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P1071 Comparison of effectiveness between Vedolizumab and Filgotinib in patients with ulcerative colitis previously exposed to at least one anti-TNF agent: Results from the real-world evidence multicenter VEDOFIL study
No full textInternational audienceBackground We aimed to compare the effectiveness of vedolizumab and filgotinib in patients with ulcerative colitis (UC) previously exposed to at least one anti-TNF agent. Methods This was a multicenter real-world evidence retrospective study that consecutively included all UC patients aged ≥18 years with symptomatic UC (partial Mayo score > 2) who initiated vedolizumab (VDZ) or filgotinib (FLG) after prior exposure to at least one anti-TNF. VDZ was administered intravenously with induction at 300 mg at weeks 0, 2, and 6, and subsequent IV infusions every 4 or 8 weeks according to the investigator’s choice. FLG was prescribed at a unique dose of 200 mg orally once daily. The primary endpoint was symptomatic remission (partial Mayo score ≤2) without corticosteroids (CFREM) at week 16 (W16). Secondary endpoints were clinical remission per modified Mayo score, and histological and endoscopic improvement (HEMI). Comparisons were made using propensity-score analyses (IPTW) adjusted the usual potential confounders. Results Overall, 230 patients were included (151 in the VDZ group and 79 in the FLG group. The two groups were comparable except for higher proportion of patients with prior exposure to at least 2 biologics (36.1% vs 92.1%; p < 0.001) in FLG group and concomitant corticosteroids (31.1% vs 19.0%) or an associated immunosuppressant (20.5% vs 0%) in VDZ group. After propensity adjustment, CFREM at W16 was achieved in 38.1% and 31.1% of patients in VDZ and FLG groups, respectively (p = 0.51). Subgroup analyses (after IPTW) showed that VDZ was more effective than FLG after failure of a single biologic (p < 0.001), with no difference after two prior failures (OR = 2.05 [0.36–11.71], p = 0.41), whereas FLG was more effective after failure of at least three prior biologics (OR = 10.4 [1.1–102.4], p = 0.045). No predictor of FLG effectiveness was identified. Factors associated with absence of CFREM at W16 on VDZ were UC severity (p = 0.035), failure of ≥ 3 biologics (p = 0.013), and primary failure to at least one biologic (p = 0.013). No difference was observed between the two treatments regarding clinical remission and HEMI at W16 (p = 0.47 and 0.18, respectively). With a median follow-up of over 12 months, no significant differences were noted between the two treatments in time to treatment discontinuation, UC-related hospitalization, or colectomy. Conclusion In this real-world evidence study, VDZ appeared to be a more effective option than FLG as a second-line biologic (after anti-TNF failure), whereas FLG became a better option in third- or fourth-line of advanced therapies. These data may help physicians managing patients with UC to guide therapeutic decision-making. Conflict of interest: Prof. Dr. Buisson, Anthony: Consulting fees from: Abbvie, AlfaSigma, Amgen, Arena, Biogen, Celltrion, CTMA, Ferring, Galapagos, Guty Care, Janssen, Hikma, Lilly, Mylan, Nexbiome, Pfizer, Roche, Takeda, Tillotts Lecture fees from: Abbvie, AlfaSigma, Amgen, Biogen, Celltrion, Ferring, Galapagos, Hikma, Janssen, Lilly, Mayoli-Spindler, MSD, Pfizer, Roche, Sanofi-Aventis, Takeda, Tillotts, Vifor-Pharma Research fundings from: Abbvie, AlfaSigma, Celltrion, Janssen, Lessaffre, Lilly, Pfizer, Takeda Bouguen, Guillaume: Grant: Abbvie, Ferisinus Personal Fees: Abbvie, Takeda, Fresinus, Amgen, Biogène, Arena, Ferring, Gilead, Janssen, MSD, Pfizer, Sandoz, Takeda, Tillots, Vifor pharma Nachury, Maria: Abbvie, Alfa Sigma, Biosynex, Celltrion, Galapagos, Janssen, Lilly, MSD, Pfizer, Takeda Uzzan, Mathieu: Grant: ECCO-IOIBD, Fondation pour la Recherche Medicale (FRM), SNFGE Personal Fees: Abbvie, Takeda, Celltrion, Janssen, Amgen, Alfasigma, Pfizer Domas, Quentin: No conflict of interest Serrero, Melanie: No conflict of interest Altwegg, Romain: Advisory boards from Abbvie, Takeda, Johnson and Johnson, Lilly, Alphasigma, Celltrion, Pfizer, Amgen, Biogen, Sandoz, Ferring Fumery, Mathurin: Grant: Pfizer Personal Fees: Abbvie, Janssen, Takeda, MSD, Biogen, Amgen, Sandoz, Fresenius, Gilead, Celgene, Galapagos, Mylan, Tillots, Ferring, Pfizer, Hospira, CTMA, Boehringer, Lilly, Arena Non-financial Support: Abbvie, Janssen, Takeda, MSD, Galapagos, Ferring, Pfizer Amiot, Aurelien: Personal Fees: Abbvie, Fresenius-Kabi, Adacyte, Tillotts pharma, Janssen, Pfizer, Biogen, AMgen, Sandoz, Takeda, Galapagos, Eli Lilly Caillo, Ludovic: Abbvie, Amgen, Celltrion, Ferring, Fresenius, Lilly, Jonhson&Jonhson, MSD, Pfizer, Takeda, Sandoz Hupé, Marianne: No conflict of interest Gilletta de Saint Joseph, Cyrielle: Speaker/ consultant fees from Abbvie, AlfaSigma, Amgen, Celltrion, Ferring, Fresenius, Janssen, Lilly, Pfizer, Takeda and Tillots Treton, Xavier: Personal Fees: Lectures and advisory board : Abbvie, Celltrion, MSD, johnson&Johnson, Takeda, Amgen, Alphasigma, Lilly, Pfizer Other: participations: Thabor Therapeutics Pereira, Bruno: No conflict of interes
[Responsabilité - Dossier spécial] L’indemnisation par l’assurance automobile à la suite de la loi Badinter
No full textInternational audienceLa loi Badinter poursuivait l’objectif d’une indemnisation rapide des victimes de dommages corporels par les assureurs automobiles dans un cadre amiable. Quarante ans plus tard, sa mise en application reste perfectible : des offres proposant parfois une indemnisation insuffisante et le non-respect fréquent des délais légaux conduisent encore à un abondant contentieux.L’objectif de la loi « Badinter » était fort ambitieux (1) : permettre une indemnisation amiable et rapide des victimes de dommages corporels issus d’un accident de la circulation. Cependant, sa mise en application, quarante ans plus tard, reste perfectible, entre risque de sous-indemnisation et difficulté pour les assureurs à respecter les délais légaux (2).I. Un objectif ambitieux : une indemnisation amiable et rapide des victimes de dommages corporelsII. Une réalité perfectible : entre non-respect des délais légaux et risque de sous-indemnisatio
Effects of Napping on Cognitive and Physical Performance in Sleep-Deprived Elite Kung-Fu Athletes
No full textInternational audienceBackground: Total sleep deprivation (TSD) negatively affects athletic performance by impairing mood, anaerobic performance, and decision-making in martial arts athletes. This study examined whether a 45 min nap can alleviate deficits in mood, anaerobic performance, and decision-making caused by TSD in elite Kung-Fu athletes. Methods: Twenty-four elite male Kung-Fu athletes (age: 20.67 ± 1.76 years) participated in four randomised conditions: normal sleep, without sleep deprivation + nap, total sleep deprivation (36 h awake), and TSD + nap. Mood states were assessed in terms of the POMS-f, perceptual responses, decision-making via video-based tasks, barrage test, anaerobic performance through vertical and horizontal jumps, and isometric strength. Results: Sleep deprivation significantly affected mood, with vigour dropping by 53.8% (p < 0.001), impaired physical performance, with vertical jump declining from 36.80 ± 6.47 cm to 33.23 ± 6.03 cm (p < 0.001), and reduced cognitive function, with decision accuracy declining from 24.00 ± 2.16% to 18.44 ± 2.24% (p < 0.001) and reaction time increasing from 0.58 ± 0.08 s to 0.93 ± 0.13 s (p < 0.001). Strategic napping significantly enhanced cognitive recovery, with decision accuracy increasing by 14.1% (p < 0.001) and reaction time improving by 16.1% (p < 0.001). Physical performance showed modest gains, with vertical jump height increasing by 2.4% (p < 0.05). Conclusions: Strategic 45 min naps offer superior cognitive recovery compared to physical recovery in sleep-deprived elite Kung-Fu athletes, suggesting that coaches should incorporate strategic napping to enhance decision-making abilities during competitions involving sleep deprivation
A visualizable and widely applicable steric repulsion descriptor for guiding experimental chemistry
No full textInternational audienceWhile steric effects fundamentally shape molecular behavior and are experiencing renewed interest across chemistry, visualizing where they occur remains challenging. Indeed, steric interactions have traditionally been depicted in a qualitative, often sketchy manner. We present SELF (Steric Exclusion Localization Function), which enables the quantification, atomic resolution, and visualization of steric repulsion in three dimensions (whether between molecules or between fragments of a single molecule) directly from quantum-mechanical calculations. Accessible through the user-friendly IGMPlot software, SELF transforms abstract quantum-mechanical concepts into visual insights that chemists can immediately interpret and apply. We illustrate SELF's versatility across diverse chemical systems: from understanding atropisomerism in pharmaceutical scaffolds to rationalizing selectivity in catalysis through steric effects of phosphorus ligands in organometallic chemistry. Unlike traditional quantum-mechanical methods which condense the characteristics of steric effects into a single number, SELF provides unprecedented spatial resolution of steric clashes while maintaining rigorous quantitative analysis. This approach bridges the gap between theoretical concepts and practical chemical understanding, making sophisticated quantum-mechanical analysis accessible to the broader chemical community. We hope this tool will prove valuable for chemical design, research applications, and teaching steric effects
Politique d’égalité de genre dans les carrières des hauts fonctionnaires: Apports et angles morts de l’approche évaluative
No full textInternational audienceConstatant la persistance des inégalités liées au genre dans les carrières de la haute fonction publique malgré l’institutionnalisation récente des politiques d’égalité, cet article examine les apports et les angles morts des évaluations quantitatives et de l’approche gestionnaire de l’égalité. La mesure des inégalités a connu plusieurs étapes qui montrent l’ampleur du travail accompli. Ce qui échappe à l’évaluation mérite néanmoins d’être questionné. La focalisation sur la mesure tend ainsi à occulter les dynamiques organisationnelles relatives aux normes de mobilité, aux soutiens hiérarchiques informels, à l’idéal masculin du « bon dirigeant » et à la faible appropriation des dispositifs. L’impératif de mesurer pour rendre visible, conjugué à celui de comprendre pour transformer, s’impose alors pour dépasser l’enjeu de gestion et porter une politique publique pleinement correctrice en faveur de l’égalité
Transformation-Domain Gaussian Smoothing for translational Direct Visual Servoing
No full textInternational audienceDirect visual servoing (DVS) uses raw pixel intensities to control robot motion, yielding high accuracy atconvergence. However, the associated photometric cost function is highly nonconvex, which leads to a narrow domain of convergence due to local minima. This work addresses that issue by adapting aGaussian homotopy framework for cost function smoothing from cross corelation to the sum of squared differences (SSD) error used in DVS. The result is a spatially varying, transformation-domain kernel that depends on the motion model, producing smoother cost landscapes and enlarging the convergence basin.We first apply the smoothing to an SSD cost, derive its corresponding transformation kernel for the motion model in the camera domain and then incorporate it into a DVS control law. The method is compared against uniform image domain blurring via Photometric Gaussian Mixtures. Experiments with an eye-in-hand robotic arm setup over three degrees of freedom translation and with different initial pose show that cost smoothing significantly increases the convergence domain while preserving the accuracy of DVS
Le tibétain parlé : exercices pratiques (vol. 2)
No full textInternational audienceUn pas de plus vers la maîtrise de la langue parlée dans la diaspora.Cet ouvrage vise à poursuivre l’acquisition pratique des bases de la langue tibétaine parlée et écrite, dans sa variante dite « commune » ou « standard », c’est-à-dire la langue parlée dans la diaspora et qui repose en grande partie sur le tibétain de Lhassa. Destiné aux étudiants ayant déjà acquis les bases présentées dans le premier volume, il s’appuie également sur le *Manuel de tibétain standard* de Nicolas Tournadre et Sangda Dorje (L’Asiathèque, 2024). Comme le premier volume, il compte douze leçons structurées autour d’objectifs de communication et de points grammaticaux. Les leçons comprennent une liste de vocabulaire, si nécessaire une synthèse de points de grammaire, et des exercices présentés selon les quatre compétences linguistiques fondamentales : compréhension écrite, expression écrite, compréhension orale et expression orale. Un corrigé est proposé en fin de leçon pour la plupart des exercices. Ce livre s’accompagne d’enregistrements sonores, disponibles en téléchargement sur la page du site de l’Inalco dédié à l’ouvrage
Influence of baby sign practice on the development of joint attention in the 18-month-old child
No full textInternational audienceThe effect of the Baby Sign on children’s communicative development has not been confirmed, and many areas of pre-linguistic communication remain under-researched. The aim of this study is to investigate the impact of the practice of Baby Sign on joint attention in the 18-month-old child. We assessed the early social communication skills with the Early Social Communication Scale of 36 normal-hearing children (20 Baby Sign children and 16 No Baby sign children). The results of the score analysis showed no significant difference between the group of children exposing to the signs and the control group. However, the micro-analysis of the game sessions shows that the children exposing to the sign present more frequent episodes of joint attention with more frequent initiations and responses. These data demonstrate that the use of this gestural communication aid allows the child to interact more easily with others
How Particle Size Affects Consolidation Behavior, Strain and Properties of Li 6 PS 5 Cl Fast Ionic Conductors
No full textInternational audienceSolid‐state battery fabrication requires the densification of solid electrolytes to achieve optimal cycling performance and high energy density. However, the underlying compaction mechanisms of these electrolytes remain poorly understood. Here, we investigate the effect of pressure consolidation on the ionic conductor Li 6 PS 5 Cl with particle size distributions (PSD) ranging from 4 to 40 µm. Heckel analysis reveals that samples with smaller PSDs exhibit higher compressibility at lower pressures. X‐ray diffraction peak profiling shows that applied pressure induces lattice strain, leading to peak broadening, while pair distribution function analysis demonstrates a reduction in coherence length upon pressing. Dark‐field X‐ray microscopy further provides spatially resolved orientation maps, uncovering intragranular structural variations within individual Li 6 PS 5 Cl agglomerates after compression. To better understand the origin of stress fluctuations, we performed discrete element method simulations using the experimental PSDs. The results indicate that smaller particles and broader PSDs experience higher stresses, whereas monodisperse systems do not exhibit significant stress fluctuations with position or particle size. This suggests that the high strain observed cannot be attributed solely to smaller particles, but rather to size inhomogeneity. Overall, these findings highlight that both particle size and its distribution play a critical role in processing solid electrolytes for solid‐state batteries
Adult male patients with DKC1 mutations present early-onset pulmonary fibrosis and severe prognosis
No full textInternational audienceBackground Mutations in telomere-related genes (TRGs) are the main cause of monogenic familial pulmonary fibrosis. Dyskerin, encoded by the X-localised gene DKC1 , is involved in telomere maintenance. Methods This retrospective study aimed to further characterise the pulmonary phenotype of DKC1 -deficient patients with pulmonary fibrosis identified between 2010 and 2025 in our laboratory. Results We reported eight, as yet undescribed, to our knowledge, probands affected by pulmonary fibrosis associated with X-linked DKC1 deficiency. The median age at interstitial lung disease (ILD) diagnosis was 47 years. Four had idiopathic pulmonary fibrosis, two unclassifiable fibrosis, one idiopathic nonspecific interstitial pneumonia and one unknown. All patients displayed ectodermal abnormalities (premature hair greying, nail dystrophies, reticulated hyper- or hypopigmentation, tooth abnormalities and oral leukoplasia). Haematological abnormalities were found in four patients. Seven patients died during follow-up and one patient received a transplant. Median survival after ILD diagnosis was 22 months (range 3–81 months). Conclusions Compared with patients with pulmonary fibrosis associated with other TRG variants, those with pulmonary fibrosis associated with X-linked recessive DKC1 variants are younger and have a shorter survival time. Early identification and referral of these patients to an expert transplantation centre should be considered