33 research outputs found
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
TEPhI - Photochemically induced electron and hydrogen transfer with imines - Photoinduced radical reactions
Les rĂ©actions photochimiques, dans leur ensemble, prĂ©sentent de nombreux avantages en synthĂšse organique. Le photon, considĂ©rĂ© comme un rĂ©actif Ă part entiĂšre, permet de limiter l'utilisation de composĂ©s onĂ©reux et/ou risquĂ©s Ă la manipulation et pour l'environnement. La photochimie organique s'inscrit alors dans les recommandations de la chimie durable.Trois des plus importants domaines de la photochimie organique sont Ă©tudiĂ©s dans cette thĂšse. PremiĂšrement une rĂ©action de transfert d'atome d'hydrogĂšne photoinduit par absorption directe de l'Ă©nergie lumineuse est Ă©tudiĂ©e dans le cas des imines, fonction chimique peu Ă©tudiĂ©e dans les photorĂ©actions. Une cyclisation radicalaire induit par ce transfert d'hydrogĂšne est prĂ©sentĂ©e dans le cas des pseudo-oxazolones. DeuxiĂšmement, la catalyse photorĂ©dox, qui a participĂ© Ă la renaissance de la photochimie est utilisĂ©e dans une rĂ©action de transfert d'atome d'hydrogĂšne impliquant la LĂ©voglucosĂ©none, une molĂ©cule issue de la biomasse lignocellulosique. Les diffĂ©rents dĂ©rivĂ©s obtenus peuvent ĂȘtre asujettis Ă des rĂ©actions futures et des applications dans des domaines variĂ©s de la chimie. Enfin, la photooxygĂ©nation du furfural, elle aussi molĂ©cule issue de la biomasse est Ă©tudiĂ©e dans la conception de colorants polymĂ©thines, ces derniers ayant de vastes utilisations dans les domaines de la physico-chimie.Photochemical reactions, as a whole, display numerous benefits in organic synthesis. The photon, considered as a complete reagent, enables to lessen the use of expensive and/or hazardous compounds to handle and for the environment. Thus, organic photochemistry forms part of sustainable chemistry recommandations.Three of the most important fields in organic photochemistry are studied in this thesis. Firstly, photoinduced hydrogen atom transfer via direct absorption of light energy is presented in the case of imine moiety, a chemical function whose few studies have been done to date. A radical intramolecular cyclisation induced by a hydrogen atom transfer is introduced in the case of pseudo-oxazolone structures. Secondly, photoredox catalysis, involved in the revival of photochemistry, is used to make a hydrogen atom transfer engaging Levoglucosenone, a molecule coming from lignocellulosic biomass. Derivatives of this latter obtained from photoreactions could be subjected to further reactions and applications in various areas of chemistry. In closing, photooxygenation of furfural, a molecule also issued from biomass is studied to design polymethine dyes, these latter having extensive uses in the fields of physico-chemistry
"L'importance du renseignement dans la définition, l'application et la conduite de la politique étrangÚre française."
Le renseignement est, en France, un objet d'Ă©tude peu rĂ©pandu. Jusque dans les annĂ©es 90, la mĂ©fiance structurelle du politique et du militaire Ă son Ă©gard empĂȘche l'Ă©mergence d'un dispositif Ă mĂȘme de rĂ©pondre aux objectifs stratĂ©giques de la France. Aujourd'hui cependant, plus que jamais, il occupe une place fondamentale dans la prise de dĂ©cision en politique Ă©trangĂšre. Son rĂŽle dans l'anticipation, la planification et la conduite des opĂ©rations militaires est mĂȘme incompressible. Ce mĂ©moire de fin d'Ă©tude a pour objectif d'analyser la place du dispositif de renseignement extĂ©rieur français dans la dĂ©finition, l'application et la conduite de la politique Ă©trangĂšre de la France.Master [120] en sciences politiques, orientation relations internationales, UniversitĂ© catholique de Louvain, 201
La sĂ©curitĂ© du personnel humanitaire en zone de conflit : Ăvolutions, mĂ©thodes et application au CICR dans le conflit afghan, de 2001 Ă 2010
Ce mĂ©moire de synthĂšse est consacrĂ© Ă la sĂ©curitĂ© des organismes humanitaires opĂ©rant en zone de guerre. Face au sentiment dâinsĂ©curitĂ© croissante dans le milieu de lâaide, dont fait Ă©tat une partie de la littĂ©rature Ă propos des annĂ©es 2000, ce travail a comme objet la comprĂ©hension des Ă©volutions des contextes conflictuel et humanitaire, qui ont menĂ© Ă cette hausse du risque, ainsi que la rĂ©ponse apportĂ©e par les organisations quant Ă la gestion opĂ©rationnelle de celui-ci. Pour ce faire, il sâagit dans un premier temps dâanalyser lâĂ©volution des conflits de lâaprĂšs-Guerre froide et de dresser un aperçu des mĂ©thodes de gestion opĂ©rationnelles appliquĂ©es par les organisations en zone dangereuse. Puis, dans un second temps, dâanalyser spĂ©cifiquement les mĂ©thodes utilisĂ©es par le ComitĂ© international de la Croix-Rouge et le rĂŽle de lâacceptation en matiĂšre de sĂ©curitĂ©, illustrĂ©s au travers de lâaction du CICR dans le conflit afghan, entre 2001 et 2010.Master [120] en sciences politiques, orientation relations internationales, UniversitĂ© catholique de Louvain, 201
Ălaboration d'un systĂšme de labellisation destinĂ©s aux clubs sportifs : le cas de la Ligue Handisport Francophone
La Ligue Handisport Francophone a demandĂ© lâaide dâĂ©tudiants en Education Physique, finalitĂ© Management des organisations sportives. Le projet de la LHF Ă©tait de mettre en place un outil de labellisation de ses clubs. Nous avons rĂ©pondu positivement Ă cette demande. Pour Ă©tablir cet outil de labellisation, nous nous sommes posĂ©s 2 questions auxquelles nous avons essayĂ© dâapporter des rĂ©ponses : - Quels sont les Ă©lĂ©ments dâun systĂšme de labellisation dâune organisation sportive ? - Comment mettre en oeuvre un systĂšme de labellisation sportive au sein de la Ligue Handisport Francophone ? Suite Ă une recherche dans la littĂ©rature, un benchmarking et des rencontres avec des experts du handisport, nous avons entamĂ© lâĂ©laboration de lâoutil de labellisation, en collaboration avec notre groupe de travail. Celui-ci Ă©tant composĂ© de membres de la LHF, dâexperts du handisport et des Ă©tudiants. Notre travail a abouti Ă deux versions : une version adaptĂ©e aux clubs « loisirs » et une version adaptĂ©e aux clubs « compĂ©tition ». Le « Label Loisir », multidisciplinaire, comprend 14 critĂšres â dont 5 obligatoires et 1 bonus â et le « Label CompĂ©tition », uni disciplinaire, comprend 18 critĂšres â dont 5 obligatoires. Chaque label donne la possibilitĂ© au club dâobtenir un certain niveau de qualitĂ©. Il existe 3 niveaux par catĂ©gorie de label et ceux-ci sont reprĂ©sentĂ©s par un logo reconnu dans le handisport : lâagito de lâIPC pour le « Label Loisir » et le coq de la LHF pour le « Label CompĂ©tition ».Master [120] en sciences de la motricitĂ©, orientation Ă©ducation physique, UniversitĂ© catholique de Louvain, 201
Structuration reÌgionale et deÌterminants ethnoreligieux de la violence politique au Nigeria depuis la fin de la dictature militaire
Cet article explore les deÌterminants de la violence politique au Nigeria aÌ lâappui de donneÌes recensant les conflits qui ont impliqueÌ des partis politiques et entraiÌneÌ des morts entre 2006 et 2014. Il deÌfend lâideÌe que, depuis la fin de la dictature militaire en 1999, la politique nigeÌriane sous la IVe ReÌpublique reste structureÌe par les ancrages locaux et reÌgionaux des partis. Partant de la litteÌrature existante qui se focalise sur les confrontations au moment des eÌlections geÌneÌrales, nous montrons dâabord que ces eÌlections ne repreÌsentent que la moitieÌ des deÌceÌs sur la peÌriode et que les violences politiques repreÌsentent en reÌaliteÌ un pheÌnomeÌne large avec des speÌcificiteÌs et enjeux locaux en dehors des logiques eÌlectorales. Dans un second temps, nous montrons que les ancrages reÌgionaux des partis structurent toujours la vie politique nigeÌriane. Câest le cas en ce qui concerne les violences entre partis, qui sont souvent limiteÌes aÌ quelques EÌtats ouÌ ces partis sont forts et eÌtaient en mesure de contester le monopole du Peopleâs Democratic Party (PDP). Les violences intra-partis, peu analyseÌes, confirment aussi le poids des enjeux locaux et la forte implication du PDP. Enfin, les violences entre partis se concentrent dans les EÌtats de la Middle Belt en proie aÌ des conflits religieux ou ethniques. Nous analysons lâimportance de ces deux facteurs dans les violences de masse et montrons quâelles sont provoqueÌes par leur imbrication avec la compeÌtition politique.How national are Nigerian political parties ? Regionalism and ethno-religious factors of political violence since the end of the military regimes.
This paper explores the factors of political violence in Nigeria through the analysis of data concerning deadly clashes involving political parties between 2006 and 2014. We claim that Nigeria political system under the 4th republic remains deeply influenced by local and regional logics. Starting from the existing literature â which focuses mainly on clashes during general elections â we demonstrate firstly that deaths occurring during those type of elections account for only half of the total number of casualties. Secondly, we show that the regional organization of political parties still predominates. That is more specifically the case for inter-parties violence, which is concentrated in a few states where local parties were strong enough to contest the monopoly of the ruling PDP. Ignored by the existing literature, inter-parties violence also confirms the importance of local factors and the implication of the PDP. We finally show that inter-parties violence is concentrated in the Middle Belt where ethnic and religious conflicts are most important. Along with political competition, those rivalries explain mass violence. Indeed, events combining both electoral competition and ethnic/religious factors accounted for only 5 % of the total, but caused 75% of fatalities during the period under review
Structuration reÌgionale et deÌterminants ethnoreligieux de la violence politique au Nigeria depuis la fin de la dictature militaire
How national are Nigerian political parties ? Regionalism and ethno-religious factors of political violence since the end of the military regimes.This paper explores the factors of political violence in Nigeria through the analysis of data concerning deadly clashes involving political parties between 2006 and 2014. We claim that Nigeria political system under the 4th republic remains deeply influenced by local and regional logics. Starting from the existing literature â which focuses mainly on clashes during general elections â we demonstrate firstly that deaths occurring during those type of elections account for only half of the total number of casualties. Secondly, we show that the regional organization of political parties still predominates. That is more specifically the case for inter-parties violence, which is concentrated in a few states where local parties were strong enough to contest the monopoly of the ruling PDP. Ignored by the existing literature, inter-parties violence also confirms the importance of local factors and the implication of the PDP. We finally show that inter-parties violence is concentrated in the Middle Belt where ethnic and religious conflicts are most important. Along with political competition, those rivalries explain mass violence. Indeed, events combining both electoral competition and ethnic/religious factors accounted for only 5 % of the total, but caused 75% of fatalities during the period under review.Cet article explore les deÌterminants de la violence politique au Nigeria aÌ lâappui de donneÌes recensant les conflits qui ont impliqueÌ des partis politiques et entraiÌneÌ des morts entre 2006 et 2014. Il deÌfend lâideÌe que, depuis la fin de la dictature militaire en 1999, la politique nigeÌriane sous la IVe ReÌpublique reste structureÌe par les ancrages locaux et reÌgionaux des partis. Partant de la litteÌrature existante qui se focalise sur les confrontations au moment des eÌlections geÌneÌrales, nous montrons dâabord que ces eÌlections ne repreÌsentent que la moitieÌ des deÌceÌs sur la peÌriode et que les violences politiques repreÌsentent en reÌaliteÌ un pheÌnomeÌne large avec des speÌcificiteÌs et enjeux locaux en dehors des logiques eÌlectorales. Dans un second temps, nous montrons que les ancrages reÌgionaux des partis structurent toujours la vie politique nigeÌriane. Câest le cas en ce qui concerne les violences entre partis, qui sont souvent limiteÌes aÌ quelques EÌtats ouÌ ces partis sont forts et eÌtaient en mesure de contester le monopole du Peopleâs Democratic Party (PDP). Les violences intra-partis, peu analyseÌes, confirment aussi le poids des enjeux locaux et la forte implication du PDP. Enfin, les violences entre partis se concentrent dans les EÌtats de la Middle Belt en proie aÌ des conflits religieux ou ethniques. Nous analysons lâimportance de ces deux facteurs dans les violences de masse et montrons quâelles sont provoqueÌes par leur imbrication avec la compeÌtition politique
Les reactions photochimiques Ă lâĂ©chelle industrielle
International audienc
Photochemical Rearrangements in Heterocyclic Chemistry
International audienceHeterocyclic compounds play an important role in many domains of chemistry. They are important structural elements in bioactive compounds. Photochemical reactions enable transformations of such compounds in a very convenient way. In many cases no chemical reagent is used. Members of one compound family can be transformed into members of another one. Three important types of photochemical rearrangements with heterocyclic compounds are discussed: Photochemical heteroatom isomerization involving heteroatoms and substituents, photochemical reactions involving hydrogen atom transfer (HAT) and photochemical electrocyclization