Browsing by Subject "q-bio.PE"
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Item Open Access Age-Associated Disorders As A Proxy Measure Of Biological Age: Findings From the NLTCS Data(2017-06-07) Kulminski, A; Yashin, A; Ukraintseva, S; Akushevich, I; Arbeev, K; Land, K; Manton, KBackground: The relative contribution of different aging-associated processes to the age phenotype may differ among individuals, creating variability in aging manifestations among age-peers. Capturing this variability can significantly advance understanding the aging and mortality. An index of age-associated health disorders (deficits), called a "frailty index" (FI), appears to be a promising characteristic of such processes. In this study we address the connections of the FI with age focusing on disabled individuals who might be at excessive risk of frailty. Methods: The National Long Term Care Survey (NLTCS) assessed health and functioning of the U.S. elderly in 1982, 1984, 1989, 1994, and 1999. Detailed information for our sample was assessed from about 26,700 interviews. The individual FI is defined as a proportion of deficits for a given person. We perform cross-sectional empirical analysis of the FI age-patterns. Results: FI in the NLTCS exhibits accelerated (quadratic) increase with age. Deficits might accumulate faster among the elderly who, at younger ages, had a low mean FI ("healthy" group) than a high FI ("disabled" group). Age-patterns for "healthy" and "disabled" groups converge at advanced ages. The rate of deficit accumulation is sex-sensitive. Convergence of the (sex-specific) FI for "healthy" and "disabled" groups in later ages determines biological age limits, associated with given levels of health-maintenance in the society, which correspond to 109.4 years for females and 92.5 years for males. Conclusions: The FI can be employed as a measure of biological age and population heterogeneity for modeling aging processes and mortality in elderly individuals.Item Open Access Bayesian co-estimation of selfing rate and locus-specific mutation rates for a partially selfing population(2017-07-02) Redelings, Benjamin D; Kumagai, Seiji; Wang, Liuyang; Tatarenkov, Andrey; Sakai, Ann K; Weller, Stephen G; Culley, Theresa M; Avise, John C; Uyenoyama, Marcy KWe present a Bayesian method for characterizing the mating system of populations reproducing through a mixture of self-fertilization and random outcrossing. Our method uses patterns of genetic variation across the genome as a basis for inference about pure hermaphroditism, androdioecy, and gynodioecy. We extend the standard coalescence model to accommodate these mating systems, accounting explicitly for multilocus identity disequilibrium, inbreeding depression, and variation in fertility among mating types. We incorporate the Ewens Sampling Formula (ESF) under the infinite-alleles model of mutation to obtain a novel expression for the likelihood of mating system parameters. Our Markov chain Monte Carlo (MCMC) algorithm assigns locus-specific mutation rates, drawn from a common mutation rate distribution that is itself estimated from the data using a Dirichlet Process Prior (DPP) model. Among the parameters jointly inferred are the population-wide rate of self-fertilization, locus-specific mutation rates, and the number of generations since the most recent outcrossing event for each sampled individual.Item Open Access Frailty Index as a Major Indicator of Aging Processes and Mortality in Elderly: Results From Analyses of the National Long Term Care Survey Data(2017-06-07) Kulminski, A; Yashin, A; Akushevich, I; Ukraintseva, S; Land, K; Arbeev, K; Manton, KTo better understand mortality change with age capturing the variability in individuals' rates of aging, we performed comprehensive analysis of statistical properties of a cumulative index of age-associated disorders (deficits), called a "frailty index" (FI). This index is calculated as the proportion of the health deficits in an individual. It is found, first, that frequency, time-to-death, mortality-rate, and relative-risk-of-death exhibit remarkably similar FI- and age- patterns. Second, the FI, on the one hand, and mortality rate and relative risk, on the other hand, also exhibit similar age patterns with accelerated increase up to oldest-old ages and with subsequent deceleration and even decline. Third, distribution of the FI with time-to-death is sharper than that of age with time-to-death. These and related findings support the conclusion that the FI can describe aging processes and population heterogeneity. We also discuss the ability of the FI to capture physiological processes underlying aging both on individual and population levels.Item Open Access Scaling limits of a model for selection at two scales(2015) Luo, S; Mattingly, JCThe dynamics of a population undergoing selection is a central topic in evolutionary biology. This question is particularly intriguing in the case where selective forces act in opposing directions at two population scales. For example, a fast-replicating virus strain outcompetes slower-replicating strains at the within-host scale. However, if the fast-replicating strain causes host morbidity and is less frequently transmitted, it can be outcompeted by slower-replicating strains at the between-host scale. Here we consider a stochastic ball-and-urn process which models this type of phenomenon. We prove the weak convergence of this process under two natural scalings. The first scaling leads to a deterministic nonlinear integro-partial differential equation on the interval $[0,1]$ with dependence on a single parameter, $\lambda$. We show that the fixed points of this differential equation are Beta distributions and that their stability depends on $\lambda$ and the behavior of the initial data around $1$. The second scaling leads to a measure-valued Fleming-Viot process, an infinite dimensional stochastic process that is frequently associated with a population genetics.