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Real-world effectiveness of advanced therapies in microscopic colitis
No full textInternational audienceBackground and aims: Microscopic colitis (MC) is a leading cause of chronic diarrhoea, particularly in older adults. While many patients respond to budesonide, refractory and dependent cases pose major therapeutic challenges. Although the off-label use of advanced IBD therapies is expanding, robust real-world data remain scarce.Methods: Through the ECCO CONFER network, we conducted a multinational, retrospective study in MC patients treated with biologics or small molecules following budesonide failure or intolerance. We systematically analyzed clinical outcomes, treatment durability, and predictors of therapeutic success.Results: Among 229 treatment cycles in 142 patients, anti-TNF agents were most frequently initiated (55.9%), followed by vedolizumab (28.8%) and JAK inhibitors (9.2%). Short-term clinical response and remission rates were highest with JAK inhibitors (95.2% and 81.0%, respectively), significantly outperforming anti-TNFs, vedolizumab, and ustekinumab (p<0.01). Long-term drug persistence mirrored these findings: JAK inhibitors demonstrated a markedly lower discontinuation rate (23.8%) compared to other agents (56.3%, OR 5.07, 95% CI 1.52-16.9, p = 0.008). Multivariate analysis confirmed drug class as the only independent predictor of therapy continuation. Despite advanced therapies, 4.2% of patients ultimately required surgical intervention.Conclusion: This real-world study demonstrates the promising short- and long-term effectiveness of advanced therapies-particularly JAK inhibitors-in budesonide-refractory and budesonide-dependent MC. These findings pave the way for dedicated prospective trials and highlight evolving therapeutic strategies in MC
L’instruction. Des évolutions spatiales liées à la démographie et à une recomposition de l’offre
No full textNational audienceHow closely does the geography of education reflect the spatial distribution of young people? Generally speaking, enrolment figures reflect recent changes in birth rates. They vary depending on the urban hierarchy. Enrolment has mainly increased in large cities for secondary education and only in their suburbs for primary education. However, these dynamics are neither uniform within French cities nor between them. School closures mainly affect the north-eastern quarter of the country and rural municipalities. However, these have also seen the highest number of new school openings. This indicates a restructuring of school provision in rural areas. The private sector has seen many more new school openings than the public sector, particularly in secondary education. A redeployment of private provision towards the largest cities and their suburbs is taking place, to the detriment of certain traditional areas of establishment.Dans quelle mesure la géographie de l’instruction reflète la répartition spatiale des plus jeunes ? De façon globale, les effectifs reflètent les évolutions récentes de la natalité. Elle diffère selon la situation dans la hiérarchie urbaine. Les effectifs ont principalement augmenté dans les grandes métropoles pour le second degré et seulement dans leurs périphéries pour le premier. Néanmoins ces dynamiques ne sont pas uniformes au sein des métropoles française ni entre ces dernières. Les fermetures d’établissements concernent principalement quart nord-est du pays et les communes rurales. Pour autant, c’est aussi dans ces dernières qu’il y a eu le plus grand nombre d’ouvertures d’établissements. Cela dénote une recomposition de l’offre scolaire en milieu rural. Le secteur privé a connu beaucoup plus d’ouvertures d’établissements que le public, notamment dans le second degré. On assiste à un redéploiement de l’offre privée vers les plus grandes métropoles et leurs périphéries, au détriment de certaines régions traditionnelles d’implantation
Mathias Quéré, Quand nos désirs font désordre. Une histoire du mouvement homosexuel en France, 1974-1986
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« “Je ne sais pas ce que c’est que cette médecine”. Voltaire et la purgation des passions au théâtre »
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Unveiling the Global Oceanic Influence of Atlantic Multidecadal Variability Using Pacemaker Experiments
No full textInternational audienceAbstract Atlantic multidecadal variability (AMV) significantly impacts regional and global climate, as evidenced by observations and climate model simulations. Previous sensitivity experiments investigating the AMV were mostly based on climate model simulations in which the North Atlantic sea surface temperatures (NASSTs) were nudged to a fixed AMV pattern. Here, the global influence of AMV is explored using an ensemble of pacemaker experiments where NASSTs are nudged to the time-varying observational records. Ten ensemble members proved sufficient to distinguish forced signals from internal climate variability. Using high-pass-filtered data to inform how the response to the AMV is established, we confirm that the AMV primarily affects the global ocean through its tropical component. The oceanic response to a warm AMV anomaly unfolds in four phases: 1) warming of the western Pacific warm pool and development of anomalous easterlies in the western Indo-Pacific driven by diabatic heating over the tropical Atlantic within the first 6 months, 2) eastward propagation of equatorial thermocline anomalies and establishment of La Niña–like conditions in the eastern Pacific after 7–10 months, 3) persistence of La Niña conditions during 11–20 months via Bjerknes feedback and weakening of the Aleutian low through tropical teleconnections, and 4) emergence of a negative Pacific decadal oscillation pattern in the North Pacific after 21–25 months. Our findings highlight the importance of using time-varying SST observations in pacemaker experiments to capture the full complexity of interbasin connections
Cumulative Extreme Events Threaten Penguin Habitats Across the Southern Hemisphere
No full textInternational audienceABSTRACT Upon the rise in the intensity, duration and frequency of extreme events threatening life on Earth across land and ocean, there is a need to select ecologically significant areas for targeted management interventions. This study assesses the spatial overlap of multiple extreme events and calculates the cumulative magnitude faced across the Southern Hemisphere during the last decades, focusing on the 18 species of penguins as ecosystem sentinels that rely on terrestrial and marine environments. Our analysis identifies African, Snares, Emperor, Adélie and Galápagos as the penguin species experiencing the highest cumulative values of extreme events. Additionally, when looking at the trends, we identify that all penguin species, except the Galápagos penguin, will face a potential increase in extreme events if current trends are maintained. This study carries a crucial message in conservation, establishing a spatial framework that allows sounding the alert in ecologically important areas to reduce vulnerability during present and future extreme events
La chambre commerciale internationale de la Cour d’appelde Paris, juridiction-modèle ?
No full textInternational audienceThe International Commercial Chamber of the Paris Court of Appeal (CCIP-CA) was created in 2018 and is now well established in the French international commercial law landscape. A specialised court par excellence, operating according to adapted rules of procedure, it has distinguished itself by building a jurisprudence that can be identified by three characteristics: a concern for pedagogy in its reasoning; openness to innovations in case law; and a search for balance between the protection of the public interest and the preservation of private interests. Its contribution to improving the quality of cross-border dispute resolution is undeniable.La chambre commerciale internationale de la Cour d’appel de Paris (CCIP-CA) a été créée en 2018 et elle est désormais bien installée dans le paysage du droit commercial international français. Juridiction spécialisée par excellence, fonctionnant selon des règles de procédure adaptée, elle a su se distinguer en construisant une jurisprudence identifiable par trois caractéristiques : un souci de pédagogie dans les motivations ; une ouverture aux innovations jurisprudentielles ; et une recherche d’équilibre entre la protection de l’intérêt public et la préservation des intérêts privés. Sa contribution à l’amélioration de la qualité du traitement des litiges transfrontières est à ce titre incontestable
Neuroepigenetic programming by the maternal environment: Independent contribution of methylation and hydroxymethylation in the offspring's olfactory bulb following preconceptional weight loss in mice
No full textInternational audienceMaternal environment, particularly nutritional status before conception, can durably shape offspring brain function through epigenetic mechanisms. Cytosine methylation (5mC) and hydroxymethylation (5hmC) are key DNA modifications involved in neural development and synaptic regulation, yet their respective contributions remain insufficiently characterized. Building on previous findings showing that maternal preconception weight loss (WL) alters olfactory-driven behaviors in mouse offspring (Panchenko et al., 2019 ; Safi-Stibler et al., 2020), we investigated whether these effects are linked to distinct epigenetic signatures in the olfactory bulb (OB). Using combined RRBS and oxidative RRBS, we quantified 5mC and 5hmC at identical CpG sites in OBs of offspring from control or WL dams. While 5mC was globally more abundant, 5hmC represented a stable and functionally relevant fraction of cytosine modifications (average 5.5%). Maternal WL induced extensive changes in both marks, with a stronger impact on hydroxymethylation (2,631 DhMCs vs. 1,834 DMCs). Although one-third of genes were co-regulated by both modifications, uniquely modified CpGs revealed distinct functional enrichments: uniqDhMCs were associated with neuronal signaling and plasticity, whereas uniqDMCs primarily mapped to chromatin organization and transcriptional regulation. These results demonstrate that 5mC and 5hmC, while partly overlapping, play complementary and functionally divergent roles in shaping gene regulation. Our study highlights the importance of integrating both marks to fully understand how early-life nutritional environments influence brain development and behavior.</div
Who do they think you are? Inconsistencies in self- and proxy-reports of education within families
No full textInternational audienceEstimates of intergenerational educational mobility are generally computed using a combination of self- and proxy-reports of one’s and one’s parents’ education. Such reports are easily collected, offering a cost-effective alternative to collecting multiple self-reports or register data. However, the bias that proxy-reports could introduce in the measurement of intergenerational educational mobility is rarely assessed. Our study fills this gap and assesses how reliable people are when they report their parents’ or their child’s educational attainment. We find that both parents and children tend to underestimate the educational distance between themselves and their family members, thus inflating estimates of educational reproduction. This trend is larger when children act as proxy-reporters. Another limitation of using children’s proxy-reported information is the number of missing answers, which is lower when parents are asked to proxy-report their child’s education. In a simulation exercise, we establish that the bias introduced by proxy reports is not negligible, with self-reported intergenerational regression coefficients being 9% higher when a proxy-report is used