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Hierarchical latency models for dose-time-response associations.

ABSTRACT: Exposure lagging and exposure-time window analysis are 2 widely used approaches to allow for induction and latency periods in analyses of exposure-disease associations. Exposure lagging implies a strong parametric assumption about the temporal evolution of the exposure-disease association. An exposure-time window analysis allows for a more flexible description of temporal variation in exposure effects but may result in unstable risk estimates that are sensitive to how windows are defined. The authors describe a hierarchical regression approach that combines time window analysis with a parametric latency model. They illustrate this approach using data from 2 occupational cohort studies: studies of lung cancer mortality among 1) asbestos textile workers and 2) uranium miners. For each cohort, an exposure-time window analysis was compared with a hierarchical regression analysis with shrinkage toward a simpler, second-stage parametric latency model. In each cohort analysis, there is substantial stability gained in time window-specific estimates of association by using a hierarchical regression approach. The proposed hierarchical regression model couples a time window analysis with a parametric latency model; this approach provides a way to stabilize risk estimates derived from a time window analysis and a way to reduce bias arising from misspecification of a parametric latency model.

SUBMITTER: Richardson DB

PROVIDER: S-EPMC3105259 | biostudies-literature | 2011 Mar

REPOSITORIES: biostudies-literature

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Hierarchical latency models for dose-time-response associations.

Richardson David B DB MacLehose Richard F RF Langholz Bryan B Cole Stephen R SR

American journal of epidemiology 20110208 6

Exposure lagging and exposure-time window analysis are 2 widely used approaches to allow for induction and latency periods in analyses of exposure-disease associations. Exposure lagging implies a strong parametric assumption about the temporal evolution of the exposure-disease association. An exposure-time window analysis allows for a more flexible description of temporal variation in exposure effects but may result in unstable risk estimates that are sensitive to how windows are defined. The au ...[more]

PMID: 21303803

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Project description:The number and type of synthetic chemicals that are being produced worldwide continues to increase significantly. While these industrial chemicals provide numerous benefits, there is no doubt that some have potential to damage the environment and health. Toxicity must be evaluated and use must be carefully controlled and monitored in order to minimize potential damage. DNA microarray technology has become an important new technique in toxicology. We are using the yeast Saccharomyces cerevisiae as a model organism for toxicological study because it is a simple, fast-growing eukaryote that has been thoroughly characterized. In order to evaluate toxicity by newly synthesized or mixture chemicals, toxicity-induced gene expression alteration profiles by known chemicals should be collected. In our study, cells need to be exposed with same experimental cellular condition, semi lethal (IC50), respectively. In the case of iodine (CAS; 7553-56-2), the IC50 was 1 mM by growth curve with continuously diluted exposure. // Effects of Iodine on Global Gene Expression in Saccharomyces cerevisiae : It is well documented that iodine kills microorganisms with broad spectrum. However, a systematic study of its mechanism of action has not yet been reported. Here we have demonstrated the action of iodine on gene expression level, using the yeast Saccharomyces cerevisiae with a DNA microarray. It was found that like antimicrobial activity, iodine causes an immediate and dose-dependent (0.5 mM, 0.75 mM and 1 mM) transcriptional alteration on yeast cells. The effects of iodine continued after the first immediate response. Genes for C-compound and carbohydrate metabolism, for energy, and for cell rescue were continuously up-regulated. On the other hand, genes related to protein fate were induced especially at 0.5 h. The gene expression profile at 0.5 h was significantly different from other longer iodine exposed condition. The main reaction at 0.5 h after iodine addition may be due to the oxidative toxicity, and the profile at 0.5 h was similar to agricultural bactericide. Keywords: stress response

Project description:IntroductionRecently, testosterone (T) has been shown to be associated with premature ejaculation (PE) symptoms in the literature. Furthermore, studies suggest that the etiology of PE is partly under genetic control.AimThe aim of this study was to reassess findings suggesting an association between testosterone (T) and a key symptom of PE, ejaculation latency time (ELT), as well as exploratively investigating associations between six androgen-related genetic polymorphisms and ELT.Materials and methodsStatistical analyses were performed on a population-based sample of 1,429 Finnish men aged 18-45 years (M = 26.9, SD = 4.7). Genotype information was available for 1,345-1,429 of these (depending on the polymorphism), and salivary T samples were available from 384 men. Two androgen receptor gene-linked, two 5-alpha-reductase type 2-gene-linked, and two sex hormone-binding globuline gene-linked polymorphisms were genotyped.Main outcome measuresEjaculatory function was assessed using self-reported ELT.ResultsWe found no association between salivary T levels and ELT. We found a nominally significant association between a 5-alpha-reductase type 2-gene-linked polymorphism (rs2208532) and ELT, but this association did not remain significant after correction for multiple testing. One single nucleotide polymorphism in the sex hormone-binding globulin gene (rs1799941) moderated (significantly after correction for multiple testing) the association between salivary T and ELT, so that A:A genotype carriers had significantly lower salivary T levels as a function of increasing ELT compared with other genotype groups.ConclusionsWe were unable to find support for the hypothesis suggesting an association between T levels and ELT, possibly because of the low number of phenotypically extreme cases (the sample used in the present study was population based). Our results concerning genetic associations should be interpreted with caution until replication studies have been conducted. Jern P, Westberg L, Ankarberg-Lindgren C, Johansson A, Gunst A, Sandnabba NK, and Santtila P. Associations between salivary testosterone levels, androgen-related genetic polymorphisms, and self-estimated ejaculation latency time. Sex Med 2014;2:107-114.

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Hierarchical latency models for dose-time-response associations.

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Hierarchical latency models for dose-time-response associations.

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