This paper develops a method for appraising health status in elderly people. A frailty index was defined as the proportion of accumulated deficits (symptoms, signs, functional impairments, and laboratory abnormalities). It serves as an individual state variable, reflecting severity of illness and proximity to death. In a representative database of elderly Canadians we found that deficits accumulated at 3% per year, and show a gamma distribution, typical for systems with redundant components that can be used in case of failure of a given subsystem. Of note, the slope of the index is insensitive to the individual nature of the deficits, and serves as an important prognostic factor for life expectancy. The formula for estimating an individual's life span given the frailty index value is presented. For different patterns of cognitive impairments the average within-group index value increases with the severity of the cognitive impairment, and the relative variability of the index is significantly reduced. Finally, the statistical distribution of the frailty index sharply differs between well groups (gamma distribution) and morbid groups (normal distribution). This pattern reflects an increase in uncompensated deficits in impaired organisms, which would lead to illness of various etiologies, and ultimately to increased mortality. The accumulation of deficits is as an example of a macroscopic variable, i.e., one that reflects general properties of aging at the level of the whole organism rather than any given functional deficiency. In consequence, we propose that it may be used as a proxy measure of aging.

/pdf/accumulation-of-deficits-as-a-proxy-measure-of-aging-4na99r1itb.pdf

Accumulation of deficits as a proxy measure of aging.

Preface. 1. Introduction. 2. Observable Queues. 3. Unobservable Queues. 4. Priorities. 5. Reneging and Jockeying. 6. Schedules and Retrials. 7. Competition Among Servers. 8. Service Rate Decisions. Index.

/pdf/to-queue-or-not-to-queue-equilibrium-behavior-in-queueing-5c9jnzn4em.pdf

To Queue or Not to Queue: Equilibrium Behavior in Queueing Systems

We introduce a new Empirical Bayes approach for large-scale hypothesis testing, including estimating false discovery rates (FDRs), and effect sizes. This approach has two key differences from existing approaches to FDR analysis. First, it assumes that the distribution of the actual (unobserved) effects is unimodal, with a mode at 0. This "unimodal assumption" (UA), although natural in many contexts, is not usually incorporated into standard FDR analysis, and we demonstrate how incorporating it brings many benefits. Specifically, the UA facilitates efficient and robust computation-estimating the unimodal distribution involves solving a simple convex optimization problem-and enables more accurate inferences provided that it holds. Second, the method takes as its input two numbers for each test (an effect size estimate and corresponding standard error), rather than the one number usually used ($p$ value or $z$ score). When available, using two numbers instead of one helps account for variation in measurement precision across tests. It also facilitates estimation of effects, and unlike standard FDR methods, our approach provides interval estimates (credible regions) for each effect in addition to measures of significance. To provide a bridge between interval estimates and significance measures, we introduce the term "local false sign rate" to refer to the probability of getting the sign of an effect wrong and argue that it is a superior measure of significance than the local FDR because it is both more generally applicable and can be more robustly estimated. Our methods are implemented in an R package ashr available from http://github.com/stephens999/ashr.

/pdf/false-discovery-rates-a-new-deal-1qnrlx0bt9.pdf

False discovery rates: a new deal.

This book provides a theoretical background of branching processes and discusses their biological applications. Branching processes are a well-developed and powerful set of tools in the field of applied probability. The range of applications considered includes molecular biology, cellular biology, human evolution and medicine. The branching processes discussed include Galton-Watson, Markov, Bellman-Harris, Multitype, and General Processes. As an aid to understanding specific examples, two introductory chapters, and two glossaries are included that provide background material in mathematics and in biology. The book will be of interest to scientists who work in quantitative modeling of biological systems, particularly probabilists, mathematical biologists, biostatisticians, cell biologists, molecular biologists, and bioinformaticians. The authors are a mathematician and cell biologist who have collaborated for more than a decade in the field of branching processes in biology for this new edition.This second expanded edition adds new material published during the last decade, with nearly 200 new references. More material has been added on infinitely-dimensional multitype processes, including the infinitely-dimensional linear-fractional case. Hypergeometric function treatment of the special case of the Griffiths-Pakes infinite allele branching process has also been added. There are additional applications of recent molecular processes and connections with systems biology are explored, and a new chapter on genealogies of branching processes and their applications.Reviews of First Edition:"This is a significant book on applications of branching processes in biology, and it is highly recommended for those readers who are interested in the application and development of stochastic models, particularly those with interests in cellular and molecular biology." (Siam Review, Vol. 45 (2), 2003)This book will be very interesting and useful for mathematicians, statisticians and biologists as well, and especially for researchers developing mathematical methods in biology, medicine and other natural sciences. (Short Book Reviews of the ISI, Vol. 23 (2), 2003)

/pdf/branching-processes-in-biology-2ta0fa9sgq.pdf

Branching processes in biology

In a randomized experiment comparing two treatments, there is interference between units if applying the treatment to one unit may affect other units. Interference implies that treatment effects are not comparisons of two potential responses that a unit may exhibit, one under treatment and the other under control, but instead are inherently more complex. Interference is common in social settings where people communicate, compete, or spread disease; in studies that treat one part of an organism using a symmetrical part as control; in studies that apply different treatments to the same organism at different times; and in many other situations. Available statistical tools are limited. For instance, Fisher's sharp null hypothesis of no treatment effect implicitly entails no interference, and so his randomization test may be used to test no effect, but conventional ways of inverting the test to obtain confidence intervals, say for an additive effect, are not applicable with interference. Another commonly used ...

Interference Between Units in Randomized Experiments

Introduction to Probability and its Applications. By R. L. Scheaffer. ISBN 0 534 91970 7. PWS–Kent, Boston, 1990. 364 pp. £16.95.

Introduction to Probability and its Applications

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Introduction to Probability and its Applications