Généralement, dans les situations d’hypothèses multiples on cherche à rejeter toutes les hypothèses ou bien une seule d’entre d’elles. Depuis quelques temps on voit apparaître le besoin de répondre à la question : « Peut-on rejeter au moins r hypothèses ? ». Toutefois, les outils statisques pour répondre à cette question sont rares dans la littérature. Nous avons donc entrepris de développer les formules générales de puissance pour les procédures les plus utilisées, soit celles de Bonferroni, de Hochberg et de Holm. Nous avons développé un package R pour le calcul de la taille échantilonnalle pour les tests à hypothèses multiples (multiple endpoints), où l’on désire qu’au moins r des m hypothèses soient significatives. Nous nous limitons au cas où toutes les variables sont continues et nous présentons quatre situations différentes qui dépendent de la structure de la matrice de variance-covariance des données. / Generally, in multiple endpoints situations we want to reject all hypotheses or at least only one of them. For some time now, we see emerge the need to answer the question : "Can we reject at least r hypotheses ?" However, the statistical tools to answer this new problem are rare in the litterature. We decide to develop general power formulas for the principals procedures : Bonferroni’s, Hochberg’s and Holm’s procedures. We also develop an R package for the sample size calculation for multiple endpoints, when we want to reject at least r hypotheses. We limit ourselves in the case where all the variables are continuous and we present four different situations depending on the structure of the data’s variance-covariance matrix.

Thèse (D. en sciences de l'environnement)--Université du Québec à Montréal, 2005. / En tête du titre: Université du Québec à Montréal. Bibliogr.: f. 275-289. Publié aussi en version électronique.

Th. Méd.--Nancy 1, 1983. N°: 96.

Publicación a texto completo no autorizada por el autor / El documento digital no refiere asesor / Aplica el método de Proceso de Análisis Jerárquico (AHP) como herramienta para la toma de decisiones multicriterio, en los problemas que requieren incluir juicios y evaluaciones subjetivas de los criterios de decisión, para la selección de la mejor ubicación de un distrito para la apertura de un nuevo centro de estudio. Los resultados obtenidos dan como localización al distrito de San Juan de Lurigancho si se toma como referencia a la demanda estudiantil, pero si se toma en cuenta a la plana docente de la institución se tendría que optar por el distrito de Santa Anita. / Trabajo de suficiencia profesional

Dans un contexte d'inégalités socio-économiques marquées dans les risques d'accouchement prématuré, de mortinatalité ou de mortalité néonatale, notre objectif était de déterminer dans quelle mesure cette vulnérabilité impactait le devenir à court terme des enfants nés prématurés, d'étudier si l'amélioration des taux de survie observée ces deux dernières décennies bénéficiait de manière similaire à tous les niveaux socio-économiques, de décrire la prématurité dans les départements d'Outre-mer où la santé périnatale est plus défavorable que dans d'autres territoires. À partir des cohortes EPIPAGE nous avons montré que, bien qu'un niveau élevé de vulnérabilité soit associé à un risque augmenté de morbidité sévère chez les enfants survivants, c'est dans ce groupe que l'amélioration de la survie était la plus grande. / In a context of socio-economic inequalities supported in the risk of premature birth, stillbirth or neonatal death, our aim was to determine how this socio-economic vulnerability impacted on the short term outcome of preterm born infants , to study whether the improvement in survival rate and survival without severe morbidity observed over the last two decades in very premature infants was similar whatever the family socio-economic context and to describe the context of preterm birth in 2011 in the Département d'Outer-Mer (D.O.M) where perinatal health is less favorable than in other jurisdictions. From the EPIPAGE cohorts we showed that although a high level of vulnerability is associated with an increased risk of severe morbidity in survivor infants, it is in this group that improvement of the quality of survival over time is the greatest.

Tous les travaux effectués dans le cadre de cette thèse peuvent être placés sous la bannière de la chimie supramoléculaire. Différentes thématiques ont été abordées au cours de ces projets, qui s’inscrivent dans la continuité de ceux effectués précédemment au laboratoire.Les polymères, qu’ils soient supramoléculaires ou dynamiques (dynamères), ont constitué le squelette de cette thèse en étant étudiés en solution et à l’interface surface-solution. Le développement de certains autres axes de recherche s’est imposé à nous. Certains monomères utilisés dans la formation de nouveaux polymères ayant présenté un comportement inattendu aussi bien à l’interface surface-solution qu’en solution ; une étude approfondie a été menée pour en comprendre les raisons.Les résultats présentés dans ce manuscrit de thèse permettent d’affiner la compréhension de certains concepts en chimie supramoléculaire et dynamique. La première partie s’attache à montrer que la multiplication (ou la diversification) des fonctions dynamiques dans la chaîne principale d’un dynamère est une stratégie exploitable pour augmenter la complexité d’un système polymérique. La seconde partie de ce manuscrit présente différents auto-assemblages à l’interface surface-solution ainsi que l’étude approfondie d’un système auto-assemblé particulier et inattendu. Ces travaux tendent donc à améliorer la compréhension de la matière (par l’augmentation de la complexité dans des polymères dynamiques) et de ses interactions (par l’étude et la caractérisation de nouveaux auto-assemblages). / All the work described in this thesis falls within the domain of supramolecular chemistry. All the themes developed represent significant extensions of those previously developed in the laboratory. The focus has been on polymers, both supramolecular and dynamic covalent (dynamer) types, and their behaviour in solution and at the solid-solution interface.It has been essential to study also various other underlying aspects of this chemistry. Some of the monomers used as a source of new polymers have proven to exhibit unanticipated properties in solution and at interfaces, and a detailed investigation has been devoted to attempting to rationalise their behaviour.The results presented in this thesis provide a deeper understanding of several concepts central to supramolecular and dynamic chemistry. In the first section, it is shown that the multiplication or diversification of the dynamic links within the main chain of a dynamer is an effective strategy for enhancing the sophistication of a polymer system. The second section of the thesis concerns self-assembly processes at solid-solution interfaces and includes a detailed study of one completely unexpected self-assembled entity. The results obtained for this novel species have enabled its detailed characterisation and an analysis of its sensitivity to its environment and chemical stimuli.This work in total advances both an understanding of the nature of complex matter (through embellishment of the variety in dynamic polymers) and of the interactions which lead to its assembly (through the detailed characterisation of new materials).

La Multidrug resistance Protein 1 (MRP1) est impliquée dans le phénotype de résistance multiple aux médicaments (MDR) des cellules cancéreuses. Les substrats physiologiques de MRP1 comprennent notamment le glutathion (GSH). Certains médicaments anti-cancéreux tels que la doxorubicine sont co-transportés avec le glutathion. Pour contourner le phénotype MDR induit par MRP1, nous proposons une nouvelle stratégie thérapeutique basée sur la sensibilité collatérale (SC) des cellules résistantes surexprimant MRP1. Certains composés, comme le vérapamil, provoquent la mort sélective des cellules résistantes (les cellules témoins ne sont pas affectées) en stimulant l'efflux du glutathion médié par MRP1. La déplétion intracellulaire très rapide et très forte du glutathion induit probablement un stress oxydatif déclenchant la mort cellulaire. Nous avons identifié de nouveaux agents de sensibilité collatérale puissants in vitro et nous avons montré l'effet du meilleur composé sur la réduction de la croissance des tumeurs chimiorésistantes chez la souris. Nous avons étudié le mécanisme moléculaire d'action des agents de SC et identifié un résidu, localisé dans une région inattendue, impliqué dans la stimulation de l'efflux de glutathion induit par ces molécules / Multidrug resistance Protein 1 (MRP1) is involved in the multidrug resistance (MDR) phenotype of cancer cells. Physiological substrates of MRP1 include glutathione (GSH) and drugs such as doxorubicin are co-transported with glutathione. To circumvent the MDR phenotype induced by MRP1, we propose a new therapeutic strategy based on collateral sensitivity (CS) of resistant cell expressing MRP1, its overexpression becoming the Achilles heel of the cell. Some compounds, like verapamil, act as MRP1 modulators. They trigger selective death of resistant cells (control cells are not affected) by stimulating MRP1-mediated glutathione efflux. The fast and huge intracellular depletion of glutathione probably induces an oxidative stress triggering cell death. We identified new potent collateral sensitivity agents in vitro and we checked the effect of the strongest compound on reducing resistant tumor growth in nude mice. We studied the molecular mechanism of action of CS agents and identified an unexpected residue involved in the stimulation of glutathione efflux induced by these molecules

Objetivos: estabelecer o diagnóstico de uma amostra de indivíduos com deficiência auditiva (DA) e comprometimento de outras estruturas anatômicas e/ou sistemas fisiológicos, cadastrados no CEDALVI/HRAC-USP-Bauru; verificar possíveis fatores etiológicos envolvidos e investigar possível correlação do tipo de DA com as diferentes síndromes encontradas. Local: Serviço de Genética Clínica do CEDALVI/HRAC-USP, Bauru-SP. Participantes: 93 indivíduos com DA e comprometimento de outras estruturas anatômicas e/ou sistemas fisiológicos. Intervenções: Avaliação genética-clínica; estudo citogenético; avaliações radiológica, oftalmológica, otorrinolaringológica, audiológica e outras. Resultados: Dos 93 indivíduos, 51 eram do sexo masculino e 42, do feminino. Recorrência familial foi observada em 31 casos e, consangüinidade parental em 8. Na amostra, 25 síndromes gênicas conhecidas, 5 síndromes cromossômicas, 5 quadros de etiologia ambiental e 2 quadros de etiologia heterogênea foram estabelecidos em 87 indivíduos. Em 1 caso, não foi possível definir entre 2 condições gênicas e em 5, não foi possível se chegar a um diagnóstico. Conclusões: a casuística se compôs de síndromes etiologicamente heterogêneas, com maior freqüência de etiologia genética; o tipo de DA nas síndromes gênicas foi condizente com o quadro diagnosticado; 3 indivíduos apresentaram síndromes ambientais clássicas, com diferentes tipos de DA; 2 indivíduos apresentaram quadro clínico, possivelmente decorrente de efeito teratogênico; implicação direta de fatores de risco para DA, na etiologia dessa, nos indivíduos com síndromes gênicas conhecidas sem DA; 1 caso, possivelmente, representa uma síndrome nova de padrão único, de etiologia desconhecida; o aconselhamento genético está na dependência da fase em que se encontra o processo de delineamento das diferentes condições estabelecidas. / Objectives: The purposes of this study were to establish the diagnostic of the individuals with hearing loss and presenting other additional anatomic structures and/or physiologic systems involvement, recorded in the CEDALVI/HRAC-USP-Bauru; to verify possible etiologic factors involved and to investigate a possible correlation of the hearing loss type with the different diagnosis syndromes. Setting: Clinical genetic service of the CEDALVI/HRAC-USP, Bauru- P. Participants: The sample was comprised of 93 individuals with hearing loss and involvement of other anatomic structures and/or physiologic systems. Interventions: Clinical genetic evaluation; cytogenetic study; radiological, ophtalmological, othorinolaryngological, audiologycal evaluation, etc. Results: From the total of the sample, 51 were male and 42 were female. Familial recurrence was observed in 31 cases and parental consanguinity in 8. In the present sample, 25 known genic syndromes, 5 chromosomal syndromes, 5 environmental conditions, and 2 heterogeneous conditions were established in 87 individuals. The diagnosis was not established in 5 individuals and in 1 case it was not possible to define between 2 genic conditions. Conclusions: The casuistic was composed of etiologically heterogeneous syndromes with greater frequency of genetic etiology; the type of hearing loss in the genic syndromes was concordant with the diagnosed condition; 3 individuals presented classic environmental syndromes with different types of hearing loss; 2 individuals presented clinical picture, possibly due to teratogenic effect; hearing impairment related to risk factors of the hearing loss in the individuals with known genic syndromes without hearing loss; probable a new unique-pattern syndrome, of unknown etiology in 1 case; the genetic counseling will depend on the step of delineation process of the different diagnosed condition.

nÃo hà / Em 2008, desencadeou-se nos Estados Unidos a crise que foi considerada a maior desde 1929, com a quebra da bolsa de Nova York. Este evento afetou substancialmente todo o cenÃrio econÃmico mundial, pois provocou falta de liquidez no mercado. Conhecida como a crise do sub-prime, comeÃou inicialmente no mercado imobiliÃrio, passou pelos bancos, bolsa de valores atà atingir a economia dos paÃses. O Brasil sentiu os impactos da crise mundial, refletida no seu PIB. Pesquisas apontaram que o mercado financeiro foi o segundo maior atingido e os bancos foram afetados, uma vez que os crÃditos externos foram restringidos. Neste cenÃrio, analistas e investidores buscaram ferramentas que pudessem oferecer uma visÃo analÃtica do desempenho das empresas afetadas. A avaliaÃÃo de empresas atravÃs dos mÃltiplos contÃbeis à utilizada por ser de simples abordagem e por permitir o uso padronizado de variÃveis comuns Ãs empresas comparÃveis. O presente trabalho pretende avaliar comparativamente, atravÃs de anÃlise de demonstrativos contÃbeis, o desempenho de instituiÃÃes bancÃrias brasileiras no perÃodo de 2007 a 2010, analisando os efeitos da crise financeira de 2008 sobre as aÃÃes dos mesmos. O estudo evidencia forte impacto da crise nas instituiÃÃes estudadas, afetando de sobremaneira seu lucro lÃquido. / In 2007, it unleashes in the United States the crisis that has to be considered the largest since 1929, with the broke of the New York stock exchange. This event affected substantially the whole world economic scenario, because it caused lack of liquidity in the financial market. Known as the crisis in the sub-prime, it began originally in the real estate market, going to the banks, stock exchange until it reaches the economy of the countries.Brazil has felt the impact of global crisis, reflected in its PIB. Research indicates that the financial market was the second biggest hit and the banks have been affected since the foreign credits were restricted. In this scenario, analysts and investors are looking for tools that provide an analytical overview of the performance of affected companies. The valuation of companies through multiple accounting is used because of its simple approach and allows the use of standardized variables common to comparable companies. This work intends to comparatively evaluate, through analysis of financial statements, the performance of Brazilian banks in the period 2007 to 2010, analyzing the effects of the 2008 financial crisis on its assets.

The subject for this thesis is to find a basis which minimizes the number of bit operations involved in a finite field multiplication. The number of bases of a finite field increases quickly with the extension degree, and it is therefore important to find efficient search algorithms. Only fields of characteristic two are considered. A complexity measure is introduced, in order to compare bases. Different methods and algorithms are tried out, limiting the search in order to explore larger fields. The concept of equivalent bases is introduced. A comparison is also made between the Polynomial, Normal and Triangular Bases, referred to as known bases, as they are commonly used in implementations. Tables of the best found known bases for all fields up to GF(2^24) is presented. A list of the best found bases for all fields up to GF(2^25) is also given.