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Will Mortality Rate of HIV-Infected Patients Decrease After Starting Antiretroviral Therapy (ART)?Bahakeem, Shaher 07 1900 (has links)
Indiana University-Purdue University Indianapolis (IUPUI) / Background: Many authors have indicated that HIV-infected patients mortality risk is higher immediately following the start of Antiretroviral Therapy. However, mortality rate of HIV-infected patients is expected to decrease after starting Antiretroviral Therapy (ART) potentially complicating accurate statistical estimation of patient survival and, more generally, effective monitoring of the evolution of the worldwide epidemic.
Method: In this thesis, we determine if mortality of HIV-patients increases or decreases after the initiation of ART therapy using flexible survival modelling techniques. To achieve this objective, this study uses semi-parametric statistical models for fitting and estimating survival time using different covariates. A combination of the Weibull distribution with splines is compared to the usual Weibull, exponential, and gamma distribution parametric models, and the Cox semi-parametric model. The objective of this study is to compare these models to find the best fitting model so that it can then be used to improve modeling of the survival time and explore the pattern of change in mortality rates for a cohort of HIV-infected patients recruited in a care and treatment program in Uganda.
Results: The analysis shows that flexible survival Weibull models are better than usualoff-parametric and semi-parametric model fitting according to the AIC criterion.
Conclusion: The mortality of HIV-patients is high right after the initiation of ART therapy and decreases rapidly subsequently.
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Association Between Tobacco Related Diagnoses and Alzheimer Disease: A population StudyAlmalki, Amwaj Ghazi 05 1900 (has links)
Indiana University-Purdue University Indianapolis (IUPUI) / Background: Tobacco use is associated with an increased risk of developing Alzheimer's disease (AD). 14% of the incidence of AD is associated with various types of tobacco exposure. Additional real-world evidence is warranted to reveal the association between tobacco use and AD in age/gender-specific subpopulations.
Method: In this thesis, the relationships between diagnoses related to tobacco use and diagnoses of AD in gender- and age-specific subgroups were investigated, using health information exchange data. The non-parametric Kaplan-Meier method was used to estimate the incidence of AD. Furthermore, the log-rank test was used to compare incidence between individuals with and without tobacco related diagnoses. In addition, we used semi-parametric Cox models to examine the association between tobacco related diagnoses and diagnoses of AD, while adjusting covariates.
Results: Tobacco related diagnosis was associated with increased risk of developing AD comparing to no tobacco related diagnosis among individuals aged 60-74 years (female hazard ratio [HR] =1.26, 95% confidence interval [CI]: 1.07 – 1.48, p-value = 0.005; and male HR =1.33, 95% CI: 1.10 - 1.62, p-value =0.004). Tobacco related diagnosis was associated with decreased risk of developing AD comparing to no tobacco related diagnosis among individuals aged 75-100 years (female HR =0.79, 95% CI: 0.70 - 0.89, p-value =0.001; and male HR =0.90, 95% CI: 0.82 - 0.99, p-value =0.023).
Conclusion: Individuals with tobacco related diagnoses were associated with an increased risk of developing AD in older adults aged 60-75 years. Among older adults aged 75-100 years, individuals with tobacco related diagnoses were associated with a decreased risk of developing AD.
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Estimation récursive dans certains modèles de déformation / Recursive estimation for some deformation modelsFraysse, Philippe 04 July 2013 (has links)
Cette thèse est consacrée à l'étude de certains modèles de déformation semi-paramétriques. Notre objectif est de proposer des méthodes récursives, issues d'algorithmes stochastiques, pour estimer les paramètres de ces modèles. Dans la première partie, on présente les outils théoriques existants qui nous seront utiles dans la deuxième partie. Dans un premier temps, on présente un panorama général sur les méthodes d'approximation stochastique, en se focalisant en particulier sur les algorithmes de Robbins-Monro et de Kiefer-Wolfowitz. Dans un second temps, on présente les méthodes à noyaux pour l'estimation de fonction de densité ou de régression. On s'intéresse plus particulièrement aux deux estimateurs à noyaux les plus courants qui sont l'estimateur de Parzen-Rosenblatt et l'estimateur de Nadaraya-Watson, en présentant les versions récursives de ces deux estimateurs.Dans la seconde partie, on présente tout d'abord une procédure d'estimation récursive semi-paramétrique du paramètre de translation et de la fonction de régression pour le modèle de translation dans la situation où la fonction de lien est périodique. On généralise ensuite ces techniques au modèle vectoriel de déformation à forme commune en estimant les paramètres de moyenne, de translation et d'échelle, ainsi que la fonction de régression. On s'intéresse finalement au modèle de déformation paramétrique de variables aléatoires dans le cadre où la déformation est connue à un paramètre réel près. Pour ces trois modèles, on établit la convergence presque sûre ainsi que la normalité asymptotique des estimateurs paramétriques et non paramétriques proposés. Enfin, on illustre numériquement le comportement de nos estimateurs sur des données simulées et des données réelles. / This thesis is devoted to the study of some semi-parametric deformation models.Our aim is to provide recursive methods, related to stochastic algorithms, in order to estimate the different parameters of the models. In the first part, we present the theoretical tools which we will use in the next part. On the one hand, we focus on stochastic approximation methods, in particular the Robbins-Monro algorithm and the Kiefer-Wolfowitz algorithm. On the other hand, we introduce kernel estimators in order to estimate a probability density function and a regression function. More particularly, we present the two most famous kernel estimators which are the one of Parzen-Rosenblatt and the one of Nadaraya-Watson. We also present their recursive version.In the second part, we present the results we obtained in this thesis.Firstly, we provide a recursive estimation method of the shift parameter and the regression function for the translation model in which the regression function is periodic. Secondly, we extend this estimation procedure to the shape invariant model, providing estimation of the height parameter, the translation parameter and the scale parameter, as well as the common shape function.Thirdly, we are interested in the parametric deformation model of random variables where the deformation is known and depending on an unknown parameter.For these three models, we establish the almost sure convergence and the asymptotic normality of each estimator. Finally, we numerically illustrate the asymptotic behaviour of our estimators on simulated data and on real data.
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Modelo linear parcial generalizado simétrico / Linear Model Partial Generalized SymmetricVasconcelos, Julio Cezar Souza 06 February 2017 (has links)
Neste trabalho foi proposto o modelo linear parcial generalizado simétrico, com base nos modelos lineares parciais generalizados e nos modelos lineares simétricos, em que a variável resposta segue uma distribuição que pertence à família de distribuições simétricas, considerando um preditor linear que possui uma parte paramétrica e uma não paramétrica. Algumas distribuições que pertencem a essa classe são as distribuições: Normal, t-Student, Exponencial potência, Slash e Hiperbólica, dentre outras. Uma breve revisão dos conceitos utilizados ao longo do trabalho foram apresentados, a saber: análise residual, influência local, parâmetro de suavização, spline, spline cúbico, spline cúbico natural e algoritmo backfitting, dentre outros. Além disso, é apresentada uma breve teoria dos modelos GAMLSS (modelos aditivos generalizados para posição, escala e forma). Os modelos foram ajustados utilizando o pacote gamlss disponível no software livre R. A seleção de modelos foi baseada no critério de Akaike (AIC). Finalmente, uma aplicação é apresentada com base em um conjunto de dados reais da área financeira do Chile. / In this work we propose the symmetric generalized partial linear model, based on the generalized partial linear models and symmetric linear models, that is, the response variable follows a distribution that belongs to the symmetric distribution family, considering a linear predictor that has a parametric and a non-parametric component. Some distributions that belong to this class are distributions: Normal, t-Student, Power Exponential, Slash and Hyperbolic among others. A brief review of the concepts used throughout the work was presented, namely: residual analysis, local influence, smoothing parameter, spline, cubic spline, natural cubic spline and backfitting algorithm, among others. In addition, a brief theory of GAMLSS models is presented (generalized additive models for position, scale and shape). The models were adjusted using the package gamlss available in the free R software. The model selection was based on the Akaike criterion (AIC). Finally, an application is presented based on a set of real data from Chile\'s financial area.
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Modelo linear parcial generalizado simétrico / Linear Model Partial Generalized SymmetricJulio Cezar Souza Vasconcelos 06 February 2017 (has links)
Neste trabalho foi proposto o modelo linear parcial generalizado simétrico, com base nos modelos lineares parciais generalizados e nos modelos lineares simétricos, em que a variável resposta segue uma distribuição que pertence à família de distribuições simétricas, considerando um preditor linear que possui uma parte paramétrica e uma não paramétrica. Algumas distribuições que pertencem a essa classe são as distribuições: Normal, t-Student, Exponencial potência, Slash e Hiperbólica, dentre outras. Uma breve revisão dos conceitos utilizados ao longo do trabalho foram apresentados, a saber: análise residual, influência local, parâmetro de suavização, spline, spline cúbico, spline cúbico natural e algoritmo backfitting, dentre outros. Além disso, é apresentada uma breve teoria dos modelos GAMLSS (modelos aditivos generalizados para posição, escala e forma). Os modelos foram ajustados utilizando o pacote gamlss disponível no software livre R. A seleção de modelos foi baseada no critério de Akaike (AIC). Finalmente, uma aplicação é apresentada com base em um conjunto de dados reais da área financeira do Chile. / In this work we propose the symmetric generalized partial linear model, based on the generalized partial linear models and symmetric linear models, that is, the response variable follows a distribution that belongs to the symmetric distribution family, considering a linear predictor that has a parametric and a non-parametric component. Some distributions that belong to this class are distributions: Normal, t-Student, Power Exponential, Slash and Hyperbolic among others. A brief review of the concepts used throughout the work was presented, namely: residual analysis, local influence, smoothing parameter, spline, cubic spline, natural cubic spline and backfitting algorithm, among others. In addition, a brief theory of GAMLSS models is presented (generalized additive models for position, scale and shape). The models were adjusted using the package gamlss available in the free R software. The model selection was based on the Akaike criterion (AIC). Finally, an application is presented based on a set of real data from Chile\'s financial area.
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Apprentissage ciblé et Big Data : contribution à la réconciliation de l'estimation adaptative et de l’inférence statistique / Targeted learning in Big Data : bridging data-adaptive estimation and statistical inferenceZheng, Wenjing 21 July 2016 (has links)
Cette thèse porte sur le développement de méthodes semi-paramétriques robustes pour l'inférence de paramètres complexes émergeant à l'interface de l'inférence causale et la biostatistique. Ses motivations sont les applications à la recherche épidémiologique et médicale à l'ère des Big Data. Nous abordons plus particulièrement deux défis statistiques pour réconcilier, dans chaque contexte, estimation adaptative et inférence statistique. Le premier défi concerne la maximisation de l'information tirée d'essais contrôlés randomisés (ECRs) grâce à la conception d'essais adaptatifs. Nous présentons un cadre théorique pour la construction et l'analyse d'ECRs groupes-séquentiels, réponses-adaptatifs et ajustés aux covariable (traduction de l'expression anglaise « group-sequential, response-adaptive, covariate-adjusted », d'où l'acronyme CARA) qui permettent le recours à des procédures adaptatives d'estimation à la fois pour la construction dynamique des schémas de randomisation et pour l'estimation du modèle de réponse conditionnelle. Ce cadre enrichit la littérature existante sur les ECRs CARA notamment parce que l'estimation des effets est garantie robuste même lorsque les modèles sur lesquels s'appuient les procédures adaptatives d'estimation sont mal spécificiés. Le second défi concerne la mise au point et l'étude asymptotique d'une procédure inférentielle semi-paramétrique avec estimation adaptative des paramètres de nuisance. A titre d'exemple, nous choisissons comme paramètre d'intérêt la différence des risques marginaux pour un traitement binaire. Nous proposons une version cross-validée du principe d'inférence par minimisation ciblée de pertes (« Cross-validated Targeted Mimum Loss Estimation » en anglais, d'où l'acronyme CV-TMLE) qui, comme son nom le suggère, marie la procédure TMLE classique et le principe de la validation croisée. L'estimateur CV-TMLE ainsi élaboré hérite de la propriété typique de double-robustesse et aussi des propriétés d'efficacité du TMLE classique. De façon remarquable, le CV-TMLE est linéairement asymptotique sous des conditions minimales, sans recourir aux conditions de type Donsker. / This dissertation focuses on developing robust semiparametric methods for complex parameters that emerge at the interface of causal inference and biostatistics, with applications to epidemiological and medical research in the era of Big Data. Specifically, we address two statistical challenges that arise in bridging the disconnect between data-adaptive estimation and statistical inference. The first challenge arises in maximizing information learned from Randomized Control Trials (RCT) through the use of adaptive trial designs. We present a framework to construct and analyze group sequential covariate-adjusted response-adaptive (CARA) RCTs that admits the use of data-adaptive approaches in constructing the randomization schemes and in estimating the conditional response model. This framework adds to the existing literature on CARA RCTs by allowing flexible options in both their design and analysis and by providing robust effect estimates even under model mis-specifications. The second challenge arises from obtaining a Central Limit Theorem when data-adaptive estimation is used to estimate the nuisance parameters. We consider as target parameter of interest the marginal risk difference of the outcome under a binary treatment, and propose a Cross-validated Targeted Minimum Loss Estimator (TMLE), which augments the classical TMLE with a sample-splitting procedure. The proposed Cross-Validated TMLE (CV-TMLE) inherits the double robustness properties and efficiency properties of the classical TMLE , and achieves asymptotic linearity at minimal conditions by avoiding the Donsker class condition.
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Modelos parcialmente lineares com erros simétricos autoregressivos de primeira ordem / Symmetric partially linear models with first-order autoregressive errors.Relvas, Carlos Eduardo Martins 19 April 2013 (has links)
Neste trabalho, apresentamos os modelos simétricos parcialmente lineares AR(1), que generalizam os modelos parcialmente lineares para a presença de erros autocorrelacionados seguindo uma estrutura de autocorrelação AR(1) e erros seguindo uma distribuição simétrica ao invés da distribuição normal. Dentre as distribuições simétricas, podemos considerar distribuições com caudas mais pesadas do que a normal, controlando a curtose e ponderando as observações aberrantes no processo de estimação. A estimação dos parâmetros do modelo é realizada por meio do critério de verossimilhança penalizada, que utiliza as funções escore e a matriz de informação de Fisher, sendo todas essas quantidades derivadas neste trabalho. O número efetivo de graus de liberdade e resultados assintóticos também são apresentados, assim como procedimentos de diagnóstico, destacando-se a obtenção da curvatura normal de influência local sob diferentes esquemas de perturbação e análise de resíduos. Uma aplicação com dados reais é apresentada como ilustração. / In this master dissertation, we present the symmetric partially linear models with AR(1) errors that generalize the normal partially linear models to contain autocorrelated errors AR(1) following a symmetric distribution instead of the normal distribution. Among the symmetric distributions, we can consider heavier tails than the normal ones, controlling the kurtosis and down-weighting outlying observations in the estimation process. The parameter estimation is made through the penalized likelihood by using score functions and the expected Fisher information. We derive these functions in this work. The effective degrees of freedom and asymptotic results are also presented as well as the residual analysis, highlighting the normal curvature of local influence under different perturbation schemes. An application with real data is given for illustration.
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Modelos parcialmente lineares com erros simétricos autoregressivos de primeira ordem / Symmetric partially linear models with first-order autoregressive errors.Carlos Eduardo Martins Relvas 19 April 2013 (has links)
Neste trabalho, apresentamos os modelos simétricos parcialmente lineares AR(1), que generalizam os modelos parcialmente lineares para a presença de erros autocorrelacionados seguindo uma estrutura de autocorrelação AR(1) e erros seguindo uma distribuição simétrica ao invés da distribuição normal. Dentre as distribuições simétricas, podemos considerar distribuições com caudas mais pesadas do que a normal, controlando a curtose e ponderando as observações aberrantes no processo de estimação. A estimação dos parâmetros do modelo é realizada por meio do critério de verossimilhança penalizada, que utiliza as funções escore e a matriz de informação de Fisher, sendo todas essas quantidades derivadas neste trabalho. O número efetivo de graus de liberdade e resultados assintóticos também são apresentados, assim como procedimentos de diagnóstico, destacando-se a obtenção da curvatura normal de influência local sob diferentes esquemas de perturbação e análise de resíduos. Uma aplicação com dados reais é apresentada como ilustração. / In this master dissertation, we present the symmetric partially linear models with AR(1) errors that generalize the normal partially linear models to contain autocorrelated errors AR(1) following a symmetric distribution instead of the normal distribution. Among the symmetric distributions, we can consider heavier tails than the normal ones, controlling the kurtosis and down-weighting outlying observations in the estimation process. The parameter estimation is made through the penalized likelihood by using score functions and the expected Fisher information. We derive these functions in this work. The effective degrees of freedom and asymptotic results are also presented as well as the residual analysis, highlighting the normal curvature of local influence under different perturbation schemes. An application with real data is given for illustration.
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