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Vous avez dit "Situation de Handicap" ?
No full textFiche thématique, issue projet européen ISAID, à destination des professionnels et des parents. Elle applique de concept de "situation de handicap" à la déficience intellectuelle
Patients atteints d’un cancer gastrique localisé MSI/dMMR, pas de chimiothérapie mais une immunothérapie périopératoire : l’essai de phase II GERCOR NEONIPIGA vient d’être ouvert au recrutement
No full textInternational audienceIntroductionPerioperative chemotherapy is the standard strategy for localized gastric cancers. Nevertheless, this strategy seems to be inefficient, if not deleterious, for patients with tumors harboring microsatellite instability (MSI) and/or mismatch repair deficiency (dMMR), a tumor phenotype predictive for the efficacy of immune checkpoint inhibitors (ICKi).AimThe GERCOR NEONIPIGA single-arm phase II study (NCT04006262; EUDRACT 2018-004712-22) aims at evaluating the efficacy of a peri-operative strategy with nivolumab and ipilimumab in neoadjuvant setting, then nivolumab alone after surgery for patients with resectable MSI/dMMR gastric cancer.Material and methodsMain inclusion criteria are: gastric and oesogastric junction adenocarcinoma (GOA), T2-T4, all N stage and M0, MSI/dMMR. Patients will be treated with nivolumab 240 mg Q2 W, 6 infusions, and ipilimumab 1 mg/kg Q6 W, 2 infusions in neoadjuvant setting. Following surgery, patients with TRG 1-2-3 (Mandard tumor regression grade), acceptable tolerance of neoadjuvant treatment and postoperative ECOG performance status 0–1, will be treated with adjuvant nivolumab 480 mg Q4 W, 9 infusions.ResultsThe primary endpoint is pathological complete response rate (pCR-R). Based on a Fleming design, with α = 5% and β = 20%, 27 patients have to be evaluated (H0 = 5%; H1 = 20%). Secondary endpoints include disease-free survival, overall survival and safety.ConclusionThis study is planned to include 32 patients to evaluate the pCR-R with the combination of nivolumab and ipilimumab in neoadjuvant setting for MSI/dMMR localized GOA. The MSI/MMR status should be systematically assessed on diagnostic biopsies of all GOA. If it meets its primary endpoint, the GERCOR NEONIPIGA study might mark a turning point in the management of localized MSI/dMMR GOA patients.IntroductionLa chimiothérapie périopératoire est la stratégie de référence pour les cancers gastriques (CG) localisés, mais semble inefficace voire délétère pour les patients avec un cancer MSI/dMMR (microsatellites instables/MMR-déficient), biomarqueur prédictif de l’efficacité de l’immunothérapie.ObjectifL’essai de phase 2 mono-bras GERCOR NEONIPIGA (NCT04006262; EUDRACT 2018-004712-22) évalue l’efficacité du nivolumab plus ipilimumab en néo-adjuvant puis nivolumab seul en adjuvant pour les CG ou de la jonction œsogastrique (JOG) MSI/dMMR résécables.Matériel et méthodesLes principaux critères d’inclusion sont : CG/JOG, T2-4 tout N M0, MSI/dMMR. Les patients sont traités en néo-adjuvant par nivolumab 240 mg Q2 W, 6 perfusions, et ipilimumab 1 mg/kg Q6 W, deux injections. Les patients avec un degré de régression tumorale 1-3 selon Mandard, une tolérance acceptable du traitement néo-adjuvant et un indice de performance postopératoire ECOG 0-1 recevront neuf perfusions mensuelles de nivolumab 480 mg en adjuvant.RésultatsL’objectif principal est le taux de réponse complète pathologique (pCR). Selon un design de Fleming avec α = 5 % et β = 20 %, 27 patients évaluables sont à analyser (H0 = 5 % ; H1 = 20 %). Les critères secondaires de jugement sont la survie sans maladie, la survie globale et le profil de tolérance.ConclusionIl est prévu d’inclure 32 patients pour évaluer le taux de pCR pour les CG/JOG MSI/dMMR traités par nivolumab et ipilimumab néo-adjuvant. Le statut MSI/MMR doit être systématiquement analysé sur les biopsies diagnostiques de tout CG/JOG. L’étude NEONIPIGA pourrait marquer un tournant dans la prise en charge des CG/JOG MSI/dMMR si elle atteint son objectif principal
Oblivious and Semi-Oblivious Boundedness for Existential Rules
No full textWe study the notion of boundedness in the context of positive existential rules, that is, whether there exists an upper bound to the depth of the chase procedure , that is independent from the initial instance. By focussing our attention on the oblivious and the semi-oblivious chase variants, we give a characterization of boundedness in terms of FO-rewritability and chase termination. We show that it is decidable to recognize if a set of rules is bounded for several classes and outline the complexity of the problem. This report contains the paper published at IJCAI 2019 [Bourhis et al., 2019] and an appendix with full proofs
International Comparative Evidence of E-Government Success and Economic Growth: Technology Adoption as an Anti-Corruption Tool
No full textPurpose: This paper aims to explore the impact of information communication technology (ICT) use and government efficiency on the economic growth. It assesses empirically the impact of government success in ICT promotion and government efficiency to enhance economic growth and catalyzing corruption control through technology adoption. Design/methodology/approach: This paper examines the relationship between ICT and economic growth in a large sample of 149 countries for the period 2012\textendash2016. The empirical evidence is based on the generalized method of moments. Findings: There is a significant relationship between e-government development, ICT development and institutional quality, and not ICT development and corruption. The empirical results show that a negative value of the interaction suggests that the impact of corruption on economic growth is smaller for countries with a higher level of technology adoption. Practical implications: The differences in e-government success across countries in the world are influenced by the digital divide due to income and corruption control level. Originality/value: The efficiency of technology adoption and promotion will ensure stronger effects of corruption control on economic growth. Relevant practical implications derive from the research that can guide public policy in the area of e-government. © 2020, Emerald Publishing Limited
Testosterone‐androgen receptor: The steroid link inhibiting TRPM8‐mediated cold sensitivity
No full textInternational audienceRecent studies have revealed gender differences in cold perception, and pointed to a possible direct action of testosterone (TST) on the cold-activated TRPM8 (Transient Receptor Potential Melastatin Member 8) channel. However, the mechanisms by which TST influences TRPM8-mediated sensory functions remain elusive. Here, we show that TST inhibits TRPM8-mediated mild-cold perception through the nonca-nonical engagement of the Androgen Receptor (AR). Castration of both male rats and mice increases sensitivity to mild cold, and this effect depends on the presence of intact TRPM8 and AR. TST in nanomolar concentrations suppresses whole-cell TRPM8-mediated currents and single-channel activity in native dorsal root ganglion (DRG) neurons and HEK293 cells co-expressing recombinant TRPM8 and AR, but not TRPM8 alone. AR cloned from rat DRGs shows no difference from standard AR. However, biochemical assays and confocal imaging reveal the presence of AR on the cell surface and its interaction with TRPM8 in response to TST, leading to an inhibition of channel activity
Aggressiveness potential of spontaneous canine mucosal melanoma can dictate distinct cancer stem cell compartment behaviors in regard to their initial size and expansion abilities
No full textInternational audienceMucosal melanoma represents one of the most highly metastatic and aggressive subtypes of melanoma. The biology of mucosal melanoma is poorly documented, and the lack of experimental models makes it difficult to design and test new therapies. Dogs are frequently affected by melanomas of the oral cavity, making spontaneous canine melanoma a potentially predictable model for their human counterpart. We recently established and characterized two new canine mucosal melanoma cell lines named OCR_OCMM1 and OCR_OCMM2. Here, we identified quiescent cancer stem cell (CSC) subpopulations in both canine cell lines that displayed similarities to human quiescent CSCs: canine melanoma CSCs had the ability to self-renew, produced nonstem cell (SC) progeny, and formed melanospheres that recapitulated the phenotypic profile of the parental tumor. These CSCs also formed melanoma in immunodeficient mice, and the inhibition of PI3K/AKT signaling expanded the CSC pool. A subset of non-CSCs transitioned to become CSCs. OCR_OCMM1 and OCR_OCMM2 displayed different CSC compartment behaviors in regard to their initial size and expansion abilities. Collectively, this study showed that the OCR_OCMM1 and OCR_OCMM2 canine melanoma cell lines are powerful cellular tools to study melanoma SCs, not only for mucosal but also for the more common human cutaneous melanoma
Matheuristics to optimize refueling and maintenance planning of nuclear power plants
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Impact of the Discretization of VOCs for Cancer Prediction Using a Multi-Objective Algorithm
No full textInternational audienceVolatile organic compounds (VOCs) are continuous medical data regularly studied to perform non-invasive diagnosis of diseases using machine learning tasks for example. The project PATHACOV aims to use VOCs in order to predict invasive diseases such as lung cancer. In this context, we propose to use a multi-objective modeling for the partial supervised classification problem and the MOCA-I algorithm specifically designed to solve these problems for discrete data, to perform the prediction. In this paper, we apply various discretization techniques on VOCs data, and we analyze their impact on the performance results of MOCA-I. The experiments show that the discretization of the VOCs strongly impacts the classification task and has to be carefully chosen according to the evaluation criterion
The Border as a Resource in Right-wing Populist Discourse: Viktor Orbán and the Diasporas in a Multi-scalar Europe
No full textInternational audienceEurope and now the United States are characterized by the growing presence of populist parties and leaders able to attract a significant share of the electorate. The successful strategy of populist politicians consists in proposing a series of discourses based on a differentiation between an endangered “Us” and a threatening “Them”. The protection of the “Us” community from the evil “Them” formulated by right-wing populist politicians is often expressed through the necessity of closing the national border, this measure being a key discursive resource incorporated in their speeches. However, is the border only presented by populist leaders as a boundary which has to be controlled, securitized and sealed? Based on the analysis of discourses produced by Viktor Orbán, the only long-standing European populist leader in power, the research shows that populist discourses can be based on opposed and complementary conceptions of the state border to entrench the opposition between an “Us” and “Them”
