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Abstract Until recent events, the Antarctic was the only major geographical region in which high pathogenicity avian influenza virus (HPAIV) had never previously been detected. Here we report on the detection of clade 2.3.4.4b H5N1 HPAIV in the Antarctic and sub-Antarctic regions of South Georgia and the Falkland Islands, respectively. We initially detected H5N1 HPAIV in samples collected from brown skuas at Bird Island, South Georgia on 8th October 2023. Since this detection, mortalities were observed in several avian and mammalian species at multiple sites across South Georgia. Subsequent testing confirmed H5N1 HPAIV across several sampling locations in multiple avian species and two seal species. Simultaneously, we also confirmed H5N1 HPAIV in southern fulmar and black-browed albatross in the Falkland Islands. Genetic assessment of the virus indicates spread from South America, likely through movement of migratory birds. Critically, genetic assessment of sequences from mammalian species demonstrates no increased risk to human populations above that observed in other instances of mammalian infections globally. Here we describe the detection, species impact and genetic composition of the virus and propose both introductory routes and potential long-term impact on avian and mammalian species across the Antarctic region. We also speculate on the threat to specific populations following recent reports in the area.

Introduction: Optimizing the performance of emergency department (ED) teams impacts patient care, but the utility of current, team-based performance assessment tools to comprehensively measure this impact is underexplored. In this study we aimed to 1) evaluate ED team performance using current team-based assessment tools during an interprofessional in situ simulation and 2) identify characteristics of effective ED teams. Methods: This mixed-methods study employed case study methodology based on a constructivist paradigm. Sixty-three eligible nurses, technicians, pharmacists, and postgraduate year 2–4 emergency medicine residents at a tertiary academic ED participated in a 10-minute in situ simulation of a critically ill patient. Participants self-rated performance using the Team Performance Observation Tool (TPOT) 2.0 and completed a brief demographic form. Two raters independently reviewed simulation videos and rated performance using the TPOT 2.0, Team Emergency Assessment Measure (TEAM), and Ottawa Crisis Resource Management Global Rating Scale (Ottawa GRS). Following simulations, we conducted semi-structured interviews and focus groups with in situ participants. Transcripts were analyzed using thematic analysis. Results: Eighteen team-based simulations took place between January–April 2021. Raters’ scores were on the upper end of the tools for the TPOT 2.0 (R1 4.90, SD 0.17; R2 4.53, SD 0.27, IRR [inter-rater reliability] 0.47), TEAM (R1 3.89, SD 0.19; R2 3.58, SD 0.39, IRR 0.73), and Ottawa GRS (R1 6.6, SD 0.56; R2 6.2, SD 0.54, IRR 0.68). We identified six themes from our interview data: team member entrustment; interdependent energy; leadership tone; optimal communication; strategic staffing; and simulation empowering team performance. Conclusion: Current team performance assessment tools insufficiently discriminate among high performing teams in the ED. Emergency department-specific assessments that capture features of entrustability, interdependent energy, and leadership tone may offer a more comprehensive way to assess an individual’s contribution to a team’s performance.

Abstract Proline is widely known as the only proteogenic amino acid with a secondary amine. In addition to its crucial role in protein structure, the secondary amino acid modulates neurotransmission and regulates the kinetics of signaling proteins. To understand the structural basis of proline import, we solved the structure of the proline transporter SIT1 in complex with the COVID-19 viral receptor ACE2 by cryo-electron microscopy. The structure of pipecolate-bound SIT1 reveals the specific sequence requirements for proline transport in the SLC6 family and how this protein excludes amino acids with extended side chains. By comparing apo and substrate-bound SIT1 states, we also identify the structural changes that link substrate release and opening of the cytoplasmic gate and provide an explanation for how a missense mutation in the transporter causes iminoglycinuria.

Abstract There is limited data regarding the added benefit of adjuvant systemic therapy in the management of small, node-negative, HER2+ breast cancer. In a multi-institutional retrospective analysis using the American Society of Clinical Oncology CancerLinQ database, we compared survival outcomes among T1a-c N0 HER2+ patients diagnosed between 2010 to 2021 who received locoregional therapy alone or in combination with adjuvant trastuzumab (+/− chemotherapy). Primary outcomes were invasive disease-free survival (iDFS) and overall survival (OS). Of the 1,184 patients, 436 received locoregional therapy alone. We found a statistically significant improvement in iDFS (HR 0.73, P = 0.003) and OS (HR 0.63, P = 0.023) on univariate analysis with adjuvant trastuzumab with or without chemotherapy which remained statistically significant on multivariate analysis. Three-arm univariate analysis found that iDFS was significantly improved with trastuzumab monotherapy (P = 0.003) and combination therapy (P = 0.027) compared to observation. Subgroup data suggests that T1b/c tumors derive the greatest benefit.

Abstract Potassium channels of the Two-Pore Domain (K2P) subfamily, KCNK1-KCNK18, play crucial roles in controlling the electrical activity of many different cell types and represent attractive therapeutic targets. However, the identification of highly selective small molecule drugs against these channels has been challenging due to the high degree of structural and functional conservation that exists not only between K2P channels, but across the whole K+ channel superfamily. To address the issue of selectivity, here we generate camelid antibody fragments (nanobodies) against the TREK-2 (KCNK10) K2P K+ channel and identify selective binders including several that directly modulate channel activity. X-ray crystallography and CryoEM data of these nanobodies in complex with TREK-2 also reveal insights into their mechanisms of activation and inhibition via binding to the extracellular loops and Cap domain, as well as their suitability for immunodetection. These structures facilitate design of a biparatropic inhibitory nanobody with markedly improved sensitivity. Together, these results provide important insights into TREK channel gating and provide an alternative, more selective approach to modulation of K2P channel activity via their extracellular domains.

BackgroundRegular physical activity is associated with improved quality of life in patients with inflammatory bowel diseases (IBDs), although much of the existing research is based on self-reported data. Wearable devices provide objective data on many rich physical activity dimensions including steps, duration, distance, and intensity. Little is known about how patients with IBDs engage in these varying dimensions of exercise and how it may influence their symptom and disease-specific patient-reported outcomes (PROs). ObjectiveThis study aims to (1) cluster physical activity patterns from consumer-grade wearable devices and (2) assess the relationship between the clusters and PROs in patients with IBDs. MethodsWe conducted a cross-sectional and longitudinal cohort study among adults with IBDs in the Crohn’s and Colitis Foundation IBD Partners cohort. Participants contribute physical activity data through smartphone apps or wearable devices in a bring-your-own-device model. Participants also complete biannual PRO questionnaires from the Patient-Reported Outcomes Measurement Information System short forms and IBD-specific questionnaires. K-means cluster analysis was used to generate physical activity clusters based on 3 key features: number of steps, duration of moderate to vigorous activity (minutes), and distance of activity (miles). Based on the clusters, we conducted a cross-sectional analysis to examine differences in mean questionnaire scores and participant characteristics using one-way ANOVA and chi-square tests. We also conducted a longitudinal analysis to examine individual cluster transitions among participants who completed multiple questionnaires, and mean differences in questionnaire scores were compared using 2-tailed paired sample t tests across 6-month periods. ResultsAmong 430 participants comprising 1255 six-week physical activity periods, we identified clusters of low (33.7%, n=423), moderate (46%, n=577), and high (20.3%, n=255) physical activity. Scores varied across clusters for depression (P=.004), pain interference (P

Cardiac fibrosis is characterized by excessive accumulation and deposition of ECM proteins. Cardiac fibrosis is commonly implicated in a variety of cardiovascular diseases, including post-myocardial infarction (MI). We have previously developed a dual-delivery nanogel therapeutic to deliver tissue plasminogen activator (tPA) and Y-27632 (a ROCK inhibitor) to address MI-associated coronary artery occlusion and downregulate cell-contractility mediated fibrotic responses. Initial in vitro studies were conducted on glass substrates. The study presented here employs the use of polyacrylamide (PA) gels and microgel thin films to mimic healthy and fibrotic cardiac tissue mechanics. Soft and stiff polyacrylamide substrates or high and low loss tangent microgel thin films were utilized to examine the influence of cell-substrate interactions on dual-loaded nanogel therapeutic efficacy. In the presence of Y-27632 containing nanogels, a reduction of fibrotic marker expression was noted on traditional PA gels mimicking healthy and fibrotic cardiac tissue mechanics. These findings differed on more physiologically relevant microgel thin films, where early treatment with the ROCK inhibitor intensified the fibrotic related responses.

Abstract Postnatal growth restriction (PGR) can increase the risk of cardiovascular disease (CVD) potentially due to impairments in oxidative phosphorylation (OxPhos) within cardiomyocyte mitochondria. The purpose of this investigation was to determine if PGR impairs cardiac metabolism, specifically OxPhos. FVB (Friend Virus B‐type) mice were fed a normal‐protein (NP: 20% protein), or low‐protein (LP: 8% protein) isocaloric diet 2 weeks before mating. LP dams produce ∼20% less milk, and pups nursed by LP dams experience reduced growth into adulthood as compared to pups nursed by NP dams. At birth (PN1), pups born to dams fed the NP diet were transferred to LP dams (PGR group) or a different NP dam (control group: CON). At weaning (PN21), all mice were fed the NP diet. At PN22 and PN80, mitochondria were isolated for respirometry (oxygen consumption rate, JO2) and fluorimetry (reactive oxygen species emission, JH2O2) analysis measured as baseline respiration (LEAK) and with saturating ADP (OxPhos). Western blotting at PN22 and PN80 determined protein abundance of uncoupling protein 3, peroxiredoxin‐6, voltage‐dependent anion channel and adenine nucleotide translocator 1 to provide further insight into mitochondrial function. ANOVAs with the main effects of diet, sex and age with α‐level of 0.05 was set a priori. Overall, PGR (7.8 ± 1.1) had significant (P = 0.01) reductions in respiratory control in complex I when compared to CON (8.9 ± 1.0). In general, our results show that PGR led to higher electron leakage in the form of free radical production and reactive oxygen species emission. No significant diet effects were found in protein abundance. The observed reduced respiratory control and increased ROS emission in PGR mice may increase risk for CVD in mice.

Over the years, the field of forensic anthropology has become more diverse, bringing unique perspectives to a previously homogeneous field. This diversification has been accompanied by recognizing the need for advocacy and activism in an effort to support the communities we serve: marginalized communities that are often overrepresented in the forensic population. As such, forensic anthropologists see the downstream effects of colonialism, white supremacy, inequitable policies, racism, poverty, homophobia, transphobia, gun violence, and misogyny. Some argue that advocacy and activism have no place in forensic anthropological praxis. The counterarguments for engaging in advocacy and activism uphold white, heterosexual, cisgender, and ableist privilege by arguing that perceived objectivity and unbiased perspectives are more important than personally biasing experiences and positionality that supposedly jeopardize the science and expert testimony. Advocacy and activism, however, are not new to the practice of anthropology. Whether through sociocultural anthropology, archaeology, or other areas of biological anthropology, activism and advocacy play an important role, using both the scientific method and community engagement. Using a North American approach, we detail the scope of the issues, address how advocacy and activism are perceived in the wider discipline of anthropology, and define ways in which advocacy and activism can be utilized more broadly in the areas of casework, research, and education.

Abstract Background Studies investigating the relationship between food insecurity and sleep among older populations are limited. This study aimed to cross-sectionally examine the associations between food sufficiency status and sleep outcomes in a nationally representative sample of older adults. Methods Our study included 1,665 older adults (≥ 65 years), using data from the 2013 and 2014 National Health and Aging Trends Study (NHATS). Food insufficiency was determined via participants’ experience and utilization of food assistance programs (FAP). Sleep outcomes, including nighttime and total sleep hours, sleep latency, and sleep quality, were derived from self-reported data. Multivariable linear regression and logistic regression models were used to estimate the associations between food sufficiency status and sleep outcomes. Results In 2013–2014, 86.1% of older adults were classified as food sufficient without FAP, 9.85% as food sufficient with FAP, and 4.08% as food insufficient. Adjusting for sociodemographic characteristics, food sufficient older adults with FAP reported more total sleep hours (𝛽 = 0.31, 95% CI: -0.02, 0.64) than those participants who are food sufficient without FAP. Further adjusting for health factors, food sufficient participants with FAP had more nighttime sleep hours and greater total sleep hours compared to those participants food sufficient without FAP. Compared to those deemed as food sufficient without FAP, food sufficient participants with FAP had lower odds of having longer sleep latency (OR = 0.50, 95% CI: 0.28, 0.89), after further adjusting for physical function performance. Conclusions Among older adults, food sufficiency with FAP is associated with greater total sleep hours, greater nighttime sleep hours, and lower odds of longer sleep latency. Our findings may help inform nutrition food assistance programs targeting older populations.

Abstract Both food insecurity and home and wild food procurement (HWFP), including gardening, increased in many countries during the COVID-19 pandemic; yet little evidence has demonstrated what impact HWFP had on food security. Using data from a representative sample of nearly 1000 residents in the two most rural US states (Vermont and Maine) conducted via an online survey in Spring/Summer 2021, as well as matching techniques, we compare food security outcomes among households who did and did not participate in HWFP in the first year of the pandemic. Nearly 60% of respondents engaged in HWFP in some way during the first year of the pandemic, with food insecure households more likely to do HWFP. Furthermore, HWFP early in the COVID-19 pandemic is associated with improved food security in the 9–12 months later, though these improvements were primarily associated with newly, not chronically, food insecure households. Newly and chronically food insecure households were more likely to want to continue these activities in the future, but also exhibited greater barriers to land access and costs associated with these activities. These results suggest that HWFP may provide food security improvements for certain households that utilize them, especially during crisis situations. Future research about HWFP should continue to explore multiple HWFP strategies, their barriers, and their potentially myriad relationships to food security, diet, and health outcomes, especially with longitudinal data.

Europe has suffered unprecedented epizootics of high pathogenicity avian influenza (HPAI) clade 2.3.4.4b H5N1 since Autumn 2021. As well as impacting upon commercial and wild avian species, the virus has also infected mammalian species more than ever observed previously. Mammalian species involved in spill over events have primarily been scavenging terrestrial carnivores and farmed mammalian species although marine mammals have also been affected. Alongside reports of detections of mammalian species found dead through different surveillance schemes, several mass mortality events have been reported in farmed and wild animals. In November 2022, an unusual mortality event was reported in captive bush dogs (Speothos venaticus) with clade 2.3.4.4b H5N1 HPAIV of avian origin being the causative agent. The event involved an enclosure of 15 bush dogs, 10 of which succumbed during a nine-day period with some dogs exhibiting neurological disease. Ingestion of infected meat is proposed as the most likely infection route.

A free-range organic broiler (Gallus gallus domesticus) premises in Staffordshire was infected by high pathogenicity avian influenza virus (HPAIV) H5N8 during the 2020–2021 epizootic in the United Kingdom (UK). Following initial confirmation of the infection in poultry, multiple wild bird species were seen scavenging on chicken carcasses. Detected dead wild birds were subsequently demonstrated to have been infected and succumbed to HPAIV H5N8. Initially, scavenging species, magpie (Pica pica) and raven (Corvus corax) were found dead on the premises but over the following days, buzzards (Buteo buteo) were also found dead within the local area with positive detection of HPAIV in submitted carcasses. The subacute nature of microscopic lesions within a buzzard was consistent with the timeframe of infection. Finally, a considerable number of free-living pheasants (Phasianus colchicus) were also found dead in the surrounding area, with carcasses having higher viral antigen loads compared to infected chickens. Limited virus dissemination was observed in the carcasses of the magpie, raven, and buzzard. Further, an avirulent avian paramyxovirus type 1 (APMV-1) was detected within poultry samples as well as in the viscera of a magpie infected with HPAIV. Immunohistochemistry did not reveal colocalization of avian paramyxovirus antigens with lesions, supporting an avirulent APMV-1 infection. Overall, this case highlights scenarios in which bi-directional transmission of avian viral diseases between commercial and wild bird species may occur. It also underlines the importance of bio separation and reduced access when infection pressure from HPAIV is high.

Abstract Bee declines pose a serious risk to agricultural sustainability, wild plant diversity, and the commercial bee industry, generating local and global concerns about bee health. Parasites, including micro‐parasites and macro‐parasites, negatively impact bee population dynamics. Management of parasites requires an understanding of the cyclic trends in prevalence and the factors impacting these patterns. In this study, we advance understanding of parasite epidemiology and transmission among members of the bee community toward the goal of improving predictability of parasite prevalence seasonally. Honey bees and bumble bees were collected throughout an active season and across multiple overwintering periods. These bees were molecularly tested for two common bee viruses—deformed wing virus (DWV) and black queen cell virus (BQCV)—and morphologically screened for Vairimorpha spp., nematodes, and parasitic flies to determine whether these parasites exhibit unique seasonal trends, if overwintering behavior impacts parasite survival, and how these patterns differ between honey bees and bumble bees. The results suggest consistent seasonal trends between honey bees and bumble bees; however, these trends are parasite‐specific. Honey bees consistently exhibited a higher magnitude of viral prevalence compared with bumble bees. Both honey bees and bumble bees reduced viral prevalence over the winter; however, only in bumble bees did this drop to negligible prevalence each spring. These data suggest that honey bees may have a larger impact on parasite transmission, as they pose to reinfect bees which otherwise would have very low prevalence each spring and sustain high levels of infection in communities year‐round.

Recently, politicians and legislative bodies have cited neurodevelopmental literature to argue that brain immaturity undermines decision-making regarding gender-affirming care (GAC) in youth. Here, we review this literature as it applies to adolescents’ ability to make decisions regarding GAC. The research shows that while adolescence is a time of peak risk-taking behavior that may lead to impulsive decisions, neurocognitive systems supporting adult-level decisions are available given deliberative processes that minimize influence of short-term rewards and peers. Since GAC decisions occur over an extended period and with support from adult caregivers and clinicians, adolescents can engage adult-level decision-making in this context. We also weigh the benefits of providing GAC access during adolescence and consider the significant costs of blocking or delaying GAC. Transgender and non-binary (TNB) adolescents face significant mental health challenges, many of which are mitigated by GAC access. Further, initiating the GAC process during adolescence, which we define as beginning at pubertal onset, leads to better long-term mental health outcomes than waiting until adulthood. Taken together, existing research indicates that many adolescents can make informed decisions regarding gender-affirming care, and that this care is critical for the well-being of TNB youth. We highlight relevant considerations for policy makers, researchers, and clinicians.

Parastagonospora nodorum is a necrotrophic pathogen of wheat that is particularly destructive in major wheat-growing regions of the United States, northern Europe, Australia, and South America. P. nodorum secretes necrotrophic effectors that target wheat susceptibility genes to induce programmed cell death (PCD), resulting in increased colonization of host tissue and, ultimately, sporulation to complete its pathogenic life cycle. Intensive research over the last two decades has led to the functional characterization of five proteinaceous necrotrophic effectors, SnTox1, SnToxA, SnTox267, SnTox3, and SnTox5, and three wheat susceptibility genes, Tsn1, Snn1, and Snn3D-1. Functional characterization has revealed that these effectors, in addition to inducing PCD, have additional roles in pathogenesis, including chitin binding that results in protection from wheat chitinases, blocking defense response signaling, and facilitating plant colonization. There are still large gaps in our understanding of how this necrotrophic pathogen is successfully manipulating wheat defense to complete its life cycle. This review summarizes our current knowledge, identifies knowledge gaps, and provides a summary of well-developed tools and resources currently available to study the P. nodorum–wheat interaction, which has become a model for necrotrophic specialist interactions. Further functional characterization of the effectors involved in this interaction and work toward a complete understanding of how P. nodorum manipulates wheat defense will provide fundamental knowledge about this and other necrotrophic interactions. Additionally, a broader understanding of this interaction will contribute to the successful management of Septoria nodorum blotch disease on wheat. [Graphic: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

The virulent form of Avian paramyxovirus-1 (APMV-1), commonly known as Newcastle Disease Virus (NDV), is a pathogen with global implications for avian health, affecting both wild and domestic bird populations. In Pakistan, recurrent Newcastle Disease (caused by NDV) outbreaks have posed significant challenges to the poultry industry. Extensive surveillance in Pakistan over 20 years has demonstrated a dynamic genetic diversity among circulating APMV-1 strains, emphasizing the potential necessity for customized vaccination strategies and continuous surveillance. In this study, 13 APMV-1-positive isolates harboring four different APMV-1 genotypes circulating throughout Pakistan were identified. These included the highly virulent genotypes VII and XIII, genotype XXI, commonly associated with Columbiformes, and genotype II, hypothesized to have been detected following vaccination. These findings underscore the intricate interplay of mutational events and host-immune interactions shaping the evolving NDV landscape. This study advances our understanding of the evolutionary dynamics of APMV-1 in Pakistan, highlighting the need for tailored vaccination strategies and continuous surveillance to enable effective APMV-1 management in avian populations, further emphasizing the importance of globally coordinated strategies to tackle APMV-1, given its profound impact on wild and domestic birds.

Adolescence has been hypothesized to be a critical period for the development of human association cortex and higher-order cognition. A defining feature of critical period development is a shift in the excitation: inhibition (E/I) balance of neural circuitry, however how changes in E/I may enhance cortical circuit function to support maturational improvements in cognitive capacities is not known. Harnessing ultra-high field 7 T MR spectroscopy and EEG in a large, longitudinal cohort of youth (N = 164, ages 10–32 years old, 347 neuroimaging sessions), we delineate biologically specific associations between age-related changes in excitatory glutamate and inhibitory GABA neurotransmitters and EEG-derived measures of aperiodic neural activity reflective of E/I balance in prefrontal association cortex. Specifically, we find that developmental increases in E/I balance reflected in glutamate:GABA balance are linked to changes in E/I balance assessed by the suppression of prefrontal aperiodic activity, which in turn facilitates robust improvements in working memory. These findings indicate a role for E/I-engendered changes in prefrontal signaling mechanisms in the maturation of cognitive maintenance. More broadly, this multi-modal imaging study provides evidence that human association cortex undergoes physiological changes consistent with critical period plasticity during adolescence.

The Institutional Review Board (IRB) is fundamental to conducting ethical research involving human subjects. IRB applications require detailed descriptions of the research and specific indications of how the research will be implemented. This can be difficult for inexperienced researchers. Preparing the application is a significant time commitment, even for experienced researchers. In order to lighten the administrative burden on busy clinical professionals, this software application will automatically generate a draft human subject research protocol (the most laborious element of an IRB application) based on responses to a short form. This technology uses generative AI and a custom literature search plug-in to draft the protocol from succinct, user-provided details. User inputs include a brief description of the research, including the hypothesis, inclusion/exclusion criteria, and the study design type (e.g., randomized clinical trial). This tool can expedite the IRB application creation process, provide additional consistency for reviewers, and may reduce clinician researcher burnout through a reduction in clerical work thereby facilitating participation in meaningful research.

Abstract Theories of human neurobehavioral development suggest executive functions mature from childhood through adolescence, underlying adolescent risk-taking and the emergence of psychopathology. Investigations with relatively small datasets or narrow subsets of measures have identified general executive function development, but the specific maturational timing and independence of potential executive function subcomponents remain unknown. Integrating four independent datasets (N = 10,766; 8–35 years old) with twenty-three measures from seventeen tasks, we provide a precise charting, multi-assessment investigation, and replication of executive function development from adolescence to adulthood. Across assessments and datasets, executive functions follow a canonical non-linear trajectory, with rapid and statistically significant development in late childhood to mid-adolescence (10–15 years old), before stabilizing to adult-levels in late adolescence (18–20 years old). Age effects are well captured by domain-general processes that generate reproducible developmental templates across assessments and datasets. Results provide a canonical trajectory of executive function maturation that demarcates the boundaries of adolescence and can be integrated into future studies.

Abstract The effects of heterogeneous infection, vaccination and boosting histories prior to and during pregnancy have not been extensively studied and are likely important for protection of neonates. We measure levels of spike binding antibodies in 4600 patients and their neonates with different vaccination statuses, with and without history of SARS-CoV-2 infection. We investigate neutralizing antibody activity against different SARS-CoV-2 variant pseudotypes in a subset of 259 patients and determined correlation between IgG levels and variant neutralizing activity. We further study the ability of maternal antibody and neutralizing measurements to predict neutralizing antibody activity in the umbilical cord blood of neonates. In this work, we show SARS-CoV-2 vaccination and boosting, especially in the setting of previous infection, leads to significant increases in antibody levels and neutralizing activity even against the recent omicron BA.1 and BA.5 variants in both pregnant patients and their neonates.

In January 2020, increased mortality was reported in a small broiler breeder flock in County Fermanagh, Northern Ireland. Gross pathological findings included coelomitis, oophoritis, salpingitis, visceral gout, splenomegaly, and renomegaly. Clinical presentation included inappetence, pronounced diarrhoea, and increased egg deformation. These signs, in combination with increased mortality, triggered a notifiable avian disease investigation. High pathogenicity avian influenza virus (HPAIV) was not suspected, as mortality levels and clinical signs were not consistent with HPAIV. Laboratory investigation demonstrated the causative agent to be a low-pathogenicity avian influenza virus (LPAIV), subtype H6N1, resulting in an outbreak that affected 15 premises in Northern Ireland. The H6N1 virus was also associated with infection on 13 premises in the Republic of Ireland and six in Great Britain. The close genetic relationship between the viruses in Ireland and Northern Ireland suggested a direct causal link whereas those in Great Britain were associated with exposure to a common ancestral virus. Overall, this rapidly spreading outbreak required the culling of over 2 million birds across the United Kingdom and the Republic of Ireland to stamp out the incursion. This report demonstrates the importance of investigating LPAIV outbreaks promptly, given their substantial economic impacts.

Urbanization can influence many environmental factors that can affect the condition, immunity, and gut microbiota of birds. Over the past several decades, the Galápagos Islands of Ecuador have experienced increasing human activity, which has led to recent changes in the morphology, gut microbiota, and immunity of Darwin’s finches. However, these traits have not been characterized before the exponential growth of human population size and tourist visitation rates, i.e., before 2009. The goal of this study was to determine the effect of land use on the fecal microbiota, immune response, and body measurements of Darwin’s finches in 2008, at a time of rapidly increasing human activity on the islands. Specifically, we compared fecal microbiota (bacterial diversity, community structure and membership, and relative abundance of bacterial taxa), proxies of immunity (lysozyme activity and haptoglobin, complement antibody, and natural antibody levels), and body measurements (body mass and condition, tarsus length) across undeveloped, agricultural, and urban areas for medium ground finches ( Geospiza fortis ) and small ground finches ( G. fuliginosa ). Lysozyme activity was lower and observed bacterial species richness was higher in urban areas compared to non-urban areas across both finch species. In medium ground finches, four genera ( Methylobacterium-Methylorubrum , Escherichia-Shigella , Brucella , and Citrobacter spp.) were higher in urban areas compared to undeveloped areas. In small ground finches, Paucibacter , Achromobacter , Delftia , Stenotrophomonas , and Brucella spp. had higher relative abundances in undeveloped and agricultural areas whereas the genus Cutibacterium was more abundant in finches from urban and agricultural areas than in finches from undeveloped areas. Medium ground finches were smaller in undeveloped areas compared to the other two areas, but body mass of small ground finches did not differ across areas. Our results suggest that human activity can have an impact on immune measures and gut microbiota of Darwin’s finches.

High pathogenicity avian influenza viruses (HPAIVs) cause high morbidity and mortality in poultry species. HPAIV prevalence means high numbers of infected wild birds could lead to spill over events for farmed poultry. How these pathogens survive in the environment is important for disease maintenance and potential dissemination. We evaluated the temperature-associated survival kinetics for five clade 2.3.4.4 H5Nx HPAIVs (UK field strains between 2014 and 2021) incubated at up to three temperatures for up to ten weeks. The selected temperatures represented northern European winter (4 °C) and summer (20 °C); and a southern European summer temperature (30 °C). For each clade 2.3.4.4 HPAIV, the time in days to reduce the viral infectivity by 90% at temperature T was established (DT), showing that a lower incubation temperature prolonged virus survival (stability), where DT ranged from days to weeks. The fastest loss of viral infectivity was observed at 30 °C. Extrapolation of the graphical DT plots to the x-axis intercept provided the corresponding time to extinction for viral decay. Statistical tests of the difference between the DT values and extinction times of each clade 2.3.4.4 strain at each temperature indicated that the majority displayed different survival kinetics from the other strains at 4 °C and 20 °C.

Forensic anthropology and, more broadly, the forensic sciences have only recently begun to acknowledge the importance of lived gender identity in the resolution of forensic cases, the epidemic of anti-transgender violence, and the need to seek practical solutions. The current literature suggests that forensic anthropologists are becoming aware of these issues and are working toward efforts to improve identification of transgender and gender diverse (TGD) persons. The scope of the problem, however, is not limited to methodology and instead can be traced to systemic anti-trans stigma ingrained within our cultural institutions. As such, we call on forensic anthropologists to counteract cisgenderism and transphobia and promote gender equity and inclusion in their practice. In this paper, we identify three areas in which forensic anthropologists may be positioned to intervene on cisgenderist practices and systems: in casework, research, and education. This paper aims to provide strategies for forensic anthropologists to improve resolution of TGD cases, produce more nuanced, gender-informed research, and promote gender equity and inclusion in the field.

Abstract In the present study, we tested a visual feedback triggering system based on real-time tracking of response time (RT) in a sustained attention task. In our task, at certain points, brief visual feedback epochs were presented without interrupting the task itself. When these feedback epochs were performance-linked—meaning that they were triggered because participants were responding more quickly than usual—RTs were slowed after the presentation of feedback. However, visual feedback epochs displayed at predetermined times that were independent of participants’ performance did not slow RTs. Results from a second experiment support the idea that this is not simply a return to baseline that would have occurred had the feedback not been presented, but instead suggest that the feedback itself was effective in altering participants’ responses. In a third experiment, we replicated this result across with both written word feedback and visual symbolic feedback, as well as in cases where the participant was explicitly told that the feedback was linked to their performance. All together, these data provide insight into potential mechanisms for detecting and disrupting lapses in sustained attention without interrupting a continuous task.

Introduction There is an urgent need for scalable strategies for treating overweight and obesity in clinical settings. PROPS 2.0 (Partnerships for Reducing Overweight and Obesity with Patient-Centered Strategies 2.0) aims to adapt and implement the combined intervention from the PROPS Study at scale, in a diverse cross-section of patients and providers.Methods and analysis We are implementing PROPS 2.0 across a variety of clinics at Brigham and Women’s Hospital, targeting enrolment of 5000 patients. Providers can refer patients or patients can self-refer. Eligible patients must be ≥20 years old and have a body mass index (BMI) of ≥30 kg/m2 or a BMI of 25–29.9 kg/m2 plus another cardiovascular risk factor or obesity-related condition. After enrolment, patients register for the RestoreHealth online programme/app (HealthFleet Inc.) and participate for 12 months. Patients can engage with the programme and receive personalized feedback from a coach. Patient navigators help to enrol patients, enter updates in the electronic health record, and refer patients to additional resources. The RE-AIM (Reach, Effectiveness, Adoption, Implementation, and Maintenance) framework is guiding the evaluation.Ethics and dissemination The Mass General Brigham Human Research Committee approved this protocol. An implementation guide will be created and disseminated, to help other sites adopt the intervention in the future.Trial registration number NCT0555925.

The STABILISE (stent-assisted balloon-induced intimal disruption and relamination in aortic dissection repair) technique has shown promising results for treating type B aortic dissections, but the potential exists for fatal adverse effects. We present a case of infrarenal aortic rupture while using a compliant balloon to balloon mold the true lumen inside previously placed bare metal stents during the STABILISE technique. Caution is advised for providers who wish to perform the STABILISE technique, and we recommend using a semi-compliant balloon sized to the smallest total aortic diameter to mitigate the risk of rupture.

Sepsis is a common and life-threatening disorder with an alarmingly high mortality rate. Unfortunately, this rate has not decreased significantly over the last decade and the number of septic cases is increasing each year. Despite sepsis affecting millions of people annually, there is still not an established standard of care. The development of a therapy that targets the thromboinflammation characteristic of sepsis is imperative. Until recently, research has focused on uncovering individual pathways to target. As more of the pathophysiology of sepsis has become understood and more biomarkers uncovered, the interplay between endothelial cells, platelets, and leukocytes has emerged as a critical event. Therefore, a multi-targeted approach is clearly required for designing an effective treatment for sepsis. The versatility of biomaterials offers a promising solution in that they can be designed to target and affect multiple pathways and systems and safely inhibit excessive inflammation while maintaining hemostasis. Already, studies have demonstrated the ability of biomaterials to target different processes and stages in sepsis-induced inflammation and coagulopathy. Moreover, some biomaterials offer inherent anti-inflammatory and hemostatic qualities. This review aims to discuss the most recent advancements in biomaterial development designed to address inflammation, coagulopathy, and thromboinflammation.

IntroductionThe Eidolon helvum fruit bat is one of the most widely distributed fruit bats in Africa and known to be a reservoir for several pathogenic viruses that can cause disease in animals and humans. To assess the risk of zoonotic spillover, we conducted a serological survey of 304 serum samples from E. helvum bats that were captured for human consumption in Makurdi, Nigeria.MethodsUsing pseudotyped viruses, we screened 304 serum samples for neutralizing antibodies against viruses from the Coronaviridae, Filoviridae, Orthomyxoviridae and Paramyxoviridae families.ResultsWe report the presence of neutralizing antibodies against henipavirus lineage GH-M74a virus (odds ratio 6.23; p

Abstract Background The COVID‐19 pandemic resulted in a lapse in routine health care and cancer screenings for many individuals. This study sought to improve our understanding of the impact of the COVID‐19 pandemic on women being treated for breast cancer, both in general, and specifically related to their diagnosis. Methods Semi‐structured interviews were conducted between August 2021 and February 2022 with women who were receiving neoadjuvant chemotherapy for early‐stage breast cancer at the Stefanie Spielman Comprehensive Breast Center in Columbus, Ohio. Interviews were recorded and transcribed verbatim. Transcripts were coded using deductive dominant thematic analysis and inductive coding that allowed for categorization of data as well as identification of emergent themes. Results Data collected from our 19 interviews revealed that the COVID‐19 pandemic posed important challenges for breast cancer patients including fear of COVID‐19 infection and feelings of isolation. Most interviewees noted they had been vaccinated against COVID‐19 because of a desire to protect themselves and others from getting sick. Some women also expressed concerns about having delayed their screening mammograms due to the pandemic. Several patients described unexpected positive aspects of the pandemic such as being able to spend more time with family and having the ability to continue working because of the option to work from home during their cancer treatment. Conclusions Our findings provide important insight about the impact of COVID‐19 on breast cancer patients. We highlight the positives that have been reported because of the pandemic, as well as the need to address delayed breast cancer screening.

Summary: Background: Multisystem inflammatory syndrome in children (MIS-C) is a severe complication of SARS-CoV-2 infection. It remains unclear how MIS-C phenotypes vary across SARS-CoV-2 variants. We aimed to investigate clinical characteristics and outcomes of MIS-C across SARS-CoV-2 eras. Methods: We performed a multicentre observational retrospective study including seven paediatric hospitals in four countries (France, Spain, U.K., and U.S.). All consecutive confirmed patients with MIS-C hospitalised between February 1st, 2020, and May 31st, 2022, were included. Electronic Health Records (EHR) data were used to calculate pooled risk differences (RD) and effect sizes (ES) at site level, using Alpha as reference. Meta-analysis was used to pool data across sites. Findings: Of 598 patients with MIS-C (61% male, 39% female; mean age 9.7 years [SD 4.5]), 383 (64%) were admitted in the Alpha era, 111 (19%) in the Delta era, and 104 (17%) in the Omicron era. Compared with patients admitted in the Alpha era, those admitted in the Delta era were younger (ES −1.18 years [95% CI −2.05, −0.32]), had fewer respiratory symptoms (RD −0.15 [95% CI −0.33, −0.04]), less frequent non-cardiogenic shock or systemic inflammatory response syndrome (SIRS) (RD −0.35 [95% CI −0.64, −0.07]), lower lymphocyte count (ES −0.16 × 109/uL [95% CI −0.30, −0.01]), lower C-reactive protein (ES −28.5 mg/L [95% CI −46.3, −10.7]), and lower troponin (ES −0.14 ng/mL [95% CI −0.26, −0.03]). Patients admitted in the Omicron versus Alpha eras were younger (ES −1.6 years [95% CI −2.5, −0.8]), had less frequent SIRS (RD −0.18 [95% CI −0.30, −0.05]), lower lymphocyte count (ES −0.39 × 109/uL [95% CI −0.52, −0.25]), lower troponin (ES −0.16 ng/mL [95% CI −0.30, −0.01]) and less frequently received anticoagulation therapy (RD −0.19 [95% CI −0.37, −0.04]). Length of hospitalization was shorter in the Delta versus Alpha eras (−1.3 days [95% CI −2.3, −0.4]). Interpretation: Our study suggested that MIS-C clinical phenotypes varied across SARS-CoV-2 eras, with patients in Delta and Omicron eras being younger and less sick. EHR data can be effectively leveraged to identify rare complications of pandemic diseases and their variation over time. Funding: None.

Summary: Background: Characterizing Post-Acute Sequelae of COVID (SARS-CoV-2 Infection), or PASC has been challenging due to the multitude of sub-phenotypes, temporal attributes, and definitions. Scalable characterization of PASC sub-phenotypes can enhance screening capacities, disease management, and treatment planning. Methods: We conducted a retrospective multi-centre observational cohort study, leveraging longitudinal electronic health record (EHR) data of 30,422 patients from three healthcare systems in the Consortium for the Clinical Characterization of COVID-19 by EHR (4CE). From the total cohort, we applied a deductive approach on 12,424 individuals with follow-up data and developed a distributed representation learning process for providing augmented definitions for PASC sub-phenotypes. Findings: Our framework characterized seven PASC sub-phenotypes. We estimated that on average 15.7% of the hospitalized COVID-19 patients were likely to suffer from at least one PASC symptom and almost 5.98%, on average, had multiple symptoms. Joint pain and dyspnea had the highest prevalence, with an average prevalence of 5.45% and 4.53%, respectively. Interpretation: We provided a scalable framework to every participating healthcare system for estimating PASC sub-phenotypes prevalence and temporal attributes, thus developing a unified model that characterizes augmented sub-phenotypes across the different systems. Funding: Authors are supported by National Institute of Allergy and Infectious Diseases, National Institute on Aging, National Center for Advancing Translational Sciences, National Medical Research Council, National Institute of Neurological Disorders and Stroke, European Union, National Institutes of Health, National Center for Advancing Translational Sciences.

Children with attention-deficit/hyperactivity disorder (ADHD) exhibit impairments in response inhibition. These impairments are ameliorated by modulating dopamine (DA) via the administration of rewards or stimulant medication like methylphenidate (MPH). It is currently unclear whether intrinsic DA availability impacts these effects of dopaminergic modulation on response inhibition. Thus, we estimated intrinsic DA availability using magnetic resonance-based assessments of basal ganglia and thalamic tissue iron in 36 medication-naïve children with ADHD and 29 typically developing (TD) children (8–12 y) who underwent fMRI scans and completed standard and rewarded go/no-go tasks. Children with ADHD additionally participated in a double-blind, randomized, placebo-controlled, crossover MPH challenge. Using linear regressions covarying for age and sex, we determined there were no group differences in brain tissue iron. We additionally found that higher putamen tissue iron was associated with worse response inhibition performance in all participants. Crucially, we observed that higher putamen and caudate tissue iron was associated with greater responsivity to MPH, as measured by improved task performance, in participants with ADHD. These results begin to clarify the role of subcortical brain tissue iron, a measure associated with intrinsic DA availability, in the cognitive effects of reward- and MPH-related dopaminergic modulation in children with ADHD and TD children.

Background: Adult zebrafish are capable of photoreceptor (PR) regeneration following acute phototoxic lesion (AL). We developed a chronic low light (CLL) exposure model that more accurately reflects chronic PR degeneration observed in many human retinal diseases.Methods: Here, we characterize the morphological and transcriptomic changes associated with acute and chronic models of PR degeneration at 8 time-points over a 28-day window using immunohistochemistry and 3′mRNA-seq.Results: We first observed a differential sensitivity of rod and cone PRs to CLL. Next, we found no evidence for Müller glia (MG) gliosis or regenerative cell-cycle re-entry in the CLL model, which is in contrast to the robust gliosis and proliferative response from resident MG in the AL model. Differential responses of microglia between the models was also observed. Transcriptomic comparisons between the models revealed gene-specific networks of PR regeneration and degeneration, including genes that are activated under conditions of chronic PR stress. Finally, we showed that CLL is at least partially reversible, allowing for rod and cone outer segment outgrowth and replacement of rod cell nuclei via an apparent upregulation of the existing rod neurogenesis mechanism.Discussion: Collectively, these data provide a direct comparison of the morphological and transcriptomic PR degeneration and regeneration models in zebrafish.

Abstract Dietary supplement use is common in the United States. Supplements are regulated by the US Food and Drug Administration (FDA) under a separate set of guidelines from typical food and drug products. This case report describes a patient who presented to the emergency department (ED) with abdominal pain, vomiting, and generalized weakness. On detailed history, we learned that he had been taking a supplement called Artri Ajo King for 18 months, followed by recent abrupt cessation before his ED presentation. He was subsequently found to have a low serum cortisol level and was diagnosed with secondary adrenal insufficiency by a cosyntropin stimulation test. Ultimately, he was started on hydrocortisone with resolution of his symptoms. This case illustrates the consequence of allowing dietary supplements to be sold before FDA evaluation as well as the importance of physicians eliciting history of supplement use and offering a culturally competent discussion with their patients regarding supplement use.

ABSTRACT Since 2020, the United Kingdom and Europe have experienced annual epizootics of high-pathogenicity avian influenza virus (HPAIV). The first epizootic, during the autumn/winter of 2020–2021, involved six H5Nx subtypes, although H5N8 HPAIV dominated in the United Kingdom. While genetic assessments of the H5N8 HPAIVs within the United Kingdom demonstrated relative homogeneity, there was a background of other genotypes circulating at a lower degree with different neuraminidase and internal genes. Following a small number of detections of H5N1 in wild birds over the summer of 2021, the autumn/winter of 2021–2022 saw another European H5 HPAIV epizootic that dwarfed the prior epizootic. This second epizootic was dominated almost exclusively by H5N1 HPAIV, although six distinct genotypes were defined. We have used genetic analysis to evaluate the emergence of different genotypes and proposed reassortment events that have been observed. The existing data suggest that the H5N1 viruses circulating in Europe during late 2020 continued to circulate in wild birds throughout 2021, with minimal adaptation, but then went on to reassort with AIVs in the wild bird population. We have undertaken an in-depth genetic assessment of H5 HPAIVs detected in the United Kingdom over two winter seasons and demonstrate the utility of in-depth genetic analyses in defining the diversity of H5 HPAIVs circulating in avian species, the potential for zoonotic risk, and whether incidents of lateral spread can be defined over independent incursions of infections from wild birds. This provides key supporting data for mitigation activities. IMPORTANCE High-pathogenicity avian influenza virus (HPAIV) outbreaks devastate avian species across all sectors, having both economic and ecological impacts through mortalities in poultry and wild birds, respectively. These viruses can also represent a significant zoonotic risk. Since 2020, the United Kingdom has experienced two successive outbreaks of H5 HPAIV. While H5N8 HPAIV was predominant during the 2020–2021 outbreak, other H5 subtypes were also detected. The following year, there was a shift in the subtype dominance to H5N1 HPAIV, but multiple H5N1 genotypes were detected. Through the thorough utilization of whole-genome sequencing, it was possible to track and characterize the genetic evolution of these H5 HPAIVs in United Kingdom poultry and wild birds. This enabled us to assess the risk posed by these viruses at the poultry-wild bird and the avian-human interfaces and to investigate the potential lateral spread between infected premises, a key factor in understanding the threat to the commercial sector.

Rapid development and adoption of natural language processing (NLP) techniques has led to a multitude of exciting and innovative societal and health care applications. These advancements have also generated concerns around perpetuation of historical injustices and that these tools lack cultural considerations. While traditional health care NLP techniques typically include clinical subject matter experts to extract health information or aid in interpretation, few NLP tools involve community stakeholders with lived experiences. In this perspective paper, we draw upon the field of community-based participatory research, which gathers input from community members for development of public health interventions, to identify and examine ways to equitably involve communities in developing health care NLP tools. To realize the potential of community-based NLP (CBNLP), research and development teams must thoughtfully consider mechanisms and resources needed to effectively collaborate with community members for maximal societal and ethical impact of NLP-based tools.

Abstract Aim To compare factors associated with exclusive breastfeeding (EBF) within 1 h of birth, within 3 days, and within the first 6 months post‐birth. Methods We used multivariate logistic regression models and data from “The Alive and Thrive Phase 2 Amhara Baseline Survey 2015” from Ethiopia (N = 3113). Results Giving colostrum was strongly associated with EBF at all three time points, controlling for multiple confounders. Putting the baby to the breast before cleaning the baby and before cleaning the mother was significantly associated with EBF within 1 h and for the first 3 days. EBF within an hour of birth was more likely for girl babies than boy babies. Having a healthcare professional check whether the baby was sucking well was significantly associated with EBF 3 days post‐birth. Conclusions The World Health Organization recommends breastfeeding within 1 h of birth and exclusively thereafter for 6 months, which can improve health outcomes for infants and children. In Ethiopia, many factors influence breastfeeding practices, but little is known about how these factors differ at various key timepoints in the 6 months after birth. Our study provides important information on correlates of EBF at three timepoints and shows that factors that are significantly correlated with EBF vary over time. Future research should assess the potential causal links among statistically significant associations between EBF and risk factors at various times between birth and 6 months of age. Ultimately, these findings have the potential to inform areas of intervention related to promoting EBF.

Abstract Background Plants are found in a large percentage of indoor environments, yet the potential for bacteria associated with indoor plant leaves and soil to colonize human skin remains unclear. We report results of experiments in a controlled climate chamber to characterize bacterial communities inhabiting the substrates and leaves of five indoor plant species, and quantify microbial transfer dynamics and residence times on human skin following simulated touch contact events. Controlled bacterial propagule transfer events with soil and leaf donors were applied to the arms of human occupants and repeatedly measured over a 24-h period using 16S rRNA gene amplicon sequencing. Results Substrate samples had greater biomass and alpha diversity compared to leaves and baseline skin bacterial communities, as well as dissimilar taxonomic compositions. Despite these differences in donor community diversity and biomass, we observed repeatable patterns in the dynamics of transfer events. Recipient human skin bacterial communities increased in alpha diversity and became more similar to donor communities, an effect which, for soil contact only, persisted for at least 24 h. Washing with soap and water effectively returned communities to their pre-perturbed state, although some abundant soil taxa resisted removal through washing. Conclusions This study represents an initial characterization of bacterial relationships between humans and indoor plants, which represent a potentially valuable element of biodiversity in the built environment. Although environmental microbiota are unlikely to permanently colonize skin following a single contact event, repeated or continuous exposures to indoor biodiversity may be increasingly relevant for the functioning and diversity of the human microbiome as urbanization continues.

Song et al. study the relationship between agonist-antagonist muscle strain (AMS) and motor control and perception in lower limb amputees, with some receiving a myoneural interface intervention. The authors report that the degree of AMS within the residual limb is associated with preserved motor control and perception.

Epithelial tissues can be polarized along two axes: in addition to apical-basal polarity they are often also polarized within the plane of the epithelium, known as planar cell polarity (PCP). PCP depends upon the conserved Wnt/Frizzled (Fz) signaling factors, including Fz itself and Van Gogh (Vang/Vangl in mammals). Here, taking advantage of the complementary features of Drosophila wing and mouse skin PCP establishment, we dissect how Vang/Vangl phosphorylation on a specific conserved tyrosine residue affects its interaction with two cytoplasmic core PCP factors, Dishevelled (Dsh/Dvl1-3 in mammals) and Prickle (Pk/Pk1-3). We demonstrate that Pk and Dsh/Dvl bind to Vang/Vangl in an overlapping region centered around this tyrosine. Strikingly, Vang/Vangl phosphorylation promotes its binding to Prickle, a key effector of the Vang/Vangl complex, and inhibits its interaction with Dishevelled. Thus phosphorylation of this tyrosine appears to promote the formation of the mature Vang/Vangl-Pk complex during PCP establishment and conversely it inhibits the Vang interaction with the antagonistic effector Dishevelled. Intriguingly, the phosphorylation state of this tyrosine might thus serve as a switch between transient interactions with Dishevelled and stable formation of Vang-Pk complexes during PCP establishment.

IntroductionThe primary goal of this work is to broaden and enhance the options for induction of protective CD8+ T cells against HIV-1 and respiratory pathogens.MethodsWe explored the advantages of the parainfluenza virus 5 (PIV5) vector for delivery of pathogen-derived transgenes alone and in combination with the in-human potent regimen of simian adenovirus ChAdOx1 prime-poxvirus MVA boost delivering bi-valent mosaic of HIV-1 conserved regions designated HIVconsvX.ResultsWe showed in BALB/c mice that the PIV5 vector expressing the HIVconsvX immunogens could be readily incorporated with the other two vaccine modalities into a single regimen and that for specific vector combinations, mucosal CD8+ T-cell induction was enhanced synergistically by a combination of the intranasal and intramuscular routes of administration.DiscussionEncouraging safety and immunogenicity data from phase 1 human trials of ChAdOx1- and MVA-vectored vaccines for HIV-1, and PIV5-vectored vaccines for SARS-CoV-2 and respiratory syncytial virus pave the way for combining these vectors for HIV-1 and other indications in humans.

ABSTRACT: Adolescence is a stage of development characterized by neurodevelopmental specialization of cognitive processes. In particular, working memory continues to improve through adolescence, with increases in response accuracy and decreases in response latency continuing well into the twenties. Human electroencephalogram (EEG) studies indicate that gamma oscillations (35–65 Hz) during the working memory delay period support the maintenance of mnemonic information guiding subsequent goal-driven behavior, which decrease in power with development. Importantly, recent electrophysiological studies have shown that gamma events, more so than sustained activity, may underlie working memory maintenance during the delay period. However, developmental differences in gamma events during working memory have not been studied. Here, we used EEG in conjunction with a novel spectral event processing approach to investigate age-related differences in transient gamma band activity during a memory guided saccade (MGS) task in 164 10- to 30-year-olds. Total gamma power was found to significantly decrease through adolescence, replicating prior findings. Results from the spectral event pipeline showed age-related decreases in the mean power of gamma events and trial-by-trial power variability across both the delay period and fixation epochs of the MGS task. In addition, we found that while event number decreased with age during the fixation period, the developmental decrease during the delay period was more dramatic, resulting in an increase in event spiking from fixation to delay in adolescence but not adulthood. While average power of the transient gamma events was found to mediate age-related differences in total gamma power in the fixation and delay periods, the number of gamma events was related to total power in only the delay period, suggesting that the power of gamma events may underlie the sustained gamma activity seen in EEG literature while the number of events may directly support age-related improvements in working memory maintenance. Our findings provide compelling new evidence for mechanistic changes in neural processing characterized by refinements in neural function as behavior becomes optimized in adulthood.

Shifting motor actions from reflexively reacting to an environmental stimulus to predicting it allows for smooth synchronization of behavior with the outside world. This shift relies on the identification of patterns within the stimulus – knowing when a stimulus is predictable and when it is not – and launching motor actions accordingly. Failure to identify predictable stimuli results in movement delays whereas failure to recognize unpredictable stimuli results in early movements with incomplete information that can result in errors. Here we used a metronome task, combined with video-based eye-tracking, to quantify temporal predictive learning and performance to regularly paced visual targets at 5 different interstimulus intervals (ISIs). We compared these results to the random task where the timing of the target was randomized at each target step. We completed these tasks in female pediatric psychiatry patients (age range: 11–18 years) with borderline personality disorder (BPD) symptoms, with (n = 22) and without (n = 23) a comorbid attention-deficit hyperactivity disorder (ADHD) diagnosis, against controls (n = 35). Compared to controls, BPD and ADHD/BPD cohorts showed no differences in their predictive saccade performance to metronome targets, however, when targets were random ADHD/BPD participants made significantly more anticipatory saccades (i.e., guesses of target arrival). The ADHD/BPD group also significantly increased their blink rate and pupil size when initiating movements to predictable versus unpredictable targets, likely a reflection of increased neural effort for motor synchronization. BPD and ADHD/BPD groups showed increased sympathetic tone evidenced by larger pupil sizes than controls. Together, these results support normal temporal motor prediction in BPD with and without ADHD, reduced response inhibition in BPD with comorbid ADHD, and increased pupil sizes in BPD patients. Further these results emphasize the importance of controlling for comorbid ADHD when querying BPD pathology.

The United Kingdom (UK) and Europe have seen successive outbreaks of H5N1 clade 2.3.4.4b high-pathogenicity avian influenza virus (HPAIV) since 2020 peaking in the autumn/winter periods. During the 2021/22 season, a mass die-off event of Svalbard Barnacle Geese (Branta leucopsis) was observed on the Solway Firth, a body of water on the west coast border between England and Scotland. This area is used annually by Barnacle Geese to over-winter, before returning to Svalbard to breed. Following initial identification of HPAIV in a Barnacle Goose on 8 November 2021, up to 32% of the total Barnacle Goose population may have succumbed to disease by the end of March 2022, along with other wild bird species in the area. Potential adaptation of the HPAIV to the Barnacle Goose population within this event was evaluated. Whole-genome sequencing of thirty-three HPAIV isolates from wild bird species demonstrated that there had been two distinct incursions of the virus, but the two viruses had remained genetically stable within the population, whilst viruses from infected wild birds were closely related to those from poultry cases occurring in the same region. Analysis of sera from the following year demonstrated that a high percentage (76%) of returning birds had developed antibodies to H5 AIV. This study demonstrates genetic stability of this strain of HPAIV in wild Anseriformes, and that, at the population scale, whilst there is a significant impact on survival, a high proportion of birds recover following infection.

Abstract Background To respond to the COVID-19 pandemic, the Substance Abuse and Mental Health Services Administration-funded Technology Transfer Centers had to rapidly adapt to ensure that the behavioral health workforce had continuous access to remote training and technical assistance (TTA). Although the Technology Transfer Centers have historically relied partially upon virtual methods for delivering TTA, the shift to a strictly virtual approach necessitated by COVID-19 restrictions has raised new questions for how to best proceed with services when social distancing guidelines are relaxed. The objective of this exploratory paper was to compare TTA provision in the six-month period prior to (9/1/19 thru 2/28/20) and during (4/1/20 thru 9/30/20) early COVID-19 restrictions to determine the extent to which the shift to virtual service provision impacted the behavioral health and medical workforce. Specifically, we examined participants’ access to TTA, geographic reach of TTA, and workforce perceptions of satisfaction and utility with TTA provision. Method Participant and event-level data were analyzed to compare the following metrics before and during the COVID pandemic: number of events and attendees; participant demographics; zip codes reached; coverage of rural, suburban, and urban areas; and perceptions of satisfaction with and utility of training. Results Findings showed a 40% increase in the number of events delivered (p

Research has linked childhood sexual trauma (CST) with adverse adult outcomes (AAOs) that span physical, psychological, and social domains of functioning. Differences in conceptualizing and measuring CST, however, have inhibited the examination of trauma-related variables hypothesized to impact adult outcomes. We used National Sexual Health Survey (NSHS; 1995–1996) data to examine trauma chronicity (i.e., duration) and AAOs (domains: physical and mental health, close relationships, and achievement). The NSHS (N = 6537, 18–70 years) assessed duration using perpetrator-specific CST reports. Adjusting for background characteristics, we examined CST duration in relation to AAOs and CST-related help-seeking. Approximately 8% of participants reported CST. Chronic (vs. single-exposure) CST survivors were at substantially higher risk of experiencing AAOs [i.e., mean AAOs and specific AAOs (e.g., physical and emotional health problems, divorce/separation, and poverty)]. CST had direct effects on sexual dysfunction and satisfaction, and on relationship stressors which may impact sexual relationship quality. Although 62% of CST survivors did not seek help, those with more chronic CST histories reported a higher prevalence of trauma-related help-seeking. Our work underscores the importance of examining CST chronicity in relation to long-term developmental outcomes. Chronicity assessment may be an important screening tool in the therapeutic context and in broader community screening efforts.