Made available in DSpace on 2014-12-17T15:34:49Z (GMT). No. of bitstreams: 1 DeborahGPG_DISSERT.pdf: 1421770 bytes, checksum: da1c0ade32fb8610306243b0cf52f13d (MD5) Previous issue date: 2014-02-20 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior / Among the traits of economic importance to dairy cattle livestock those related to sexual precocity and longevity of the herd are essential to the success of the activity, because the stayability time of a cow in a herd is determined by their productive and reproductive lives. In Brazil, there are few studies about the reproductive efficiency of Swiss-Brown cows and no study was found using the methodology of survival analysis applied to this breed. Thus, in the first chapter of this study, the age at first calving from Swiss-Brown heifers was analyzed as the time until the event by the nonparametric method of Kaplan-Meier and the gamma shared frailty model, under the survival analysis methodology. Survival and hazard rate curves associated with this event were estimated and identified the influence of covariates on such time. The mean and median times at the first calving were 987.77 and 1,003 days, respectively, and significant covariates by the Log-Rank test, through Kaplan-Meier analysis, were birth season, calving year, sire (cow s father) and calving season. In the analysis by frailty model, the breeding values and the frailties of the sires (fathers) for the calving were predicted modeling the risk function of each cow as a function of the birth season as fixed covariate and sire as random covariate. The frailty followed the gamma distribution. Sires with high and positive breeding values possess high frailties, what means shorter survival time of their daughters to the event, i.e., reduction in the age at first calving of them. The second chapter aimed to evaluate the longevity of dairy cows using the nonparametric Kaplan-Meier and the Cox and Weibull proportional hazards models. It were simulated 10,000 records of the longevity trait from Brown-Swiss cows involving their respective times until the occurrence of five consecutive calvings (event), considered here as typical of a long-lived cow. The covariates considered in the database were age at first calving, herd and sire (cow s father). All covariates had influence on the longevity of cows by Log-Rank and Wilcoxon tests. The mean and median times to the occurrence of the event were 2,436.285 and 2,437 days, respectively. Sires that have higher breeding values also have a greater risk of that their daughters reach the five consecutive calvings until 84 months / Dentre as caracter?sticas de import?ncia econ?mica para a pecu?ria leiteira aquelas relacionadas com a precocidade sexual e a longevidade do rebanho s?o determinantes para o sucesso da atividade, uma vez que o tempo de perman?ncia de uma vaca num rebanho ? determinado por suas vidas produtiva e reprodutiva. No Brasil, existem poucos estudos sobre a efici?ncia reprodutiva de vacas Pardo-Su??as e n?o foi encontrado nenhum estudo abordando o uso da metodologia de an?lise de sobreviv?ncia aplicada a esta ra?a. Assim, no primeiro cap?tulo deste trabalho, a idade ao primeiro parto de novilhas Pardo-Su??as foi analisada como o tempo at? o evento por meio do m?todo n?o-param?trico de Kaplan-Meier e do modelo de fragilidade compartilhado gama, sob a metodologia de an?lise de sobreviv?ncia. Foram estimadas curvas de sobreviv?ncia e de taxa de risco associadas com este evento e verificada a influ?ncia das covari?veis consideradas sobre o tempo. Os tempos m?dio e mediano ao primeiro parto foram 987,77 e 1.003 dias, respectivamente; e as covari?veis significativas pelo teste de Log-Rank, na an?lise por Kaplan-Meier, foram esta??o de nascimento, ano de parto, touro (pai da vaca) e esta??o de parto. Na an?lise pelo modelo de fragilidade, foram preditos os valores gen?ticos e as fragilidades dos touros (pais) para o parto, modelando-se a fun??o de risco de cada vaca em fun??o da covari?vel fixa esta??o de nascimento e da covari?vel aleat?ria touro. A fragilidade seguiu a distribui??o gama. Touros com valores gen?ticos positivos e altos possuem fragilidades altas, o que significa menor tempo de sobreviv?ncia de suas filhas ao evento, ou seja, redu??o na idade ao primeiro parto delas. O segundo cap?tulo teve como objetivo avaliar a longevidade de vacas leiteiras utilizando o estimador n?o-param?trico de Kaplan-Meier e os modelos de riscos proporcionais de Weibull e de Cox. Foram simulados 10.000 registros da caracter?stica longevidade de f?meas Pardo-Su??as denotando seus respectivos tempos at? a ocorr?ncia de cinco partos consecutivos (evento), considerados aqui como t?picos de uma vaca longeva. As covari?veis consideradas no banco de dados foram a idade da vaca ao primeiro parto, o rebanho e o pai da vaca. Todas as covari?veis exerceram influ?ncia sobre a longevidade das vacas de acordo com os testes de Log-Rank e Wilcoxon. Os tempos m?dio e mediano para a ocorr?ncia do evento foram de 2.436,285 e 2.437 dias. Touros com maior valor gen?tico tamb?m possuem um maior risco de que as suas filhas alcancem os cinco partos aos 84 meses

Dans cette thèse, nous étudions les propriétés asymptotiques de paramètres fonctionnels conditionnels en statistique non paramétrique, quand la variable explicative prend ses valeurs dans un espace de dimension infinie. Dans ce cadre non paramétrique, on considère les estimateurs des paramètres fonctionnels usuels, tels la loi conditionnelle, la densité de probabilité conditionnelle, ainsi que le quantile conditionnel. Le premier travail consiste à proposer un estimateur du quantile conditionnel et de prouver sa convergence uniforme sur un sous-ensemble compact. Afin de suivre la convention dans les études biomédicales, nous considérons une suite de v.a {Ti, i ≥ 1} identiquement distribuées, de densité f, censurée à droite par une suite aléatoire {Ci, i ≥ 1} supposée aussi indépendante, identiquement distribuée et indépendante de {Ti, i ≥ 1}. Notre étude porte sur des données fortement mélangeantes et X la covariable prend des valeurs dans un espace à dimension infinie.Le second travail consiste à établir la normalité asymptotique de l’estimateur à noyau du quantile conditionnel convenablement normalisé, pour des données fortement mélangeantes, et repose sur la probabilité de petites boules. Plusieurs applications à des cas particuliers ont été traitées. Enfin, nos résultats sont appliqués à des données simulées et montrent la qualité de notre estimateur. / In this thesis, we study some asymptotic properties of conditional functional parameters in nonparametric statistics setting, when the explanatory variable takes its values in infinite dimension space. In this nonparametric setting, we consider the estimators of the usual functional parameters, as the conditional law, the conditional probability density, the conditional quantile. We are essentially interested in the problem of forecasting in the nonparametric conditional models, when the data are functional random variables. Firstly, we propose an estimator of the conditional quantile and we establish its uniform strong convergence with rates over a compact subset. To follow the convention in biomedical studies, we consider an identically distributed sequence {Ti, i ≥ 1}, here density f, right censored by a random {Ci, i ≥ 1} also assumed independent identically distributed and independent of {Ti, i ≥ 1}. Our study focuses on dependent data and the covariate X takes values in an infinite space dimension. In a second step we establish the asymptotic normality of the kernel estimator of the conditional quantile, under α-mixing assumption and on the concentration properties on small balls of the probability measure of the functional regressors. Many applications in some particular cases have been also given.

Health technology assessment: case study on breast carcinoma treatment in the Czech Republic Bc. Lenka Šlegerová January 4, 2019 Abstract This thesis proposes an original method for assessing total costs of med- ical treatment. It defines the semi-Markov model with four states that are associated with specific costs of the treatment, and not with patients' health statuses. This method is applied to individuals' treatment data drawn from the Czech clinical practice in the treatment of the metastatic HER2+ breast cancer. The aim is to assess the cost-effectiveness of adding medication per- tuzumab to the combination of trastuzumab+docetaxel within first-line therapy and to examine whether using individual data on Czech patients and the economic conditions leads to different results from foreign stud- ies. Furthermore, employing censored data from the clinical practice in the thesis complicates the estimation of patients' overall survival in compari- son to clinical-trials data that form random samples. Therefore, survival functions were not only estimated by the Kaplan-Meier estimator but also using the Cox proportional hazard model and the Accelerated failure time model that both control for the effects of included covariates. The addition of pertuzumab does not result in significantly longer pa- tients'...

Le risque attribuable (RA) mesure la proportion de cas de maladie qui peuvent être attribués à une exposition au niveau de la population. Plusieurs définitions et méthodes d'estimation du RA ont été proposées pour des données de survie. En utilisant des simulations, nous comparons quatre méthodes d'estimation du RA dans le contexte de l'analyse de survie : deux méthodes non paramétriques basées sur l'estimateur de Kaplan-Meier, une méthode semi-paramétrique basée sur le modèle de Cox à risques proportionnels et une méthode paramétrique basée sur un modèle à risques proportionnels avec un risque de base constant par morceaux. Nos travaux suggèrent d'utiliser les approches semi-paramétrique et paramétrique pour l'estimation du RA lorsque l'hypothèse des risques proportionnels est vérifiée. Nous appliquons nos méthodes aux données de la cohorte E3N pour estimer la proportion de cas de cancer du sein invasif attribuables à l'utilisation de traitements hormonaux de la ménopause (THM). Nous estimons qu'environ 9 % des cas de cancer du sein sont attribuables à l'utilisation des THM à l'inclusion. Dans le cas d'une exposition protectrice, une alternative au RA est la fraction préventive (FP) qui mesure la proportion de cas de maladie évités. Cette mesure n'a pas été considérée dans le contexte de l'analyse de survie. Nous proposons une définition de la FP dans ce contexte et des méthodes d'estimation en utilisant des approches semi-paramétrique et paramétrique avec une extension permettant de prendre en compte les risques concurrents. L'application aux données de la cohorte des Trois Cités (3C) estime qu'environ 9 % de cas d'accident vasculaire cérébral peuvent être évités chez les personnes âgées par l'utilisation des hypolipémiants. Notre étude montre que la FP peut être utilisée pour évaluer l'impact des médicaments bénéfiques dans les études de cohorte tout en tenant compte des facteurs de confusion potentiels et des risques concurrents. / The attributable risk (AR) measures the proportion of disease cases that can be attributed to an exposure in the population. Several definitions and estimation methods have been proposed for survival data. Using simulations, we compared four methods for estimating AR defined in terms of survival functions: two nonparametric methods based on Kaplan-Meier's estimator, one semiparametric based on Cox's model, and one parametric based on the piecewise constant hazards model. Our results suggest to use the semiparametric or parametric approaches to estimate AR if the proportional hazards assumption appears appropriate. These methods were applied to the E3N women cohort data to estimate the AR of breast cancer due to menopausal hormone therapy (MHT). We showed that about 9% of cases of breast cancer were attributable to MHT use at baseline. In case of a protective exposure, an alternative to the AR is the prevented fraction (PF) which measures the proportion of disease cases that could be avoided in the presence of a protective exposure in the population. The definition and estimation of PF have never been considered for cohort studies in the survival analysis context. We defined the PF in cohort studies with survival data and proposed two estimation methods: a semiparametric method based on Cox’s proportional hazards model and a parametric method based on a piecewise constant hazards model with an extension to competing risks. Using data of the Three-City (3C) cohort study, we found that approximately 9% of cases of stroke could be avoided using lipid-lowering drugs (statins or fibrates) in the elderly population. Our study shows that the PF can be estimated to evaluate the impact of beneficial drugs in observational cohort studies while taking potential confounding factors and competing risks into account.

The objective of the study was to identify the factors that affect the survival lifetime of HIV+ terminal patients in rural district hospitals of Albert Luthuli municipality in the Mpumalanga province of South Africa. A cohort of HIV+ terminal patients was retrospectively followed from 2010 to 2017 until a patient died, was lost to follow-up or was still alive at the end of the observation period. Nonparametric survival analysis and semiparametric survival analysis methods were used to analyse the data. Through Cox proportional hazards regression modelling, it was found that ART adherence (poor, fair, good), Age, Follow-up mass, Baseline sodium, Baseline viral load, Follow CD4 count by Treatment (Regimen 1) interaction and Follow-up lymphocyte by TB history (yes, no) interaction had significant effects on survival lifetime of HIV+ terminal patients (p-values<0.1). Furthermore, through quantile regression modelling, it was found that short, medium and long survival times of HIV+ patients, respectively represented by the 0.1, 0.5 and 0.9 quantiles, were not necessarily significantly affected by the same factors. / Statistics / M. Sc. (Statistics)