Nonlinear progression across the occult transition establishes cancer lethality.

Cancer screening is based upon a linear model of growth and invasion. Yet, early dissemination during the lengthy pre-diagnostic phase suggests that nonlinearity in growth can also occur. Therefore, we quantitatively traced the invisible and visible phases of tumorigenesis in the mammary gland for more than two-thousand tumors. Dynamic mathematical models of the invisible phase revealed an occult checkpoint resulting in nonlinear progression of transformed field cells. We found that expansile fields have increased dwell time at the occult checkpoint resulting in a large reservoir of image detectable precursors prior to invasion. In contrast, slowly proliferating lesions disseminate early and then transition rapidly through an occult checkpoint in a process we term nascent lethality. Our data illustrate how nonlinear growth across an occult checkpoint can account for a paradoxical increase in early-stage cancer detection without a dramatic reduction in metastatic burden. Highlights: Growth during the invisible phase of tumorigenesis is a nonlinear processField size and field growth rate are uncoupled from metastatic potentialOccult transition rates vary by genotypeNascent lethal lesions are currently undetectable.

A review of bat hibernacula across the western United States: Implications for white-nose syndrome surveillance and management.

Efforts to conserve bats in the western United States have long been impeded by a lack of information on their winter whereabouts, particularly bats in the genus Myotis. The recent arrival of white-nose syndrome in western North America has increased the urgency to characterize winter roost habitats in this region. We compiled 4,549 winter bat survey records from 2,888 unique structures across 11 western states. Myotis bats were reported from 18.5% of structures with 95% of aggregations composed of ≤10 individuals. Only 11 structures contained ≥100 Myotis individuals and 6 contained ≥500 individuals. Townsend's big-eared bat (Corynorhinus townsendii) were reported from 38% of structures, with 72% of aggregations composed of ≤10 individuals. Aggregations of ≥100 Townsend's big-eared bats were observed at 41 different caves or mines across 9 states. We used zero-inflated negative binomial regression to explore biogeographic patterns of winter roost counts. Myotis counts were greater in caves than mines, in more recent years, and in more easterly longitudes, northerly latitudes, higher elevations, and in areas with higher surface temperatures and lower precipitation. Townsend's big-eared bat counts were greater in caves, during more recent years, and in more westerly longitudes. Karst topography was associated with higher Townsend's big-eared bat counts but did not appear to influence Myotis counts. We found stable or slightly-increasing trends over time in counts for both Myotis and Townsend's big-eared bats from 82 hibernacula surveyed ≥5 winters since 1990. Highly-dispersed winter roosting of Myotis in the western USA complicates efforts to monitor population trends and impacts of disease. However, our results reveal opportunities to monitor winter population status of Townsend's big-eared bats across this region.