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ObjectivesThe Short-Form HIV Disability Questionnaire (SF-HDQ) was developed to measure the presence, severity and episodic nature of health challenges across six domains. Our aim was to assess the sensibility, utility and implementation of the SF-HDQ in clinical practice.DesignMixed methods study design involving semistructured interviews and questionnaire administration.ParticipantsWe recruited adults living with HIV and HIV clinicians in Canada, Ireland and the USA.MethodsWe electronically administered the SF-HDQ followed by a Sensibility Questionnaire (face and content validity, ease of usage, format) and conducted semistructured interviews to explore the utility and implementation of the SF-HDQ in clinical practice. The threshold for sensibility was a median score of >5/7 (adults living with HIV) and>4/7 (HIV clinicians) for ≥80% of items. Qualitative interview data were analysed using directed content analysis.ResultsMedian sensibility scores were >5 (adults living with HIV; n=29) and >4 (HIV clinicians; n=16) for 18/19 (95%) items. Interview data indicated that the SF-HDQ represents the health-related challenges of living with HIV and other concurrent health conditions; captures the daily episodic nature of HIV; and is easy to use. Clinical utility included measuring health challenges and change over time, guiding referral to specialists and services, setting goals, facilitating communication and fostering a multidisciplinary approach to care. Considerations for implementation included flexible, person-centred approaches to administration, and communicating scores based on personal preferences.ConclusionsThe SF-HDQ possesses sensibility and utility for use in clinical settings with adults living with HIV and HIV clinicians in three countries.

Between 1790 and 1848, a period that witnessed a revolution, a conservative reaction, and the establishment of novel-reading as the predominant form of recreation for a rising middle class, theater became associated with revolution and emerges in literature as the antithesis of the great house. While the novels I discuss share an interest in keeping theater out of the house, my readings suggest the extent to which revolutionary passion may circulate, in houses and novels, in disguised, theatricalized form. My argument runs counter to a critical tendency to treat theater as an isolated disturbance, a temporary threat to the continuous history of the great house. Focusing on what is genuinely strange about revolutionary performances, and discussing these performances under the psychoanalytic rubric of \"acting out,\" I point instead toward the ongoing theatricalization of the house during this period. The novel becomes a \"stage\" on which ambivalence--manifested as boredom, melancholia, and mania--assumes theatrical form. The Introduction reinterprets Edmund Burke's Reflections on the Revolution in France, situating Burke's condemnation of revolutionary theater in the context of his subtler but extensive preoccupation with boredom; politically frustrated at home, Burke finds in the French Revolution an opportunity to act out his ambivalence about the English \"house.\" Chapter One argues that although Austen's Mansfield Park disparages Inchbald's adaptation of the popular drama, Lovers' Vows, as a revolutionary threat, her \"antitheatrical\" heroine, Fanny Price acts out: she becomes a source of theatrical and revolutionary disturbances in the household. Turning to Inchbald's own A Simple Story, Chapter Two traces the career of its bored and melodramatic actress-heroine. Reconsidering Austen's relationship with Inchbald, I suggest that Austen acts out by at once loudly repudiating Inchbald's play and quietly citing A Simple Story, covertly identifying with a popular writer associated with theater and revolution. Chapter Three treats Mary Shelley's utopian and apocalyptic novel, The Last Man, as the self-dramatization of a bored, post-revolutionary moderate. Chapter Four focuses on Thackeray's Vanity Fair and the manic performance of Becky Sharp, the novel's theatrical and Napoleonic protagonist.

Endogenous thymic regeneration is a crucial function that allows for renewal of immune competence after stress, infection, or immunodepletion. However, the mechanisms governing this regeneration remain poorly understood. We detail such a mechanism, centered on interleukin-22 (IL-22) and triggered by the depletion of CD4⁺CD8⁺ double-positive thymocytes. Intrathymic levels of IL-22 were increased after thymic insult, and thymic recovery was impaired in IL-22—deficient mice. IL-22, which signaled through thymic epithelial cells and promoted their proliferation and survival, was up-regulated by radio-resistant RORy(t)⁺CCR6⁺NKp46⁻ lymphoid tissue inducer cells after thymic injury in an IL-23-dependent manner. Administration of IL-22 enhanced thymic recovery after total body irradiation. These studies reveal mechanisms of endogenous thymic repair and offer innovative regenerative strategies for improving immune competence.

Swirls are sinuous high-reflectance lunar surface features collocated with crustal magnetic anomalies. These bright features and their geographical relationship to magnetic anomalies have been studied for decades, although their cause remains unclear. Several mechanisms for swirl formation have been proposed, including altered space weathering due to solar wind shielding, scouring of the surface by cometary impacts, and sorting of regolith materials. We use an empirical phase curve analysis and Hapke radiative transfer modeling of single-scattering albedo, bidirectional reflectance, and the angular width of the shadow hiding opposition effect to investigate regolith and crater ejecta properties at three prominent swirl sites: Reiner Gamma, Firsov, and Mare Ingenii. We assess the photometric differences between swirls, nearby background regolith, and fresh impact crater ejecta, and discuss implications for swirl formation. Our results suggest that both swirl and background regolith are consistently less backscattering than fresh crater ejecta, although swirl regolith and crater ejecta within swirls maintain higher single-scattering albedo values than the corresponding background materials. Physical processing via micrometeoroid impacts may explain the similar backscattering characteristics of swirl and background regolith, while additional space weathering of background regolith by solar wind causes differences in single-scattering albedo. In contrast, fresh crater ejecta is more backscattering than both swirl and background regolith, likely due to the impact process that exposes blocky material and alters the nearby surface. As a result, an anomalous space weathering environment caused by solar wind shielding remains a compelling hypothesis for the high-reflectance nature of lunar swirls.

This study investigated a link between adverse community environments and adverse childhood experiences (ACEs) using the pair of ACEs (POA) framework to better understand community members’ perspectives on how they were impacted across the lifespan by their childhood experiences. In addition, we identified mitigating factors that played a role for participants in building individual and community resilience. Researchers utilized a community-based participatory research approach in conjunction with qualitative methodology to explore the experiences of 15 community members. Nine themes emerged identifying both adversity and protective factors across the family, community, institutional, and structural levels. Findings have implications for the counseling profession in terms of practice, education, advocacy, and future research.

Emerging zoonotic viral diseases remain a challenge to global public health. Recent surveillance studies have implicated bats as potential reservoirs for a number of viral pathogens, including coronaviruses and Ebola viruses. Caliciviridae represent a major viral family contributing to emerging diseases in both human and animal populations and have been recently identified in bats. In this study, we blended metagenomics, phylogenetics, homology modeling, and in vitro assays to characterize two novel bat calicivirus (BtCalV) capsid sequences, corresponding to strain BtCalV/A10/USA/2009, identified in Perimyotis subflavus near Little Orleans, MD, and bat norovirus. We observed that bat norovirus formed virus-like particles and had epitopes and receptor-binding patterns similar to those of human noroviruses. To determine whether these observations stretch across multiple bat caliciviruses, we characterized a novel bat calicivirus, BtCalV/A10/USA/2009. Phylogenetic analysis revealed that BtCalV/A10/USA/2009 likely represents a novel Caliciviridae genus and is most closely related to \"recoviruses.\" Homology modeling revealed that the capsid sequences of BtCalV/A10/USA/2009 and bat norovirus resembled human norovirus capsid sequences and retained host ligand binding within the receptor-binding domains similar to that seen with human noroviruses. Both caliciviruses bound histo-blood group antigens in patterns that overlapped those seen with human and animal noroviruses. Taken together, our results indicate the potential for bat caliciviruses to bind histo-blood group antigens and overcome a significant barrier to cross-species transmission. Additionally, we have shown that bat norovirus maintains antigenic epitopes similar to those seen with human noroviruses, providing further evidence of evolutionary descent. Our results reiterate the importance of surveillance of wild-animal populations, especially of bats, for novel viral pathogens. IMPORTANCE Caliciviruses are rapidly evolving viruses that cause pandemic outbreaks associated with significant morbidity and mortality globally. The animal reservoirs for human caliciviruses are unknown; bats represent critical reservoir species for several emerging and zoonotic diseases. Recent reports have identified several bat caliciviruses but have not characterized biological functions associated with disease risk, including their potential emergence in other mammalian populations. In this report, we identified a novel bat calicivirus that is most closely related to nonhuman primate caliciviruses. Using this new bat calicivirus and a second norovirus-like bat calicivirus capsid gene sequence, we generated virus-like particles that have host carbohydrate ligand binding patterns similar to those of human and animal noroviruses and that share antigens with human noroviruses. The similarities to human noroviruses with respect to binding patterns and antigenic epitopes illustrate the potential for bat caliciviruses to emerge in other species and the importance of pathogen surveillance in wild-animal populations. Caliciviruses are rapidly evolving viruses that cause pandemic outbreaks associated with significant morbidity and mortality globally. The animal reservoirs for human caliciviruses are unknown; bats represent critical reservoir species for several emerging and zoonotic diseases. Recent reports have identified several bat caliciviruses but have not characterized biological functions associated with disease risk, including their potential emergence in other mammalian populations. In this report, we identified a novel bat calicivirus that is most closely related to nonhuman primate caliciviruses. Using this new bat calicivirus and a second norovirus-like bat calicivirus capsid gene sequence, we generated virus-like particles that have host carbohydrate ligand binding patterns similar to those of human and animal noroviruses and that share antigens with human noroviruses. The similarities to human noroviruses with respect to binding patterns and antigenic epitopes illustrate the potential for bat caliciviruses to emerge in other species and the importance of pathogen surveillance in wild-animal populations.

North America's scoter species are poorly monitored relative to other waterfowl. Black Melanitta americana, surf M. perspicillata, and white‐winged M. deglandi scoter abundance and trend estimates are thus uncertain in many parts of these species' ranges. The most extensive source of waterfowl abundance and distribution data in North America is the Waterfowl breeding population and habitat survey (WBPHS). Although the WBPHS effectively monitors most species, both its timing and geographic coverage may preclude accurate scoter monitoring. Therefore, our goal was to better define when and where scoters breed to help interpret survey results and optimize potential supplemental survey efforts for scoters. We integrated satellite telemetry tracking data from scoters marked at multiple molting, staging, breeding, and wintering areas along the Atlantic and Pacific coasts to quantify continent‐wide breeding chronology and distribution. We also examined possible drivers of variation in timing of arrival, length of stay, and departure at nesting locations. We documented a northwest to southeast distribution of estimated breeding sites across Alaska and Canada. On average, scoters arrived at nest sites on 1 June. Surf scoters and Pacific black scoters arrived earliest and departed earliest. Pacific‐wintering black and white‐winged scoters began breeding earlier than Atlantic‐wintering birds. Additionally, birds arrived at nesting locations earlier in years with earlier snowmelt, and later snowmelt reduced lengths of stay for males. Breeding chronology also varied by age group, with adults arriving earlier than subadults. Our study is the first to comprehensively describe spatial variation in timing of breeding of both Atlantic and Pacific populations of all three scoter species across North America. Our results increase our understanding of how current surveys enumerate scoters and will inform possible supplemental efforts to improve continental monitoring of scoter populations.

We examined white blood cell profiles of marine birds breeding in the Arctic, as an index of stress. Within species, birds that had to migrate farther had higher heterophil:lymphocyte ratios during incubation (i.e., residual stress) than those that migrated short distances. These reference values will be important as global warming and anthropogenic activities change the Arctic marine landscape.AbstractMost Arctic marine birds are migratory, wintering south of the limit of annual pack ice and returning north each year for the physiologically stressful breeding season. The Arctic environment is changing rapidly due to global warming and anthropogenic activities, which may influence the timing of breeding in relation to arrival times following migration, as well as providing additional stressors (e.g. disturbance from ships) to which birds may respond. During stressful parts of their annual cycle, such as breeding, birds may reallocate resources so that they have increased heterophil-to-lymphocyte ratios in their white blood cell (leucocyte) profiles. We analysed leucocyte profiles of nine species of marine birds to establish reference ranges for these species in advance of future Arctic change. Leucocyte profiles tended to cluster among taxonomic groups across studies, suggesting that reference values for a particular group can be established, and within species there was evidence that birds from colonies that had to migrate farther had higher heterophil-to-lymphocyte ratios during incubation than those that did not have to travel as far, particularly for species with high wing loading.

Despite the wide availability of several safe and effective vaccines that can prevent severe COVID-19 disease, the emergence of SARS-CoV-2 variants of concern (VOC) that can partially evade vaccine immunity remains a global health concern. In addition, the emergence of highly mutated and neutralization-resistant SARS-CoV-2 VOCs such as BA.1 and BA.5 that can partially or fully evade (1) many therapeutic monoclonal antibodies in clinical use underlines the need for additional effective treatment strategies. Here, we characterize the antiviral activity of GS-5245, Obeldesivir (ODV), an oral prodrug of the parent nucleoside GS-441524, which targets the highly conserved RNA-dependent viral RNA polymerase (RdRp). Importantly, we show that GS-5245 is broadly potent in vitro against alphacoronavirus HCoV-NL63, severe acute respiratory syndrome coronavirus (SARS-CoV), SARS-CoV-related Bat-CoV RsSHC014, Middle East Respiratory Syndrome coronavirus (MERS-CoV), SARS-CoV-2 WA/1, and the highly transmissible SARS-CoV-2 BA.1 Omicron variant in vitro and highly effective as antiviral therapy in mouse models of SARS-CoV, SARS-CoV-2 (WA/1), MERS-CoV and Bat-CoV RsSHC014 pathogenesis. In all these models of divergent coronaviruses, we observed protection and/or significant reduction of disease metrics such as weight loss, lung viral replication, acute lung injury, and degradation in pulmonary function in GS-5245-treated mice compared to vehicle controls. Finally, we demonstrate that GS-5245 in combination with the main protease (M ) inhibitor nirmatrelvir had increased efficacy in vivo against SARS-CoV-2 compared to each single agent. Altogether, our data supports the continuing clinical evaluation of GS-5245 in humans infected with COVID-19, including as part of a combination antiviral therapy, especially in populations with the most urgent need for more efficacious and durable interventions.