL), a multicriteria MM to evaluate the maturity of a MAM technology coupled with a use case, offering a context-aware approach that bridges technological capability and operational applicability. The model features 8 dimensions, divided into 22 sub-items to be assessed, referring to Industry 5.0 pillars, including environmental and social considerations. To develop and validate the proposal, an iterative methodology is followed where the AMRL is applied to compare the maturity of three Directed Energy Deposition technologies coupled with nine use cases in the context of a French Technology Transfer Centre. Direct interviews with experts and measures of agreement granted validation. AMRL aims to contribute to the adoption of MAM by assisting decision makers. Future research could investigate its use in different industry sectors and decision configuration
Évaluation de l’impact de la classification moléculaire sur la prise en charge adjuvante du cancer de l’endomètre
No full textIntroduction: endometrial cancer is the most common gynecological cancer in developed countries. Its adjuvant management is now based on molecular classification, including tumors with a deoxyribonucleic acid (ADN) polymerase ε (POLE) gene mutation. The objective of this study was to evaluate, in routine practice, the impact of POLE mutation testing on treatment initiation time, management modifications, and survival of patients with endometrial cancer. Methods: the EndoMol study is a retrospective single-center cohort conducted at the cancer control Iinstitute of Nouvelle-Aquitaine between 2018 and 2025. Patients who underwent surgery for endometrial cancer between 2018 and 2024 were included. The difference in pathological report turnaround time was estimated, as well as overall and recurrence-free survival. Results: among 257 included patients, 127 (49.4%) underwent POLE mutation testing, of whom 14 (11.0%) were mutated. This analysis increased the mean pathological report turnaround time by 9.1 days (p < 0.001). In POLE-mutated patients, international federation of gynaecology and obstetrics (FIGO) staging was modified in 7 cases and therapeutic strategy adjusted in 6 cases. No recurrence or death was observed among these patients after a median follow-up of 19 months. No significant difference in overall or recurrence-free survival was found between tested and untested patients. Discussion: molecular classification influences the therapeutic management of endometrial cancer, although its implementation lengthens diagnostic delays. The impact of POLE mutation testing on survival remains to be confirmed. Multicenter prospective studies are needed to validate these findings.Introduction : le cancer de l’endomètre est le cancer gynécologique le plus fréquent dans les pays développés. Sa prise en charge adjuvante repose désormais sur la classification moléculaire, intégrant notamment les tumeurs présentant une mutation du gène acide désoxyribonucléique (ADN) polymérase ε (POLE). L’objectif de cette étude était d’évaluer, en pratique courante, l’impact de la recherche de mutation POLE sur le délai de mise en traitement, les modifications de prise en charge et la survie des patientes atteintes d’un cancer de l’endomètre. Méthodes : l’étude EndoMol est une cohorte rétrospective monocentrique menée à l’Institut de lutte contre le cancer de Nouvelle-Aquitaine entre 2018 et 2025. Ont été incluses les patientes opérées pour cancer de l’endomètre entre 2018 et 2024. La différence de délais de rendu anatomopathologique a été estimé ainsi que les survies globales et sans récidive Résultats : parmi 257 patientes incluses, 127 (49,4 %) ont bénéficié d’une recherche de mutation POLE, dont 14 (11,0 %) étaient mutées. Cette analyse a allongé le délai moyen de rendu anatomopathologique de 9,1 jours (p < 0,001). Chez les patientes POLE-mutées, la stadification fédération internationale de gynécologie et obstétrique (FIGO) a été modifiée dans 7 cas et la stratégie thérapeutique ajustée dans 6 cas. Aucune récidive ni décès n’a été observé chez ces patientes après un suivi médian de 19 mois. Aucune différence significative de survie globale ou sans récidive n’a été mise en évidence entre les patientes testées et non testées. Discussion : la classification moléculaire influence la prise en charge thérapeutique du cancer de l’endomètre, bien que sa mise en œuvre allonge les délais diagnostiques. L’impact de la recherche de mutation POLE sur la survie reste à confirmer. Des études multicentriques prospectives sont nécessaires pour valider ces observations
Tout ne se calcule pas … et pas que l’amour :)
No full textNational audienceAllez avouez-le : quand on observe certains de nos congénères, ne souhaite-t-on pas aux ordinateurs de surtout pas devenir « intelligents » comme nous ? Bonne nouvelle pour ces machines : ça fonctionne vraiment différemment de notre cerveau. Oui … mais comment ces machines peuvent-elles exécuter des algorithmes aussi déraisonnablement efficaces au quotidien que ce dont nous disposons désormais ? David Louapre qui anime la [super] chaîne de popularisation scientifique Science Étonnante avec son blog associé, nous fait découvrir ici la « première machine » qui a fonctionné comme un ordinateur sans … avoir besoin de la construire ! Et nous permet d’approfondir notre réflexion sur ces questionnements entre intelligence humaine et ce qu’on dit être de l’intelligence artificielle. Benjamin Ninassi et Pierre Paradinas