CTACG - CTA Computing Grid

International audienceCTACG - CTA Computing Gri

Manganese Cytotoxicity Assay on Hippocampal Neuronal Cell Culture

Compared to an in vivo experiment, neuronal cell cultures are immediately accessibleto observation and manipulation. In this protocol, we describe a technique to evaluate thecytotoxicity of a metal, manganese (Mn2+), on hippocampal neuronal cell cultures. Interestingly, this protocol is easily adaptable to any type of primary culture (e.g., cortical neurons) and any type of toxic compound (e.g., chemical product).Fil: Daoust, Alexia. Inserm; Francia. Universite Joseph Fourier; FranciaFil: Saoudi, Yasmina. Inserm; Francia. Universite Joseph Fourier; FranciaFil: Brocard, Jacques. Inserm; Francia. Universite Joseph Fourier; FranciaFil: Collomb, Nora. Inserm; Francia. Universite Joseph Fourier; FranciaFil: Batandier, Cecile. Laboratoire de Bioénergétique Fondamentale et Appliquée; FranciaFil: Bisbal, Mariano. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; Argentina. Inserm; Francia. Universite Joseph Fourier; FranciaFil: Salome, Murielle. European Synchrotron Radiation Facility; FranciaFil: Andrieux, Annie. Inserm; Francia. Universite Joseph Fourier; FranciaFil: Bohic, Sylvain. Inserm; Francia. Universite Joseph Fourier; Francia. European Synchrotron Radiation Facility; FranciaFil: Barbier, Emmanuel. Inserm; Francia. Universite Joseph Fourier; Franci

Capturing Ecosystem Services, Stakeholders' Preferences and Trade-Offs in Coastal Aquaculture Decisions : A Bayesian Belief Network Application

Aquaculture activities are embedded in complex social-ecological systems. However, aquaculture development decisions have tended to be driven by revenue generation, failing to account for interactions with the environment and the full value of the benefits derived from services provided by local ecosystems. Trade-offs resulting from changes in ecosystem services provision and associated impacts on livelihoods are also often overlooked. This paper proposes an innovative application of Bayesian belief networks - influence diagrams - as a decision support system for mediating trade-offs arising from the development of shrimp aquaculture in Thailand. Senior experts were consulted (n = 12) and primary farm data on the economics of shrimp farming (n = 20) were collected alongside secondary information on ecosystem services, in order to construct and populate the network. Trade-offs were quantitatively assessed through the generation of a probabilistic impact matrix. This matrix captures nonlinearity and uncertainty and describes the relative performance and impacts of shrimp farming management scenarios on local livelihoods. It also incorporates export revenues and provision and value of ecosystem services such as coastal protection and biodiversity. This research shows that Bayesian belief modeling can support complex decision-making on pathways for sustainable coastal aquaculture development and thus contributes to the debate on the role of aquaculture in social-ecological resilience and economic development

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

Dielectric Properties of Hexagonal Perovskite Ceramics Prepared by Different Routes

International audienceIn this work, four different methods, i.e. solid state reaction, citrate sol–gel process, Pechini and microwave are employed to synthesize Ba4YMn3O11.5±δ ceramics. The phase structure of the powders can be well indexed as a 12R hexagonal perovskite crystallizing in space group . The density and morphology (average grain size) of sintered samples vary with the synthesis processes. The dielectric permittivity and loss tangent of the samples have been measured in the frequency range 1 kHz–1 MHz. The results show that they are very sensitive to the synthesis process. The best properties are obtained for the sample synthetized by citrate process. This compound has a high dielectric permittivity (), which is almost frequency independent over the 100 Hz–100 kHz range from room temperature to 150 °C. This has been attributed to the IBLC mechanism. By impedance spectroscopy analysis, all the compounds were found to be electrically heterogeneous, exhibiting semiconducting grains and insulating grain boundaries. Finally, we show that the IBLC model is well adapted to the materials obtained by the modified citrate synthesis route, but not to the ones from the other routes

Cu-Doping Effect on Dielectric Properties of Organic Gel Synthesized Ba4YMn3-xCuxO11.5±δ

International audienceCopper doped-Ba4YMn3ÀxCuxO11.5 7 δ samples were synthesized by an organic gel assisted citrate process. X-ray diffraction of compositions with x \textonequarter0.002, 0.005, 0.01, 0.02 and 0.04 does not reveal any change of hexagonal perovskite structure on doping. The effects of Cu-doping on the microstructure and dielectric properties were investigated. Cu doping modifies the electrical properties at the level of the impedance characteristics of both grain and grain boundary and to understand these different behaviours, we have carried out high-resolution transmission electron microscopy analysis

Prise en compte des anomalies génétiques en sélection : le cas des bovins

Pendant plusieurs dizaines d’années après la mise en place des programmes de sélection génétique, la découverte de nouvelles anomalies est restée sporadique. Cela a incité jusqu’à présent les gestionnaires de ces programmes à appliquer une politique d’éradication drastique des reproducteurs porteurs, combinée à la procréation de futurs reproducteurs non porteurs. Mais la situation est en train de changer avec l’avènement de la sélection génomique et des technologies associées, qui permettent de détecter les anomalies plus rapidement et donc en plus grand nombre. Il est donc indispensable de faire évoluer la façon de les prendre en compte dans les programmes de sélection. Un état de la situation dans la population doit d’abord être établi en estimant la fréquence allélique de l’anomalie et en caractérisant le statut des reproducteurs les plus importants avec les tests moléculaires disponibles, en particulier avec les puces à « Single Nucleotide Polymorphism » (SNP). Dans certains cas, une prédiction indirecte, à partir d’haplotypes ou d’imputation, permet de connaître le statut à la mutation des reproducteurs plus anciens avec une forte probabilité sans nécessité de ré-analyser leur ADN. Une fois ce bilan établi, les mesures à prendre dépendent du poids économique des anomalies qui est fonction de deux paramètres, le coût par individu atteint et la fréquence allélique dans la population. La méthode optimale permettant une éradication progressive des anomalies repose sur l’utilisation d’un objectif de sélection combinant les anomalies aux autres caractères. Une phase délicate à gérer, principalement au travers des accouplements, est celle de l’utilisation de reproducteurs porteurs durant la période de transition entre la découverte de l’anomalie et l’éradication complète. Enfin, il est rappelé qu’une mesure simple permettant de limiter l’émergence de nouvelles anomalies est d’utiliser un nombre élevé de reproducteurs tout en restreignant leur taille de descendance.For years, genetic defects were discovered sporadically and this led breeders to eradicate drastically all the carriers in combination with the procreation of non carrier future reproducing animals. However there is a new paradigm with the setting up of genomic selection since genetic defects are now detected much faster and, consequently, in larger numbers. Therefore it is necessary to adapt the way genetic defects are taken into account in selection. A good overview of the genetic situation must be obtained by estimating the allelic frequency in the population and by assessing the status of most major reproducing animals with the available diagnosis tests, now often included in SNP chips. Noteworthy, this status may also be assessed indirectly through haplotypic prediction for older animals and does not always require to genotype them again. Then the selection plan must be set up in the light of the economic weight of the defects, which depends on the cost of affected cases and allelic frequency. The optimal method to gradually eradicate genetic defects relies on the use of a breeding objective combining genetic defects with the other traits, with their economic weights. The transition phase between the discovery of a genetic defect and its complete eradication is always delicate and is usually coped by orienting the matings to avoid cases. Finally, it is recalled that using a large number of breeding animals while restricting their number of offspring is a simple measure that efficiently limits the outbreaks of new genetic defects

Influence of the Immune Microenvironment Provided by Implanted Biomaterials on the Biological Properties of Masquelet-Induced Membranes in Rats: Metakaolin as an Alternative Spacer

International audienceMacrophages play a key role in the inflammatory phase of wound repair and foreign body reactions-two important processes in the Masquelet-induced membrane technique for extremity reconstruction. The macrophage response depends largely on the nature of the biomaterials implanted. However, little is known about the influence of the macrophage microenvironment on the osteogenic properties of the induced membrane or subsequent bone regeneration. We used metakaolin, an immunogenic material, as an alternative spacer to standard polymethylmethacrylate (PMMA) in a Masquelet model in rats. Four weeks after implantation, the PMMA-and metakaolin-induced membranes were harvested, and their osteogenic properties and macrophage microenvironments were investigated by histology, immunohistochemistry, mass spectroscopy and gene expression analysis. The metakaolin spacer induced membranes with higher levels of two potent pro-osteogenic factors, transforming growth factor-β (TGF-β) and bone morphogenic protein-2 (BMP-2). These alternative membranes thus had greater osteogenic activity, which was accompanied by a significant expansion of the total macrophage population, including both the M1-like and M2-like subtypes. Microcomputed tomographic analysis showed that metakaolin-induced membranes supported bone regeneration more effectively than PMMA-induced membranes through better callus properties (+58%), although this difference was not significant. This study provides the first evidence of the influence of the immune microenvironment on the osteogenic properties of the induced membranes

Does neoadjuvant FOLFOX chemotherapy improve the prognosis of high-risk Stage II and III colon cancers? Three years' follow-up results of the PRODIGE 22 phase II randomized multicentre trial

International audienceAim Neoadjuvant chemotherapy has proven valuable in locally advanced resectable colon cancer (CC) but its effect on oncological outcomes is uncertain. The aim of the present paper was to report 3-year oncological outcomes, representing the secondary endpoints of the PRODIGE 22 trial. Method PRODIGE 22 was a randomized multicentre phase II trial in high-risk T3, T4 and/or N2 CC patients on CT scan. Patients were randomized between 6 months of adjuvant FOLFOX (upfront surgery) or perioperative FOLFOX (four cycles before surgery and eight cycles after; FOLFOX perioperative). In wild-type RAS patients, a third arm testing perioperative FOLFOX-cetuximab was added. The primary endpoint was the tumour regression grade. Secondary endpoints were 3-year overall survival (OS), disease-free survival (DFS), recurrence-free survival (RFS) and time to recurrence (TTR). Results Overall, 120 patients were enrolled. At interim analysis, the FOLFOX-cetuximab arm was stopped for futility. The remaining 104 patients represented our intention-to-treat population. In the perioperative group, 96% received the scheduled four neoadjuvant cycles and all but one had adjuvant FOLFOX for eight cycles. In the control arm, 38 (73%) patients received adjuvant FOLFOX. The median follow-up was 54.3 months. Three-year OS was 90.4% in both arms [hazard ratio (HR) = 0.85], 3-year DFS, RFS and TTR were, respectively, 76.8% and 69.2% (HR=0.94), 73% and 69.2% (HR = 0.86) and 82% and 72% (HR = 0.67) in the perioperative and control arms, respectively. Forest plots did not show any subgroup with significant difference for survival outcomes. No benefit from adding cetuximab was observed. Conclusion Perioperative FOLFOX has no detrimental effect on long-term oncological outcomes and may be an option for some patients with locally advanced CC

L'insertion territoriale des systèmes d'activités des ménages agricoles en Languedoc Roussillon, France. Intersama : un projet de recherche-action

Cette communication présente un projet de recherche récemment soumis et validé par le Conseil Scientifique du troisième programme français PSDR 3 « Pour et Sur le Développement Régional ». Consacré à l'analyse des dynamiques territoriales et au rôle qu’y jouent les activités économiques et les espaces ruraux, une des originalités de ce programme est d'être conçu et construit au coeur des régions françaises concernées, en lien direct avec les préoccupations des acteurs et avec un co-financement égal entre les Régions et les organismes de recherche. D’une durée de 3 ans (2008-2011), le projet baptisé « Intersama » rassemble 13 chercheurs et enseignants-chercheurs de divers organismes et 6 institutions professionnelles partenaires