BAY 43-9006 is a novel dual-action Raf kinase and vascular endothelial growth factor receptor (VEGFR) inhibitor that targets tumour cell proliferation angiogenesis. This Phase I study was undertaken to determine the safety profile, maximum tolerated dose (MTD), dose-limiting toxicities (DLTs), pharmacokinetics, response profile of oral in patients with advanced, refractory solid tumours. administered daily for repeated cycles 21 days on/7 off. A total 44 were enrolled at doses from 50 800 mg...

Physiological stress may result in short-term benefits to organismal performance, but also long-term costs health or longevity. Yet, we lack an understanding of the variation hormone levels (i.e. glucocorticoids) that exist within and across species. Here, present comparative analyses link primary most mammals cortisol) metabolic rate. We show baseline concentrations plasma cortisol vary with mass-specific rate among cortisol-dominant mammals, both elevated scale predictably body mass. The...

Parasites, by definition, extract energy from their hosts and thus affect trophic food web dynamics even when the parasite may have limited effects on host population size. We studied energetic costs of mange (Sarcoptes scabiei) in wolves (Canis lupus) using thermal cameras to estimate heat losses associated with compromised insulation during winter. combined field data known, naturally infected a set captive shaved patches fur as positive control simulate mange-induced hair loss. predict...

Processes associated with recovery of survivors are understudied components wildlife infectious diseases. White-nose syndrome (WNS) in bats provides an opportunity to study disease survivors, understand implications for individual energetics, and assess the role pathogen transmission. We documented temporal patterns from WNS little brown (Myotis lucifugus) following hibernation test hypotheses that: (1) wing structure matches a rapid time scale (i.e. approximately 30 days) suggested by data...

<i>Objectives:</i> The aim of this study was to evaluate a short-term non-specific home-based 6-week cognitive training for its effect on neuropsychological deficits and depression. <i>Subjects Methods:</i> Cognitive affective abilities patients with MS were compared healthy controls using an identical test battery. Re-testing performed after 6 weeks training. <i>Results:</i> Patients already showed at baseline. resulted in significant improvement several...

Abstract Caves and other subterranean features provide unique environments for many species. The importance of cave microclimate is particularly relevant at temperate latitudes where bats make seasonal use caves hibernation. White‐nose syndrome (WNS), a fungal disease that has devastated populations hibernating across eastern central North America, brought renewed interest in bat hibernation hibernaculum conditions. A recent review synthesized current understanding climatology, exploring the...

Abstract In multihost disease systems, differences in mortality between species may reflect variation host physiology, morphology, and behavior. systems where the pathogen can persist environment, microclimate conditions, adaptation of to these also impact mortality. White‐nose syndrome (WNS) is an emerging hibernating bats caused by environmentally persistent fungus, Pseudogymnoascus destructans . We assessed effects body mass, torpid metabolic rate, evaporative water loss, hibernaculum...

White-nose syndrome (WNS) has decimated hibernating bat populations across eastern and central North America for over a decade. Disease severity is driven by the interaction between characteristics, cold-loving fungal agent, hibernation environment. While we further improve energetics models, have yet to examine how spatial heterogeneity in host traits linked survival this disease system. Here, develop predictive models of body mass little brown myotis (Myotis lucifugus) reassess previous...

Abstract Genetic differentiation in aquatic systems is often driven by geographic distance (isolation distance) due to the linear and hierarchical distribution of populations, but habitat fragmentation exacerbates this effect decreasing population connectivity, leading isolation resistance. Stronghold populations Kentucky Arrow Darter ( Etheostoma spilotum ) South Fork River system within Daniel Boone National Forest eastern Kentucky, USA have a high structure not explained alone. Higher...

Hibernation consists of extended durations torpor interrupted by periodic arousals. The 'dehydration hypothesis' proposes that hibernating mammals arouse to replenish water lost through evaporation during torpor. Arousals are energetically expensive, and increased arousal frequency can alter survival throughout hibernation. Yet we lack a means assess the effect evaporative loss (EWL), determined animal physiology hibernation microclimate, on bout duration subsequent survival. White-nose...

Abstract Hibernation is widespread among mammals in a variety of environmental contexts. However, few experimental studies consider interspecific comparisons, which may provide insight into general patterns hibernation strategies. We studied 13 species free-living bats, including populations spread over thousands kilometers and diverse habitats. measured torpid metabolic rate (TMR) evaporative water loss (two key parameters for understanding energetics) across range temperatures. There was...

Long-term development of psychological deficits in disability-free early multiple sclerosis (MS) was evaluated 27 female patients over a period 7 years and compared with healthy controls. Physical cognitive parameters deteriorated significantly but not depression scores. In particular, the self-assessed somatic complaints remained non-similar between This indicates that although is clinically relevant frequent MS, contrast to cognition it related physical disease progression.

Dive duration in air-breathing vertebrates is thought to be constrained by the volume of oxygen stored body and rate at which it consumed (i.e., "oxygen store/usage hypothesis"). The mass-dependence dive among endothermic largely supportive this model, but previous analyses ectothermic show no such mass-dependence. Here we that both endotherms ectotherms support hypothesis after accounting for well-established effects temperature on consumption rates. Analyses mass dependence 181 species 29...

Abstract Central-place foragers can be constrained by the distance between habitats. When an organism relies on a central place for thermal refuge, to food resources potentially constrain foraging behavior. We investigated effect of refuges and forage patches cold-intolerant marine mammal, Florida manatee (Trichechus manatus latirostris), duration. tested alternative hypotheses time minimization energy maximization as response also determined if manatees mitigate constraints with increased...

Climate change and disease are threats to biodiversity that may compound interact with one another in ways difficult predict. White-nose syndrome (WNS), caused by a cold-loving fungus (Pseudogymnoascus destructans), has had devastating impacts on North American hibernating bats, impact severity been linked hibernaculum microclimate conditions. As WNS spreads across the continent climate conditions change, anticipating these stressors’ combined improve conservation outcomes for bats. We build...

White-nose syndrome (WNS) is an infectious disease that disrupts hibernation in bats, leading to premature exhaustion of fat stores. Though we know WNS does impact reproduction hibernating female are unsure how these impacts exacerbated by local climate factors. We compiled data from four southeastern U.S. states and used generalized linear mixed effects models compare WNS, pre-hibernation variables, winter duration on the number reproductive females species across range susceptibility....

3049 Background:BAY 43–9006 (BAY) is a novel signal transduction inhibitor that prevents tumor cell proliferation and angiogenesis through blockade of the Raf/MEK/ERK pathway at level Raf kinase receptor tyrosine kinases VEGFR-2 PDGFR-β. Previous single-agent phase I studies show BAY well tolerated, with manageable reversible side effects, most commonly hand-foot skin (HFS) reaction, rash, fatigue, diarrhea. This study was initiated to determine safety pharmacokinetics (PK) in combination...

The aim of the GARPTools package is to provide tools prepare data for input into desktop version genetic algorithm rule‐set prediction (GARP), evaluation accuracy output models, and summary/examination environmental coverages used in GARP rule sets best models an experiment. a software biodiversity ecological research that allows user predict analyze wild species' geographic distributions. presence‐background potential distributions through iterative process training testing occurs...

Brucellosis, caused by bacteria in the genus Brucella, is an infectious zoonosis affecting animals and humans worldwide. Free-ranging Rocky Mountain elk ( Cervus canadensis nelsoni) bison Bison bison) Greater Yellowstone Ecosystem (areas of southwestern Montana, eastern Idaho, northwestern Wyoming, US) are self-sustaining reservoirs bovine brucellosis Brucella abortus) considered primary source livestock infections. It has been hypothesized that Brucella-exposed might have different...