Stage De Français Langue Étrangére Projet FLE Comme Outil D´ Integration

Université De Bretagne Occidentale

Le multiple evanescent white dot syndrome: une prédisposition génétique [Multiple evanescent white dot syndrome: a genetic predisposition?]

BACKGROUND: Multiple evanescent white dot syndrome (MEWDS) is a benign acquired isolated chorioretinal disorder. Symptoms include photopsia, visual blur and scotomas. Ocular examination reveals multiple white dots at the level of the deep retina. A parainfectious disorder was suggested but the exact mechanism of MEWDS is still unknown. Postulating that MEWDS might be an antigen driven inflammatory reaction, we analyzed HLA subtypes in patients with MEWDS. PATIENTS AND METHODS: Sixteen patients were diagnosed with MEWDS in Lausanne from 1985 to 1994. Blood was withdrawn in 9/16 patients. HLA-A, -B and -DR were sought. RESULTS: HLA-B51 was detected in 4/9 patients (44.4%). Other HLA subtypes were detected sporadically. CONCLUSIONS: The frequency of HLA-B51 haplotype was found to be 3.7 times more elevated than in a normal control caucasian group. This suggests the possibility that MEWDS might be a genetically determined disorder as it is the case for other ocular diseases like Birdshot chorioretinopathy (HLA-A29), Harada's disease (HLA-DRMT3), acute anterior uveitis (HLA-B27) or Behçet's disease (HLA-B51). We have no explanation for the presence of HLA-B51 in both Behçet's disease and MEWDS. The association of HLA-B51 and MEWDS needs confirmation by further testing.

Memoire de Stage L’analyse des Dossiers de Crédit Professionnels

Université Jean Monnet Saint Etienne

Mediastinal lymph node clearance after docetaxel-cisplatin neoadjuvant chemotherapy is prognostic of survival in patients with stage IIIA pN2 non-small-cell lung cancer: a multicenter phase II trial.

PURPOSE: A multicenter, phase II trial investigated the efficacy and toxicity of neoadjuvant docetaxel-cisplatin in locally advanced non-small-cell lung cancer (NSCLC) and examined prognostic factors for patients not benefiting from surgery. PATIENTS AND METHODS: Ninety patients with previously untreated, potentially operable stage IIIA (mediastinoscopically pN2) NSCLC received three cycles of docetaxel 85 mg/m2 day 1 plus cisplatin 40 mg/m2 days 1 and 2, with subsequent surgical resection. RESULTS: Administered dose-intensities were docetaxel 85 mg/m2/3 weeks (range, 53 to 96) and cisplatin 95 mg/m2/3 weeks (range, 0 to 104). The 265 cycles were well tolerated, and the overall response rate was 66% (95% confidence interval [CI], 55% to 75%). Seventy-five patients underwent tumor resection with positive resection margin and involvement of the uppermost mediastinal lymph node in 16% and 35% of patients, respectively (perioperative mortality, 3%; morbidity, 17%). Pathologic complete response occurred in 19% of patients with tumor resection. In patients with tumor resection, downstaging to N0-1 at surgery was prognostic and significantly prolonged event-free survival (EFS) and overall survival (OS; P =.0001). At median follow-up of 32 months, the median EFS and OS were 14.8 months (range, 2.4 to 53.4) and 33 months (range, 2.4 to 53.4), respectively. Local relapse occurred in 27% of patients with tumor resection, with distant metastases in 37%. Multivariate analyses identified mediastinal clearance (hazard ratio, 0.22; P =.0003) and complete resection (hazard ratio, 0.26; P =.0006) as strongly prognostic for increased survival. CONCLUSION: Neoadjuvant docetaxel-cisplatin is effective and tolerable in stage IIIA pN2 NSCLC. Resection is recommended only for patients with mediastinal downstaging after chemotherapy.

Time Series Input Selection using Multiple Kernel Learning

In this paper we study the relevance of multiple kernel learning (MKL) for the automatic selection of time series inputs. Recently, MKL has gained great attention in the machine learning community due to its flexibility in modelling complex patterns and performing feature selection. In general, MKL constructs the kernel as a weighted linear combination of basis kernels, exploiting different sources of information. An efficient algorithm wrapping a Support Vector Regression model for optimizing the MKL weights, named SimpleMKL, is used for the analysis. In this sense, MKL performs feature selection by discarding inputs/kernels with low or null weights. The approach proposed is tested with simulated linear and nonlinear time series (AutoRegressive, Henon and Lorenz series).

Current multiple myeloma treatment strategies with novel agents: a European perspective.

The treatment of multiple myeloma (MM) has undergone significant developments in recent years. The availability of the novel agents thalidomide, bortezomib, and lenalidomide has expanded treatment options and has improved the outcome of patients with MM. Following the introduction of these agents in the relapsed/refractory setting, they are also undergoing investigation in the initial treatment of MM. A number of phase III trials have demonstrated the efficacy of novel agent combinations in the transplant and nontransplant settings, and based on these results standard induction regimens are being challenged and replaced. In the transplant setting, a number of newer induction regimens are now available that have been shown to be superior to the vincristine, doxorubicin, and dexamethasone regimen. Similarly, in the front-line treatment of patients not eligible for transplantation, regimens incorporating novel agents have been found to be superior to the traditional melphalan plus prednisone regimen. Importantly, some of the novel agents appear to be active in patients with high-risk disease, such as adverse cytogenetic features, and certain comorbidities, such as renal impairment. This review presents an overview of the most recent data with these novel agents and summarizes European treatment practices incorporating the novel agents.

Alternativas de Investimentos Financeiros para as empresas em São Vicente

A tendência, hoje em dia, é para a captação directa das poupanças aos investidores. Esta captação faz-se através da emissão de produtos financeiros. Dada a incerteza e diversidade de produtos financeiros, o investidor terá de analisar cuidadosamente as múltiplas alternativas existentes e tomar a decisão de investir de acordo com a rendibilidade que pretende obter e o nível de risco que está disposto a correr. O trabalho ora apresentado espelha uma análise dos Riscos/Rendibilidade associados aos Investimentos Financeiros tais como Depósitos a Prazos, Obrigações, Acções e Bilhetes de Tesouro, com foco nos dois primeiros. O desenvolvimento da temática foi orientado numa primeira etapa para através da pesquisa necessária a construção do referencial teórico centrado por um lado, nos conceitos associados a mercados financeiros bem como os riscos associados as transacções desses produtos financeiros nesse mercado. Mencionamos diferentes tipos de produtos financeiros transaccionados neste mercado, bem como a importância da cotação destes produtos na Bolsa de Valores. A sustentabilidade deste rico referencial teórico ficou evidenciada através de um estudo de caso de uma empresa que dedica ao comércio - geral de Materiais de Construção, partindo de uma análise gráfica comparada que irá demonstrar qual o risco e a rendibilidade que há em canalizar parte do valor aplicado no depósito a prazo para investir em obrigações do BCA emitidas em Dezembro de 2010. Nowadays the tendency is for the reception all-nighter of the savings to the investors. This reception is made through the emission of financial products. Owing to the uncertainty and diversity of financial products, the investor has to analyze carefully the multiple existent alternatives and then decide to invest according to the profitability he intends to obtain and the risk level he is willing to run. The work for now presented mirrors an analysis of the risks / profitability associated to the Financial Investments as Deposits to periods, Obligations, Shares, Tickets of Treasury, with focus in the first two. The development of the theme was guided in a first stage for through the necessary research for the construction of the theoretical referential system centered on one side, in the concepts associated to financial markets as well as the risks associated to the transactions of those financial products in that market. We referred to different types of financial products transacted in this market, as well as the importance of the quotation of these products in the stock exchange. The sustainability of this rich theoretical referential system was evidenced through a study of case of a company that dedicates to the trade of construction materials, leaving from a compared analysis that will demonstrate Which the risk and the profitability that there is in channeling part of the applied value in the deposit to period to invest in obligations of „BCA‟ emitted in December of 2010.

Formação dos preços de venda nas Empresas Importadoras de São Vicente

As decisões de preços de venda, é uma das funções com mais relevância no ambiente empresarial para os gerentes, devido o seu carácter estratégico para o sucesso das empresas. O processo de formação de preço (FP) é fundamental para as empresas, embora apresenta graus de dificuldade e de complexidade, por implicar diversos factores. A primeira etapa para a FP consiste na estimativa correcta de custos, para obtenção de preços ideais. Para além dos custos, outros factores internos e externos devem ser analisados para que as decisões possam ser tomadas de forma correcta e obter um preço competitivo. Portanto, os gerentes precisam de informações precisas para poderem tomar decisões com segurança, levando em consideração todos os aspectos relevantes para a FP. O presente trabalho tem como objectivo principal, conhecer uma politica adequada de FP, bem como, descobrir quais os factores mais relevantes considerados na formação desses preços nas empresas e ainda conhecer quais os métodos de FP utilizado pelas empresas de importação de S.Vicente para a FP. A metodologia, consistiu primeiramente numa pesquisa bibliográfica e exploratória. Para a recolha dos dados,foram aplicados questionários com perguntas fechadas múltipla escolha, aos gerentes e aos responsáveis pelos processos de EC e FP e para complementar, foi feita uma entrevista a um especialista da área. Para a análise dos dados, foram utilizadas técnicas qualitativas e quantitativas, feito através das respostas obtidas dos questionários. Os resultados obtidos da pesquisa, mostram que o método de formação de preços de venda adoptado pelas empresas de S.Vicente, é o método baseado no custo e no mercado (método misto), ou seja, o preço é definido com base nos seus custos, mas é ajustado tendo por base o preço da concorrência. The sale prices decisions; it is one of the functions with more relevance in the managerial atmosphere for the managers, due your strategic character for the success of the companies. The process of price formation (FP) it is fundamental for the companies,although it presents degrees of difficulty and of complexity, for implicating several factors. The first stage for FP consists in estimate correct costs, to obtaining ideal prices. Besides the costs, others internal and external factors should be analyzed so that decisions can be made in a correct form to obtain a competitive price. Therefore, the managers need necessary information to make safety decisions, taking in consideration all the important aspects of FP. The main objective of this present work, is to know the appropriate politics of FP, as well as, to discover which the most important factors considered in the formation of those prices to purchases and still to know which of the FP methods used by the import companies in São Vicente. The methodology consisted firstly in a bibliographical and exploratory research. To collect the data, were applied uestionnaires with closed questions, multiple choice to the managers and the responsible for the processes of ECP and EP and to complement, it was made an interview to a specialist. For the analysis of the data, qualitative techniques were used, done through to obtained answers of the questionnaires. The results of the research, show that the method of formation of sale prices adopted for São Vicente's companies, is the method based on the cost and in the market (mixed method), in other words, the price is defined with base in the costs, but it is adjusted tends for base of the competition.

Interferon-gamma impacts at multiple points during the progression of autoimmune diabetes.

The role of interferon-gamma in autoimmune diabetes was assessed by breeding a null mutation of the interferon-gamma receptor alpha chain into the nonobese diabetic mouse strain, as well as into a simplified T cell receptor transgenic model of diabetes. In contrast to a previous report on abrogation of the interferon-gamma gene, mutation of the gene encoding its receptor led to drastic effects on disease in both mouse lines. Nonobese diabetic mice showed a marked inhibition of insulitis-both the kinetics and penetrance-and no signs of diabetes; the transgenic model exhibited near-normal insulitis, but this never evolved into diabetes, either spontaneously or after experimental provocation. This failure could not be explained by perturbations in the ratio of T helper cell phenotypes; rather, it reflected a defect in antigen-presenting cells or in the islet beta cell targets.

Assessing risks of multiple sclerosis therapies.

Over the last two decades, thanks to the discovery of several pharmaceutical agents, multiple sclerosis (MS) has been transformed into a treatable disorder although the degree of therapeutic response may vary considerably. As more medications find their entry into the MS market, a clinician faces a mounting challenge of comparing risk and benefit profiles of various agents in an attempt to find the best treatment approach for each individual patient. In this review, we aim to summarize the available data on safety profiles of available MS therapies while focusing mostly on serious medication specific potential adverse events without discussing the teratogenic potential of each agent (unless there is a black box warning) or hypersensitivity reactions. Our goal is to provide a clinician with guidance on assuring the appropriate safety monitoring for patients treated with one of the agents discussed. We also comment on the future of risk management in MS and discuss possible enhancements to the current model of drug approval process and general strategies to improve the patient safety.

Dispersal strategies, few dominating or many coexisting: the effect of environmental spatial structure and multiple sources of mortality.

Interspecific competition, life history traits, environmental heterogeneity and spatial structure as well as disturbance are known to impact the successful dispersal strategies in metacommunities. However, studies on the direction of impact of those factors on dispersal have yielded contradictory results and often considered only few competing dispersal strategies at the same time. We used a unifying modeling approach to contrast the combined effects of species traits (adult survival, specialization), environmental heterogeneity and structure (spatial autocorrelation, habitat availability) and disturbance on the selected, maintained and coexisting dispersal strategies in heterogeneous metacommunities. Using a negative exponential dispersal kernel, we allowed for variation of both species dispersal distance and dispersal rate. We showed that strong disturbance promotes species with high dispersal abilities, while low local adult survival and habitat availability select against them. Spatial autocorrelation favors species with higher dispersal ability when adult survival and disturbance rate are low, and selects against them in the opposite situation. Interestingly, several dispersal strategies coexist when disturbance and adult survival act in opposition, as for example when strong disturbance regime favors species with high dispersal abilities while low adult survival selects species with low dispersal. Our results unify apparently contradictory previous results and demonstrate that spatial structure, disturbance and adult survival determine the success and diversity of coexisting dispersal strategies in competing metacommunities.

High-resolution 3D whole-heart coronary MRA: a study on the combination of data acquisition in multiple breath-holds and 1D residual respiratory motion compensation.

OBJECT: To study a scan protocol for coronary magnetic resonance angiography based on multiple breath-holds featuring 1D motion compensation and to compare the resulting image quality to a navigator-gated free-breathing acquisition. Image reconstruction was performed using L1 regularized iterative SENSE. MATERIALS AND METHODS: The effects of respiratory motion on the Cartesian sampling scheme were minimized by performing data acquisition in multiple breath-holds. During the scan, repetitive readouts through a k-space center were used to detect and correct the respiratory displacement of the heart by exploiting the self-navigation principle in image reconstruction. In vivo experiments were performed in nine healthy volunteers and the resulting image quality was compared to a navigator-gated reference in terms of vessel length and sharpness. RESULTS: Acquisition in breath-hold is an effective method to reduce the scan time by more than 30 % compared to the navigator-gated reference. Although an equivalent mean image quality with respect to the reference was achieved with the proposed method, the 1D motion compensation did not work equally well in all cases. CONCLUSION: In general, the image quality scaled with the robustness of the motion compensation. Nevertheless, the featured setup provides a positive basis for future extension with more advanced motion compensation methods.

Cellular distribution of glucose and monocarboxylate transporters in human brain white matter and multiple sclerosis lesions.

To ensure efficient energy supply to the high demanding brain, nutrients are transported into brain cells via specific glucose (GLUT) and monocarboxylate transporters (MCT). Mitochondrial dysfunction and altered glucose metabolism are thought to play an important role in the progression of neurodegenerative diseases, including multiple sclerosis (MS). Here, we investigated the cellular localization of key GLUT and MCT proteins in human brain tissue of non-neurological controls and MS patients. We show that in control brain tissue GLUT and MCT proteins were abundantly expressed in a variety of central nervous system cells, particularly in microglia and endothelial cells. In active MS lesions, GLUTs and MCTs were highly expressed in infiltrating leukocytes and reactive astrocytes. Astrocytes manifest increased MCT1 staining and maintain GLUT expression in inactive lesions, whereas demyelinated axons exhibit significantly reduced GLUT3 and MCT2 immunoreactivity in inactive lesions. Finally, we demonstrated that the co-transcription factor peroxisome proliferator-activated receptor gamma co-activator 1-alpha (PGC-1α), an important protein involved in energy metabolism, is highly expressed in reactive astrocytes in active MS lesions. Overexpression of PGC-1α in astrocyte-like cells resulted in increased production of several GLUT and MCT proteins. In conclusion, we provide for the first time a comprehensive overview of key nutrient transporters in white matter brain samples. Moreover, our data demonstrate an altered expression of these nutrient transporters in MS brain tissue, including a marked reduction of axonal GLUT3 and MCT2 expression in chronic lesions, which may impede efficient nutrient supply to the hypoxic demyelinated axons thereby contributing to the ongoing neurodegeneration in MS. GLIA 2014;62:1125-1141.