L'Isoloir, Citoyenneté & Numérique, Documentation du joueur

National audienceDans ce monde devenu numérique, il faut que chaque citoyenne et citoyen maîtrise, au-delà des usages, les principaux fondements de cette mutation numérique de façon à faire collectivement des choix éclairés sur ces sujets. C'est l'acquisition d'une culture scientifique et technique qui est le levier de cette appropriation. Voilà pourquoi à travers le jeu sérieux de "L'Isoloir " on offre en partage à chacune et chacun les éléments qui permettent de répondre en toute connaissance et en toute conscience à quelques questions fondamentales liées au numérique. C'est ce que ce document rassemble ici pour permettre aux animateur-e-s des activités utilisant L'Isoloir d'avoir une vue globale du matériel proposé

Nivolumab and brentuximab vedotin with or without bendamustine for R/R Hodgkin lymphoma in children, adolescents, and young adults

Children, adolescents, and young adults (CAYA) with relapsed/refractory (R/R) classic Hodgkin lymphoma (cHL) without complete metabolic response (CMR) before autologous hematopoietic cell transplantation (auto-HCT) have poor survival outcomes. CheckMate 744, a phase 2 study for CAYA (aged 5-30 years) with R/R cHL, evaluated a risk-stratified, response-adapted approach with nivolumab plus brentuximab vedotin (BV) followed by BV plus bendamustine for patients with suboptimal response. Risk stratification was primarily based on time to relapse, prior treatment, and presence of B symptoms. We present the primary analysis of the standard-risk cohort. Data from the low-risk cohort are reported separately. Patients received 4 induction cycles with nivolumab plus BV; those without CMR (Deauville score &gt;3, Lugano 2014) received BV plus bendamustine intensification. Patients with CMR after induction or intensification proceeded to consolidation (high-dose chemotherapy/auto-HCT per protocol). Primary end point was CMR any time before consolidation. Forty-four patients were treated. Median age was 16 years. At a minimum follow-up of 15.6 months, 43 patients received 4 induction cycles (1 discontinued), 11 of whom received intensification; 32 proceeded to consolidation. CMR rate was 59% after induction with nivolumab plus BV and 94% any time before consolidation (nivolumab plus BV ± BV plus bendamustine). One-year progression-free survival rate was 91%. During induction, 18% of patients experienced grade 3/4 treatment-related adverse events. This risk-stratified, response-adapted salvage strategy had high CMR rates with limited toxicities in CAYA with R/R cHL. Most patients did not require additional chemotherapy (bendamustine intensification). Additional follow-up is needed to confirm durability of disease control. This trial was registered at www.clinicaltrials.gov as #NCT02927769.</p

Nivolumab and brentuximab vedotin with or without bendamustine for R/R Hodgkin lymphoma in children, adolescents, and young adults

Children, adolescents, and young adults (CAYA) with relapsed/refractory (R/R) classic Hodgkin lymphoma (cHL) without complete metabolic response (CMR) before autologous hematopoietic cell transplantation (auto-HCT) have poor survival outcomes. CheckMate 744, a phase 2 study for CAYA (aged 5-30 years) with R/R cHL, evaluated a risk-stratified, response-adapted approach with nivolumab plus brentuximab vedotin (BV) followed by BV plus bendamustine for patients with suboptimal response. Risk stratification was primarily based on time to relapse, prior treatment, and presence of B symptoms. We present the primary analysis of the standard-risk cohort. Data from the low-risk cohort are reported separately. Patients received 4 induction cycles with nivolumab plus BV; those without CMR (Deauville score &gt;3, Lugano 2014) received BV plus bendamustine intensification. Patients with CMR after induction or intensification proceeded to consolidation (high-dose chemotherapy/auto-HCT per protocol). Primary end point was CMR any time before consolidation. Forty-four patients were treated. Median age was 16 years. At a minimum follow-up of 15.6 months, 43 patients received 4 induction cycles (1 discontinued), 11 of whom received intensification; 32 proceeded to consolidation. CMR rate was 59% after induction with nivolumab plus BV and 94% any time before consolidation (nivolumab plus BV ± BV plus bendamustine). One-year progression-free survival rate was 91%. During induction, 18% of patients experienced grade 3/4 treatment-related adverse events. This risk-stratified, response-adapted salvage strategy had high CMR rates with limited toxicities in CAYA with R/R cHL. Most patients did not require additional chemotherapy (bendamustine intensification). Additional follow-up is needed to confirm durability of disease control. This trial was registered at www.clinicaltrials.gov as #NCT02927769.</p

Intestinal gluconeogenesis and glucose transport according to body fuel availability in rats

Intestinal hexose absorption and gluconeogenesis have been studied in relation to refeeding after two different fasting phases: a long period of protein sparing during which energy expenditure is derived from lipid oxidation (phase II), and a later phase characterized by a rise in plasma corticosterone triggering protein catabolism (phase III). Such a switch in body fuel uses, leading to changes in body reserves and gluconeogenic precursors, could modulate intestinal gluconeogenesis and glucose transport. The gene and protein levels, and the cellular localization of the sodium-glucose cotransporter SGLT1, and of GLUT5 and GLUT2, as well as that of the key gluconeogenic enzymes phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (Glc6Pase) were measured. PEPCK and Glc6Pase activities were also determined. In phase III fasted rats, SGLT1 was up-regulated and intestinal glucose uptake rates were higher than in phase II fasted and fed rats. PEPCK and Glc6Pase mRNA, protein levels and activities also increased in phase III. GLUT5 and GLUT2 were down-regulated throughout the fast, but increased after refeeding, with GLUT2 recruited to the apical membrane. The increase in SGLT1 expression during phase III may allow glucose absorption at low concentrations as soon as food is available. Furthermore, an increased epithelial permeability due to fasting may induce a paracellular movement of glucose. In the absence of intestinal GLUT2 during fasting, Glc6Pase could be involved in glucose release to the bloodstream via membrane trafficking. Finally, refeeding triggered GLUT2 and GLUT5 synthesis and apical recruitment of GLUT2, to absorb larger amounts of hexoses

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Histoire naturelle du syndrome de Barth (une cohorte nationale de 22 patients)

LIMOGES-BU Médecine pharmacie (870852108) / SudocSudocFranceF

Introduction

Antony Gormley, Angel of the NorthAcier; 20 × 54 × 2,2 mInstallation permanente, Gateshead, AngleterrePhotographie de Sally Ann Norman© Antony Gormley Arts contemporains britannique et américain donnent à voir une forme avancée de la dispersion du monument. La dissémination du monumental héritée de la dématérialisation de l’œuvre d’art au cours du XXe siècle pose en effet un certain nombre de questions relatives aux modes d’exposition mais aussi de sociabilité concernant l’inscription de l’œu..

Multi-objective optimization of rotary-wing aircrafts at the predesign stage

International audienceSubsystems of rotary-wing aircrafts, such as helicopters for instance, are strongly interrelated due to their intrinsic specificities. Convergence to a feasible design is then not ensured and implies an iterative process. Moreover, rotorcrafts must cover a much wider range of missions than their fixed-wing counterparts. For those reasons a correctly sized rotorcraft is difficult to obtain and finding the best design for a defined set of missions needs numerous iterations. This article presents the application of a multi-objective optimization approach from the predesign stage. The standard predesign approach has been reformulated to highlight sizing constraints and three strategies are then proposed to solve those constraints: the first one is the basic transcription of the standard predesign approach; the second one leaves the problem solving to the genetic optimizer through penalization; the third one is a hybrid of both previous methods based on a constraint repairing approach. Those strategies also involved the adaptation of the helicopter modelling. Here, the focus is on two components of that new model: namely the main rotor polar and the weight assessment model

Monument et Modernité : Dans l'art et la littérature britanniques et américains

C'est le paradoxe du monument moderne que ce livre se propose d'explorer. À mesure que l'enjeu de l'inscription mémorielle devient idéologiquement plus suspect, le monument se métamorphose, et l'art anglais et américain vient interroger sans relâche, par-delà le rapport à l'Histoire, les enjeux sociaux et environnementaux de la commémoration. Le marbre grec est-il blanc, le toponyme indien laisse-t-il une trace ? Construire ou décrire un monument, est-ce conforter son identité ou subtiliser la mémoire de l'autre ? Peu à peu, l'art et la littérature revisitent, brisent et transfigurent le monumental. Comment définir le monument contemporain, autrement qu'à travers ses échelles variables, du jardin de Finley au labyrinthe d'acier de Richard Serra, installations éphémères et solides à la fois ? D'où cette force proprement poétique du monument, que cette « promenade » permet d'approcher et réévaluer