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Remboursement intégral du voyage à forfait, CJUE, 23 oct. 2025, aff. C-469/24, Tuleka
No full textInternational audienceUn acte de puissance publique ne constitue pas, en principe, une circonstance exceptionnelle et inévitable exonérant l’organisateur de voyage à forfait. La réduction de prix est destinée à rétablir l’équilibre contractuel et commande un remboursement intégral en cas de défaillance de grande ampleur laquelle équivaut de fait à une inexécutio
The Proinflammatory Secretome of Senescent Cells Can Be Controlled by a HIF2A ‐Dependent Upregulation and a FURIN ‐Dependent Cleavage of the ANGPTL4 Secreted Factor
No full textInternational audienceSenescent cells are characterized by a stable proliferation arrest and a senescence-associated secretory phenotype or SASP. Although these cells can have some beneficial effects, including protecting from tumor formation, their accumulation is deleterious during aging as it promotes age-related diseases, including cancer initiation and progression. Although the SASP has a critical role, its composition, regulation and dual role in cancer remain largely misunderstood. Here, we show that ANGPTL4 is one of the rare secreted factors induced in many different types of senescent cells. Importantly, ANGPTL4 knockdown during senescence or its constitutive expression, respectively inhibits or induces classical proinflammatory SASP factors, such as IL1A, IL6 and IL8. The latter effect is mediated upstream of IL1A, an early SASP factor, suggesting an upstream role of ANGPTL4 in SASP induction. This ANGPTL4-dependent proinflammatory SASP can promote human neutrophil activation in ex vivo assays, or tumor initiation in a KRAS-dependent lung tumorigenesis model in mice. This upstream activity of ANGPTL4 in regulating the proinflammatory SASP depends on its upregulation following a hypoxia-like response and HIF2A activation, and its proteolytic processing by the FURIN proprotein convertase. Altogether these findings shed light on a two-step activation of ANGPTL4 by HIF2A and FURIN in senescent cells and its upstream role in promoting the proinflammatory SASP, cancer and potentially other senescence-associated diseases.</div
Jeux Olympiques et Paralympiques de Paris 2024 : motivation des volontaires et image des territoires hôtes
No full textInternational audienceParis has a close relationship with the modern Games, as it is the city where the International Olympic Committee (IOC) was founded in 1894.After 130 years, the Paris Games have been transformative, including in terms of volunteer engagement, both on the part of the COJOP and local actors such as the City of Paris and the Department of Seine-Saint-Denis. During the Paris 2024 Olympic Games, more than 42,000 volunteers were mobilised to help organise this mega-event (INJEP, 2025). The use of volunteers is a long-standing practice, as there were already volunteers at the 1896 Athens Games, mainly from the Scouts, the army or sports clubs. Then, between the London Games in 1948 and those in Montreal in 1976, volunteer participation gradually increased, driven by the growing commitment of individuals wishing to contribute to the organisation of the Games (Olympic World Library, n.d.). The current model of Olympic volunteering emerged in the 1980s. Furthermore, the concept of Olympic volunteers appeared for the first time at the 1992 Games (ibid). A report then provides the definition of an Olympic volunteer: "The volunteer is a personwho makes an individual, altruistic commitment to collaborate, to the best of his/her abilities, in the organisation of the Olympic Games, carrying out the tasks assigned to him/her without receiving payment or rewards of any other nature" (ibid). As mentioned by Cousineau and Sohier (2024) in their study of volunteer motivations, the authors adapted scales on "the specific motivations of volunteers linked to sporting events or specific events."Through a questionnaire survey (550 responses) conducted among volunteers at the Games, as well as volunteers from the City of Paris and Seine-Saint-Denis mobilised for the event, we examined the motivations and profiles of volunteers and the impact of the volunteering experience on the image of the regions. These quantitative data are supplemented by observations made during our own immersion in volunteering during the Olympic Games, in Paris at the Invalides and La Concorde sites, and in Seine-Saint-Denis during specific volunteering events (training, arrival of the Paralympic flame, etc.). We ask ourselves how volunteering can impact the image of the host territories and whether the motivations of volunteers and their satisfaction have consequences on these images. Our initial analyses show, for example, that for volunteers in Seine-Saint-Denis, the image of the area has been greatly improved for 36% of them. Additional analyses will be carried out on our 33 questionnaire questions and will be compared with our observations during the event
Array Processing using Mathematics of Arrays for a Unified Approach to Embedded Processing with Application to The Internet of Things
No full textIn the development and deployment of embedded digital signal processing functionality within edge devices for the Internet of Things, the key requirements are effective and efficient implementation of the data processing, data storage, and data communications operations. This is becoming a major consideration for designers who are now, for example, routinely embedding Machine Learning and Deep Learning functionality within deployed embedded systems. In the design of such systems, there is a sequence of steps to undertake and realize a concept through to deployment, with an integrated approach to hardware and software design required to maximize the role that the hardware and software parts take to fulfill the overall required system functionality. How the data processing and memory organisation is achieved will depend on the data processing algorithms to employ. In this paper, the embedding of data processing for data within multi-dimensional arrays is considered, and the processing of dense and sparse arrays is developed with different approaches to efficiently store and process data. This paper will utilize the Mathematics of Arrays (MoA) approach for data processing on both dense and sparse arrays using Python and C coding that can be deployed in both software and, with extension, as a hardware solution. The approach illustrated here on basic examples constitutes both a new family of target hardware for MoA-based programming and, a new formalized and mechanisable technique for implementing a large family of computations
Prise en charge des symptômes perçus du burnout professionnel et d’insomnie associés chez l’adulte via un programme thérapeutique de groupe - Protocole d’étude clinique longitudinale contrôlée non andomisée
No full textInternational audienceIntroductionLorsqu’un travailleur vit une situation de stress sur une longue période sans possibilité de regénérer ses ressources personnelles, il peut développer un syndrome de burnout défini selon la CIM-11 et selon le modèle tridimensionnel de Maslach (1976), avec l’association de symptômes d’insomnie (Schiller and al., 2018).La thérapie comportementale et cognitive individuelle ou de groupe appliquée à l’insomnie (TCCi), est le traitement de première intention non médicamenteux (Riemann et al., 2023). Il n’existe pas à ce jour de consensus dans le traitement du burnout, plusieurs programmes thérapeutiques basés sur les TCCE ont été évalués (Maricutoiu et al., 2016) avec des résultats non concluants. Une revue systématique de la littérature démontre que peu d’études cliniques évaluent des prises en charge combinant burnout et insomnie ou avec une évaluation de ces deux syndromes. Devant la divergence des données concernant leur lien bidirectionnel (Yang et al., 2018 ; Jansson-Frömark et al., 2010), il est important aujourd’hui de proposer un modèle théorique et un programme thérapeutique efficace. Méthode Cette étude non randomisée contrôlée évalue un groupe thérapeutique construit sur le modèle des TCCE comparé à un groupe contrôle (liste d’attente). Le groupe se situe dans le cadre d’un hôpital de jour psychiatrique, intégrant des patients présentant des symptômes de burnout et d’insomnie. Les mesures quantitatives principales sont le niveau de burnout (Maslach Burnout Inventory), la sévérité de l’insomnie (Insomnia Severity Index), l’anxiété (General Anxiety Disorders) et la dépression (Patient Health Questionnaire). Les mesures secondaires sont les symptômes d’insomnie (Pittsburgh Sleep Quality Index et Epworth Sleepiness Scale), la présence de cauchemars (Nightmare Severity Index) et l’hyperéveil (The Hyperarousal Scale). Une étude qualitative sera réalisée par analyse thématique du contenu onirique, des ruminations diurnes et nocturnes.L’évaluation sera réalisée au long cours à 1, 3, 6 et 12 mois après l’intervention.Résultats À notre connaissance, c’est la seule étude contrôlée évaluant les symptômes d’insomnie dont les contenus oniriques et l’hyperéveil, jusqu’à 12 mois post-intervention. Nous nous attendons à une diminution significative de la dimension épuisement émotionnel du burnout avec une absence post intervention des symptômes d’insomnie. Si ce programme thérapeutique démontre son efficacité, il permettra de proposer un traitement basé sur la TCCE de groupe structurée et validée pour des patients adulte présentant des symptômes de burnout et d’insomnie associés
A practical guide to using games in university teaching
No full textTimes Higher EducationWhat is game-oriented learning, what criteria must games follow to have true educational value and how to use them in your own teaching? Find out her
Randomized multi-class classification under system constraints: a unified approach via post-processing
No full textWe study the problem of multi-class classification under system-level constraints expressible as linear functionals over randomized classifiers. We propose a post-processing approach that adjusts a given base classifier to satisfy general constraints without retraining. Our method formulates the problem as a linearly constrained stochastic program over randomized classifiers, and leverages entropic regularization and dual optimization techniques to construct a feasible solution. We provide finite-sample guarantees for the risk and constraint satisfaction for the final output of our algorithm under minimal assumptions. The framework accommodates a broad class of constraints, including fairness, abstention, and churn requirements
Curve registration for non-linear mixed effect ordinary differential equation models
No full textCurve registration refers to the alignment of temporal trajectories when individuals experience similar dynamics at different speeds. We study this problem in the context of nonlinear mixed-effects models based on ordinary differential equations (NLME-ODEs), which are commonly used to describe biological mechanisms in longitudinal data. We extend NLME-ODEs by introducing subject and state specific time-warping functionsthat represent local accelerations or decelerations of the dynamics. The goal is to propose mechanistic longitudinal population data analysiswhich incorporates and locates model error presence to mitigate its effect on model parameter estimation and acknowledge the action of mechanisms ignored by the ODE structure. We then focus on the treatment effect inference problem where these warping functions help to locate as accurately and exhaustively as possible the effects of a given therapy from a followed treated population. From the original model, we quantify treatment effects on well-identified mechanisms specified as ODE parameter covariates, now robustly estimated in model error presence. From the time-warping functions, we infer its action on mechanisms not included in the assumed ODE but appearing as distorted dynamics for treated subjects compared to the untreated ones. We formulate the joint estimation of ODE parameters and warping functions in amixed-effects likelihood framework and implement it in standard softwares such as Monolix implementing SAEM algorithm. Simulation studies show that including time warping improves estimation accuracy. Application to simian immunodeficiency virus (SIV) pre-clinical trial data demonstrates that the method can detect treatment effects on both modeled mechanisms and unmodeled processes. This framework combines mechanistic interpretability with descriptive flexibility, enhancing robustness in the analysis of longitudinal trial data
Allogeneic hematopoietic stem cell transplantation in germline DDX41 mutated patients with myeloid malignancies
No full textInternational audienceGermline DDX41 mutations (DDX41mut) are identified in approximately 5% of myeloid malignancies with excess of blasts, representing a distinct MDS/AML entity. The disease is associated with better outcomes compared to DDX41 wild-type (DDX41WT), but patients who do not undergo allogeneic hematopoietic stem cell transplantation (HSCT) may experience late relapse. Due to the recent identification of DDX41mut, data on post-HSCT outcomes remain limited. Here, we first report the HSCT outcomes of 83 DDX41mut MDS/AML patients. With a median follow-up (FU) of 4.4 years, the 2-year leukemia-free survival (LFS) was 68.6% (95% CI, 57.1 - 77.6), with a 2-year non-relapse mortality (NRM) of 21.1% (95% CI, 12.9 - 30.6). We then assessed the impact of DDX41mut using a pair match analysis performed on patients who underwent transplantation in AML clinical trials. No significant differences were observed between DDX41mut and DDX41WT patients in terms of LFS at 2 years (HR: 1.06, 95% CI, 0.59-1.90, p=0.84), overall survival (OS), NRM, relapse, or graft-versus-host disease (GVHD) incidence. The CIR for DDX41mut showed a trend toward a lower relapse rate during the first year and a higher relapse rate after 1 year. Given the familial nature of the disease, we specifically examined patients who relapsed after HSCT with a related donor, identifying 7 cases of DDX41mut donor cell leukemia (DCL). In our study, HSCT in DDX41mut AML patients was not associated with an increased risk of toxicity. However, we observed a potential for later relapse, which could potentially be mitigated by selecting related donors based on DDX41 status