Modifications of the EM algorithm for survival influenced by an unobserved stochastic process

AbstractLet Y=(Yt)t≥0) be an unobserved random process which influences the distribution of a random variable T which can be interpreted as the time to failure. When a conditional hazard rate corresponding to T is a quadratic function of covariates, Y, the marginal survival function may be represented by the first two moments of the conditional distribution of Y among survivors. Such a representation may not have an explicit parametric form. This makes it difficult to use standard maximum likelihood procedures to estimate parameters - especially for censored survival data. In this paper a generalization of the EM algorithm for survival problems with unobserved, stochastically changing covariates is suggested. It is shown that, for a general model of the stochastic failure model, the smoothing estimates of the first two moments of Y are of a specific form which facilitates the EM type calculations. Properties of the algorithm are discussed

A Model for Simulating Life Histories of the Elderly: Model Design and Implementation Plans

This paper provides a strategy for the development of a model of life-cycle change in functional status, economic well-being, and family composition, with particular attention to persons aged 65 and older. The overall goal is to use the model as the basis for individual-level projections of the later life cycle, that is, microsimulation. Specifically, the scope of the project includes: 1. Specification and estimation of equations for the dynamics of functional status, nursing home occupancy, income and death among those aged 65+, using data from the 1982, 1984, and 1989 National Long-Term Care Survey (NLTCS) linked to Medicare data for 1982-1993, based on extensions of the Grade of Membership (GoM) framework; 2. Developing equations for year-to-year income streams, determined jointly with changes of marital status, for all ages represented in the cohorts to be simulated; 3. Estimating parameters governing the dynamics of family composition (existence and characteristics of spouse, parent[s] and child[ren]); 4. Integrating the results of the above modeling efforts in a microsimulation computer program with the capacity to dynamically simulate life histories, focussing on the elderly population; 5. Validating the model by comparing its results to actual data where possible, analyzing uncertainty attached to the output from the microsimulation model, and conducting sensitivity analyses using alternative assumptions regarding trends in model parameters; and 6. Using microsimulation, producing disaggregated projections of the elderly population and its characteristics, for example cohort profiles of active life expectancy, or comparisons over time in the health, family structure and economic well-being of the oldest-old

SOD2 polymorphisms: unmasking the effect of polymorphism on splicing

BACKGROUND: The SOD2 gene encodes an antioxidant enzyme, mitochondrial superoxide dismutase. SOD2 polymorphisms are of interest because of their potential roles in the modulation of free radical-mediated macromolecular damage during aging. RESULTS: We identified a new splice variant of SOD2 in human lymphoblastoid cell lines (LCLs). The alternatively spliced product was originally detected by exon trapping of a minigene in order to examine the consequences of an intronic polymorphism found upstream of exon 4 (nucleotide 8136, 10T vs 9T). Examination of the transcripts derived from the endogenous loci in five LCLs with or without the intron 3 polymorphism revealed low levels of an in-frame deletion of exon 4 that were different from those detected by the exon trap assay. This suggested that exon trapping of the minigene unmasked the effect of the 10T vs 9T polymorphism on the splicing of the adjacent exon. We also determined the frequencies of single nucleotide polymorphisms in a sample of US African-Americans and non-African-Americans ages 65 years and older who participated in the 1999 wave of the National Long Term Care Survey (NLTCS). Particularly striking differences between African-Americans and non-African-Americans were found for the frequencies of genotypes at the 10T/9T intron 3 polymorphism. CONCLUSION: Exon trapping can unmask in vitro splicing differences caused by a 10T/9T intron 3 polymorphism. Given the recent evidence that SOD2 is in a region on chromosome 6 linked to susceptibility to hypertension, it will be of interest to investigate possible associations of this polymorphism with cardiovascular disorders

Recent trends in chronic disease, impairment and disability among older adults in the United States

<p>Abstract</p> <p>Background</p> <p>To examine concurrent prevalence trends of chronic disease, impairment and disability among older adults.</p> <p>Methods</p> <p>We analyzed the 1998, 2004 and 2008 waves of the Health and Retirement Study, a nationally representative survey of older adults in the United States, and included 31,568 community dwelling adults aged 65 and over. Measurements include: prevalence of chronic diseases including hypertension, heart disease, stroke, diabetes, cancer, chronic lung disease and arthritis; prevalence of impairments, including impairments of cognition, vision, hearing, mobility, and urinary incontinence; prevalence of disability, including activities of daily living (ADLs) and instrumental activities of daily living (IADLs).</p> <p>Results</p> <p>The proportion of older adults reporting no chronic disease decreased from 13.1% (95% Confidence Interval [CI], 12.4%-13.8%) in 1998 to 7.8% (95% CI, 7.2%-8.4%) in 2008, whereas the proportion reporting 1 or more chronic diseases increased from 86.9% (95% CI, 86.2%-89.6%) in 1998 to 92.2% (95% CI, 91.6%-92.8%) in 2008. In addition, the proportion reporting 4 or more diseases increased from 11.7% (95% CI, 11.0%-12.4%) in 1998 to 17.4% (95% CI, 16.6%-18.2%) in 2008. The proportion of older adults reporting no impairments was 47.3% (95% CI, 46.3%-48.4%) in 1998 and 44.4% (95% CI, 43.3%-45.5%) in 2008, whereas the proportion of respondents reporting 3 or more was 7.2% (95% CI, 6.7%-7.7%) in 1998 and 7.3% (95% CI, 6.8%-7.9%) in 2008. The proportion of older adults reporting any ADL or IADL disability was 26.3% (95% CI, 25.4%-27.2%) in 1998 and 25.4% (95% CI, 24.5%-26.3%) in 2008.</p> <p>Conclusions</p> <p>Multiple chronic disease is increasingly prevalent among older U.S. adults, whereas the prevalence of impairment and disability, while substantial, remain stable.</p

Methods for Evaluating the Heterogeneity of Aging Processes in Human Populations Using Vital Statistics Data: Explaining the Black/White Mortality Crossover by a Model of Mortality Selection

The progress of physiological aging processes in human populations is often studied by analyzing the age trajectory of total and cause specific mortality rates under the assumption that the rate of increase in the risk of death indexes the average rate of change in the physiology of the individuals comprising the population. Unfortunately, such efforts have usually assumed that the age trajectory of the average mortality rate is the same as the age trajectory of any given individual’s risk of death—equivalent to the assumption that all individuals in the population have the identical rate of aging. In this paper, we present a model that permits the evalua­tion of the aging process of individuals from the age trajectory of mortality rates in the population by a. positing a model of the distribution of individual constitutional differences in the age trajectory of mortality risks, and b. adjusting the population mortality rates under the model of heterogeneity to retrieve the individual risks.This model is applied to human mortality data from the U.S. Black and White populations for the period 1935 to 1975. This example was selected because of the observation of a mortality crossover (Blacks having relatively lower mortality rates) about age 75. The crossover could be explained under the proposed model of population heterogeneity and differential mortality selection. The implications of the model for estimating the heterogeneity of aging processes for individuals from human population data are discussed as well as implications for our existing perception of the human aging mechanism