Biotransformation of the triketone herbicide Mesotrione by a Bacillus strain. Metabolite profiling using liquid chromatography/electrospray ionization quadrupole-time of flight mass spectrometry.

The metabolic pathway involved in the biotransformation of the herbicide mesotrione by the bacterial strain Bacillus sp. 3B6 was investigated by a reliable liquid chromatography/electrospray ionization quadrupole time-of-flight mass spectrometry (LC/ESI-QTOF-MS) method. The LC/ESI-MS method, both in positive and negative mode, with the assistance of MS2 fragments and isotopic pattern analyses, allowed us to identify five metabolites. This work constitutes the first complete monitoring of mesotrione degradation kinetics. Among the transformation products found by both techniques, one was formed by intramolecular cyclization between a hydroxylamine and a keto function, which is quite a rare biological reactivity process. For each identified metabolite, a fragmentation pathway is proposed for negative and positive mod

Survival of patients with non-small cell lung cancer having leptomeningeal metastases treated with immune checkpoint inhibitors

Introduction: Patients with non-small cell lung cancer (NSCLC) experience leptomeningeal metastases (LM) in 3-9% of cases. Because overall survival (OS) and performance status are very poor, they are mostly excluded from clinical trials. Here, we evaluated survival of patients with NSCLC having LM treated with immune checkpoint inhibitors (ICIs).Methods: A prospectively collected list of patients with advanced NSCLC treated with ICIs between November 2012 and July 2018 in 7 European centres was merged. All patients with LM before ICI start were selected, data were retrospectively added and patients were classified according to the National Comprehensive Cancer Network (NCCN) LM prognostic classification (good/poor). Progression-free survival (PFS) and OS on ICIs were evaluated.Results: Nineteen of 1288 (1.5%) patients had LM; 73.7% had synchronous brain metastases; 73.7% had neurological symptoms at the start of ICIs and 52.6% were in the NCCN LM good prognosis group. Programmed death ligand-1 (PD-L1) expression was known for 42.1% of patients (87.5% positive). Median follow-up was 13 months from the start of ICIs, and median (95% confidence interval [CI]) PFS on ICIs was 2.0 (1.8-2.2) months. Six-month PFS rate was 21.0% and was significantly higher in the NCCN good versus poor prognostic group: 40% vs 0% (p = 0.05). Twelve-month PFS rate was 0%. Median (95% CI) OS from the start of ICIs was 3.7 (0.9-6.6) months. Six-month OS rate was 36.8%, and 12-month OS rate was 21.1%; both were not statistically significantly different for the good versus poor NCCN prognostic group (p = 0.40 and p = 0.56, respectively).Conclusion: Some patients with NSCLC having LM do benefit from ICI treatment; specifically, those in the NCCN LM good prognosis group can obtain a long survival. (C) 2019 Elsevier Ltd. All rights reserved.</p

Outcome of Patients with Non-Small Cell Lung Cancer and Brain Metastases Treated with Checkpoint Inhibitors

Introduction: Although frequent in NSCLC, patients with brain metastases (BMs) are often excluded from immune checkpoint inhibitor (ICI) trials. We evaluated BM outcome in a less-selected NSCLC cohort. Methods: Data from consecutive patients with advanced ICI-treated NSCLC were collected. Active BMs were defined as new and/or growing lesions without any subsequent local treatment before the start of ICI treatment. Objective response rate (ORR), progression-free survival, and overall survival (OS) were evaluated. Multivariate analyses were performed by using a Cox proportional hazards model and logistic regression. Results: A total of 1025 patients were included; the median follow-up time from start of ICI treatment was 15.8 months. Of these patients, 255 (24.9%) had BMs (39.2% active, 14.3% symptomatic, and 27.4% being treated with steroids). Disease-specific Graded Prognostic Assessment (ds-GPA) score was known for 94.5% of patients (35.7% with a score of 0-1, 58.5% with a score of 1.5-2.5, and 5.8% with a score of 3). The ORRs with BM versus without BM were similar: 20.6% (with BM) versus 22.7% (without BM) (p = 0.484). The intracranial ORR (active BM with follow-up brain imaging [n = 73]) was 27.3%. The median progression-free survival times were 1.7 (95% confidence interval [CI]: 1.5-2.1) and 2.1 (95% CI: 1.9-2.5) months, respectively (p = 0.009). Of the patients with BMs, 12.7% had a dissociated cranial-extracranial response and two (0.8%) had brain pseudoprogression. Brain progression occurred more in active BM than in stable BM (54.2% versus 30% [p <0.001]). The median OS times were 8.6 months (95% CI: 6.8-12.0) with BM and 11.4 months (95% CI: 8.6-13.8) months with no BM (p = 0.035). In the BM subgroup multivariate analysis, corticosteroid use (hazard ratio [HR] = 2.37) was associated with poorer OS, whereas stable BMs (HR = 0.62) and higher ds-GPA classification (HR = 0.48-0.52) were associated with improved OS. Conclusion: In multivariate analysis BMs are not associated with a poorer survival in patients with ICI-treated NSCLC. Stable patients with BM without baseline corticosteroids and a good ds-GPA classification have the best prognosis. (C) 2019 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved

Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome associated with COVID-19: An Emulated Target Trial Analysis.

RATIONALE: Whether COVID patients may benefit from extracorporeal membrane oxygenation (ECMO) compared with conventional invasive mechanical ventilation (IMV) remains unknown. OBJECTIVES: To estimate the effect of ECMO on 90-Day mortality vs IMV only Methods: Among 4,244 critically ill adult patients with COVID-19 included in a multicenter cohort study, we emulated a target trial comparing the treatment strategies of initiating ECMO vs. no ECMO within 7 days of IMV in patients with severe acute respiratory distress syndrome (PaO2/FiO2 <80 or PaCO2 ≥60 mmHg). We controlled for confounding using a multivariable Cox model based on predefined variables. MAIN RESULTS: 1,235 patients met the full eligibility criteria for the emulated trial, among whom 164 patients initiated ECMO. The ECMO strategy had a higher survival probability at Day-7 from the onset of eligibility criteria (87% vs 83%, risk difference: 4%, 95% CI 0;9%) which decreased during follow-up (survival at Day-90: 63% vs 65%, risk difference: -2%, 95% CI -10;5%). However, ECMO was associated with higher survival when performed in high-volume ECMO centers or in regions where a specific ECMO network organization was set up to handle high demand, and when initiated within the first 4 days of MV and in profoundly hypoxemic patients. CONCLUSIONS: In an emulated trial based on a nationwide COVID-19 cohort, we found differential survival over time of an ECMO compared with a no-ECMO strategy. However, ECMO was consistently associated with better outcomes when performed in high-volume centers and in regions with ECMO capacities specifically organized to handle high demand. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Caractéristiques des langues et apprentissage de la lecture en langue première et en français langue seconde : perspective évolutive et comparative entre l'arabe et le portugais

First, this crosslinguistic study aimed to investigate graphophonological, grapho-morphological and grapho-syntactical implicit and explicit knowledge development and the contribution of this knowledge to reading in vocalised Arabic and Portuguese mother tongue. Results indicate that Arabic pupils focus on root/pattern morpho-derivational structure, more than on inflected cues, whereas Portuguese pupils show a phonological sensitivity to rime and syllable but also better knowledge about inflexional than derivational morphology. Moreover, whatever mother tongue we studied, morphological knowledge plays a role on written words recognition, when more decontextualized knowledge occurs mainly in Arabic. The grapho-morpho-derivational knowledge contribution in Arabic reading comprehension accentuates the significance of morphology in this written language. Lastly, reading comprehension seems to be more dependent from automatised processes in Portuguese because of its relatively irregular orthography. The second aim of this research was to study the role of reading acquisition in mother tongue (Arabic vs. Portuguese) on learning to read in French as a second language. Comparisons allow to conclude that the special status of morphology in Arabic can conduct learners to pay attention on internal structure of French words in order to read it. In the other hand, similarity between Portuguese and French facilitates the development of graphophonological sensitivity and emphasises the symmetry between first and second language reading words skills. French second language reading comprehension profiles and their development are also very different between Arabic and Portuguese speakers.Cette recherche interlangue a pour premier objectif d'analyser l'évolution des connaissances graphophonologiques, grapho-morphologiques et grapho-syntaxiques, implicites et explicites et la contribution de ces connaissances à la lecture en arabe vocalisé et en portugais langue première. Les résultats indiquent que les élèves de langue arabe se focalisent davantage sur la structure morpho- dérivationnelle en racine/schème que sur le marquage flexionnel, alors que les élèves de langue portugaise développent, non seulement une sensibilité phonologique à la rime et à la syllabe mais aussi de meilleures connaissances grapho-morpho-flexionnelles que grapho-morpho-dérivationnelles. Par ailleurs, si les connaissances morphologiques jouent un rôle sur la reconnaissance des mots écrits quelle que soit la langue, on remarque que ce sont celles les plus écontextualisées qui interviennent en arabe. La contribution des connaissances grapho-morpho-dérivationnelles à la compréhension de phrases en arabe souligne là encore l'importance de la morphologie dans cette langue écrite. Enfin, la compréhension en lecture apparaît plus dépendante des processus d'automatisation en portugais, du fait de l'opacité relative de son orthographe. Le deuxième objectif de ce travail est d'étudier le rôle des acquisitions de la lecture en langue première (arabe vs. portugais) sur l'apprentissage de la lecture en français langue seconde. Les comparaisons ont permis de conclure que le statut privilégié de la morphologie en arabe peut inciter les apprenants à porter attention à la structure interne des mots français pour les lire. En revanche, les similitudes entre le portugais et le français facilitent le développement de la sensibilité graphophonologique et amplifient la symétrie entre les habiletés de lecture de mots en L1 et en L2. Les profils de compréhension en français L2 et leur évolution sont également très différents entre arabophones et lusophones

Caractéristiques des langues premières et apprentissage de la lecture en français langue seconde : perspective comparative interlangue entre l’arabe et le portugais

Introduction Lors de l’apprentissage de la lecture en langue seconde (L2) et dans la mesure où l’apprentissage de la littéracie a été amorcé en langue première (L1), les apprenants ont préalablement acquis des connaissances sur l’écrit. De nombreuses recherches ont, en effet, mis en évidence l’influence des expériences de la lecture en L1 sur l’apprentissage d’une L2, sans nier que les apprentissages portant spécifiquement sur la langue cible interviennent pour parvenir à maîtriser le système..

Caractéristiques des langues et apprentissage de la lecture en langue première et en français langue seconde (perspective évolutive et comparative entre l arabe et le portugais)

Cette recherche interlangue a pour premier objectif d analyser l évolution des connaissances graphophonologiques, grapho-morphologiques et grapho-syntaxiques, implicites et explicites et la contribution de ces connaissances à la lecture en arabe vocalisé et en portugais langue première. Les résultats indiquent que les élèves de langue arabe se focalisent davantage sur la structure morphodérivationnelle en racine/schème que sur le marquage flexionnel, alors que les élèves de langue portugaise développent, non seulement une sensibilité phonologique à la rime et à la syllabe mais aussi de meilleures connaissances grapho-morpho-flexionnelles que grapho-morpho-dérivationnelles. Par ailleurs, si les connaissances morphologiques jouent un rôle sur la reconnaissance des mots écrits quelle que soit la langue, on remarque que ce sont celles les plus décontextualisées qui interviennent en arabe. La contribution des connaissances grapho-morpho-dérivationnelles à la compréhension de phrases en arabe souligne là encore l importance de la morphologie dans cette langue écrite. Enfin, la compréhension en lecture apparaît plus dépendante des processus d automatisation en portugais, du fait de l opacité relative de son orthographe. Le deuxième objectif de ce travail est d étudier le rôle des acquisitions de la lecture en langue première (arabe vs. portugais) sur l apprentissage de la lecture en français langue seconde. Les comparaisons ont permis de conclure que le statut privilégié de la morphologie en arabe peut inciter les apprenants à porter attention à la structure interne des mots français pour les lire. En revanche, les similitudes entre le portugais et le français facilitent le développement de la sensibilité graphophonologique et amplifient la symétrie entre les habiletés de lecture de mots en L1 et en L2. Les profils de compréhension en français L2 et leur évolution sont également très différents entre arabophones et lusophonesFirst, this crosslinguistic study aimed to investigate graphophonological, grapho-morphological and grapho-syntactical implicit and explicit knowledge development and the contribution of this knowledge to reading in vocalised Arabic and Portuguese mother tongue. Results indicate that Arabic pupils focus on root/pattern morpho-derivational structure, more than on inflected cues, whereas Portuguese pupils show a phonological sensitivity to rime and syllable but also better knowledge about inflexional than derivational morphology. Moreover, whatever mother tongue we studied, morphological knowledge plays a role on written words recognition, when more decontextualized knowledge occurs mainly in Arabic. The grapho-morpho-derivational knowledge contribution in Arabic reading comprehension accentuates the significance of morphology in this written language. Lastly, reading comprehension seems to be more dependent from automatised processes in Portuguese because of its relatively irregular orthography. The second aim of this research was to study the role of reading acquisition in mother tongue (Arabic vs. Portuguese) on learning to read in French as a second language. Comparisons allow to conclude that the special status of morphology in Arabic can conduct learners to pay attention on internal structure of French words in order to read it. In the other hand, similarity between Portuguese and French facilitates the development of graphophonological sensitivity and emphasises the symmetry between first and second language reading words skills. French second language reading comprehension profiles and their development are also very different between Arabic and Portuguese speakersRENNES2-BU Centrale (352382101) / SudocSudocFranceF

Développement métalinguistique et apprentissage de la lecture chez les enfants bilingues

SJR 2010 Q

Grapheme coding during sublexical processing in French third and fifth graders

International audienc

« Singularité, pluralité et Nom collectif : une étude psycholinguistique »

Conférence invitée, Séminaire de l’INSERM, laboratoire de neurosciences, Strasbour