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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
201

Transtorno de déficit de atenção e hiperatividade na vida adulta : estudo sobre o curso e seus moderadores a partir de um seguimento de sete anos

Karam, Rafael Gomes January 2014 (has links)
O conhecimento sobre o curso dos transtornos mentais durante a vida e os fatores que influenciam o seu comportamento fazem parte das primeiras informações buscadas por pacientes e por profissionais de saúde, objetivando um melhor planejamento e intervenções mais acuradas. No caso do Transtorno de Déficit de Atenção e Hiperatividade (TDAH), as informações existentes limitam-se a responder sobre o prognóstico do TDAH para amostras de crianças e adolescentes. Estudos longitudinais prospectivos a partir de amostras clínicas de adultos possuem um delineamento capaz de trazer informação sobre o comportamento do TDAH durante a vida adulta. A amostra de Porto Alegre de adultos com TDAH, coletada nos últimos 12 anos no ambulatório de TDAH em adultos do HCPA, possui extensa caracterização em nível fenotípico e genético. O objetivo principal deste trabalho é investigar em pacientes adultos o curso do TDAH e as características sociais e psiquiátricas envolvidas em sua trajetória, sete anos após a avaliação inicial. Para isso, foram realizados dois estudos a fim de observar o comportamento do transtorno e dos seus domínios durante a vida adulta. O primeiro artigo investiga a persistência do diagnóstico formal do TDAH e a possibilidade de remissão completa sete anos após a primeira avaliação. Mesmo após o período de maior neurodesenvolvimento cerebral, e independentemente da idade dos indivíduos, em torno de 30% da amostra perdeu o diagnóstico do transtorno. A remissão completa ocorreu em 12.4% dos pacientes. Indivíduos com diagnóstico de TOD e Fobia Social, maior número de sintomas de hiperatividade/impulsividade e os que se apresentavam no maior quartil de desatenção durante a avaliação inicial persistiram mais frequentemente com o diagnóstico. Nível de prejuízo pelo TDAH, gênero e tempo de uso de metilfenidato não tiveram efeito significativo. No segundo artigo, analisamos separadamente o comportamento dos dois domínios do TDAH e os possíveis moderadores do seu curso, incluindo o efeito de um grupo de sintomas sobre o outro. Diferentemente dos resultados encontrados nos estudos que avaliaram os períodos da infância e adolescência, os sintomas de hiperatividade/impulsividade declinaram na mesma proporção que os de desatenção. A análise dos domínios individualmente também permitiu identificar que cada grupo de sintomas possui moderadores distintos. O declínio dos sintomas de desatenção foi menor nos pacientes com história de suspensão escolar, enquanto que a hiperatividade/impulsividade declinou menos nos indivíduos que possuem história de problemas com álcool e maior número de sintomas de desatenção. A partir dos resultados encontrados e da literatura existente, esta Tese propõe questionamentos sobre variáveis que podem influenciar o curso do TDAH na vida adulta, bem como perspectivas para intervenções preventivas. / A better comprehension regarding the course of mental disorders across the lifespan and the factors that influence its trajectory are among the first goals sought by patients and health professionals in the intent to improve planning and interventions. In the case of Attention Deficit/Hyperactivity Disorder (ADHD), prognosis information is limited to data derived from samples of children and adolescents. Prospective longitudinal studies from clinical samples of adults have the appropriate design to provide information of ADHD trajectory during adulthood. The Porto Alegre sample of adults with ADHD, collected over the past 12 years at the ADHD Outpatient Program – Adult division at the Hospital de Clínicas de Porto Alegre (HCPA), has an extensive phenotypic characterization and genetic level. The main goal of this work is to investigate the course of ADHD, as well as other psychiatric and social characteristics involved in its trajectory, in a sample of adult patients seven years after the initial assessment. For this purpose, two studies were conducted to examine the course of the disorder and its domains during adulthood. The first paper investigates the persistence of formal ADHD diagnosis and the possibility of complete remission seven years after the first evaluation. It shows that, even after the most intense period of brain neurodevelopment, and regardless of the age of the individuals, around 30% of the sample no longer fulfilled the diagnostic criteria for the disorder. Complete remission occurred in 12.4% of patients. Individuals diagnosed with Oppositional Defiant Disorder and Social Phobia, with more symptoms of hyperactivity/impulsivity and those who performed in the top quartile of inattention symptoms during the initial evaluation were more likely to persist with the diagnosis. Level of impairment due to ADHD symptoms, gender and the extent of methylphenidate use (months) had no significant effect. In the second article, the trajectory of the two ADHD domains (inattention and hyperactivity/impulsivity), along with their possible moderators, were analysed separately. Differently from the results found by studies evaluating the course of ADHD domains during childhood and adolescence, this study indicated that symptoms of hyperactivity/impulsivity declined in the same proportion as inattention during adulthood. The analysis of the two ADHD domains separately also identified that each group of symptoms has distinct moderators. The decline of inattention symptoms was lower in patients with a history of school suspension, whereas hyperactivity/impulsivity decline was lower in individuals with a history of problems with alcohol use and more symptoms of inattention. Based on the overall results and the existing literature, this Thesis raises questions about characteristics that may influence the course of ADHD during adulthood, as well as perspectives for preventive interventions.
202

A prospecção do futuro como suporte à busca de informações para a decisão empresarial: um estudo exploratório / The use of future studies to support information searching for decision making: exploratory research.

Nelson Daishiro Yoshida 13 October 2011 (has links)
Nesta pesquisa foi estudada a prática de prospecção do futuro (estudos do futuro) como suporte à busca de informações para a decisão empresarial. Dentre os objetivos da pesquisa se encontram a busca de associações entre os métodos de prospecção e as diferentes categorias de informação, a avaliação da importância atribuída à atividade de prospecção, a identificação da frequência de uso e dos horizontes de tempo para os quais os métodos são utilizados, bem como a obtenção do grau de satisfação percebida com os resultados obtidos. A pesquisa é realizada por metodologia mista, quantitativa e qualitativa. Foram feitos levantamento de dados quantitativos e estudos de casos, e os resultados foram analisados de forma complementar. Na amostra de respondentes foi identificado que há associação entre a categoria da informação que está sendo prospectada e os métodos de estudos do futuro. Determinados métodos são mais utilizados para algumas categorias de informação, a exemplo do método de Cenários para buscar informações sobre Política e Sociedade. Por outro lado, determinadas combinações apresentaram menor uso, como o método Roadmap Tecnológico para buscar informação sobre Tecnologia. É atribuída elevada importância para a prospecção do futuro. Tal avaliação depende do tipo de decisão ser estratégico ou tático, e este último fator também influencia a frequência em que a atividade é praticada. O horizonte de tempo da prospecção também está associado aos métodos, sendo que Cenários apresenta maior uso para horizontes de mais de cinco anos. Há métodos que apresentam maior satisfação dos respondentes da amostra, sendo eles: Cenários, Previsões e Projeções de Executivos e Pesquisas de Mercado. Os métodos mais praticados são os que apresentam a possibilidade de interatividade pessoal, como Cenários e Previsões e Projeções de Executivos. Por outro lado, os métodos mais objetivos, como os que utilizam modelos matemáticos e os que possuem metodologia mais estruturada, não figuraram entre os mais praticados. Nos casos estudados foi identificado que os métodos mais praticados são baseados em opinião e julgamento e utilizam a interatividade pessoal como principal forma de condução. Houve também preocupação manifestada sobre a necessidade de estruturação da atividade nas empresas e sobre a prática da mesma seguindo recomendações metodológicas. / The use of future studies methodologies to provide information for decision making has been studied in this research. The objectives of the research are to analyze the association of methods to different information categories, to evaluate the importance of future studies, to identify the frequency of use of future studies and the time horizon in which the methods are used in searching information, and to gather users perceived satisfaction with the results. The research is implemented through a mixed-methods methodology, quantitative and qualitative. Quantitative survey and case studies have been made and combined results have been analyzed in a complementary approach. Results from the sample indicate that there is an association of methods with information categories. Some methods are more used to deal with some information categories, e.g. Scenario method with Political and Social information. On the other hand, some method-information category combinations are less used, e.g. Technology Roadmap method with Technology. Evaluation of the importance of future studies is high and depends on the decision type to be strategic or tactical. These types of decision influence the frequency of use of future studies methodologies. Time horizon is associated to methods, as in Scenario method to time horizons greater than five years ahead. There are methods with higher satisfaction ratings: Scenario, jury of Executive Opinion and Market Survey. The most used methods are the ones with high personal interaction possibility, e.g. Scenario and jury of Executive Opinion. On the other hand, objective methods, as those that make use of mathematical techniques or more structured methodologies are not among the most used. In the case studies results, methods based on judgment and opinion with high personal interaction are the most used. There were concerns about the need for more structure to deal with future studies in the company and also about its practice in accordance with methodological recommendations.
203

Quantificação do colágeno na camada muscular da bexiga de pacientes com obstrução infravesical por hiperplasia prostática benigna: correlação com parâmetros urodinâmicos / -

Wesley de Oliveira Ribeiro 05 November 2004 (has links)
Avaliou-se prospectivamente 19 pacientes com obstrução infravesical por hiperplasia prostática benigna selecionados pra prostatectomia transvesical. Obteve-se um fragmento da parede da bexiga e quantificou-se o colágeno no epimísio, perimísio e endomísio do detrusor. Amostra vesicais de oito doadores cadavéricos de órgãos serviram como controles. Observou-se padrão focal de aumento do colágeno na camada muscular da bexiga dos pacientes com obstrução. Demonstrou-se que a idade correlaciona-se positivamente com o aumento da quantidade de colágeno com a diminuição da complacência vesical, o aumento da prevalência de hiperatividade detrusora e a maior chance de retenção urinária / We prospectively evaluated 19 patients with bladder outlet obstruction by benign prostatic hyperplasia selected for transvesical prostatectomy. A sample of the bladder wall was obtained and the collagen was measured at the level of epimysium, premysium and endomysium. Bladder samples from eight cadaveric organ donors were used as controls. A focal pattern of collagen increase was observed at the bladder smooth muscle layer of obstructed patients. Age was shown to correlate with increased collagen quantity. Increased collagen quantity also correlated with decreased bladder compliance, higher prevalence of detrusor overactivity and of urinary retention
204

"Estudo prospectivo do comprometimento linfonodal do câncer do reto distal. Comparação entre linfocintilografia e tomografia pélvica" / RECTAL NEOPLASMS/radionuclide imaging, LYMPH NODES, TOMOGRAPHY

Lilian Ramos Todinov 02 December 2005 (has links)
Foram estudados prospectivamente os linfonodos, em 19 pacientes com adenocarcinoma de reto distal através de tomografia pélvica e linfocintilografia pélvica e realizado o estudo comparativo dos métodos, tendo como base à anatomia patológica e o estadiamento clinico-cirúrgico. Foram comparados os exames obtendo-se que os métodos não são concordantes. E a linfocintilografia é método mais sensível para linfonodos do que a tomografia / They were studied prospectivamente the lymph nodes, in 19 patient with adenocarcinoma of distal rectum through pelvic tomography and pelvic lymphoscintigraphy and accomplished the comparative study of the methods, having as based to the pathological anatomy and the staging practise-surgical. It compared the exams to each other obtaining itself that the methods are not concordant. And the lymphoscintigraphy is more sensitive method for lymph nodes than for
205

Prospecção e bases de formação da demanda e oferta de etanol combustível nos Estados Unidos / Prospection and formation basis of supply and demand for ethanol fuel in the United States

Aline Ishikawa 03 December 2013 (has links)
Desde o primeiro choque do petróleo, em 1973, os países têm despendido esforços para reduzir sua dependência pelo produto, produzido principalmente em regiões politicamente instáveis. Os Estados Unidos são os maiores consumidores mundiais do combustível, e cerca de 70% são destinados ao transporte. Desde o final da década de 70, o governo americano tem incentivado o uso de etanol como substituto parcial da gasolina. No entanto, o crescimento do biocombustível levantou polêmicas porque a matéria-prima utilizada na sua produção no país é o milho, o que poderia estar afetando a oferta do grão para a produção de alimentos. Dessa forma, foi aprovado em 2007 o RFS2, uma legislação que prevê o consumo mandatório de volumes crescentes de etanol até 2022, mas limita a produção a partir de milho. Os investimentos em pesquisas de combustíveis alternativos passaram a se focar no desenvolvimento de etanol de segunda geração, que utiliza material celulósico como matéria-prima. Sua viabilidade técnica já foi confirmada, mas ainda são necessárias melhorias no processo de produção para que o produto possa ser ofertado em escala comercial. Por outro lado, o Brasil tem uma indústria de etanol madura e também tem feito pesquisas na tecnologia de segunda geração. Se bem sucedida, o país tem planos de exportar o excedente de produção, e os Estados Unidos são um mercado de interesse. O objetivo desta dissertação é auxiliar na avaliação das necessidades de os Estados Unidos importarem etanol de outros países, o que pode criar uma oportunidade para o Brasil. Para isso, foi utilizada a abordagem lógico-intuitiva de construção de cenários - voltada a aspectos qualitativos - para estudar o mercado de etanol combustível nos Estados Unidos até o ano de 2022. A coleta de informações foi feita por meio da revisão bibliográfica, focada em artigos internacionais. A política energética americana e a evolução da tecnologia de segunda geração de etanol foram identificadas como as principais incertezas que devem moldar o futuro do mercado em estudo. A partir delas, foram gerados quatro cenários, nomeados como \"Filho pródigo\", \"Pais esperançosos\", \"Filho independente\" e \"Filho preterido\". Concluiu-se que, enquanto o governo americano continuar incentivando o consumo de etanol, haverá boas oportunidades de exportação do biocombustível brasileiro. Os maiores volumes são esperados em \"Pais esperançosos\". Por outro lado, caso outras alternativas energéticas sejam priorizadas, nossas exportações podem reduzir substancialmente, e o volume comercializado dependerá do preço do nosso produto em relação ao deles e à gasolina. / Since the first oil shock in 1973, countries have made efforts to reduce their dependence on the product, mainly produced in politically unstable regions. The United States is the world\'s largest consumer of the fuel, and about 70 % is allocated to transport. Since the late 70s, the U.S. government has encouraged the use of ethanol as a partial substitute for gasoline. However, the growth of the biofuel arose controversy because the raw material used for the domestic production is corn, which could be affecting the supply of the grain for food production. Thus, it was approved in 2007 the RFS2, a legislation that requires mandatory use of increasing volumes of ethanol until 2022, but limits production from corn. Investments in alternative fuels research started to focus on the development of second generation ethanol, which uses cellulosic material as feedstock. Its technical feasibility has been confirmed, but improvements are still needed in the production process so that the product can be offered on a commercial scale. On the other hand, Brazil has a mature ethanol industry and is also doing research on second-generation technology. If successful, the country plans to export the surplus production, and the United States is a market of interest. The objective of this thesis is to assist the assessment of the United States needs to import ethanol from other countries, which may create an opportunity for Brazil. The logical-intuitive approach of scenario building - focused on qualitative aspects - was used to study the market for fuel ethanol in the United States until the year 2022. Data collection was done through literature review, focused on international articles. The U.S. energy policy and developments in the technology of second generation ethanol were identified as the major uncertainties that are shaping the future of the market under study. Four scenarios were generated from these two uncertainties and named as \"Prodigal Son\", \"Hopeful parents\", \"Independent Son\" and \"Deprecated Son\". It was concluded that while the U.S. government continues to encourage the consumption of ethanol, there are good opportunities to export the Brazilian biofuel. The largest volumes are expected in \"Hopeful parents\". On the other hand, if other energy alternatives are prioritized, our exports can reduce substantially, and sales volume will depend on the price of our product relative to theirs and gasoline.
206

La prospective territoriale dans tous ses états. Rationalités, savoirs et pratiques de la prospective (1957 - 2014) / Territorial Foresight Studies in All of Its States. Rationalities, Knowledge, and the Practices of Foresight Studies (1957-2014)

Vidal-Kratochvil, Chloë 05 June 2015 (has links)
Développée dès la fin des années 1960 en France à partir de l’application des principes de la prospective, issus des travaux du philosophe Gaston Berger, à l’aménagement du territoire, la prospective territoriale fait aujourd’hui l’objet de nombreuses démarches tant au niveau étatique qu’au niveau des collectivités territoriales. Cette recherche propose d’interroger le sens des pratiques hétérogènes auxquelles elle a donné lieu, et entreprend pour ce faire de dénaturaliser la prospective devenue, au gré de ses différentes traductions dans les mécanismes de la décision publique, un « objet » aux contours imprécis. Nous proposons d’appréhender la prospective, d’abord présentée par Berger comme une « technique rationnelle » œuvrant à rendre l’action efficace pour l’homme, comme un « instrument de gouvernementalité » ou encore un « instrument d’action publique » producteur de normes (et en particulier de normes territoriales), ainsi que de mettre en exergue les conséquences des métamorphoses de la régulation politique sur l’état de cet « instrument prospective » et ses effets. En tant que rationalité cognitive (mode de connaissance du territoire), la prospective territoriale semble d’une part opérer un retour à la question anthropologique : elle se fait sociétale, toujours plus attentive aux pratiques spatiales. En tant que rationalité politique (mode d’administration de l’institution et du territoire), ses démarches deviennent d’autre part le lieu d’une mise à l’épreuve des catégories démocratiques encore liées à l’idéal moderne du territoire. Il appert ainsi que l’examen des dispositifs de prospective territoriale présente un intérêt pour l’analyse de la dimension spatiale de l’action politique, comme pour celle des modalités évolutives de l’action publique. / Territorial Foresight Studies, developed in France at the end of the 1960s based on the application of philosopher Gaston Berger’s work to territorial management, has today become an area for numerous approaches at the state level as well as at the level of regional and local authorities. This thesis proposes to question the meaning of the heterogeneous practices to which it has given rise, and undertake, to that end, to denaturalize Foresight Studies which have become, in their various translations into the mechanisms of public decision, an “object” of imprecise outline. We propose to understand Foresight Studies, first presented by Berger as a “rational technique” working to render action effective for Man, as an “instrument of governmentality”, or again, an “instrument of public action” productive of norms (and in particular territorial norms), as well as to underline the consequences of the metamorphoses in political regulation on the state of this “foresight tool” and its effects. As a cognitive rationality (a mode of knowledge about territory), territorial foresight appears, on the one hand, to prepare for a return to the anthropological question: it becomes societal, ever more attentive to spatial practices; yet as political rationality (a mode of institutional and territorial administration), its approaches become, on the other hand, the site at which are tested democratic categories still tied to the modern ideal of territory. Evidently, the examination of apparatuses of territorial foresight are of interest for the analysis of the spatial dimension of political action, as well as for the evolutionary modalities of public action.
207

Evaluation of the perceived sense of speed in a driving simulator

Procaccini, Marco January 2013 (has links)
In this project we evaluated the perception of speedin a driving simulator. The study provides a preliminary survey that focuses onhow human beings can perceive moving in space. We have developed and implemented some techniques to study how we modify the perception of speed in adriving simulator. We targeted the driving perspective, trying to create certain effects in order to affect the perceived sense of speed. Changing the contrast of the scene we studied how the perception of the speed has been modified. Testing this modification we saw a change in the perception of the speed by the driver, who noticed an increase of the perceived speed through the alteration of the contrast of the scene.
208

Métodos de cenários prospectivos como ferramente de apoio ao planejamento relativo a substituição do atual uso do solo por florestamento: estudo de caso: a Bacia do Rio Ibicuí - RS / Methods of prospective sceneries as tool of support to the relative planning the substitution of the current use of the soil for forestry: in case of study: Ibicuí River Basin

Cortez, Alexandre Schmidt 20 December 2007 (has links)
Planet Earth seen from outer space, as shown by numerous satellites photographs, reveals an impressive beauty. What is the cause of such beauty? Surely it is water. Throughout the centuries, the complexity of the multiple uses of water by man increased and produced an enormous set of degradation and pollution. On the other hand, the excessive multiple uses and permanent extractions for diverse means has decreased, considerably, the availability of water and has produced many problems of scarcity in many regions and countries. In 2004, after announcing an investment of 3 billion reals (approximately 1.6 billion dollars) in forestry and the opening of a cellulose industry for the manufacturing of paper in the southern half of the state of Rio Grande do Sul, Votorantim Celulose e Papel, began to be criticized. The main criticisms claim that eucalyptus is an exotic specie which increases water deficit, reduces soil fertility and pH, frightens the fauna, the plantations form great landed estates and monoculture, presents little contribution for the generation of jobs, provokes rural exodus, diminishing property value and which could cause a serious environmental damage in Rio Grande do Sul. This paper shows subsidies for discussion and elaboration of prospective scenarios, about matters related to hydric, social, economic, environmental, technological, political and legal resources, previewing a temporal horizon of the year of 2020, for the Ibicuí River Hydrographic Basin. Key points were identified through future bearer events and the perception of the principal factors which influence the current system. The general objective of research is to evaluate the perception of the involved factors on the effects caused by the substitution of the use of the soil for eucalyptus in relation to hydric resources, motivating a stage setting as a tool for the management strategy and basing committee decision planning, with the intuition to avoid future surprise and unpredictability. It was used the "Grumbach method" and the "Lince method" obtaining as result three sceneries More Probable Scenery, Ideal Scenery, Scenery of Tendency. / O planeta Terra visto do espaço, como mostram as inúmeras fotos de satélite, revela uma beleza impressionante. Qual é a causa da beleza? Seguramente é a água. Através dos séculos, a complexidade dos usos múltiplos da água pelo homem aumentou e produziu enorme conjunto de degradação e poluição. Por outro lado, os usos múltiplos excessivos e retiradas permanentes para diversas finalidades têm diminuído consideravelmente a disponibilidade de água e produzido inúmeros problemas de escassez em muitas regiões e países. Em 2004, após anunciar o investimento de R$ 3 bilhões em florestamento e a abertura de uma indústria de celulose para a fabricação de papel na Metade Sul, a Votorantim Celulose e Papel (VCP), passa a ser criticada. As principais críticas alegam que o eucalipto é uma espécie exótica que aumenta o déficit hídrico, reduz a fertilidade e o pH do solo, afugenta a fauna, as plantações formam grandes latifúndios e monocultura, apresenta pouca contribuição na geração de emprego, provocam o êxodo rural reduzindo o valor da propriedade e que causariam um grave dano ambiental no Rio Grande do Sul. Neste trabalho são apresentados subsídios para que se discuta a elaboração de cenários prospectivos, sobre as questões relacionadas aos recursos hídricos, sociais, econômicos, ambientais, tecnológicos, políticas, e legais, vislumbrando um horizonte temporal do ano 2020, para a Bacia Hidrográfica do Rio Ibicuí. Foram identificados os pontos chaves do estudo através de eventos portadores de futuro, e a percepção dos principais atores que influenciam o sistema no presente. O objetivo geral deste estudo foi o de avaliar a percepção dos atores envolvidos sobre os efeitos causados pela substituição do uso do solo pelo eucalipto com relação aos recursos hídricos, motivando a cenarização como uma ferramenta para o planejamento estratégico de gestão e de decisão do comitê de bacia, com o intuito de evitar surpresa e imprevisibilidade de futuro. Foi utilizado o Método Grumbach e o Método Lince obtendo como resultado três cenários Cenário Mais Provável, Cenário Ideal, Cenário de Tendência.
209

Etude préclinique et clinique de la phase précoce de la maladie d'Alzheimer / Clinical and preclinical studies of the early phase of Alzheimer's disease

Epelbaum, Stéphane 28 September 2015 (has links)
Dans cette thèse nous avons étudié le stade débutant de la maladie d'Alzheimer par deux approches distinctes. D'un point de vue fondamental, nous avons étudié le rôle des oligomères d'Aß dans un modèle d'injection intracérébrale de ces espèces solubles chez la souris sauvage. Nous avons notamment montré que ces injections engendraient chez l'animal des désordres mnésiques aigus et réversibles qui s'apparentent à la maladie d'Alzheimer. Nous avons aussi mis en évidence une diminution d'expression d'une protéine post-synaptique (PSD95), une augmentation de la phosphorylation de la protéine Tau et une hyperactivation neuronale induites par ces injections, Ces modifications histo-fonctionnelles généralisées concordent avec le profil de dissémination diffus des solutions peptidiques injectées comme en atteste la mise en évidence de peptide Aß dans des régions distantes du site d'injection en immunohistochimie mais aussi en spectrométrie de masse. D'un point de vue clinique nous avons étudié la valeur du Rappel Libre/Rappel Indicé 16 items (RLRI16), un test de mémoire épisodique, au sein d'une cohorte de patients consultant pour une plainte mnésique ayant participé à un essai thérapeutique multicentrique national. Dans cette cohorte, le RLRI16 s'est avéré être le meilleur prédicteur de la survenue d'une démence d'Alzheimer probable dans les 5 ans qui ont suivi son administration. Le grand nombre de participants, la durée de l'étude et le mode de recrutement (par les généralistes) nous ont permis de proposer des valeurs seuils qui pourront aider le clinicien dans sa pratique quotidienne et permettront de définir des critères d'inclusion dans de nouveaux essais thérapeutiques. / We studied the early phase of Alzheimer’s disease with two approaches, experimental and clinical. Firstly, experimentally, we injected Aβ oligomers in the brain of wild type mice. We showed that these soluble species elicited memory impairment reminiscent of those found in AD although in our case they were both acute and reversible. We also evidenced a decrease in the expression of a postsynaptic protein (PSD95), an increase in the phosphorylation of Tau and a neuronal hyperactivity one week after these injections. These histo-functional changes were observed throughout the brain. The diffusion of the Aß injectate shown by immunohistochemistry and by mass spectrometry imaging was widespread. Clinically, we confirmed the usefulness of a memory test, the Free and Cued Selective Reminding Test (FCSRT) to predict the risk of dementia of the Alzheimer’s type (DAt) up to 5 years prior to its onset. This was made possible by the study of a cohort of patients who consulted for memory complaints and were then included in a multicentric national clinical trial conducted in France. In this cohort, the FCSRT proved to be the best predictor of the further conversion to a DAt. The large number of participants, length of the follow-up and recruitment type (mainly by the general practitioners) allowed us to derive thresholds to be used by clinicians in their daily practice or as inclusion criteria in new clinical trials.
210

A Formal Approach to Combining Prospective and Retrospective Security

Amir-Mohammadian, Sepehr 01 January 2017 (has links)
The major goal of this dissertation is to enhance software security by provably correct enforcement of in-depth policies. In-depth security policies allude to heterogeneous specification of security strategies that are required to be followed before and after sensitive operations. Prospective security is the enforcement of security, or detection of security violations before the execution of sensitive operations, e.g., in authorization, authentication and information flow. Retrospective security refers to security checks after the execution of sensitive operations, which is accomplished through accountability and deterrence. Retrospective security frameworks are built upon auditing in order to provide sufficient evidence to hold users accountable for their actions and potentially support other remediation actions. Correctness and efficiency of audit logs play significant roles in reaching the accountability goals that are required by retrospective, and consequently, in-depth security policies. This dissertation addresses correct audit logging in a formal framework. Leveraging retrospective controls beside the existing prospective measures enhances security in numerous applications. This dissertation focuses on two major application spaces for in-depth enforcement. The first is to enhance prospective security through surveillance and accountability. For example, authorization mechanisms could be improved by guaranteed retrospective checks in environments where there is a high cost of access denial, e.g., healthcare systems. The second application space is the amelioration of potentially flawed prospective measures through retrospective checks. For instance, erroneous implementations of input sanitization methods expose vulnerabilities in taint analysis tools that enforce direct flow of data integrity policies. In this regard, we propose an in-depth enforcement framework to mitigate such problems. We also propose a general semantic notion of explicit flow of information integrity in a high-level language with sanitization. This dissertation studies the ways by which prospective and retrospective security could be enforced uniformly in a provably correct manner to handle security challenges in legacy systems. Provable correctness of our results relies on the formal Programming Languages-based approach that we have taken in order to provide software security assurance. Moreover, this dissertation includes the implementation of such in-depth enforcement mechanisms for a medical records web application.

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