ArticleProceedings of the National Academy of Sciences of the United States of America2026
Hazard curvature makes within-host variability costly for survival.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Tumors, pathogens, and immune responses are increasingly modeled as ecological and evolutionary systems inside hosts. Yet the clinically meaningful endpoint is usually not the trajectory of those internal populations but the fate of the host. In this article a framework is developed that links mechanistic within-host dynamics to outcomes through a hazard map. The framework gives rise to a curvature principle: If the instantaneous hazard is a convex function of a harmful host state, variability in that state is costly: That is, among trajectories with the same temporal mean, the path with least variance minimizes cumulative hazard, and any mean-preserving spread increases it. A local expansion shows that the penalty is set by hazard curvature and temporal variance. We extend the framework to proportional-hazards joint models, where the standard exponential link is convex by construction. This yields a curvature penalty, ½γ
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