Nonlinear progression during the occult transition establishes cancer lethality.

Cancer screening is based upon a linear model of neoplastic growth and malignant progression. Yet, historical observations suggest that malignant progression is uncoupled from growth which may explain the paradoxical increase in early-stage breast cancer detection without a dramatic reduction in metastatic burden. Here we lineage trace millions of genetically transformed field cells and thousands of screen detectable and symptomatic tumors using a cancer rainbow mouse model of HER2+ breast cancer. Transition rates from field cell to screen detectable tumor and then to symptomatic tumors were estimated from a dynamical model of tumor development. Field cells are orders of magnitude less likely to transition to a screen detectable tumor than the subsequent transition of a screen detectable tumor to a symptomatic tumor. Our model supports a critical occult transition in tumor development during which time a transformed cell becomes a bona fide neoplasm. Lineage tracing and test-by-transplantation reveals that nonlinear progression during or prior to the occult transition gives rise to nascent lethal cancers at screen detection. Simulations illustrate how occult transition rates are a critical determinant of tumor growth and malignancy in the lifetime of a host. Our data provides direct experimental evidence that cancers can deviate from the predictable linear progression model foundational to current screening paradigms.

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.