138 research outputs found
Contrôle de la morphologie des poudres par l'ajout de fondants : Application à un luminophore
National audienceCe travail porte sur l'amélioration du procédé de fabrication des luminophores et en particulier un phosphate de lanthane : LaPO4:Ce,Tb (LaCeT). L'influence de fondants carbonatés (Li2CO3, Na2CO3, K2CO3, ...) sur la taille et la forme des grains du luminophore y est décrite. Pour ce faire des analyses par microscopie électronique à balayage ont été effectuées. Des résultats concluants ont pu en être tirés : des grains de morphologie contrôlée (forme de sphères ou de plaquettes) et de taille adaptée (modulable de 0,1 à 10 μm) ont pu être synthétisés. Par ailleurs, la photoluminescence des poudres obtenues a été contrôlée et il a été montré que l'effet du fondant n'est pas dommageable aux propriétés optiques des luminophores finales
Early acute microvascular kidney transplant rejection in the absence of anti-HLA antibodies is associated with preformed IgG antibodies against diverse glomerular endothelial cell antigens
International audienceBACKGROUND: Although anti-HLA antibodies (Abs) cause most antibody-mediated rejections of renal allografts, non-anti-HLA Abs have also been postulated to contribute. A better understanding of such Abs in rejection is needed.METHODS: We conducted a nationwide study to identify kidney transplant recipients without anti-HLA donor-specific Abs who experienced acute graft dysfunction within 3 months after transplantation and showed evidence of microvascular injury, called acute microvascular rejection (AMVR). We developed a crossmatch assay to assess serum reactivity to human microvascular endothelial cells, and used a combination of transcriptomic and proteomic approaches to identify non-HLA Abs.RESULTS: We identified a highly selected cohort of 38 patients with early acute AMVR. Biopsy specimens revealed intense microvascular inflammation and the presence of vasculitis (in 60.5%), interstitial hemorrhages (31.6%), or thrombotic microangiopathy (15.8%). Serum samples collected at the time of transplant showed that previously proposed anti-endothelial cell Abs-angiotensin type 1 receptor (AT1R), endothelin-1 type A and natural polyreactive Abs-did not increase significantly among patients with AMVR compared with a control group of stable kidney transplant recipients. However, 26% of the tested AMVR samples were positive for AT1R Abs when a threshold of 10 IU/ml was used. The crossmatch assay identified a common IgG response that was specifically directed against constitutively expressed antigens of microvascular glomerular cells in patients with AMVR. Transcriptomic and proteomic analyses identified new targets of non-HLA Abs, with little redundancy among individuals.CONCLUSIONS: Our findings indicate that preformed IgG Abs targeting non-HLA antigens expressed on glomerular endothelial cells are associated with early AMVR, and that cell-based assays are needed to improve risk assessments before transplant
Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19
Background: We previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15–20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in ~ 80% of cases. Methods: We report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded. Results: No gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5–528.7, P = 1.1 × 10−4) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR = 3.70[95%CI 1.3–8.2], P = 2.1 × 10−4). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR = 19.65[95%CI 2.1–2635.4], P = 3.4 × 10−3), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR = 4.40[9%CI 2.3–8.4], P = 7.7 × 10−8). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD] = 43.3 [20.3] years) than the other patients (56.0 [17.3] years; P = 1.68 × 10−5). Conclusions: Rare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old
Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome associated with COVID-19: An Emulated Target Trial Analysis.
RATIONALE: Whether COVID patients may benefit from extracorporeal membrane oxygenation (ECMO) compared with conventional invasive mechanical ventilation (IMV) remains unknown. OBJECTIVES: To estimate the effect of ECMO on 90-Day mortality vs IMV only Methods: Among 4,244 critically ill adult patients with COVID-19 included in a multicenter cohort study, we emulated a target trial comparing the treatment strategies of initiating ECMO vs. no ECMO within 7 days of IMV in patients with severe acute respiratory distress syndrome (PaO2/FiO2 <80 or PaCO2 ≥60 mmHg). We controlled for confounding using a multivariable Cox model based on predefined variables. MAIN RESULTS: 1,235 patients met the full eligibility criteria for the emulated trial, among whom 164 patients initiated ECMO. The ECMO strategy had a higher survival probability at Day-7 from the onset of eligibility criteria (87% vs 83%, risk difference: 4%, 95% CI 0;9%) which decreased during follow-up (survival at Day-90: 63% vs 65%, risk difference: -2%, 95% CI -10;5%). However, ECMO was associated with higher survival when performed in high-volume ECMO centers or in regions where a specific ECMO network organization was set up to handle high demand, and when initiated within the first 4 days of MV and in profoundly hypoxemic patients. CONCLUSIONS: In an emulated trial based on a nationwide COVID-19 cohort, we found differential survival over time of an ECMO compared with a no-ECMO strategy. However, ECMO was consistently associated with better outcomes when performed in high-volume centers and in regions with ECMO capacities specifically organized to handle high demand. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/)
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
Prise en charge de la douleur des fractures fermées déplacées des os longs aux urgences pédiatriques
BREST-BU Médecine-Odontologie (290192102) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF
Applications des Systèmes d'Information Géographiques en Aquaculture
L'actuelle demande alimentaire croissante sur les produits de la mer met l'aquaculture en situation de développement; les stratégies de développement mises en place incluent des questions de durabilité économique, sociale et environnementale. Au cœur de celles-ci, l'accès à l'espace (sélection de sites, conflits d'usage, etc…) place cette dimension au premier plan. La planification spatiale du développement des projets aquacoles est donc un élément essentiel, incluse dans une démarche de gestion intégrée de la bande côtière. C'est un élément considéré comme une étape cruciale tant par les scientifiques dans le cadre d'une approche ecosystémique, que par les diverses nations et organismes Européens via le développement d’une réglementation ad-hoc. Dans ce contexte, les Systèmes d'Information Géographiques (SIG) sont des outils d'analyse spatiale et d'aide à la décision relativement incontournables. Leur capacité à agréger, présenter, et analyser des données de sources très variables (satellites, photos, réglementation, résultats de modélisation…) permet une meilleure accessibilité et un meilleur partage de l'information spatialisée. L'Ifremer utilise et structure les données marines et côtières dans ce type de système depuis les années 1990. Ce document présente une revue de différents types d'applications dans le domaine aquacole utilisant les SIG en fonctionnement dans le cadre des missions de soutien aux administrations et utilisateurs des espaces littoraux des laboratoires côtiers de l'Ifremer. Sont présentées les données et analyses géostatistiques multicritères pour la sélection de sites, les différentes évaluations de stocks de mollusques ou d'échantillonnage environnemental spatialisé. Des études utilisant la modélisation (hydrodynamique, écophysiologie) afin de qualifier les espaces littoraux sont également abordées. Une synthèse bibliographique à jour est également fournie en annexe, passant en revue les diverses applications et catégories d'usages SIG & Aquaculture
Qualification des sites à potentiel énergétique hydrolien en Charente Maritime : apports de l’Ifremer
La demande faite à l’Ifremer par le département de la Charente Maritime concerne la qualification et caractérisation de sites à potentiel hydrolien, déjà sélectionnés lors de précédentes études, à l’aide des données de type bathymétriques, et hydrodynamiques disponibles au LERPC de La Tremblade. Cela consiste à 1) Fournir les données de bathymétrie à la plus haute résolution disponible sur les sites choisis sous mise en forme de couche SIG, 2) fournir et expliciter les données de Courants ADCP réalisées par le laboratoire (J.Y. Stanisière, 2007-2013), 3) utiliser des données de courant du modèle Mars3D- PC existantes (P. Polsenaere & O. Le Moine, 2014-2017) pour en extraire après post traitement un certain nombre de variables chronologiques et/ou spatialisées nécessaires à l’étude ( profils moyens de courants, permanence des courants en fonction des profondeurs, données de vitesse de courants en fonction du temps à différentes profondeurs, etc…). Ce document est une revue des données et traitement réalisés dans le cadre de ce contrat
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