Genetic Population Structure of Mule Deer Odocoileus Hemionus Across Montana

We conducted a genetic assessment of mule deer (Odocoileus hemionus) population structure across Montana in an effort to understand dispersal routes across the landscape. To assess genetic structure we genotyped 14 microsatellite loci in 359 individuals sampled primarily within Montana. Smaller samples were included from Wyoming, Colorado and Utah in order to provide a regional context for the levels of population structure observed within Montana. Additionally, we sequenced the control region of the mitochondrial genome of 76 individuals subsampled from our original samples across Montana. To avoid potential influences of a priori population designations, individual based analyses were used to test relatedness across the landscape. Weak isolation by distance characterized mule deer individuals across this region. In addition, we did not detect any evidence of spatial autocorrelation in discrete distance classes as small as 10 km. Female mule deer had higher average individual pairwise genetic distances than males, indicating the presence of a contemporary male bias in dispersal rates. Mitochondrial DNA indicated the potential for either reduced overall or female-specific dispersal between a subset of the sampling regions within Montana. Finally, we were unable to detect a genetic signature of past translocations of mule deer across Montana. Taken together these results indicate that within this landscape mule deer populations are characterized by high levels of connectivity and experience few, if any, barriers to dispersal

Good Animals in Bad Places: Evaluating Landscape Attributes Associated with Elk Vulnerability to Wolf Predation

Vulnerability of prey to predators is heavily influenced by their respective physical and behavioral characteristics; however their interactions with landscape, and climate, collectively termed “environmental vulnerability,” may also assume considerable importance. Little is known about the impact of environmental vulnerability in large mammal systems, where post-encounter vulnerability may assume more importance than encounter probability. This study utilized 18 years of survival and mortality data for radio-collared elk (Cervus elaphus), in concert with abundance, distribution, and habitat use data prior to and following restoration of wolves (Canis lupus) to Yellowstone National Park to evaluate the relationship between environmental attributes and elk mortality. We modeled the odds of mortality for 108 elk in 1257 animal sample intervals from 1991-2009 across a range of environmental conditions and gradients of wolf predation risk to evaluate: 1) The relationship between landscape, habitat, and environmental attributes and elk vulnerability to wolf predation and 2) Changes in the attributes related to elk mortality before and after wolf colonization. In the absence of wolf predation, mortality risk for elk was primarily associated with physical attributes of elk known to influence starvation mortality. Following wolf reintroduction mortality risk was more strongly associated with characteristics of the landscape and climate within an animal’s home range. These environmental influences resulted in substantial changes in distribution and abundance of elk in the study system and suggests environmental heterogeneity may have an important influence on wolf and elk distributions and dynamics

Trends in Causes and Distribution, and Effects of Whitebark Pine Decline on Grizzly Bear Mortality in the Greater Yellowstone Ecosystem

Documented grizzly bear (Ursus arctos) mortalities have been increasing in recent years in the Greater Yellowstone Ecosystem (GYE), due, in part, to increases in bear numbers and range expansion. Previous research has documented that variable seed production of whitebark pine (WBP; Pinus albicaulis), an important fall food, is inversely related to grizzly bear fall mortality.  However, WBP has experienced widespread mortality during the last decade because of mountain pine beetle (Dendroctonus ponderosae) infestations. We investigated trends in causes and distribution of human-caused mortalities for independent-aged (? 2 yrs old) grizzly bears in the GYE during 1975–2012, and the effect of WBP cone production on numbers of fall (> 1 August) mortalities (n = 172) during the period of WBP decline (2000-2012) using Poisson regression. During 1975–1982, 91 percent of mortalities occurred within the Grizzly Bear Recovery Zone and primary causes were poaching/malicious killings and losses related to conflicts with livestock. During the two most recent decades most mortalities were associated with ungulate hunting, usually involving self-defense kills, or anthropogenic sites, and an increasing percentage of mortalities occurred outside the recovery zone. Using predictor variables of cone production, sex, location in or out of the Recovery Zone, and year suggests: 1) annual cone production was still predictive of human-caused fall mortalities, 2) no evidence of a difference in annual numbers of fall mortalities between males and females, and 3) an increase in annual mortalities over the study period, with most of this increase outside the Recovery Zone

Identifying educator behaviours for high quality verbal feedback in health professions education: literature review and expert refinement

Background Health professions education is characterised by work-based learning and relies on effective verbal feedback. However the literature reports problems in feedback practice, including lack of both learner engagement and explicit strategies for improving performance. It is not clear what constitutes high quality, learner-centred feedback or how educators can promote it. We hoped to enhance feedback in clinical practice by distinguishing the elements of an educator’s role in feedback considered to influence learner outcomes, then develop descriptions of observable educator behaviours that exemplify them. Methods An extensive literature review was conducted to identify i) information substantiating specific components of an educator’s role in feedback asserted to have an important influence on learner outcomes and ii) verbal feedback instruments in health professions education, that may describe important educator activities in effective feedback. This information was used to construct a list of elements thought to be important in effective feedback. Based on these elements, descriptions of observable educator behaviours that represent effective feedback were developed and refined during three rounds of a Delphi process and a face-to-face meeting with experts across the health professions and education. Results The review identified more than 170 relevant articles (involving health professions, education, psychology and business literature) and ten verbal feedback instruments in health professions education (plus modified versions). Eighteen distinct elements of an educator’s role in effective feedback were delineated. Twenty five descriptions of educator behaviours that align with the elements were ratified by the expert panel. Conclusions This research clarifies the distinct elements of an educator’s role in feedback considered to enhance learner outcomes. The corresponding set of observable educator behaviours aim to describe how an educator could engage, motivate and enable a learner to improve. This creates the foundation for developing a method to systematically evaluate the impact of verbal feedback on learner performance

Hyperimmune immunoglobulin for hospitalised patients with COVID-19 (ITAC): a double-blind, placebo-controlled, phase 3, randomised trial

BACKGROUND: Passive immunotherapy using hyperimmune intravenous immunoglobulin (hIVIG) to SARS-CoV-2, derived from recovered donors, is a potential rapidly available, specific therapy for an outbreak infection such as SARS-CoV-2. Findings from randomised clinical trials of hIVIG for the treatment of COVID-19 are limited. METHODS: In this international randomised, double-blind, placebo-controlled trial, hospitalised patients with COVID-19 who had been symptomatic for up to 12 days and did not have acute end-organ failure were randomly assigned (1:1) to receive either hIVIG or an equivalent volume of saline as placebo, in addition to remdesivir, when not contraindicated, and other standard clinical care. Randomisation was stratified by site pharmacy; schedules were prepared using a mass-weighted urn design. Infusions were prepared and masked by trial pharmacists; all other investigators, research staff, and trial participants were masked to group allocation. Follow-up was for 28 days. The primary outcome was measured at day 7 by a seven-category ordinal endpoint that considered pulmonary status and extrapulmonary complications and ranged from no limiting symptoms to death. Deaths and adverse events, including organ failure and serious infections, were used to define composite safety outcomes at days 7 and 28. Prespecified subgroup analyses were carried out for efficacy and safety outcomes by duration of symptoms, the presence of anti-spike neutralising antibodies, and other baseline factors. Analyses were done on a modified intention-to-treat (mITT) population, which included all randomly assigned participants who met eligibility criteria and received all or part of the assigned study product infusion. This study is registered with ClinicalTrials.gov, NCT04546581. FINDINGS: From Oct 8, 2020, to Feb 10, 2021, 593 participants (n=301 hIVIG, n=292 placebo) were enrolled at 63 sites in 11 countries; 579 patients were included in the mITT analysis. Compared with placebo, the hIVIG group did not have significantly greater odds of a more favourable outcome at day 7; the adjusted OR was 1·06 (95% CI 0·77–1·45; p=0·72). Infusions were well tolerated, although infusion reactions were more common in the hIVIG group (18·6% vs 9·5% for placebo; p=0·002). The percentage with the composite safety outcome at day 7 was similar for the hIVIG (24%) and placebo groups (25%; OR 0·98, 95% CI 0·66–1·46; p=0·91). The ORs for the day 7 ordinal outcome did not vary for subgroups considered, but there was evidence of heterogeneity of the treatment effect for the day 7 composite safety outcome: risk was greater for hIVIG compared with placebo for patients who were antibody positive (OR 2·21, 95% CI 1·14–4·29); for patients who were antibody negative, the OR was 0·51 (0·29–0·90; pinteraction=0·001). INTERPRETATION: When administered with standard of care including remdesivir, SARS-CoV-2 hIVIG did not demonstrate efficacy among patients hospitalised with COVID-19 without end-organ failure. The safety of hIVIG might vary by the presence of endogenous neutralising antibodies at entry. FUNDING: US National Institutes of Health

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Actin-based protrusions of migrating neutrophils are intrinsically lamellar and facilitate direction changes.

Leukocytes and other amoeboid cells change shape as they move, forming highly dynamic, actin-filled pseudopods. Although we understand much about the architecture and dynamics of thin lamellipodia made by slow-moving cells on flat surfaces, conventional light microscopy lacks the spatial and temporal resolution required to track complex pseudopods of cells moving in three dimensions. We therefore employed lattice light sheet microscopy to perform three-dimensional, time-lapse imaging of neutrophil-like HL-60 cells crawling through collagen matrices. To analyze three-dimensional pseudopods we: (i) developed fluorescent probe combinations that distinguish cortical actin from dynamic, pseudopod-forming actin networks, and (ii) adapted molecular visualization tools from structural biology to render and analyze complex cell surfaces. Surprisingly, three-dimensional pseudopods turn out to be composed of thin (<0.75 µm), flat sheets that sometimes interleave to form rosettes. Their laminar nature is not templated by an external surface, but likely reflects a linear arrangement of regulatory molecules. Although we find that Arp2/3-dependent pseudopods are dispensable for three-dimensional locomotion, their elimination dramatically decreases the frequency of cell turning, and pseudopod dynamics increase when cells change direction, highlighting the important role pseudopods play in pathfinding