Accuracy of human sperm DNA oxidation quantification and threshold determination using an 8-OHdG immuno-detection assay

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A Framework for Knowledge Discovery in a Society of Agents

International audienceThis paper proposes initial steps towards a generic framework for modeling the scientific process. It is generic according to two main axes. First, it can be instantiated to cover various types of inferences usually considered relevant in science, second, and more important here, it allows for the modeling of the social dimension of scientific activity. After motivating this drive for genericity by looking at some results from philosophy of science, the paper presents the bases of the framework and its central reliance on the notion of consistency, both at the individual and group levels. It then instantiates the social dimension of the framework by proposing an actor-critic model of scientific interaction. The ideas proposed are illustrated with examples of hypothesis formation in medicine

Phase 1 trial of ralimetinib (LY2228820) with radiotherapy plus concomitant temozolomide in the treatment of newly diagnosed glioblastoma

International audienceBackground and purpose: This phase 1 trial aimed to determine the maximum tolerated dose (MTD; primary objective) of a p38-MAPK inhibitor, ralimetinib, with radiotherapy (RT) and chemotherapy (TMZ), in the treatment of newly diagnosed glioblastoma (GBM) patients.Materials and methods: The study was designed as an open-label dose-escalation study driven by a Tite-CRM design and followed by an expansion cohort. Ralimetinib was administered orally every 12 h, 7 days a week, for 2 cycles of 2 weeks at a dose of 100, 200 or 300 mg/12 h. Patients received ralimetinib added to standard concurrent RT (60 Gy in 30 fractions) with TMZ (75 mg/m2/day) and 6 cycles of adjuvant TMZ (150–200 mg/m2 on days 1–5 every 28 days).Results: The MTD of ralimetinib was 100 mg/12 h with chemoradiotherapy. The three patients treated at 200 mg/12 h presented a dose-limiting toxicity: one patient had a grade 3 face edema, and two patients had a grade 3 rash and grade 3 hepatic cytolysis (66%). Of the 18 enrolled patients, 15 received the MTD of ralimetinib. At the MTD, the grade ≥ 3 adverse events during concomitant chemoradiotherapy were hepatic cytolysis (2/15 patients), dermatitis/rash (1/15), lymphopenia (1/15) and nausea/vomiting (1/15). No interaction of TMZ and ralimetinib when administrated concomitantly has been observed. Inhibition of pMAPKAP-K2 (−54%) was observed in peripheral blood mononuclear cells.Conclusion:This phase 1 trial is the first trial to study the combination of a p38-MAPK inhibitor, ralimetinib, with radiotherapy (RT) and chemotherapy (TMZ), in the treatment of newly diagnosed glioblastoma (GBM) patients. The MTD of ralimetinib was 100 mg/12 h. The most frequent dose-limiting toxicities were hepatic cytolysis and rash

Une faible charge allélique JAK2V617F pourrait aider à identifier de nouveaux sous-groupes de polyglobulie de Vaquez et de thrombocytémie essentielle

# 10-12International audienc

The Spliceosome: An Another Regulating System of Gene Expression Deregulated in CP-CML CD34+CD15- Cells

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Le spliceosome : un autre mécanisme de régulation des gènes impliqués dans l’hétérogénéité intra-clonale de la Leucémie Myéloïde Chronique ?

# 09-01International audienc