ZOOTAXA

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Natalizumab treatment shows low cumulative probabilities of confirmed disability worsening to EDSS milestones in the long-term setting.

Abstract Background Though the Expanded Disability Status Scale (EDSS) is commonly used to assess disability level in relapsing-remitting multiple sclerosis (RRMS), the criteria defining disability progression are used for patients with a wide range of baseline levels of disability in relatively short-term trials. As a result, not all EDSS changes carry the same weight in terms of future disability, and treatment benefits such as decreased risk of reaching particular disability milestones may not be reliably captured. The objectives of this analysis are to assess the probability of confirmed disability worsening to specific EDSS milestones (i.e., EDSS scores ≥3.0, ≥4.0, or ≥6.0) at 288 weeks in the Tysabri Observational Program (TOP) and to examine the impact of relapses occurring during natalizumab therapy in TOP patients who had received natalizumab for ≥24 months. Methods TOP is an ongoing, open-label, observational, prospective study of patients with RRMS in clinical practice. Enrolled patients were naive to natalizumab at treatment initiation or had received ≤3 doses at the time of enrollment. Intravenous natalizumab (300 mg) infusions were given every 4 weeks, and the EDSS was assessed at baseline and every 24 weeks during treatment. Results Of the 4161 patients enrolled in TOP with follow-up of at least 24 months, 3253 patients with available baseline EDSS scores had continued natalizumab treatment and 908 had discontinued (5.4% due to a reported lack of efficacy and 16.4% for other reasons) at the 24-month time point. Those who discontinued due to lack of efficacy had higher baseline EDSS scores (median 4.5 vs. 3.5), higher on-treatment relapse rates (0.82 vs. 0.23), and higher cumulative probabilities of EDSS worsening (16% vs. 9%) at 24 months than those completing therapy. Among 24-month completers, after approximately 5.5 years of natalizumab treatment, the cumulative probabilities of confirmed EDSS worsening by 1.0 and 2.0 points were 18.5% and 7.9%, respectively (24-week confirmation), and 13.5% and 5.3%, respectively (48-week confirmation). The risks of 24- and 48-week confirmed EDSS worsening were significantly higher in patients with on-treatment relapses than in those without relapses. An analysis of time to specific EDSS milestones showed that the probabilities of 48-week confirmed transition from EDSS scores of 0.0–2.0 to ≥3.0, 2.0–3.0 to ≥4.0, and 4.0–5.0 to ≥6.0 at week 288 in TOP were 11.1%, 11.8%, and 9.5%, respectively, with lower probabilities observed among patients without on-treatment relapses (8.1%, 8.4%, and 5.7%, respectively). Conclusions In TOP patients with a median (range) baseline EDSS score of 3.5 (0.0–9.5) who completed 24 months of natalizumab treatment, the rate of 48-week confirmed disability worsening events was below 15%; after approximately 5.5 years of natalizumab treatment, 86.5% and 94.7% of patients did not have EDSS score increases of ≥1.0 or ≥2.0 points, respectively. The presence of relapses was associated with higher rates of overall disability worsening. These results were confirmed by assessing transition to EDSS milestones. Lower rates of overall 48-week confirmed EDSS worsening and of transitioning from EDSS score 4.0–5.0 to ≥6.0 in the absence of relapses suggest that relapses remain a significant driver of disability worsening and that on-treatment relapses in natalizumab-treated patients are of prognostic importance

Pollutions diffuses : mobilité et persistance des polluants organiques dans les sols

National audienc

Standard vocabulary, consensual functional groups and automated classification for phytoplankton high throughput datasets using automated flow cytometry

International audienc

Prediction of the fate of pesticides in the environment from their molecular properties

Manuela Cigolini, M. ,Luzzani, G., Sacchettini, G. (eds)Prediction of the fate of pesticides in the environment from their molecular properties. XV Symposium in Pesticide Chemistry “Environmental risk assessment and managemen

Introduction de gènes de résistance à la rouille couronnée dans la sélection française d’avoine (Avena sativa L.)

International audienceThis program aimed at characterizing oat varieties (Avena sativaL.) originating from INRAE Clermont-Ferrand collection as well as from main oat-producing countries. These varieties and some of their progenies (F6) were evaluated for their crown rust tolerance. Simultaneously, these lines were molecularlyassessed for their allelic composition for known resistance genes. A consensus map of 178 SNP markers covering 26 linkage groups was established. An association study between rust-resistance phenotype and molecular markers willbe conducted which should result in the identification of linkage between some SNPs and resistance loci. The most relevant markers will further be used in marker-assisted selection programs. Moreover, several experimentations were conducted to develop a protocol for doubled-haploid (DH) line production. The most promising technique was the one involving anther culture.Ce programme porte sur la caractérisation de variétés d’avoine (Avena sativaL.) provenant de diverses origines et notamment de la collectionINRAE de Clermont-Ferrand mais également de variétés provenant des principaux pays producteurs. Ces différentes variétés collectées, ainsi que certains de leurs croisements (F6), ont été caractérisés aux champs pour leur tolérance à la rouille par les partenaires privés. Parallèlement, ces lignées ont été évaluées au laboratoire pour leur composition allélique au niveau des principaux gènes de résistance connus et marqués. Une carte génétiqueconsensus a été établie, elle comporte 178 marqueurs SNP répartis en 26 groupes de liaison. Au final, une étude d’association entre phénotypes résistants ou sensibles et diversité allélique aux gènes a permis d’identifier des marqueurs pertinents utilisables en sélection assistée. Dans le même temps, un ensemble d’expérimentations a été mené pour mettre au point une méthode de production de plantes haploïdesdoublées(HD). La technique la plus prometteuse est la culture d’anthères

Prédiction du comportement des pesticides dans l’environnement à partir de leurs propriétés moléculaires

oral communication abstractPrédiction du comportement des pesticides dans l’environnement à partir de leurs propriétés moléculaires. 45e Congrès du Groupe Français des Pesticides "Devenir et impact des pesticides : verrous à lever et nouveaux enjeu

Does COMT val158met polymorphism influence P50 sensory gating, eye tracking or saccadic inhibition dysfunctions in schizophrenia?

International audienc

Prediction of the Fate of Organic Compounds in the Environment From Their Molecular Properties: A Review

International audienceA comprehensive review of quantitative structure-activity relationships (QSAR) allowing the prediction of the fate of organic compounds in the environment from their molecular properties was done. The considered processes were water dissolution, dissociation, volatilization, retention on soils and sediments (mainly adsorption and desorption), degradation (biotic and abiotic), and absorption by plants. A total of 790 equations involving 686 structural molecular descriptors are reported to estimate 90 environmental parameters related to these processes. A significant number of equations was found for dissociation process (pKa), water dissolution or hydrophobic behavior (especially through the KOW parameter), adsorption to soils and biodegradation. A lack of QSAR was observed to estimate desorption or potential of transfer to water. Among the 686 molecular descriptors, 5 were found to be dominant in the 790 collected equations and the most generic ones: four quantum-chemical descriptors, the energy of the highest occupied molecular orbital (EHOMO) and the energy of the lowest unoccupied molecular orbital (ELUMO), polarizability (α) and dipole moment (μ), and one constitutional descriptor, the molecular weight (MW). Keeping in mind that the combination of descriptors belonging to different categories (constitutional, topological, quantum-chemical…) led to improve QSAR performances, these descriptors should be considered for the development of new QSAR, for further predictions of environmental parameters. This review also allows finding of the relevant QSAR equations to predict the fate of a wide diversity of compounds in the environment