Feather corticosterone is lower in translocated and historical populations of the endangered Laysan duck (Anas laysanensis).

Identifying reliable bioindicators of population status is a central goal of conservation physiology. Physiological stress measures are often used as metrics of individual health and can assist in managing endangered species if linked to fitness traits. We analysed feather corticosterone, a cumulative physiological stress metric, of individuals from historical, translocated, and source populations of an endangered endemic Hawaiian bird, the Laysan duck (Anas laysanensis). We hypothesized that feather corticosterone would reflect the improved reproduction and survival rates observed in populations translocated to Midway and Kure Atolls from Laysan Island. We also predicted less physiological stress in historical Laysan birds collected before ecological conditions deteriorated and the population bottleneck. All hypotheses were supported: we found lower feather corticosterone in the translocated populations and historical samples than in those from recent Laysan samples. This suggests that current Laysan birds are experiencing greater physiological stress than historical Laysan and recently translocated birds. Our initial analysis suggests that feather corticosterone may be an indicator of population status and could be used as a non-invasive physiological monitoring tool for this species with further validation. Furthermore, these preliminary results, combined with published demographic data, suggest that current Laysan conditions may not be optimal for this species.

A burden of proof study on alcohol consumption and ischemic heart disease.

Cohort and case-control data have suggested an association between low to moderate alcohol consumption and decreased risk of ischemic heart disease (IHD), yet results from Mendelian randomization (MR) studies designed to reduce bias have shown either no or a harmful association. Here we conducted an updated systematic review and re-evaluated existing cohort, case-control, and MR data using the burden of proof meta-analytical framework. Cohort and case-control data show low to moderate alcohol consumption is associated with decreased IHD risk - specifically, intake is inversely related to IHD and myocardial infarction morbidity in both sexes and IHD mortality in males - while pooled MR data show no association, confirming that self-reported versus genetically predicted alcohol use data yield conflicting findings about the alcohol-IHD relationship. Our results highlight the need to advance MR methodologies and emulate randomized trials using large observational databases to obtain more definitive answers to this critical public health question.

Is resilience a unifying concept for the biological sciences?

There is increasing interest in applying resilience concepts at different scales of biological organization to address major interdisciplinary challenges from cancer to climate change. It is unclear, however, whether resilience can be a unifying concept consistently applied across the breadth of the biological sciences, or whether there is limited capacity for integration. In this review, we draw on literature from molecular biology to community ecology to ascertain commonalities and shortcomings in how resilience is measured and interpreted. Resilience is studied at all levels of biological organization, although the term is often not used. There is a suite of resilience mechanisms conserved across biological scales, and there are tradeoffs that affect resilience. Resilience is conceptually useful to help diverse researchers think about how biological systems respond to perturbations, but we need a richer lexicon to describe the diversity of perturbations, and we lack widely applicable metrics of resilience.

The thermoneutral zone in women takes an "arctic" shift compared to men.

Conventionally, women are perceived to feel colder than men, but controlled comparisons are sparse. We measured the response of healthy, lean, young women and men to a range of ambient temperatures typical of the daily environment (17 to 31 °C). The Scholander model of thermoregulation defines the lower critical temperature as threshold of the thermoneutral zone, below which additional heat production is required to defend core body temperature. This parameter can be used to characterize the thermoregulatory phenotypes of endotherms on a spectrum from "arctic" to "tropical." We found that women had a cooler lower critical temperature (mean ± SD: 21.9 ± 1.3 °C vs. 22.9 ± 1.2 °C, P = 0.047), resembling an "arctic" shift compared to men. The more arctic profile of women was predominantly driven by higher insulation associated with more body fat compared to men, countering the lower basal metabolic rate associated with their smaller body size, which typically favors a "tropical" shift. We did not detect sex-based differences in secondary measures of thermoregulation including brown adipose tissue glucose uptake, muscle electrical activity, skin temperatures, cold-induced thermogenesis, or self-reported thermal comfort. In conclusion, the principal contributors to individual differences in human thermoregulation are physical attributes, including body size and composition, which may be partly mediated by sex.

A quality improvement strategy to reduce unintended extubation in the very low birth weight infant: A case report.

BACKGROUND: Unintended extubations remain a common complication across neonatal intensive care units, with very low birthweight infants being the most vulnerable of them all. Ongoing efforts across different institutions exist with the goal of reducing the rate of unintended extubations to keep a median rate of <2 events per 100 ventilator days as defined by the Vermont Oxford Network. Our objective was to reduce unintended extubations in the very low birthweight infant in a large delivery hospital to ≤2/100 ventilator days. METHODS: A collaborative group was formed between two academic health institutions targeting training and implementation of the Children's National unintended extubation system, focusing on endotracheal tube securement methods and surveillance protocols. RESULTS: The unintended extubation rate decreased from 3.23 to 0.64 per 100 ventilator days. Changes were implemented from 2018-2020 with a sustained reduction in the unintended extubation rate of 1.54 per 100 ventilator days. Most events occurred between 12 : 00 pm -4 : 00 pm and the commonest cause was spontaneous (25%) followed by dislodgment during repositioning (19%). CONCLUSION: Very low birth weight infants present a challenge to endotracheal tube maintenance due to their developmental and anatomical changes during their neonatal intensive care unit stay. Successful reduction of unintended extubations in the very low birthweight infant can be achieved by adaptation of successful protocols for older infants.

Health effects associated with chewing tobacco: a Burden of Proof study.

Chewing tobacco use poses serious health risks; yet it has not received as much attention as other tobacco-related products. This study synthesizes existing evidence regarding the health impacts of chewing tobacco while accounting for various sources of uncertainty. We conducted a systematic review and meta-analysis of chewing tobacco and seven health outcomes, drawing on 103 studies published from 1970 to 2023. We use a Burden of Proof meta-analysis to generate conservative risk estimates and find weak-to-moderate evidence that tobacco chewers have an increased risk of stroke, lip and oral cavity cancer, esophageal cancer, nasopharynx cancer, other pharynx cancer, and laryngeal cancer. We additionally find insufficient evidence of an association between chewing tobacco and ischemic heart disease. Our findings highlight a need for policy makers, researchers, and communities at risk to devote greater attention to chewing tobacco by both advancing tobacco control efforts and investing in strengthening the existing evidence base.

Potential extinction cascades in a desert ecosystem: Linking food web interactions to community viability.

Desert communities are threatened with species loss due to climate change, and their resistance to such losses is unknown. We constructed a food web of the Mojave Desert terrestrial community (300 nodes, 4080 edges) to empirically examine the potential cascading effects of bird extinctions on this desert network, compared to losses of mammals and lizards. We focused on birds because they are already disappearing from the Mojave, and their relative thermal vulnerabilities are known. We quantified bottom-up secondary extinctions and evaluated the relative resistance of the community to losses of each vertebrate group. The impact of random bird species loss was relatively low compared to the consequences of mammal (causing the greatest number of cascading losses) or reptile loss, and birds were relatively less likely to be in trophic positions that could drive top-down effects in apparent competition and tri-tropic cascade motifs. An avian extinction cascade with year-long resident birds caused more secondary extinctions than the cascade involving all bird species for randomized ordered extinctions. Notably, we also found that relatively high interconnectivity among avian species has formed a subweb, enhancing network resistance to bird losses.

Health effects associated with exposure to secondhand smoke: a Burden of Proof study.

Despite a gradual decline in smoking rates over time, exposure to secondhand smoke (SHS) continues to cause harm to nonsmokers, who are disproportionately children and women living in low- and middle-income countries. We comprehensively reviewed the literature published by July 2022 concerning the adverse impacts of SHS exposure on nine health outcomes. Following, we quantified each exposure-response association accounting for various sources of uncertainty and evaluated the strength of the evidence supporting our analyses using the Burden of Proof Risk Function methodology. We found all nine health outcomes to be associated with SHS exposure. We conservatively estimated that SHS increases the risk of ischemic heart disease, stroke, type 2 diabetes and lung cancer by at least around 8%, 5%, 1% and 1%, respectively, with the evidence supporting these harmful associations rated as weak (two stars). The evidence supporting the harmful associations between SHS and otitis media, asthma, lower respiratory infections, breast cancer and chronic obstructive pulmonary disease was weaker (one star). Despite the weak underlying evidence for these associations, our results reinforce the harmful effects of SHS on health and the need to prioritize advancing efforts to reduce active and passive smoking through a combination of public health policies and education initiatives.

Investigating the effects of acute and chronic stress on DNA damage.

A hallmark of the vertebrate stress response is a rapid increase in glucocorticoids and catecholamines; however, this does not mean that these mediators are the best, or should be the only, metric measured when studying stress. Instead, it is becoming increasingly clear that assaying a suite of downstream metrics is necessary in stress physiology. One component of this suite could be assessing double-stranded DNA damage (dsDNA damage), which has recently been shown to increase in blood with both acute and chronic stress in house sparrows (Passer domesticus). To further understand the relationship between stress and dsDNA damage, we designed two experiments to address the following questions: (1) how does dsDNA damage with chronic stress vary across tissues? (2) does the increase in dsDNA damage during acute stress come from one arm of the stress response or both? We found that (1) dsDNA damage affects tissues differently during chronic stress and (2) the hypothalamic-pituitary-adrenal axis influences dsDNA damage with acute stress, but the sympathetic-adreno-medullary system does not. Surprisingly, our data are not explained by studies on changes in hormone receptor levels with chronic stress, so the underlying mechanism remains unclear.

Nasal bots carry relevant titers of CWD prions in naturally infected white-tailed deer.

Chronic wasting disease (CWD) is a prion disease affecting farmed and free-ranging cervids. CWD is rapidly expanding across North America and its mechanisms of transmission are not completely understood. Considering that cervids are commonly afflicted by nasal bot flies, we tested the potential of these parasites to transmit CWD. Parasites collected from naturally infected white-tailed deer were evaluated for their prion content using the protein misfolding cyclic amplification (PMCA) technology and bioassays. Here, we describe PMCA seeding activity in nasal bot larvae collected from naturally infected, nonclinical deer. These parasites efficiently infect CWD-susceptible mice in ways suggestive of high infectivity titers. To further mimic environmental transmission, bot larvae homogenates were mixed with soils, and plants were grown on them. We show that both soils and plants exposed to CWD-infected bot homogenates displayed seeding activity by PMCA. This is the first report describing prion infectivity in a naturally occurring deer parasite. Our data also demonstrate that CWD prions contained in nasal bots interact with environmental components and may be relevant for disease transmission.

Mechanosensory encoding in ex vivo muscle-nerve preparations.

Our objective was to evaluate an ex vivo muscle-nerve preparation used to study mechanosensory signalling by low threshold mechanosensory receptors (LTMRs). Specifically, we aimed to assess how well the ex vivo preparation represents in vivo firing behaviours of the three major LTMR subtypes of muscle primary sensory afferents, namely type Ia and II muscle spindle (MS) afferents and type Ib tendon organ afferents. Using published procedures for ex vivo study of LTMRs in mouse hindlimb muscles, we replicated earlier reports on afferent firing in response to conventional stretch paradigms applied to non-contracting, that is passive, muscle. Relative to in vivo studies, stretch-evoked firing for confirmed MS afferents in the ex vivo preparation was markedly reduced in firing rate and deficient in encoding dynamic features of muscle stretch. These deficiencies precluded conventional means of discriminating type Ia and II afferents. Muscle afferents, including confirmed Ib afferents were often indistinguishable based on their similar firing responses to the same physiologically relevant stretch paradigms. These observations raise uncertainty about conclusions drawn from earlier ex vivo studies that either attribute findings to specific afferent types or suggest an absence of treatment effects on dynamic firing. However, we found that replacing the recording solution with bicarbonate buffer resulted in afferent firing rates and profiles more like those seen in vivo. Improving representation of the distinctive sensory encoding properties in ex vivo muscle-nerve preparations will promote accuracy in assigning molecular markers and mechanisms to heterogeneous types of muscle mechanosensory neurons.

Health effects associated with exposure to intimate partner violence against women and childhood sexual abuse: a burden of proof study.

The health impacts of intimate partner violence against women and childhood sexual abuse are not fully understood. Here we conducted a systematic review by comprehensively searching seven electronic databases for literature on intimate partner violence-associated and childhood sexual abuse-associated health effects. Following the burden of proof methodology, we evaluated the evidence strength linking intimate partner violence and/or childhood sexual abuse to health outcomes supported by at least three studies. Results indicated a moderate association of intimate partner violence with major depressive disorder and with maternal abortion and miscarriage (63% and 35% increased risk, respectively). HIV/AIDS, anxiety disorders and self-harm exhibited weak associations with intimate partner violence. Fifteen outcomes were evaluated for their relationship to childhood sexual abuse, which was shown to be moderately associated with alcohol use disorders and with self-harm (45% and 35% increased risk, respectively). Associations between childhood sexual abuse and 11 additional health outcomes, such as asthma and type 2 diabetes mellitus, were found to be weak. Although our understanding remains limited by data scarcity, these health impacts are larger in magnitude and more extensive than previously reported. Renewed efforts on violence prevention and evidence-based approaches that promote healing and ensure access to care are necessary.

PMCA screening of retropharyngeal lymph nodes in white-tailed deer and comparisons with ELISA and IHC.

Chronic wasting disease (CWD) is a prion disease affecting cervids. CWD diagnosis is conducted through enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry (IHC) in retropharyngeal lymph nodes. Unfortunately, these techniques have limited sensitivity against the biomarker (CWD-prions). Two in vitro prion amplification techniques, real-time quaking-induced conversion (RT-QuIC) and protein misfolding cyclic amplification (PMCA), have shown promise in detecting CWD-prions in tissues and bodily fluids. Recent studies have demonstrated that RT-QuIC yields similar results compared to ELISA and IHC. Here, we analyzed 1003 retropharyngeal lymph nodes (RPLNs) from Texas white-tailed deer. PMCA detected CWD at a higher rate compared to ELISA/IHC, identified different prion strains, and revealed the presence of CWD-prions in places with no previous history. These findings suggest that PMCA exhibits greater sensitivity than current standard techniques and could be valuable for rapid and strain-specific CWD detection.

Identification of chronic wasting disease prions in decaying tongue tissues from exhumed white-tailed deer.

Chronic wasting disease (CWD) prions cause fatal neuropathies in farmed and free-ranging cervids. The deposition of prions in natural and humanmade environmental components has been implicated as a major mechanism mediating CWD spread in wild and captive populations. Prions can be deposited in the environment through excreta, tissues, and carcasses from pre-clinical and clinical animals. Furthermore, burial of CWD-positive animals may reduce but not completely mitigate prion spread from carcasses into the surrounding environment. Here, we analyzed exhumed, decaying deer carcasses for the presence of CWD prions. By analyzing tongue tissues through the protein misfolding cyclic amplification (PMCA) technique, we were able to identify seven out of 95 exhumed white-tailed deer carcasses as CWD prions carriers. Confirmatory analyses were performed using the real-time quaking-induced conversion (RT-QuIC) technique. In addition, we evaluated the potential contamination of the pens that housed these animals by swabbing feeders and waterers. PMCA analyses of swabs confirmed CWD contamination on farming equipment. This work demonstrates the usefulness of PMCA to detect CWD prions in a variety of contexts, including exhumed/decaying tissues. In addition, this is the first report demonstrating swabbing coupled with PMCA as a method for the detection of prion seeding activity on naturally exposed surfaces. Considering that this study was focused on a single site, further studies should confirm whether prion amplification assays are useful to identify CWD prions not only in animals but also in the environment that contains them. IMPORTANCE Environmental contamination is thought to be a major player in the spread of chronic wasting disease (CWD), a fatal prion disease affecting a wide variety of cervid species. At present, there are no officially approved methods allowing for the detection of prion infectivity in environmental components. Importantly, animal as well as anthropogenic activities are thought to contribute to prion environmental contamination. Here, we detected CWD prions in exhumed white-tailed deer carcasses by using the protein misfolding cyclic amplification (PMCA) assay. In addition, we identified CWD prions in feeders used within the infected facility. These results highlight the potential role of PMCA in identifying prion infectivity in a variety of scenarios, ranging from decaying tissues to farming equipment.

Quantifying phenological landmarks of migration shows nonuniform use of the Caribbean by shorebirds.

Of the boreal- and Arctic-breeding North American shorebirds that migrate south through the Caribbean, most individuals continue farther south. However, for many species, some individuals remain beyond the southbound migration period (i.e., throughout the temperate winter and/or summer). This variation among individuals adds complexity to observation data, obscures migration patterns, and could prevent the examination of the use of different Caribbean regions by various shorebird species during migration and in the nonmigratory seasons. Here, we present a novel method that leverages a well-established statistical approach (generalized additive models) to systematically identify migration phenology even for complex passage migrant species with individuals that remain beyond migration. Our method identifies the active migration period using derivatives of a fitted GAM and then calculates phenology metrics based on quantiles of that migration period. We also developed indices to quantify oversummering and overwintering patterns with respect to migration. We analyzed eBird data for 16 North American shorebird species as they traveled South through the insular Caribbean, identifying separate migratory patterns for Cuba, Puerto Rico, Guadeloupe, Aruba, Bonaire, Curaçao, and Trinidad and Tobago. Our results confirm past reports and provide additional detail on shorebird migration in the Caribbean, and identify several previously unpublished regional patterns. Despite Puerto Rico being farther north and closer to continental North America, most species reached Puerto Rico later than other regions, supporting a long-standing hypothesis that migration strategy (transcontinental vs. transoceanic) leads to geographic differences in migration timing. We also found distinct patterns of migration curves, with some regions and species consistently having either symmetrical or skewed curves; these differences in migration curve shape reflect different migration processes. Our novel method proved reliable and adaptable for most species and serves as a valuable tool for identifying phenological patterns in complex migration data, potentially unlocking previously intractable data.

Meningococcal A conjugate vaccine coverage in the meningitis belt of Africa from 2010 to 2021: a modelling study.

Background: As of the end of 2021, twenty-four countries in the African meningitis belt have rolled out mass campaigns of MenAfriVac®, a meningococcal A conjugate vaccine (MACV) first introduced in 2010. Twelve have completed introduction of MACV into routine immunisation (RI) schedules. Although select post-campaign coverage data are published, no study currently comprehensively estimates MACV coverage from both routine and campaign sources in the meningitis belt across age, country, and time. Methods: In this modelling study, we assembled campaign data from the twenty-four countries that had introduced any immunisation activity during or before the year 2021 (Benin, Burkina Faso, Burundi, Cameroon, Central African Republic, Chad, Côte d'Ivoire, Democratic Republic of the Congo, Ethiopia, Eritrea, the Gambia, Ghana, Guinea, Guinea Bissau, Kenya, Mali, Mauritania, Niger, Nigeria, Senegal, South Sudan, Sudan, Togo and Uganda) via WHO reports and RI data via systematic review. Next, we modelled RI coverage using Spatiotemporal Gaussian Process Regression. Then, we synthesized these estimates with campaign data into a cohort model, tracking coverage for each age cohort from age 1 to 29 years over time for each country. Findings: Coverage in high-risk locations amongst children aged 1-4 in 2021 was estimated to be highest in Togo with 96.0% (95% uncertainty interval [UI] 92.0-99.0), followed by Niger with 87.2% (95% UI 85.3-89.0) and Burkina Faso, with 86.4% (95% UI 85.1-87.6). These countries had high coverage values driven by an initial successful mass immunisation campaign, followed by a catch-up campaign, followed by introduction of RI. Due to the influence of older mass vaccination campaigns, coverage proportions skewed higher in the 1-29 age group than the 1-4 group, with a median coverage of 82.9% in 2021 in the broader age group compared to 45.6% in the narrower age group. Interpretation: These estimates highlight where gaps in immunisation remain and emphasise the need for broader efforts to strengthen RI systems. This methodological framework can be applied to estimate coverage for any vaccine that has been delivered in both routine and supplemental immunisation activities. Funding: Bill and Melinda Gates Foundation.

Community-Onset Bacterial Coinfection in Children Critically Ill With Severe Acute Respiratory Syndrome Coronavirus 2 Infection.

Background: Community-onset bacterial coinfection in adults hospitalized with coronavirus disease 2019 (COVID-19) is reportedly uncommon, though empiric antibiotic use has been high. However, data regarding empiric antibiotic use and bacterial coinfection in children with critical illness from COVID-19 are scarce. Methods: We evaluated children and adolescents aged <19 years admitted to a pediatric intensive care or high-acuity unit for COVID-19 between March and December 2020. Based on qualifying microbiology results from the first 3 days of admission, we adjudicated whether patients had community-onset bacterial coinfection. We compared demographic and clinical characteristics of those who did and did not (1) receive antibiotics and (2) have bacterial coinfection early in admission. Using Poisson regression models, we assessed factors associated with these outcomes. Results: Of the 532 patients, 63.3% received empiric antibiotics, but only 7.1% had bacterial coinfection, and only 3.0% had respiratory bacterial coinfection. In multivariable analyses, empiric antibiotics were more likely to be prescribed for immunocompromised patients (adjusted relative risk [aRR], 1.34 [95% confidence interval {CI}, 1.01-1.79]), those requiring any respiratory support except mechanical ventilation (aRR, 1.41 [95% CI, 1.05-1.90]), or those requiring invasive mechanical ventilation (aRR, 1.83 [95% CI, 1.36-2.47]) (compared with no respiratory support). The presence of a pulmonary comorbidity other than asthma (aRR, 2.31 [95% CI, 1.15-4.62]) was associated with bacterial coinfection. Conclusions: Community-onset bacterial coinfection in children with critical COVID-19 is infrequent, but empiric antibiotics are commonly prescribed. These findings inform antimicrobial use and support rapid de-escalation when evaluation shows coinfection is unlikely.

Biased assessment of thermal properties of birds from estimated body density.

Parameter approximation is often necessary when calculating species thermal properties, and researchers historically have assumed animals are spherical when estimating volume and density. We hypothesized that a spherical model would result in significantly biased measures of density for birds, which are generally longer than they are tall or wide, and that these inaccuracies would significantly alter the outputs of thermal models. We calculated the densities of 154 bird species using sphere and ellipsoid volume equations and compared these estimates to one another and to published bird densities measured using more exact volume displacement methods. We also calculated evaporative water loss as a percentage of body mass per hour, a variable known to be critical for bird survival, twice for each species, once with the sphere-based density and once with the ellipsoid-based density. We found that volume and density estimates were statistically similar between published densities and those estimated using the ellipsoid volume equation, suggesting that this method is suitable for approximating bird volume and calculating density. In contrast, the spherical model overestimated body volume and therefore underestimated body densities. This resulted in the spherical approach consistently overestimating evaporative water loss as a percent of mass lost per hour than the ellipsoid approach. This outcome would result in mischaracterizing thermal conditions as lethal for a given species, including overestimating vulnerability to increased temperatures due to climate change.

Mechanosensory encoding dysfunction emerges from cancer-chemotherapy interaction.

Persistent sensory, motor and cognitive disabilities comprise chemotherapy-induced neural disorders (CIND) that limit quality of life with little therapeutic relief for cancer survivors. Our recent preclinical study provides new insight into a condition impacting the severity of chronic CIND. We find that sensorimotor disability observed following cancer treatment exceeds that attributable to chemotherapy alone. A possible explanation for intensified disability emerged from evidence that codependent effects of cancer and chemotherapy amplify defective firing in primary sensory neurons supplying one type of low threshold mechanosensory receptor (LTMR). Here we test whether cancer's modification of chemotherapy-induced sensory defects generalizes across eight LTMR submodalities that collectively generate the signals of origin for proprioceptive and tactile perception and guidance of body movement. Preclinical study enabled controlled comparison of the independent contributions of chemotherapy and cancer to their clinically relevant combined effects. We compared data sampled from rats that were otherwise healthy or bearing colon cancer and treated, or not, with human-scaled, standard-of-care chemotherapy with oxaliplatin. Action potential firing patterns encoding naturalistic mechanical perturbations of skeletal muscle and skin were measured electrophysiologically in vivo from multiple types of LTMR neurons. All expressed aberrant encoding of dynamic and/or static features of mechanical stimuli in healthy rats treated with chemotherapy, and surprisingly also by some LTMRs in cancer-bearing rats that were not treated. By comparison, chemotherapy and cancer in combination worsened encoding aberrations, especially in slowly adapting LTMRs supplying both muscle and glabrous skin. Probabilistic modeling best predicted observed encoding defects when incorporating interaction effects of cancer and chemotherapy. We conclude that for multiple mechanosensory submodalities, the severity of encoding defects is modulated by a codependence of chemotherapy side effects and cancer's systemic processes. We propose that the severity of CIND might be reduced by therapeutically targeting the mechanisms, yet to be determined, by which cancer magnifies chemotherapy's neural side effects as an alternative to reducing chemotherapy and its life-saving benefits.