In this paper we propose a generalized rank test based on discrete interval-censored failure time data to determine whether two lifetime populations come from the same distribution. It reduces to the Logrank test or Wilcoxon test when one has exact or right-censored data. Simulation shows that the proposed test performs pretty satisfactory. An example is presented to demonstrate how the proposed test can be applied in AIDS study.

Alzheimer’s disease (AD) is a multifactorial neurological condition associated with genetic profiles that are still not completely understood. We performed a family-based low-density genome-wide association analysis of age at onset (AAO) in AD (244 patients and their relatives) using Illumina 6 K single-nucleotide polymorphisms (SNPs) panel and the FBAT-logrank statistic. We observed 10 SNPs associated with AAO in AD with p < 2 × 10−3. The most significant hit within a known gene, the neuronal protein astrotactin 2 (ASTN2), was SNP rs1334071 (p = 8.74 × 10−4). ASTN2 has been implicated in several neuropsychiatric disorders, including cognitive disorders, autism and schizophrenia. We then conducted a replication study focusing on ASTN2 gene in a Canadian sample of 791 AD patients and 782 controls using the logrank test. Five ASTN2 SNPs (highest association is rs16933774 with p = 0.0053) showed associations with AAO in this Canadian sample (p < 0.05). Furthermore, Kaplan–Meier survival analysis of SNP rs16933774 showed that the AAO of AD in individuals heterozygous for AG genotype of rs16933774 (median of AAO = 68.5 years) was approximately 4.5 years earlier than those individuals having the AA genotype (median of AAO = 73 years). In conclusion, a significant association of ASTN2 genetic variants with AAO of AD in two independent samples demonstrates a role for ASTN2 in the pathogenesis of AD. Future functional studies of this gene may help to characterize the genetic architecture of the AAO of AD. Genetic factors in AAO may be a critical factor for early AD intervention and prevention efforts.

The two and k-sample tests of equality of the survival distributions against the alternatives including cross-effects of survival functions, proportional and monotone hazard ratios, are given for the right censored data. The asymptotic power against approaching alternatives is investigated. The tests are applied to the well known chemio and radio therapy data of the Gastrointestinal Tumor Study Group. The P-values for both proposed tests are much smaller then in the case of other known tests. Differently from the test of Stablein and Koutrouvelis the new tests can be applied not only for singly but also to randomly censored data.

Made available in DSpace on 2015-03-26T13:32:04Z (GMT). No. of bitstreams: 1 texto completo.pdf: 569181 bytes, checksum: 1b525772884dca74fcef6c9c8033aaa5 (MD5) Previous issue date: 2008-09-05 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Reburning caused by Phytophthora infestansis is characterized as an aggressive disease of great destructive impact, capable of limiting or even hindering the economic cultivation of the tomato plant under conditions of high humidity and low temperatures. In view of the problems reburning can cause to tomato plant crops, this work aimed to: 1) fit models to describe the progress of the disease and form groups of tomato accesses with similar curves; 2) estimate data referring to the number of days to reach 5% severity of the disease, by means of inverse regression; 3) fit survival curves by means of the Kaplan-Meier estimator for the access groups and compare them by means of the Logrank test;4)fit survival curves by means of probabilistic models and compare these curves with Kaplan Meir´s non-parametric technique. Using tomato reburning real data, it was possible to fit the exponential model (Y = y0 exp (rX)) to describe the disease s progress. The means of the parameter estimates were submitted to grouping analysis using the centroid method, generating 10 access groups. Time up to 5% of the disease was calculated via inverse regression. Non-parametric techniques were used to estimate survival function by means of the Kaplan-Meier´s estimator to compare the survival curves by the Logrank test .The survival function was also fit using the probabilistic models, exponential Weibull and Log-normal, respectively, which were compared by means of the verisimilitude ratio test (VRT), considering the generalized Gamma model, as a general case for these models. The methodology applied allowed fitting the exponential model to describe tomato plant reburning progress and to regroup the accesses studied in the 10 groups. The access BGH-6 obtained a smaller disease progress than the others, thus characterizing its higher resistance to the disease; An inverse regression allowed time estimation up to the occurrence of 5% of the severity of the tomato plant reburning. The Kaplan-Meier ´s non-parametric technique allowed estimating the survival curves of the tomato plant accesses belonging to the groups 1, 2, 4, 6 and 8. Utilizing the Logrank test, it could be concluded that most two-by-two comparisons were significant (p<0.05), except in the comparisons of groups 2x4, 4x8 and 6x8. The use of the probabilistic models, exponential Weibull and Log-normal allowed estimating the survival curves of groups 2, 4, 6 and 8, except for group 4, to which the Weibull model was not adequate. Comparing the probabilistic models with the non-parametric technique, the curves of the probabilistic models of groups 2 and 4 presented satisfactory results, compared to the curve estimated by Kaplan-Meier. / A requeima causada por Phytophthora infestans caracteriza-se por ser uma doença agressiva e de grande impacto destrutivo, podendo limitar ou até mesmo impedir o cultivo econômico do tomateiro sob condições de alta umidade e baixas temperaturas. Diante dos problemas que a requeima pode provocar às lavouras de tomate, este trabalho teve por objetivos: 1) ajustar modelos para descrever o progresso da doença e formar grupos de acessos de tomateiro com curvas semelhantes; 2) estimar dados referentes ao número de dias até atingir 5% de severidade da doença, por meio de regressão inversa; 3) ajustar curvas de sobrevivência por meio do estimador de Kaplan-Meier para grupos de acessos e compará-las mediante o uso do teste Logrank; 4) ajustar curvas de sobrevivência por meio de modelos probabilísticos e compará-las com a técnica não-paramétrica de Kaplan-Meier. Utilizando dados reais sobre a requeima do tomateiro, foi possível ajustar o modelo exponencial (Y = y0 exp (rX)) para descrever o progresso da doença. As médias das estimativas dos parâmetros foram submetidas à análise de agrupamento pelo método Centróide, o que gerou 10 grupos de acessos, sendo o tempo até a incidência de 5% da doença calculado via regressão inversa. Foram utilizadas técnicas não-paramétricas para estimar a função de sobrevivência por meio do estimador de Kaplan-Meier e para comparar as curvas de sobrevivência pelo teste Logrank. Foi também ajustada a função de sobrevivência, empregando-se os modelos probabilísticos Exponencial, Weibull e Log-normal, os quais foram comparados por meio do Teste da Razão da Verossimilhança (TRV), considerando-se o modelo Gama generalizado por ser caso geral para esses modelos. A metodologia utilizada permitiu ajustar o modelo Exponencial para descrever o progresso da requeima do tomateiro e agrupar os acessos estudados em 10 grupos. O acesso BGH-6 sofreu um progresso de doença menor que os demais, caracterizando-se, assim, sua maior resistência à enfermidade. A regressão inversa possibilitou estimar o tempo até a ocorrência de 5% da severidade da requeima do tomateiro. Pela técnica não-paramétrica de Kaplan-Meier, foi possível estimar as curvas de sobrevivência dos acessos de tomateiro pertencentes aos grupos 1, 2, 4, 6 e 8. Utilizando o teste Logrank, pode-se concluir que a maioria das comparações duas a duas foi significativa (p<0,05), exceto nas comparações dos grupos 2x4, 4x8 e 6x8. O uso dos modelos probabilísticos Exponencial, Weibull e Log-normal possibilitou a estimação das curvas de sobrevivência nos grupos 2, 4, 6 e 8, exceto no grupo 4, em que o modelo Weibull não foi adequado. Comparando os modelos probabilísticos com a técnica não-paramétrica, as curvas dos modelos probabilísticos dos grupos 2 e 4 apresentaram ajustes satisfatórios com relação à curva estimada por Kaplan-Meier.