Patient-derived xenografts undergo murine-specific tumor evolution

Patient-derived xenografts (PDXs) have become a prominent cancer model system, as they are presumed to faithfully represent the genomic features of primary tumors. Here we monitored the dynamics of copy number alterations (CNAs) in 1,110 PDX samples across 24 cancer types. We observed rapid accumulation of CNAs during PDX passaging, often due to selection of pre-existing minor clones. CNA acquisition in PDXs was correlated with the tissue-specific levels of aneuploidy and genetic heterogeneity observed in primary tumors. However, the particular CNAs acquired during PDX passaging differed from those acquired during tumor evolution in patients. Several CNAs recurrently observed in primary tumors gradually disappeared in PDXs, indicating that events undergoing positive selection in humans can become dispensable during propagation in mice. Importantly, the genomic stability of PDXs was associated with their response to chemotherapy and targeted drugs. These findings have important implications for PDX-based modeling of human cancer

Willingness to act upon beliefs about 'treatment as prevention' among Australian gay and bisexual men

HIV 'treatment as prevention' (TasP) is highly effective in reducing HIV transmission in serodiscordant couples. There has been little examination of gay and bisexual men's attitudes towards TasP, particularly regarding men's willingness to act on beliefs about TasP. We conducted an online cross-sectional survey of Australian men in late 2012 to investigate knowledge and beliefs about new developments in HIV prevention. Amongst 839 men (mean age 39.5 years), men tended to disagree that TasP was sufficiently effective to justify reduced condom use, although HIV-positive men had more favourable attitudes. Only a minority of men were aware of any evidence for TasP; and one-quarter incorrectly believed that evidence for the effectiveness of TasP already existed for the homosexual population. One-fifth (20.5%) of men reported that they would be willing to have condomless anal intercourse with an opposite-status sexual partner when the HIV-positive partner was taking HIV treatments. Factors independently associated with such willingness were: HIV-positive serostatus, reporting any serodiscordant or serononconcordant condomless anal intercourse with a regular male partner in the previous six months, reporting any condomless anal intercourse with a casual male partner in the previous six months, and having greater beliefs in the effectiveness of TasP. This indicated that the men most willing to rely on TasP to prevent transmission were already engaging in higher risk practices. Biomedical HIV prevention represents a rapidly changing environment with new research as well as community and policy responses emerging at a fast pace. For men with serodiscordant sexual partners to successfully apply TasP to reducing transmission risk, more support and education is needed to enable better utilisation of TasP in specific relational and sexual contexts

A cortical motor nucleus drives the basal ganglia-recipient thalamus in singing birds

The pallido-recipient thalamus transmits information from the basal ganglia to the cortex and is critical for motor initiation and learning. Thalamic activity is strongly inhibited by pallidal inputs from the basal ganglia, but the role of nonpallidal inputs, such as excitatory inputs from cortex, remains unclear. We simultaneously recorded from presynaptic pallidal axon terminals and postsynaptic thalamocortical neurons in a basal ganglia–recipient thalamic nucleus that is necessary for vocal variability and learning in zebra finches. We found that song-locked rate modulations in the thalamus could not be explained by pallidal inputs alone and persisted following pallidal lesion. Instead, thalamic activity was likely driven by inputs from a motor cortical nucleus that is also necessary for singing. These findings suggest a role for cortical inputs to the pallido-recipient thalamus in driving premotor signals that are important for exploratory behavior and learning.National Institutes of Health (U.S.) (Grant R01DC009183)National Institutes of Health (U.S.) (Grant K99NS067062)Damon Runyon Cancer Research Foundation (Postdoctoral Fellowship)Charles A. King Trust (Postdoctoral Fellowship

Prevalence of Same-Sex Sexual Behavior and Associated Characteristics among Low-Income Urban Males in Peru

Peru has a concentrated HIV epidemic in which men who have sex with men are particularly vulnerable. We describe the lifetime prevalence of same-sex sexual contact and associated risk behaviors of men in Peru's general population, regardless of their sexual identity.A probability sample of males from low-income households in three Peruvian cities completed an epidemiologic survey addressing their sexual risk behavior, including sex with other men. Serum was tested for HSV-2, HIV, and syphilis. Urine was tested for chlamydia and gonorrhea. A total of 2,271 18-30 year old men and women were contacted, of whom 1,645 (72.4%) agreed to participate in the study. Among the sexually experienced men surveyed, 15.2% (85/558, 95% CI: 12.2%-18.2%) reported a history of sex with other men. Men ever reporting sex with men (MESM) had a lower educational level, had greater numbers of sex partners, and were more likely to engage in risk behaviors including unprotected sex with casual partners, paying for or providing compensated sex, and using illegal drugs. MESM were also more likely to have had previous STI symptoms or a prior STI diagnosis, and had a greater prevalence of HSV-2 seropositivity.Many low-income Peruvian men have engaged in same-sex sexual contact and maintain greater behavioral and biological risk factors for HIV/STI transmission than non-MESM. Improved surveillance strategies for HIV and STIs among MESM are necessary to better understand the epidemiology of HIV in Latin America and to prevent its further spread

Integrating data types to estimate spatial patterns of avian migration across the Western Hemisphere

For many avian species, spatial migration patterns remain largely undescribed, especially across hemispheric extents. Recent advancements in tracking technologies and high-resolution species distribution models (i.e., eBird Status and Trends products) provide new insights into migratory bird movements and offer a promising opportunity for integrating independent data sources to describe avian migration. Here, we present a three-stage modeling framework for estimating spatial patterns of avian migration. First, we integrate tracking and band re-encounter data to quantify migratory connectivity, defined as the relative proportions of individuals migrating between breeding and nonbreeding regions. Next, we use estimated connectivity proportions along with eBird occurrence probabilities to produce probabilistic least-cost path (LCP) indices. In a final step, we use generalized additive mixed models (GAMMs) both to evaluate the ability of LCP indices to accurately predict (i.e., as a covariate) observed locations derived from tracking and band re-encounter data sets versus pseudo-absence locations during migratory periods and to create a fully integrated (i.e., eBird occurrence, LCP, and tracking/band re-encounter data) spatial prediction index for mapping species-specific seasonal migrations. To illustrate this approach, we apply this framework to describe seasonal migrations of 12 bird species across the Western Hemisphere during pre- and postbreeding migratory periods (i.e., spring and fall, respectively). We found that including LCP indices with eBird occurrence in GAMMs generally improved the ability to accurately predict observed migratory locations compared to models with eBird occurrence alone. Using three performance metrics, the eBird + LCP model demonstrated equivalent or superior fit relative to the eBird-only model for 22 of 24 species–season GAMMs. In particular, the integrated index filled in spatial gaps for species with over-water movements and those that migrated over land where there were few eBird sightings and, thus, low predictive ability of eBird occurrence probabilities (e.g., Amazonian rainforest in South America). This methodology of combining individual-based seasonal movement data with temporally dynamic species distribution models provides a comprehensive approach to integrating multiple data types to describe broad-scale spatial patterns of animal movement. Further development and customization of this approach will continue to advance knowledge about the full annual cycle and conservation of migratory birds

2019 update of the WSES guidelines for management of Clostridioides (Clostridium) difficile infection in surgical patients

In the last three decades, Clostridium difficile infection (CDI) has increased in incidence and severity in many countries worldwide. The increase in CDI incidence has been particularly apparent among surgical patients. Therefore, prevention of CDI and optimization of management in the surgical patient are paramount. An international multidisciplinary panel of experts from the World Society of Emergency Surgery (WSES) updated its guidelines for management of CDI in surgical patients according to the most recent available literature. The update includes recent changes introduced in the management of this infection.Peer reviewe

Time domains of the hypoxic ventilatory response in ectothermic vertebrates

Over a decade has passed since Powell et al. (Respir Physiol 112:123–134, 1998) described and defined the time domains of the hypoxic ventilatory response (HVR) in adult mammals. These time domains, however, have yet to receive much attention in other vertebrate groups. The initial, acute HVR of fish, amphibians and reptiles serves to minimize the imbalance between oxygen supply and demand. If the hypoxia is sustained, a suite of secondary adjustments occur giving rise to a more long-term balance (acclimatization) that allows the behaviors of normal life. These secondary responses can change over time as a function of the nature of the stimulus (the pattern and intensity of the hypoxic exposure). To add to the complexity of this process, hypoxia can also lead to metabolic suppression (the hypoxic metabolic response) and the magnitude of this is also time dependent. Unlike the original review of Powell et al. (Respir Physiol 112:123–134, 1998) that only considered the HVR in adult animals, we also consider relevant developmental time points where information is available. Finally, in amphibians and reptiles with incompletely divided hearts the magnitude of the ventilatory response will be modulated by hypoxia-induced changes in intra-cardiac shunting that also improve the match between O2 supply and demand, and these too change in a time-dependent fashion. While the current literature on this topic is reviewed here, it is noted that this area has received little attention. We attempt to redefine time domains in a more ‘holistic’ fashion that better accommodates research on ectotherms. If we are to distinguish between the genetic, developmental and environmental influences underlying the various ventilatory responses to hypoxia, however, we must design future experiments with time domains in mind

WSES guidelines for management of Clostridium difficile infection in surgical patients

In the last two decades there have been dramatic changes in the epidemiology of Clostridium difficile infection (CDI), with increases in incidence and severity of disease in many countries worldwide. The incidence of CDI has also increased in surgical patients. Optimization of management of C difficile, has therefore become increasingly urgent. An international multidisciplinary panel of experts prepared evidenced-based World Society of Emergency Surgery (WSES) guidelines for management of CDI in surgical patients.Peer reviewe

WSES guidelines for management of Clostridium difficile infection in surgical patients

In the last two decades there have been dramatic changes in the epidemiology of Clostridium difficile infection (CDI), with increases in incidence and severity of disease in many countries worldwide. The incidence of CDI has also increased in surgical patients. Optimization of management of C difficile, has therefore become increasingly urgent. An international multidisciplinary panel of experts prepared evidenced-based World Society of Emergency Surgery (WSES) guidelines for management of CDI in surgical patients