Behavioral trade-offs and multitasking by elk in relation to predation risk from Mexican gray wolves.

Predator non-consumptive effects (NCE) can alter prey foraging time and habitat use, potentially reducing fitness. Prey can mitigate NCEs by increasing vigilance, chewing-vigilance synchronization, and spatiotemporal avoidance of predators. We quantified the relationship between Mexican wolf (Canis lupus baileyi) predation risk and elk (Cervus canadensis) behavior. We conducted behavioral observations on adult female elk and developed predation risk indices using GPS collar data from Mexican wolves, locations of elk killed by wolves, and landscape covariates. We compared a priori models to determine the best predictors of adult female behavior and multitasking. Metrics that quantified both spatial and temporal predation risk were the most predictive. Vigilance was positively associated with increased predation risk. The effect of predation risk on foraging and resting differed across diurnal periods. During midday when wolf activity was lower, the probability of foraging increased while resting decreased in high-risk areas. During crepuscular periods when elk and wolves were most active, increased predation risk was associated with increased vigilance and slight decreases in foraging. Our results suggest elk are temporally avoiding predation risk from Mexican wolves by trading resting for foraging, a trade-off often not evaluated in behavioral studies. Probability of multitasking depended on canopy openness and an interaction between maternal period and predation risk; multitasking decreased prior to parturition and increased post parturition in high-risk areas. Openness was inversely related to multitasking. These results suggest adult female elk are altering the type of vigilance used depending on resource availability/quality, current energetic needs, and predation risk. Our results highlight potentially important, but often-excluded behaviors and trade-offs prey species may use to reduce the indirect effects of predation and contribute additional context to our understanding of predator-prey dynamics.

The Intellectual Disability Risk Gene Kdm5b Regulates Long-Term Memory Consolidation in the Hippocampus.

The histone lysine demethylase KDM5B is implicated in recessive intellectual disability disorders, and heterozygous, protein-truncating variants in KDM5B are associated with reduced cognitive function in the population. The KDM5 family of lysine demethylases has developmental and homeostatic functions in the brain, some of which appear to be independent of lysine demethylase activity. To determine the functions of KDM5B in hippocampus-dependent learning and memory, we first studied male and female mice homozygous for a Kdm5b Δ ARID allele that lacks demethylase activity. Kdm5b Δ ARID/ Δ ARID mice exhibited hyperactivity and long-term memory deficits in hippocampus-dependent learning tasks. The expression of immediate early, activity-dependent genes was downregulated in these mice and hyperactivated upon a learning stimulus compared with wild-type (WT) mice. A number of other learning-associated genes were also significantly dysregulated in the Kdm5b Δ ARID/ Δ ARID hippocampus. Next, we knocked down Kdm5b specifically in the adult, WT mouse hippocampus with shRNA. Kdm5b knockdown resulted in spontaneous seizures, hyperactivity, and hippocampus-dependent long-term memory and long-term potentiation deficits. These findings identify KDM5B as a critical regulator of gene expression and synaptic plasticity in the adult hippocampus and suggest that at least some of the cognitive phenotypes associated with KDM5B gene variants are caused by direct effects on memory consolidation mechanisms.

Seroprevalence, Blood Chemistry, and Patterns of Canine Parvovirus, Distemper Virus, Plague, and Tularemia in Free-Ranging Coyotes (Canis latrans) in Northern New Mexico, USA.

Wildlife diseases have implications for ecology, conservation, human health, and health of domestic animals. They may impact wildlife health and population dynamics. Exposure rates of coyotes (Canis latrans) to pathogens such as Yersinia pestis, the cause of plague, may reflect prevalence rates in both rodent prey and human populations. We captured coyotes in north-central New Mexico during 2005-2008 and collected blood samples for serologic surveys. We tested for antibodies against canine distemper virus (CDV, Canine morbillivirus), canine parvovirus (CPV, Carnivore protoparvovirus), plague, tularemia (Francisella tularensis), and for canine heartworm (Dirofilaria immitis) antigen. Serum biochemistry variables that fell outside reference ranges were probably related to capture stress. We detected antibodies to parvovirus in 32/32 samples (100%), and to Y. pestis in 26/31 (84%). More than half 19/32 (59%) had antibodies against CDV, and 5/31 (39%) had antibodies against F. tularensis. We did not detect any heartworm antigens (n = 9). Pathogen prevalence was similar between sexes and among the three coyote packs in the study area. Parvovirus exposure appeared to happen early in life, and prevalence of antibodies against CDV increased with increasing age class. Exposure to Y. pestis and F. tularensis occurred across all age classes. The high coyote seroprevalence rates observed for CPV, Y. pestis, and CDV may indicate high prevalence in sympatric vertebrate populations, with implications for regional wildlife conservation as well as risk to humans via zoonotic transmission.

The FGF21 analog pegozafermin in severe hypertriglyceridemia: a randomized phase 2 trial.

Pegozafermin, a long-acting glycopegylated analog of human fibroblast growth factor 21, is in development for the treatment of severe hypertriglyceridemia (SHTG) and nonalcoholic steatohepatitis. Here we report the results of a phase 2, double-blind, randomized, five-arm trial testing pegozafermin at four different doses (n = 67; 52 male) versus placebo (n = 18; 12 male) for 8 weeks in patients with SHTG (triglycerides (TGs), ≥500 mg dl-1 and ≤2,000 mg dl-1). Treated patients showed a significant reduction in median TGs for the pooled pegozafermin group versus placebo (57.3% versus 11.9%, difference versus placebo -43.7%, 95% confidence interval (CI): -57.1%, -30.3%; P < 0.001), meeting the primary endpoint of the trial. Reductions in median TGs ranged from 36.4% to 63.4% across all treatment arms and were consistent regardless of background lipid-lowering therapy. Results for secondary endpoints included significant decreases in mean apolipoprotein B and non-high-density lipoprotein cholesterol concentrations (-10.5% and -18.3% for pooled doses compared to 1.1% and -0.6% for placebo (95% CI: -21.5%, -2.0%; P = 0.019 and 95% CI: -30.7%, -5.1%; P = 0.007, respectively), as well as a significant decrease in liver fat fraction for pooled treatment (n = 17) versus placebo (n = 6; -42.2% pooled pegozafermin, -8.3% placebo; 95% CI: -60.9%, -8.7%; P = 0.012), as assessed in a magnetic resonance imaging sub-study. No serious adverse events were observed to be related to the study drug. If these results are confirmed in a phase 3 trial, pegozafermin could be a promising treatment for SHTG (ClinicalTrials.gov registration: NCT0441186).

Anthropogenic subsidies influence resource use during a mange epizootic in a desert coyote population.

Colonization of urban areas by synanthropic wildlife introduces novel and complex alterations to established ecological processes, including the emergence and spread of infectious diseases. Aggregation at urban resources can increase disease transfer, with wide-ranging species potentially infecting outlying populations. The garrison at the National Training Center, Fort Irwin, California, USA, was recently colonized by mange-infected coyotes (Canis latrans) that also use the surrounding Mojave Desert. This situation provided an ideal opportunity to examine the effects of urban resources on disease dynamics. We evaluated seasonal space use and determined the influence of anthropogenic subsidies, water sources, and prey density on urban resource selection. We found no difference in home range size between healthy and infected individuals, but infected residents had considerably more spatial overlap with one another than healthy residents. All coyotes selected for anthropogenic subsidies during all seasons, while infected coyotes seasonally selected for urban water sources, and healthy coyotes seasonally selected for urban areas with greater densities of natural prey. These results suggest that while all coyotes were selecting for anthropogenic subsidies, infected resident coyotes demonstrated a greater tolerance for other conspecifics, which could be facilitating the horizontal transfer of sarcoptic mange to non-resident coyotes. Conversely, healthy coyotes also selected for natural prey and healthy residents exhibited a lack of spatial overlap with other coyotes suggesting they were not reliant on anthropogenic subsidies and were maintaining territories. Understanding the association between urban wildlife, zoonotic diseases, and urban resources can be critical in determining effective responses for mitigating future epizootics.

Pleistocene-Holocene vicariance, not Anthropocene landscape change, explains the genetic structure of American black bear (Ursus americanus) populations in the American Southwest and northern Mexico.

The phylogeography of the American black bear (Ursus americanus) is characterized by isolation into glacial refugia, followed by population expansion and genetic admixture. Anthropogenic activities, including overharvest, habitat loss, and transportation infrastructure, have also influenced their landscape genetic structure. We describe the genetic structure of the American black bear in the American Southwest and northern Mexico and investigate how prehistoric and contemporary forces shaped genetic structure and influenced gene flow. Using a suite of microsatellites and a sample of 550 bears, we identified 14 subpopulations organized hierarchically following the distribution of ecoregions and mountain ranges containing black bear habitat. The pattern of subdivision we observed is more likely a product of postglacial habitat fragmentation during the Pleistocene and Holocene, rather than a consequence of contemporary anthropogenic barriers to movement during the Anthropocene. We used linear mixed-effects models to quantify the relationship between landscape resistance and genetic distance among individuals, which indicated that both isolation by resistance and geographic distance govern gene flow. Gene flow was highest among subpopulations occupying large tracts of contiguous habitat, was reduced among subpopulations in the Madrean Sky Island Archipelago, where montane habitat exists within a lowland matrix of arid lands, and was essentially nonexistent between two isolated subpopulations. We found significant asymmetric gene flow supporting the hypothesis that bears expanded northward from a Pleistocene refugium located in the American Southwest and northern Mexico and that major highways were not yet affecting gene flow. The potential vulnerability of the species to climate change, transportation infrastructure, and the US-Mexico border wall highlights conservation challenges and opportunities for binational collaboration.

The abundance and persistence of Caprinae populations.

Stable or growing populations may go extinct when their sizes cannot withstand large swings in temporal variation and stochastic forces. Hence, the minimum abundance threshold defining when populations can persist without human intervention forms a key conservation parameter. We identify this threshold for many populations of Caprinae, typically threatened species lacking demographic data. Doing so helps triage conservation and management actions for threatened or harvested populations. Methodologically, we used population projection matrices and simulations, with starting abundance, recruitment, and adult female survival predicting future abundance, growth rate (λ), and population trend. We incorporated mean demographic rates representative of Caprinae populations and corresponding variances from desert bighorn sheep (Ovis canadensis nelsoni), as a proxy for Caprinae sharing similar life histories. We found a population's minimum abundance resulting in ≤ 0.01 chance of quasi-extinction (QE; population ≤ 5 adult females) in 10 years and ≤ 0.10 QE in 30 years as 50 adult females, or 70 were translocation (removals) pursued. Discovering the threshold required 3 demographic parameters. We show, however, that monitoring populations' relationships to this threshold requires only abundance and recruitment data. This applied approach avoids the logistical and cost hurdles in measuring female survival, making assays of population persistence more practical.

Intragenic CpG Islands and Their Impact on Gene Regulation.

The mammalian genome is depleted in CG dinucleotides, except at protected regions where they cluster as CpG islands (CGIs). CGIs are gene regulatory hubs and serve as transcription initiation sites and are as expected, associated with gene promoters. Advances in genomic annotations demonstrate that a quarter of CGIs are found within genes. Such intragenic regions are repressive environments, so it is surprising that CGIs reside here and even more surprising that some resist repression and are transcriptionally active within a gene. Hence, intragenic CGI positioning within genes is not arbitrary and is instead, selected for. As a wealth of recent studies demonstrate, intragenic CGIs are embedded within genes and consequently, influence 'host' gene mRNA isoform length and expand transcriptome diversity.

A case for multiscale habitat selection studies of small mammals.

Habitat information for small mammals typically consists of anecdotal descriptions or infrequent analyses of habitat use, which often are reported erroneously as signifying habitat preference, requirements, or quality. Habitat preferences can be determined only by analysis of habitat selection, a behavioral process that results in the disproportionate use of one resource over other available resources and occurs in a hierarchical manner across different environmental scales. North American chipmunks (Neotamias and Tamias) are a prime example of the lack of studies on habitat selection for small mammal species. We used the Organ Mountains Colorado chipmunk (N. quadrivittatus australis) as a case study to determine whether previous descriptions of habitat in the literature were upheld in a multiscale habitat selection context. We tracked VHF radiocollared chipmunks and collected habitat information at used and available locations to analyze habitat selection at three scales: second order (i.e., home range), third order (i.e., within home range), and microhabitat scales. Mean home range was 2.55 ha ± 1.55 SD and did not differ between sexes. At the second and third order, N. q. australis avoided a coniferous forest land cover type and favored particular areas of arroyos (gullies) that were relatively steep-sided and greener and contained montane scrub land cover type. At the microhabitat scale, chipmunks selected areas that had greater woody plant diversity, rock ground cover, and ground cover of coarse woody debris. We concluded that habitat selection by N. q. australis fundamentally was different from descriptions of habitat in the literature that described N. quadrivittatus as primarily associated with coniferous forests. We suggest that arroyos, which are unique and rare on the landscape, function as climate refugia for these chipmunks because they create a cool, wet microclimate. Our findings demonstrate the importance of conducting multiscale habitat selection studies for small mammals to ensure that defensible and enduring habitat information is available to support appropriate conservation and management actions.

Urbanization's influence on the distribution of mange in a carnivore revealed with multistate occupancy models.

Increasing urbanization and use of urban areas by synanthropic wildlife has increased human and domestic animal exposure to zoonotic diseases and exacerbated epizootics within wildlife populations. Consequently, there is a need to improve wildlife disease surveillance programs to rapidly detect outbreaks and refine inferences regarding spatiotemporal disease dynamics. Multistate occupancy models can address potential shortcomings in surveillance programs by accounting for imperfect detection and the misclassification of disease states. We used these models to explore the relationship between urbanization, slope, and the spatial distribution of sarcoptic mange in coyotes (Canis latrans) inhabiting Fort Irwin, California, USA. We deployed remote cameras across 180 sites within the desert surrounding the populated garrison and classified sites by mange presence or absence depending on whether a symptomatic or asymptomatic coyote was photographed. Coyotes selected flatter sites closer to the urban area with a high probability of use (0.845, 95% credible interval (CRI): 0.728, 0.944); site use decreased as the distance to urban areas increased (standardized [Formula: see text] = - 1.354, 95% CRI - 2.423, - 0.619). The probability of correctly classifying mange presence at a site also decreased further from the urban area and was probably related to the severity of mange infection. Severely infected coyotes, which were more readily identified as symptomatic, resided closer to the urban area and were most likely dependent on urban resources for survival; urban resources probably contributed to sustaining the disease. Multistate occupancy models represent a flexible framework for estimating the occurrence and spatial extent of observable infectious diseases, which can improve wildlife disease surveillance programs.

Guidance for Healthcare Providers Managing COVID-19 in Rural and Underserved Areas.

Coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has ravaged many urban and high-density areas in the USA. However, rural areas (despite their low population density) may be especially vulnerable to poor outcomes from COVID-19, owing to limited healthcare infrastructure, long distances to advanced health care, and population characteristics (e.g., high tobacco use, hypertension, obesity, older age). A panel of experts who are actively engaged in treating and managing COVID-19 at a rural academic center was convened to address this topic. In this commentary, we provide readers with some specific issues faced by rural healthcare providers and offer guidance in overcoming these challenges. This guidance includes alternative ventilator strategies, personal protective equipment (PPE), and common therapeutic options.

Pediatric asthma pathway in the emergency room.

Asthma is one of the leading causes of hospital admission in the pediatric population. Standardization of asthma management guidelines for patients admitted to the emergency department has been suggested to improve care delivery and patient outcomes. Utilizing a multidisciplinary asthma task force at a single academic medical center, we sought to determine if a protocol-driven approach to implementation of care for patients with asthma could improve patient outcomes by reducing wait times for administration of steroids. A prospective cohort study examined the use of a standardized asthma pathway over a 2-year period compared to historical controls. Pathway use significantly decreased time to corticosteroid administration (45 vs. 29 min [year 1] and 20 min [year 2]; P < 0.0001). By implementing this standard of care at pediatric emergency departments, time to treatment can be decreased, therefore improving the morbidity and mortality of pediatric patients with asthma nationwide.

PATHOGEN PREVALANCE IN AMERICAN BLACK BEARS (URSUS AMERICANUS AMBLYCEPS) OF THE JEMEZ MOUNTAINS, NEW MEXICO, USA.

Informed management of American black bears (Ursus americanus) requires knowledge of the distribution and pathology of diseases affecting the species. Little information is available on pathogen prevalence from black bear populations in the Southwest, US, and it is unknown how these infections may influence black bear populations or disease transmission. We captured New Mexico black bears (Ursus americanus amblyceps) during 2016-17 as part of a long-term monitoring project and opportunistically collected 36 blood samples from 12 female and 17 male black bears. We wanted to determine prior exposure to canine distemper virus, canine parvovirus, Yersinia pestis, Francisella tularensis, West Nile virus, Toxoplasma gondii, and the tick-borne pathogens, Anaplasma spp., Ehrlichia spp., Borrelia burgdorferi, Rickettsia spp., and Babesia spp. Approximately half (55%, 16/29) of the individuals sampled had antibodies to Y. pestis, and 37% (10/27) had antibodies to T. gondii. Prevalence of antibodies to West Nile virus, F. tularensis, and canine parvovirus were lower (i.e., 11, 10, and 3%, respectively). We detected no antibodies to canine distemper, B. burgdorferi, Rickettsia spp., or Babesia spp. We documented changes in antibody titer levels for both sexes of several recaptured black bears. Our data will inform managers of pathogen prevalence and distribution in black bears in north-central New Mexico and provide a vital baseline dataset for future pathogen monitoring. Additionally, these data support actions to minimize exposure through handling wild individuals or through hunter harvest activities.

Synthesis and Investigation of Mixed µ-Opioid and δ-Opioid Agonists as Possible Bivalent Ligands for Treatment of Pain.

Several studies have suggested functional association between µ-opioid and δ-opioid receptors and showed that µ-activity could be modulated by δ-ligands. The general conclusion is that agonists for the δ-receptor can enhance the analgesic potency and efficacy of µ-agonists. Our preliminary investigations demonstrate that new bivalent ligands constructed from the µ-agonist fentanyl and the δ-agonist enkephalin-like peptides are promising entities for creation of new analgesics with reduced side effects for treatment of neuropathic pain. A new superposition of the mentioned pharmacophores led to novel µ-bivalent/δ-bivalent compounds that demonstrate both µ-opioid and δ-opioid receptor agonist activity and high efficacy in anti-inflammatory and neuropathic pain models with the potential of reduced unwanted side effects.

A first look at the Accreditation Council for Graduate Medical Education anesthesiology milestones: implementation of self-evaluation in a large residency program.

STUDY OBJECTIVE: The objective was to determine if there is a correlation between resident postgraduate year (PGY) of training and self-evaluation of performance using the Accreditation Council for Graduate Medical Education milestones. DESIGN: Survey. SETTING: Residency program at a large academic center. PATIENTS: Residents and Faculty Clinical Competency Committee (CCC). INTERVENTIONS: None. MEASUREMENTS: Resident and CCC milestone scores. MAIN RESULTS: Correlation coefficients for average score for each milestone vs PGY level ranged from 0.80 for receiving and giving feedback to 0.95 for anesthetic choice and conduct. All milestones showed a relatively linear relationship with PGY of training, and none were found to be consistently reached very late or very early in training. When examining variation across the scores for the individual residents, the distributions for PGY-2 and -3 appeared to be wider than those for PGY-1 and -4. The intraclass correlation coefficients ranged from 0.718 to 0.928. CONCLUSIONS: There was a remarkable degree of consistency in the relationship between level of training and resident self-assessment score for every milestone, as well as strong agreement between the resident and CCC faculty scores. Examination of the variance in the scores, when interpreted in light of our particular training program's characteristics, suggests that the milestones accurately reflect the progression in skill across the residency. In addition, given the concordance between the self-evaluation scores and the CCC faculty scores, self-evaluation may be a reasonable starting point as programs begin the daunting task of determining scores for each of the 25 milestones as part of the biannual evaluation process.