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.

nÃo hà / Esta dissertaÃÃo tem por objetivo calcular as taxas de sobrevivÃncia dos participantes de Fundos de PensÃo do setor elÃtrico nacional, bem como encontrar o modelo paramÃtrico de sobrevivÃncia que melhor represente os dados em estudo. Para desenvolvimento do trabalho utilizamos dados de 14 entidades com informaÃÃes de participantes ativos e aposentados, com exceÃÃo dos invÃlidos, referentes ao perÃodo de 2001 a 2009, totalizando um nÃmero total de 100.000 vidas analisadas. Para calcular as taxas brutas de sobrevivÃncia, utilizamos o mÃtodo indireto, descrito em Ferreira (1985). ApÃs o cÃlculo das taxas originais, efetuamos o processo de suavizaÃÃo por mÃdias mÃveis, visando corrigir as flutuaÃÃes indesejadas obtidas na curva bruta de sobrevivÃncia. Mesmo apÃs o processo de suavizaÃÃo, optamos por restringir o estudo Ãs idades dentro do intervalo de 25 a 85 anos, dado o baixo nÃmero de Ãbitos e expostos nas idades supramencionadas. A partir da curva suavizada, aplicamos os modelos paramÃtricos de sobrevivÃncia de Gompertz, Gompertz-Makeham, Thiele e Helingman-Pollard, para testar o melhor ajuste da equaÃÃo. Os resultados mostraram que nenhum dos modelos paramÃtricos analisados se mostrou com robustez estatÃstica suficiente para se proceder a uma anÃlise preditiva com confiabilidade aceitÃvel. / This paper aims to calculate the survival rates of the participants of the Pension Funds electricity sector as well as finding the parametric survival model that best represents the data in the study. For development work we used data from 14 organizations with information of participants and retirees, with the exception of the disabled, for the period 2001 to 2009, amounting to a total of 100,000 lives analyzed. To calculate the crude rates of survival using the indirect method described in Ferreira (1985). After calculation of the original rates, we make the process of smoothing by moving averages in order to correct the unwanted fluctuations in the curve obtained crude survival. Even after the smoothing process, we chose to restrict the study to age within the range of 25 to 85 years, given the low number of deaths at ages above and exposed. From the smooth curve we apply the parametric models of survival Gompertz, Gompertz-Makeham, Thiele and Helingman-Pollard, to test the best fit of the equation. The results showed that none of the models proved to be analyzed with parametric statistical robust enough to conduct a predictive analysis with acceptable reliability.

[pt] Este trabalho apresenta um modelo de Regressão Linear Nebulosa por Partes(RLNP). Trata-se de uma estrutura que envolve modelos de regressão linear por partes ponderadas por pertinências advindas da lógica nebulosa. Este modelo é comparado com o modelo de regressão linear. Os resultados mostram que o RLNP consegue identificar a estrutura não-linear dos dados simulados e que na maioria dos casos ele possui bom poder de ajuste. / [en] In this dissertation a Fuzzy Piece-Wise Linear Regressive model FPLieR is developed. The model´s structure combines linear regressive models with fuzzy logic´s grade of membership in a piece-wise fashion. A comparision is made between this model and the linear regression one. The results show that FPLieR is able to find the linear substructure of simulated data and that in most cases it presents a good fit.

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.

Sparse regressions based on constraining the L1-norm of the coefficients became popular due to their ability to handle high dimensional data unlike the regular regressions which suffer from overfitting and model identifiability issues especially when sample size is small. They are often the method of choice in many fields of science and engineering for simultaneously selecting covariates and fitting parsimonious linear models that are better generalizable and easily interpretable. However, significant challenges may be posed by the need to accommodate extremes and other domain constraints such as dynamical relations among variables, spatial and temporal constraints, need to provide uncertainty estimates and feature correlations, among others. We adopted a hierarchical Bayesian version of the sparse regression framework and exploited its inherent flexibility to accommodate the constraints. We applied sparse regression for the feature selection problem of statistical downscaling of the climate variables with particular focus on their extremes. This is important for many impact studies where the climate change information is required at a spatial scale much finer than that provided by the global or regional climate models. Characterizing the dependence of extremes on covariates can help in identification of plausible causal drivers and inform extremes downscaling. We propose a general-purpose sparse Bayesian framework for covariate discovery that accommodates the non-Gaussian distribution of extremes within a hierarchical Bayesian sparse regression model. We obtain posteriors over regression coefficients, which indicate dependence of extremes on the corresponding covariates and provide uncertainty estimates, using a variational Bayes approximation. The method is applied for selecting informative atmospheric covariates at multiple spatial scales as well as indices of large scale circulation and global warming related to frequency of precipitation extremes over continental United States. Our results confirm the dependence relations that may be expected from known precipitation physics and generates novel insights which can inform physical understanding. We plan to extend our model to discover covariates for extreme intensity in future. We further extend our framework to handle the dynamic relationship among the climate variables using a nonparametric Bayesian mixture of sparse regression models based on Dirichlet Process (DP). The extended model can achieve simultaneous clustering and discovery of covariates within each cluster. Moreover, the a priori knowledge about association between pairs of data-points is incorporated in the model through must-link constraints on a Markov Random Field (MRF) prior. A scalable and efficient variational Bayes approach is developed to infer posteriors on regression coefficients and cluster variables. / Computer and Information Science

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.

Neste trabalho estendemos os modelos mistos semiparamétricos propostos por Zhang et al. (1998) para uma classe mais geral de modelos, a qual denominamos modelos mistos aditivos semiparamétricos com erros de contornos elípticos. Com essa nova abordagem, flexibilizamos a curtose da distribuição dos erros possibilitando a escolha de distribuições com caudas mais leves ou mais pesadas do que as caudas da distribuição normal padrão. Funções de verossimilhança penalizadas são aplicadas para a obtenção das estimativas de máxima verossimilhança com os respectivos erros padrão aproximados. Essas estimativas, sob erros de caudas pesadas, são robustas no sentido da distância de Mahalanobis contra observações aberrantes. Curvaturas de influência local são obtidas segundo alguns esquemas de perturbação e gráficos de diagnóstico são propostos. Exemplos ilustrativos são apresentados em que ajustes sob erros normais são comparados, através das metodologias de sensibilidade desenvolvidas no trabalho, com ajustes sob erros de contornos elípticos. / In this work we extend the models proposed by Zhang et al. (1998) to a more general class of models, know as semiparametric additive mixed models with elliptical errors in order to allow distributions with heavier or lighter tails than the normal ones. Penalized likelihood equations are applied to derive the maximum likelihood estimates which appear to be robust against outlying observations in the sense of the Mahalanobis distance. In order to study the sensitivity of the penalized estimates under some usual perturbation schemes in the model or data, the local influence curvatures are derived and some diagnostic graphics are proposed. Motivating examples preliminary analyzed under normal errors are reanalyzed under some appropriate elliptical errors. The local influence approach is used to compare the sensitivity of the model estimates.

Neste trabalho estendemos os modelos mistos semiparamétricos propostos por Zhang et al. (1998) para uma classe mais geral de modelos, a qual denominamos modelos mistos aditivos semiparamétricos com erros de contornos elípticos. Com essa nova abordagem, flexibilizamos a curtose da distribuição dos erros possibilitando a escolha de distribuições com caudas mais leves ou mais pesadas do que as caudas da distribuição normal padrão. Funções de verossimilhança penalizadas são aplicadas para a obtenção das estimativas de máxima verossimilhança com os respectivos erros padrão aproximados. Essas estimativas, sob erros de caudas pesadas, são robustas no sentido da distância de Mahalanobis contra observações aberrantes. Curvaturas de influência local são obtidas segundo alguns esquemas de perturbação e gráficos de diagnóstico são propostos. Exemplos ilustrativos são apresentados em que ajustes sob erros normais são comparados, através das metodologias de sensibilidade desenvolvidas no trabalho, com ajustes sob erros de contornos elípticos. / In this work we extend the models proposed by Zhang et al. (1998) to a more general class of models, know as semiparametric additive mixed models with elliptical errors in order to allow distributions with heavier or lighter tails than the normal ones. Penalized likelihood equations are applied to derive the maximum likelihood estimates which appear to be robust against outlying observations in the sense of the Mahalanobis distance. In order to study the sensitivity of the penalized estimates under some usual perturbation schemes in the model or data, the local influence curvatures are derived and some diagnostic graphics are proposed. Motivating examples preliminary analyzed under normal errors are reanalyzed under some appropriate elliptical errors. The local influence approach is used to compare the sensitivity of the model estimates.

This work presents a black box identification for a continuous methanol-water distillation column setting in open loop and closed loop response. Step changes and Pseudo-Random Binary Signal (PRBS) disturbance were used to excite the plant. The mathematical models candidates to identify were the Artificial Neural Networks (ANN) and the parametric models: ARX(autoregressive with exogenous inputs ), ARMAX (AutoRegressive Moving Average with eXogenous inputs ), OE(Output Error) and the Box-Jenkins (BJ)structure. The closed loop configuration was the R-V. The results showed that for the bottom loop, the best response were given by BJ, OE and RNA for both open and closed loop response. For the top closed loop, the best responses were also given by BJ, OE and RNA while in open loop condition, the RNA was the one that gave satisfactory outcome. It was verified that the pseudo-random binary signal was a good choice of excitation signal in identification for both open loop and closed dynamic systems. / Foi realizado neste trabalho identificação caixa preta do processo de destilação Metanol-Água nas configurações malha aberta e malha fechada, utilizando como sinais de perturbação a função degrau e o Sinal Binário Pseudo-Aleatório (PRBS) para excitar a planta. Os modelos matemáticos candidatos a identificação foram as Redes Neurais Artificiais (RNA), e os modelos paramétricos discretos lineares autorregressivo com entradas externas (ARX do inglês AutoRegressive with eXogenous Inputs), autorregressivo com média móvel e entradas exógenas (ARMAX do inglês AutoRegressive Moving Average with eXogenous Inputs), modelo do tipo erro na saída (OE do inglês Output Error) e a estrutura Box-Jenkins (BJ). Com a disposição dos modelos, foram comparados quais dos modelos matemáticos candidatos à identificação melhor representa o processo coluna de destilação metanol-água. Comparou-se qual configuração do processo no ensaio de identificação para geração de dados apresenta mais vantagens, se em malha aberta ou em malha fechada, nas condições e metodologias utilizadas. Constatou-se a funcionalidade do sinal binário pseudo-aleatório como uma boa opção de excitação na identificação em malha aberta e fechada para sistemas dinâmicos.

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.