The Age-Specific Force of Natural Selection and Walls of Death

W. D. Hamilton's celebrated formula for the age-specific force of natural selection furnishes predictions for senescent mortality due to mutation accumulation, at the price of reliance on a linear approximation. Applying to Hamilton's setting the full non-linear demographic model for mutation accumulation of Evans et al. (2007), we find surprising differences. Non-linear interactions cause the collapse of Hamilton-style predictions in the most commonly studied case, refine predictions in other cases, and allow Walls of Death at ages before the end of reproduction. Haldane's Principle for genetic load has an exact but unfamiliar generalization.Comment: 27 page

Vital Rates from the Action of Mutation Accumulation

New models for evolutionary processes of mutation accumulation allow hypotheses about the age-specificity of mutational effects to be translated into predictions of heterogeneous population hazard functions. We apply these models to questions in the biodemography of longevity, including proposed explanations of Gompertz hazards and mortality plateaus

Dataset for: A Bayesian approach to sequential meta-analysis

As evidence accumulates within a meta-analysis, it is desirable to determine when the results could be considered conclusive to guide systematic review updates and future trial designs. Adapting sequential testing methodology from clinical trials for application to pooled meta-analytic effect size estimates appears well suited for this objective. In this paper we describe a Bayesian sequential meta-analysis method, in which an informative heterogeneity prior is employed and stopping rule criteria are applied directly to the posterior distribution for the treatment effect parameter. Using simulation studies, we examine how well this approach performs under different parameter combinations by monitoring the proportion of sequential meta-analyses that reach incorrect conclusions (to yield error rates), the number of studies required to reach conclusion, and the resulting parameter estimates. By adjusting the stopping rule thresholds, the overall error rates can be controlled within the target levels and are no higher than those of alternative frequentist and semi-Bayes methods for the majority of the simulation scenarios. To illustrate the potential application of this method, we consider two contrasting meta-analyses using data from the Cochrane Library and compare the results of employing different sequential methods, while examining the effect of the heterogeneity prior in the proposed Bayesian approach