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International audience; Magnitudes of differential stress in the lithosphere, especially in the crust, are still disputed. Earthquake-based stress drop estimates indicate median values ca. 180 MPa, corresponding to a friction angle of ca. 10° to maintain the topographic relief between lowland and plateau for >10 Ma. The relative contribution of crustal strength to total lithospheric strength varies considerably laterally. In the region between lowland and plateau and inside the plateau the depth-integrated crustal strength is approximately equal to the depth-integrated strength of the mantle lithosphere. Simple analytical formulae predicting the lateral variation of depth-integrated stresses agree with numerically calculated stress fields, which show both the accuracy of the numerical results and the applicability of simple, rheology-independent, analytical predictions to highly variable, rheology-dependent stress fields. Our results indicate that (1) crustal strength can be locally equal to mantle lithosphere strength and that (2) crustal stresses must be at least one order of magnitude larger than median stress drops in order to support the plateau relief over a duration of ca. 10 Ma.

International audience; PURPOSE: Concomitant treatment with radiation therapy and cisplatin (CDDP) remains the gold standard for bladder preservation in the treatment of muscle-invasive bladder cancer (MIBC). We present the long-term results of a phase 1 clinical trial to assess the association of twice-weekly gemcitabine with CDDP and radiation therapy in this setting. METHODS AND MATERIALS: Patients with pT2-pT4N0M0 MIBC without hydronephrosis or diffuse carcinoma in situ were enrolled in this study. After maximal transurethral resection of the bladder tumor, patients received concomitant radiation therapy (63 Gy in 1.8 fractions) and chemotherapy (CDDP 20 mg/m²/day over 4 days every 21 days and gemcitabine twice a week). The starting dose of gemcitabine was 15 mg/m² with dose escalation to 20, 25, and 30 mg/m². The primary endpoint was the maximum tolerated dose (MTD). Secondary endpoints included toxicity and tumor control. RESULTS: Fourteen patients were enrolled. Dose-limiting toxicity occurred in 2 patients treated with 30 mg/m² gemcitabine (grade 4 thrombocytopenia and severe impairment of World Health Organization performance status, respectively). Nine patients received the complete chemoradiation therapy protocol. The recommended dose of gemcitabine was 25 mg/m². The median follow-up time was 53 months, and the overall and disease-specific 5-year survival rates were 62% and 77%, respectively. Among the patients who received the complete treatment, bladder-intact survival was 76% at 5 years, and the median overall survival was 69.6 months. CONCLUSIONS: This regimen was well tolerated. The gemcitabine MTD was 25 mg/m². Bladder preservation and disease control were promising. A multicenter phase 2 randomized trial is ongoing.

Abstract Background Children with sickle cell anemia (SCA) have an 11% risk of stroke by the age of 18. Chronic transfusion applied in patients detected to be at risk by transcranial Doppler allows a significant reduction of stroke risk. However, chronic transfusion exposes to several adverse events, including alloimmunization and iron overload, and is not curative. Hematopoietic stem cell transplantation allows termination of the transfusion program, but its benefit has not been demonstrated. Design DREPAGREFFE ( NCT01340404 ) is a multicenter, prospective trial enrolling SCA children younger than 15 years receiving chronic transfusion due to a history of abnormal transcranial Doppler (velocities ≥ 200 cm/s). Only those with at least one non-SCA sibling and parents accepting HLA-typing and transplantation with a genoidentical donor were eligible. Chronic transfusion was pursued in patients with no available donor, whereas others were transplanted. Comparison between the 2 arms (transfusion vs transplantation) was analyzed using both genetic randomization and propensity-score matching as a sensitivity analysis. The primary end-point was the velocity measure at 1 year. Secondary endpoints were the incidence of stroke, silent cerebral infarcts and stenoses, cognitive performance in comparison with siblings, allo-immunization, iron-overload, phosphatidyl-serine, angiogenesis/hypoxia, brain injury-related factor expression, quality of life and cost. Objectives To show that genoidentical transplantation decreases velocities significantly more than chronic transfusion in SCA children at risk of stroke. Discussion DREPAGREFFE is the first prospective study to evaluate transplantation in SCA children. It compares the outcome of cerebral vasculopathy following genoidentical transplantation versus chronic transfusion using genetic randomization and causal inference methods.

International audience; We show the benefit of considering periodic dilution rates in the chemostat model for discriminating between a growth function which does not depend on the density of the microorganisms population (such as the Monod law) and another one which does depend (such as the Contois law). This goal is achieved thanks to the measurement of the abiotic resource only. We then present a simple procedure for a robust discrimination between the two types of kinetics using a single experiment in three phases. Finally, the shape of the best periodic excitation is discussed and the method is illustrated on numerical simulations.

International audience; Gut bacteria influence brain functions and metabolism. We investigated whether this influence can be mediated by direct sensing of bacterial cell wall components by brain neurons. In mice, we found that bacterial peptidoglycan plays a major role in mediating gut-brain communication via the Nod2 receptor. Peptidoglycan-derived muropeptides reach the brain and alter the activity of a subset of brain neurons that express Nod2. Activation of Nod2 in hypothalamic inhibitory neurons is essential for proper appetite and body temperature control, primarily in females. This study identifies a microbe-sensing mechanism that regulates feeding behavior and host metabolism.

The Social Security Funding Law for 2012 introduced the Economic and Public Health Assessment Committee (Commission Evaluation Economique et de Santé Publique, or CEESP) in the Social Security Code as a specialised committee affiliated with the Haute Autorité de Santé in charge of providing recommendations and health economic opinions. This article provides an in-depth description of the CEESP's structure and working methods, and analyses the impact of health economic assessment on market access of drugs in France. It also points out the areas of uncertainty and the conflicting rules following the introduction of the health economic assessment in France. The authors also provide their personal opinion on the likely future of health economic assessment of drugs in France, including the possible merge of the CEESP and the Transparency Committee, the implementation of a French threshold, and the extension of health economic assessment to a larger number of products.Keywords: health economic assessment; CEESP; HAS; France; market access; cost-effectiveness(Published: 4 June 2015)Citation: Journal of Market Access & Health Policy 2015, 3: 27902 - http://dx.doi.org/10.3402/jmahp.v3.27902

International audience; In this paper we present a language-independent and automatic approach to extend a wordnet by recycling different types of already existing language resources, such as machine-readable dictionaries, parallel corpora and Wikipedia. The approach, applied to Slovene, takes into account monosemous and polysemous words, general and specialized vocabulary as well as simple and multi-word lexemes. The extracted words are assigned one or several synset ids based on a classifier that relies on several features including distributional similarity. In the next step we also identify and remove highly dubious (literal, synset) pairs, based on simple distributional information extracted from a large corpus in an unsupervised way. Automatic and manual evaluation show that the proposed approach yields very promising results.; V prispevku predstavljamo jezikovno neodvisno in avtomatsko razširitev wordneta z uporabo heterogenih že obstoječih jezikovnih virov, kot so strojno berljivi slovarji, vzporedni korpusi in Wikipedija. Pristop, ki ga preizkusimo na slovenščini, upošteva tako eno- kot večpomenske besede, splošno in specializirano besedišče, pa tudi eno- in večbesedne lekseme. Izluščenim besedam enega ali več pomenov pripišemo s pomočjo klasifikatorja, ki temelji na naboru različnih značilk, predvsem pa na distribucijski podobnosti. V naslednjem koraku s pomočjo distribucijskih informacij, izluščenih iz velikega korpusa, identificiramo in odstranimo zelo dvomljive kandidate. Avtomatska in ročna evalvacija rezultatov pokaže, da uporabljeni pristop daje zelo spodbudne rezultate.

CT3 ; EnjS4 ; Département EA; Mitigation of N2O emissions in agroecosystems: the role of N2O-reducers. 16. International Symposium on Microbial Ecology - ISME16

National audience

Publis014-agap-018; Background: Recurrent gene duplication and retention played an important role in angiosperm genome evolution. It has been hypothesized that these processes contribute significantly to plant adaptation but so far this hypothesis has not been tested at the genome scale.[br/]Results: We studied available sequenced angiosperm genomes to assess the frequency of positive selection footprints in lineage specific expanded (LSE) gene families compared to single-copy genes using a dN/dS-based test in a phylogenetic framework. We found 5.38% of alignments in LSE genes with codons under positive selection. In contrast, we found no evidence for codons under positive selection in the single-copy reference set. An analysis at the branch level shows that purifying selection acted more strongly on single-copy genes than on LSE gene clusters. Moreover we detect significantly more branches indicating evolution under positive selection and/or relaxed constraint in LSE genes than in single-copy genes.[br/]Conclusions: In this – to our knowledge –first genome-scale study we provide strong empirical support for the hypothesis that LSE genes fuel adaptation in angiosperms. Our conservative approach for detecting selection footprints as well as our results can be of interest for further studies on (plant) gene family evolution.