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Severe acute respiratory syndrome coronavirus 1 (SARS-CoV-1) and SARS-CoV-2 are not phylogenetically closely related; however, both use the angiotensin-converting enzyme 2 (ACE2) receptor in humans for cell entry. This is not a universal sarbecovirus trait; for example, many known sarbecoviruses related to SARS-CoV-1 have two deletions in the receptor binding domain of the spike protein that render them incapable of using human ACE2. Here, we report three sequences of a novel sarbecovirus from Rwanda and Uganda that are phylogenetically intermediate to SARS-CoV-1 and SARS-CoV-2 and demonstrate via in vitro studies that they are also unable to utilize human ACE2. Furthermore, we show that the observed pattern of ACE2 usage among sarbecoviruses is best explained by recombination not of SARS-CoV-2, but of SARS-CoV-1 and its relatives. We show that the lineage that includes SARS-CoV-2 is most likely the ancestral ACE2-using lineage, and that recombination with at least one virus from this group conferred ACE2 usage to the lineage including SARS-CoV-1 at some time in the past. We argue that alternative scenarios such as convergent evolution are much less parsimonious; we show that biogeography and patterns of host tropism support the plausibility of a recombination scenario, and we propose a competitive release hypothesis to explain how this recombination event could have occurred and why it is evolutionarily advantageous. The findings provide important insights into the natural history of ACE2 usage for both SARS-CoV-1 and SARS-CoV-2 and a greater understanding of the evolutionary mechanisms that shape zoonotic potential of coronaviruses. This study also underscores the need for increased surveillance for sarbecoviruses in southwestern China, where most ACE2-using viruses have been found to date, as well as other regions such as Africa, where these viruses have only recently been discovered.

The evolutionary origins of Middle East respiratory syndrome (MERS) coronavirus (MERS-CoV) are unknown. Current evidence suggests that insectivorous bats are likely to be the original source, as several 2c CoVs have been described from various species in the family Vespertilionidae Here, we describe a MERS-like CoV identified from a Pipistrellus cf. hesperidus bat sampled in Uganda (strain PREDICT/PDF-2180), further supporting the hypothesis that bats are the evolutionary source of MERS-CoV. Phylogenetic analysis showed that PREDICT/PDF-2180 is closely related to MERS-CoV across much of its genome, consistent with a common ancestry; however, the spike protein was highly divergent (46% amino acid identity), suggesting that the two viruses may have different receptor binding properties. Indeed, several amino acid substitutions were identified in key binding residues that were predicted to block PREDICT/PDF-2180 from attaching to the MERS-CoV DPP4 receptor. To experimentally test this hypothesis, an infectious MERS-CoV clone expressing the PREDICT/PDF-2180 spike protein was generated. Recombinant viruses derived from the clone were replication competent but unable to spread and establish new infections in Vero cells or primary human airway epithelial cells. Our findings suggest that PREDICT/PDF-2180 is unlikely to pose a zoonotic threat. Recombination in the S1 subunit of the spike gene was identified as the primary mechanism driving variation in the spike phenotype and was likely one of the critical steps in the evolution and emergence of MERS-CoV in humans.IMPORTANCE Global surveillance efforts for undiscovered viruses are an important component of pandemic prevention initiatives. These surveys can be useful for finding novel viruses and for gaining insights into the ecological and evolutionary factors driving viral diversity; however, finding a viral sequence is not sufficient to determine whether it can infect people (i.e., poses a zoonotic threat). Here, we investigated the specific zoonotic risk of a MERS-like coronavirus (PREDICT/PDF-2180) identified in a bat from Uganda and showed that, despite being closely related to MERS-CoV, it is unlikely to pose a threat to humans. We suggest that this approach constitutes an appropriate strategy for beginning to determine the zoonotic potential of wildlife viruses. By showing that PREDICT/PDF-2180 does not infect cells that express the functional receptor for MERS-CoV, we further show that recombination was likely to be the critical step that allowed MERS to emerge in humans.

Purpose: This paper describes a systematic review conducted to identify factors that have been investigated as explanations of variability in the quality of life of children with cancer and childhood cancer survivors. Our purpose was to build an evidence base that could be used to guide and direct future research.Methods: MEDLINE, CINAHL, EMBASE, PsycINFO, Cancerlit, and Sociological Abstracts were searched from the inception of each database to June 15, 2009 using the following search terms: "quality of life," "health-related quality of life," "quality adjusted life years," "health status," "functional status," "well-being," or "patient-reported outcome." Sample characteristics and information about the relationship between a quality of life domain or total scale score and at least one factor (e.g., child gender or age, coping skills, family income) were extracted from eligible studies.Results: Nine cancer-specific and nine generic QOL questionnaires were used in 58 publications described 239 factors (50 unique factors). The large number of cancer, treatment, child, and family variables considered indicates that extensive research activity has occurred. However, most of the variables identified were examined in only a few studies and most represent medical and treatment variables with less research attention paid to child and family variables.Conclusions: Our study has compiled evidence about determinants of QOL for children with cancer and childhood cancer survivors from the existing literature. Future research can build on this evidence base to expand the range of factors studied as most research to date has focused on medical and treatment factors. [ABSTRACT FROM AUTHOR]

Objective: To explore participants' shared experience attending a pilot mindfulness-based retreat (MBR) intervention supporting the psychological well-being of mothers of pediatric heart transplant (HTx) recipients., Methods: A qualitative description approach was used within a larger hybrid mixed-methods pilot study evaluating the implementation-effectiveness of a 2-day MBR tailored specifically for a pediatric HTx population. A purposive sample of mothers was recruited from a leading Canadian pediatric HTx center, and each represented a primary, female-identifying caregiver, sharing residence with a pediatric HTx recipient of at least 4 months post-transplant. Two focus groups were conducted after and 16 individual interviews 3 months after the MBR to elicit participants' in-depth experience attending the MBR. Reflexive thematic data analysis led to theme development through an iterative process with consensus among team members., Results: Sixteen mothers of pediatric HTx recipients (mean patient age 9.8 years; mean time post-transplant 8.2 years) participated in the MBR held in Ontario, Canada. Qualitative findings illuminated mothers' shared experience attending the MBR, reflecting three themes that describe key intervention elements beyond those affiliated with mindfulness practice alone: "respite," "readiness," and "relationships." Findings highlight acceptability and appropriateness as distinct yet interrelated implementation outcomes., Conclusions: Elements of "respite," "readiness," and "relationships" are key components of the MBR experience that offer valuable intervention and clinical considerations related to mothers' psychological well-being. Aligning intervention acceptability and appropriateness through tailored strategies may aid implementation. Future research considering maternal readiness relative to support intervention participation is warranted., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society of Pediatric Psychology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Randomised controlled trials have demonstrated the benefit of diet modification to improve diet quality in the treatment of adult major depressive disorder (MDD). However, research examining nutritional interventions for adolescents with MDD is sparse. This pilot study examined the feasibility of a personalised nutrition intervention for adolescents with MDD. Ten adolescents with MDD and their parents recruited from a tertiary care setting participated in an 8-week, single-arm mixed-methods study. Feasibility was assessed using five criteria (demand, acceptability, implementation, adaptation and limited efficacy testing) alongside qualitative interviews. The intervention involved four bi-weekly virtual nutrition counselling sessions with a stepped approach to dietary change, menu planning, grocery delivery and educational eHealth messages. Study participants sought positive changes in diet, health and lifestyle for adolescents and family-wide benefits. Recruitment challenges included concerns about managing mood fluctuations, anticipated dietary restrictions and the potential time and effort required for diet adherence. Feedback based on interviews emphasised moderate to high acceptability, satisfaction with menu planning and counselling and recognition of the benefits of trying new foods and sustaining positive dietary changes beyond the study. Improvements in depression symptoms (Cohen's d = 0·36, 95 % CI (-0·24, 3·36)), parent food modeling (Cohen's d = 0·24, 95 % CI (-0·43, 1·16) and the family food environment (Cohen's d = 0·61, 95 % CI (-0·04, 2·61)) were observed. This nutrition intervention was feasible for adolescents with MDD and was acceptable to both parents and depressed adolescents. These preliminary data suggest that further examination of the intervention and its potential benefits on depression symptoms and family food dynamics are warranted.

Objective: To explore the mental health experiences of adolescents and young adults (AYA) with inflammatory bowel disease (IBD) enrolled in a randomized controlled trial evaluating the impact of a multimodal transition intervention., Study Design: Virtual semistructured interviews were held with 21 AYA aged 16 through 18 years with IBD. Guided by qualitative description, interviews were digitally recorded, transcribed verbatim, and analyzed using an inductive approach to reflexive thematic analysis., Results: Three themes were generated from the data: (1) a continuum of integration between IBD and personal identity in adolescence and young adulthood; (2) manifestations of the mind-gut connection among AYA with IBD; and (3) hopes and priorities for addressing mental health in IBD care., Conclusions: AYA with IBD endorsed the criticality of incorporating mental health discussions into routine care during the transition to adult care, given the co-occurrence of psychosocial stressors throughout this period. A series of factors promoting and hindering the integration of IBD into one's identity were identified and could be explored in clinical encounters., Competing Interests: Declaration of Competing Interest This study was supported by a grant from the Leona M. and Harry B. Helmsley Charitable Trust and Crohn's and Colitis Canada. This study was also supported by The Canadian Children IBD Network (with funding provided by the CH.I.L.D. Foundation). The funding sources did not support the study design, collection, data analysis and interpretation, manuscript preparation, or the decision to submit the article for publication. David R. Mack is supported in part through a Distinguished Clinical Chair in Pediatric IBD through the Faculty of Medicine, University of Ottawa. Eric I. Benchimol holds the Northbridge Financial Corporation Chair in Inflammatory Bowel Disease, a joint Hospital-University Chair between the University of Toronto, The Hospital for Sick Children, and the SickKids Foundation. L.K. is an equity owner and scientific advisor to Trellus Health, and a consultant to Pfizer and Coprata Health. E.B. has acted as a consultant for McKesson Canada and the Dairy Farmers of Ontario for matters unrelated to medications used to treat inflammatory bowel disease. He has also acted as a consultant for the Canadian Agency for Drugs and Technology in Health (CADTH). The other authors declare no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Coronavirus genomes have evolutionary histories shaped extensively by recombination. Yet, how often recombination occurs at a cellular level, or the factors that regulate recombination rates, are poorly understood. Utilizing experimental co-infections with pairs of genetically distinct coronaviruses, we found that recombination is both frequent and rare during coinfection. Recombination occurred in every instance of co-infection yet resulted in relatively few recombinant RNAs. By integrating a discrete-time Susceptible-Infected-Removed (SIR) model, we found that rates of recombination are determined primarily by rates of cellular co-infection, rather than other possible barriers such as RNA compartmentalization. By staggering the order and timing of infection with each virus we also found that rates of co-infection are themselves heavily influenced by genetic and ecological mechanisms, including superinfection exclusion and the relative fitness of competing viruses. Our study highlights recombination as a potent yet regulated force: frequent enough to ensure a steady influx of genetic variation but also infrequent enough to maintain genomic integrity. As recombination is thought to be an important driver of host-switching and disease emergence, our study provides new insights into the factors that regulate coronavirus recombination and evolution more broadly., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Bonavita et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Electronic patient-reported outcome measures (ePROMs) are standardized digital instruments integrated into clinical care to collect subjective data regarding patients' health-related quality of life, functional status, and symptoms. In documenting patient-reported progress, ePROMs can guide treatment decisions and encourage measurement-based care practices. Voxe is a pediatric and user-centered ePROM platform for patients with chronic health conditions., Objective: We aimed to describe the user-centered design approach involving feedback from end users and usability testing of Voxe's platform features to support implementation in a pediatric health care setting., Methods: Purposive sampling was used to recruit patients aged 8-17 years from 2 chronic illness populations in 2 pediatric hospitals in Canada. Patients' health care team members were also purposively recruited. One-on-one iterative testing sessions were conducted digitally by research team members with participants to obtain feedback on the appearance and functionalities of the Voxe platform prototype. Patients and health care providers (HCPs) completed Voxe-related task-based activities. International Organization for Standardization key performance indicators were tracked during HCP task-based activities. HCPs also completed the System Usability Scale. To test platform usability, the think-aloud technique was used by participants during the completion of structured tasks. After completing all task-based activities, patient participants selected 5 words from the Microsoft Desirability Toolkit to describe their overall impression and experience with the Voxe platform. Qualitative data about likes, dislikes, and ease of use were collected through semistructured interviews. Feedback testing sessions were conducted with patients and HCPs until Voxe was acceptable to participating end users, with no further refinements identified. Quantitative and qualitative data analysis were completed using descriptive statistics and content analysis., Results: A total of 49 patients and 38 HCPs were recruited. Patients were positive about Voxe's child-centered design characteristics and notification settings. HCPs rated Voxe as user-friendly and efficient, with the time to complete tasks decreasing over time. HCPs were satisfied with the Voxe platform functionalities and identified the value of Voxe's system notifications, summarized display of ePROM results, and its capacity to integrate with electronic medical records. Patients' and HCPs' high satisfaction rates with the Voxe prototype highlight the importance of being responsive to user suggestions from the inception of eHealth platform developments to ensure their efficient and effective design., Conclusions: This paper describes the user-centered creation and usability testing of Voxe as an ePROM platform for implementation into clinical care for pediatric patients with chronic health conditions. As a patient-facing platform that can be integrated into electronic medical records, Voxe aligns with measurement-based care practices to foster quality patient-centered approaches to care. End users' positive feedback and evaluation of the platform's user-friendliness and efficiency suggest that Voxe represents a valuable and promising solution to systematically integrate patient-related outcome (PRO) data into complex and dynamic clinical health care settings., International Registered Report Identifier (irrid): RR2-10.1136/bmjopen-2021-053119., (©Samantha J Anthony, Sarah J Pol, Enid K Selkirk, Amarens Matthiesen, Robert J Klaassen, Dorin Manase, Amanda Silva, Melanie Barwick, Jennifer N Stinson, Alameen Damer, Mowa Ayibiowu, Selina X Dong, Stephan Oreskovich, Michael Brudno. Originally published in JMIR Human Factors (https://humanfactors.jmir.org), 19.09.2024.)

Background: An increase in self-management skills for adolescent thoracic transplant recipients may improve health outcomes and facilitate a successful transition to adulthood. The iPeer2Peer program is an online peer mentorship program that has been successfully implemented as a self-management intervention in multiple chronic disease populations. This study aimed to determine the implementation and effectiveness outcomes of the iPeer2Peer program for adolescent thoracic transplant recipients., Methods: A type III, hybrid implementation-effectiveness pilot study that comprised a quasi-experimental single-arm pre-post design was used to evaluate the iPeer2Peer program. Participant mentees, ages 12-17, were recruited from 2 large Canadian transplant centers. Peer mentors, ages 18-25, were thoracic transplant recipients who had successfully transitioned to adult care and self-manage their condition. A mixed methods approach for data collection was used, including interviews, focus groups, and standardized questionnaires., Results: Twenty mentees (median 15.0 years, IQR 3.3 years; 65% female) completed the iPeer2Peer program with 9 young adult mentors (median 21.0 years, IQR 3.0 years; 78% female). Implementation outcomes indicated that the iPeer2Peer program was perceived as feasible, adoptable, acceptable, and appropriate for adolescent thoracic transplant recipients. Significant findings were noted in mentees for increased self-management and a decrease in overall depression and anxiety symptoms., Conclusions: The successful implementation of the pilot iPeer2Peer program offers support to evaluate the scalability, sustainability, and cost-effectiveness of the program for adolescents with chronic illness, specifically thoracic transplant recipients. Changes to the iPeer2Peer program that facilitate a flexible delivery may help implementation and acceptance., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

This study describes mental health and psychosocial screening processes, access to care and interventions provided to children with upper limb musculoskeletal conditions. A cross-sectional e-survey study was conducted of 107 healthcare professionals who work with children with congenital hand and upper limb differences and brachial plexus birth injuries. Of them, 41 (38%) reported that they routinely screen for mental health and psychosocial concerns. Few (12%) reported the use of standardized outcome measures. In total, 51 (48%) healthcare professionals reported that there was a waiting list for mental health services at their institution. Collectively, healthcare professionals were unsatisfied with the staffing, access to care and types of interventions available. Reported barriers to care included the growing need for mental health support, lack of resources and poor continuity of care after referrals. Future research should focus on identifying and validating a mental health screening tool and investigating the processes affecting access to mental health care. Level of evidence: IV., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Healthcare workers are at risk of adverse mental health outcomes due to occupational stress. Many organizations introduced initiatives to proactively support staff's psychological well-being in the face of the COVID-19 pandemic. One example is the STEADY wellness program, which was implemented in a large trauma centre in Toronto, Canada. Program implementors engaged teams in peer support sessions, psychoeducation workshops, critical incident stress debriefing, and community-building initiatives. As part of a project designed to illuminate the experiences of STEADY program implementors, this article describes recommendations for future hospital wellness programs. Participants described the importance of having the hospital and its leaders engage in supporting staff's psychological well-being. They recommended ways of doing so (e.g., incorporating conversations about wellness in staff onboarding and routine meetings), along with ways to increase program uptake and sustainability (e.g., using technology to increase accessibility). Results may be useful in future efforts to bolster hospital wellness programming., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Public health concerns about recent viral epidemics have motivated researchers to seek novel ways to understand pathogen infection in native, wildlife hosts. With its deep history of tools and perspectives for understanding the abundance and distribution of organisms, ecology can shed new light on viral infection dynamics. However, datasets allowing deep explorations of viral communities from an ecological perspective are lacking. We sampled 1086 bats from two, adjacent Puerto Rican caves and tested them for infection by herpesviruses, resulting in 3131 short, viral sequences. Using percent identity of nucleotides and a machine learning algorithm (affinity propagation), we categorized herpesviruses into 43 operational taxonomic units (OTUs) to be used in place of species in subsequent ecological analyses. Herpesvirus metacommunities demonstrated long-tailed rank frequency distributions at all analyzed levels of host organization (i.e., individual, population, and community). Although 13 herpesvirus OTUs were detected in more than one host species, OTUs generally exhibited host specificity by infecting a single core host species at a significantly higher prevalence than in all satellite species combined. We describe the natural history of herpesvirus metacommunities in Puerto Rican bats and suggest that viruses follow the general law that communities comprise few common and many rare species. To guide future efforts in the field of viral ecology, hypotheses are presented regarding mechanisms that contribute to these patterns., Competing Interests: The authors declare no competing interests., (© 2024 The Authors. Ecology and Evolution published by John Wiley & Sons Ltd.)

Solid organ transplantation (SOT) is considered the optimal treatment for children with end-stage organ failure; however, increased efforts are needed to understand the gap surrounding equitable access to and health outcomes of SOT for Indigenous children. This scoping review summarizes the literature on the characteristics of access to and health outcomes of pediatric SOT among Indigenous children in the settler-colonial states of Canada, Aotearoa New Zealand, Australia, and the United States. A search was performed on MEDLINE, EMBASE, PsycINFO, and CINAHL for studies matching preestablished eligibility criteria from inception to November 2021. A preliminary gray literature search was also conducted. Twenty-four studies published between 1996 and 2021 were included. Studies addressed Indigenous pediatric populations within the United States (n = 7), Canada (n = 6), Aotearoa New Zealand (n = 5), Australia (n = 5), and Aotearoa New Zealand and Australia combined (n = 1). Findings showed that Indigenous children experienced longer time on dialysis, lower rates of preemptive and living donor kidney transplantation, and disparities in patient and graft outcomes after kidney transplantation. There were mixed findings about access to liver transplantation for Indigenous children and comparable findings for graft and patient outcomes after liver transplantation. Social determinants of health, such as geographic remoteness, lack of living donors, and traditional spiritual beliefs, may affect SOT access and outcomes for Indigenous children. Evidence gaps emphasize the need for action-based initiatives within SOT that prioritize research with and for Indigenous pediatric populations. Future research should include community-engaged methodologies, situated within local community contexts, to inform culturally safe care for Indigenous children., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: As of 2021, more than 6000 children and youth in Canada were living with end-stage kidney disease (ESKD), for which kidney transplantation is considered the preferred treatment by health professionals. Research shows that living donor kidney transplantation (LDKT) has superior allograft and recipient survival compared to deceased donor kidney transplantation (DDKT). However, in a pediatric setting, the choice of LDKT or DDKT is a summative consideration of factors weighed carefully by the patient's family, health care team, and patient. Decision-making surrounding transplantation may be more complex for racial and ethnic minorities as culturally specific values and beliefs are interwoven within dominant understandings and concepts of health and accepted models of health care. For example, Chinese Canadians have an increased risk of ESKD, yet reduced access to LDKT compared to White patients, despite being the largest visible minority population in Canada., Objective: The objective of this qualitative study is to deepen our understandings of the decision-making process surrounding DDKT versus LDKT among parents of Chinese Canadian pediatric patients with chronic kidney disease (CKD)., Design: Qualitative descriptive study design., Setting: The Nephrology Program at The Hospital for Sick Children in Toronto, Canada., Participants: Caregivers of Chinese Canadian patients with CKD, 18 years of age or older, and who spoke English, Cantonese, or Mandarin., Methods: One-on-one, semistructured interviews were conducted virtually, by a member of the research team and were audio-recorded and transcribed verbatim. Thematic analysis was used to explore participants' shared experience., Results: Seven interviews were conducted with 6 mothers and 1 father of 6 Chinese Canadian pediatric patients with CKD: 4 patients had undergone a kidney transplant, and 2 were not yet listed for transplant. Analysis of data highlighted that cultural influences affected whether parents shared with others about their child's illness and experience. The cultural understanding that it is inappropriate to burden others contributed to the creation of an isolating experience for participants. Cultural influences also impacted whether parents asked others to be a living donor as participants articulated this would place a physical burden on the living donor (e.g., potential risk to their health) and an emotional burden on the participant as they would be indebted to a willing donor. Ultimately, parents' decision to choose DDKT or LDKT for their patient-child was a result of evaluating both options carefully and within an understanding that the ideal treatment choice reflected what was best for all family members., Limitations: Findings reflect experiences of a small sample from a single recruitment site which may limit transferability., Conclusions: Parents in this study felt that they had access to the necessary evidence-based information to make an informed decision about the choice of DDKT versus LDKT for their child. Participant narratives described feeling isolated within cultural communities of family and friends and participants' suggestion of benefiting from increased support may guide future research directions. Practitioners can offer direct and indirect support to families, with recognition of the importance of cultural values and family-centered care on decision-making within families. Opportunities are needed for accessible, virtual social support platforms to increase parental feelings of culturally mediated peer support from parents who share similar experiences., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

In the United States (US), biosafety and biosecurity oversight of research on viruses is being reappraised. Safety in virology research is paramount and oversight frameworks should be reviewed periodically. Changes should be made with care, however, to avoid impeding science that is essential for rapidly reducing and responding to pandemic threats as well as addressing more common challenges caused by infectious diseases. Decades of research uniquely positioned the US to be able to respond to the COVID-19 crisis with astounding speed, delivering life-saving vaccines within a year of identifying the virus. We should embolden and empower this strength, which is a vital part of protecting the health, economy, and security of US citizens. Herein, we offer our perspectives on priorities for revised rules governing virology research in the US.

Purpose: The purpose of this scoping review is to synthesize the current evidence on the risk and protective factors associated with mental health in children with brachial plexus birth injury (BPBI) and associated interventions., Materials and Methods: MEDLINE, EMBASE, and Cochrane databases were searched for reports on mental health in children with BPBI between 10 and 18 years. Risk and protective factors were charted using the VicHealth review and the Person-Environment-Occupation model., Results: Of 732 records found, 133 full text reports were reviewed and 16 reports were included. Multiple mental health risks associated with BPBI were identified, while protective factors were largely unexplored. Person-related risks were most common including negative coping strategies ( n  = 8, 50%) and pain ( n  = 6, 38%). Most frequently reported environment and occupation risk factors were social difficulties ( n =  9, 56%) and challenges with upper limb function and daily activities ( n  = 6, 38%). Good self-determination and/or self-concept ( n  = 5, 30%) was the most common protective factor., Conclusions: Research using a strengths-based approach is needed to elucidate protective factors and further understanding of the intersection of person and socio-cultural risk factors of mental health in children with BPBI.

APOBEC3, an enzyme subfamily that plays a role in virus restriction by generating mutations at particular DNA motifs or mutational 'hotspots', can drive viral mutagenesis with host-specific preferential hotspot mutations contributing to pathogen variation. While previous analysis of viral genomes from the 2022 Mpox (formerly Monkeypox) disease outbreak has shown a high frequency of C>T mutations at TC motifs, suggesting recent mutations are human APOBEC3-mediated, how emerging monkeypox virus (MPXV) strains will evolve as a consequence of APOBEC3-mediated mutations remains unknown. By measuring hotspot under-representation, depletion at synonymous sites, and a combination of the two, we analyzed APOBEC3-driven evolution in human poxvirus genomes, finding varying hotspot under-representation patterns. While the native poxvirus molluscum contagiosum exhibits a signature consistent with extensive coevolution with human APOBEC3, including depletion of TC hotspots, variola virus shows an intermediate effect consistent with ongoing evolution at the time of eradication. MPXV, likely the result of recent zoonosis, showed many genes with more TC hotspots than expected by chance (over-representation) and fewer GC hotspots than expected (under-representation). These results suggest the MPXV genome: (1) may have evolved in a host with a particular APOBEC GC hotspot preference, (2) has inverted terminal repeat (ITR) regions-which may be exposed to APOBEC3 for longer during viral replication-and longer genes likely to evolve faster, and therefore (3) has a heightened potential for future human APOBEC3-meditated evolution as the virus spreads in the human population. Our predictions of MPXV mutational potential can both help guide future vaccine development and identification of putative drug targets and add urgency to the task of containing human Mpox disease transmission and uncovering the ecology of the virus in its reservoir host., Competing Interests: None declared., (© The Author(s) 2023. Published by Oxford University Press.)

Recombination is thought to be a mechanism that facilitates cross-species transmission in coronaviruses, thus acting as a driver of coronavirus spillover and emergence. Despite its significance, the mechanism of recombination is poorly understood, limiting our potential to estimate the risk of novel recombinant coronaviruses emerging in the future. As a tool for understanding recombination, here, we outline a framework of the recombination pathway for coronaviruses. We review existing literature on coronavirus recombination, including comparisons of naturally observed recombinant genomes as well as in vitro experiments, and place the findings into the recombination pathway framework. We highlight gaps in our understanding of coronavirus recombination illustrated by the framework and outline how further experimental research is critical for disentangling the molecular mechanism of recombination from external environmental pressures. Finally, we describe how an increased understanding of the mechanism of recombination can inform pandemic predictive intelligence, with a retrospective emphasis on SARS-CoV-2., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Pediatric anxiety disorders (AD) are prevalent disorders with an impact on all aspects of a child's life and functioning. 1 Although evidence supports commonly used treatments, there are notable concerns with the research to date. 2 Heterogeneity in outcome selection, measurement, analysis, and reporting is a contributing factor to the hinderance of the translation of research into clinical practice. 3 Recognition for outcome standardization in pediatric mental health disorders is evolving and there are several initiatives of importance, including the International Consortium for Health Outcomes Measurement (ICHOM), which has developed standardized outcome sets for use in the routine clinical mental health treatment of children and adolescents. 4 Similarly, the International Alliance of Mental Health Research Funders 5 advocate for use of 1 specific outcome measurement instrument (OMI) in the youth mental health research that they fund. Development of a Core Outcome Set (COS), a minimal set of outcomes that should be measured and reported in clinical trials, has been a solution in other areas of medicine to address heterogeneity in outcome selection and measurement across trials. 6 The Core Outcomes and Measures in Pediatric Anxiety Clinical Trials (COMPACT) Initiative will develop a harmonized, evidence- and consensus-based COS that is meaningful to youth and families for use in future trials in pediatric AD., (Copyright © 2023 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.)

Morbilliviruses are among the most contagious viral pathogens of mammals. Although previous metagenomic surveys have identified morbillivirus sequences in bats, full-length morbilliviruses from bats are limited. Here we characterize the myotis bat morbillivirus (MBaMV) from a bat surveillance programme in Brazil, whose full genome was recently published. We demonstrate that the fusion and receptor binding protein of MBaMV utilize bat CD150 and not human CD150, as an entry receptor in a mammalian cell line. Using reverse genetics, we produced a clone of MBaMV that infected Vero cells expressing bat CD150. Electron microscopy of MBaMV-infected cells revealed budding of pleomorphic virions, a characteristic morbillivirus feature. MBaMV replication reached 10 3 -10 5 plaque-forming units ml -1 in human epithelial cell lines and was dependent on nectin-4. Infection of human macrophages also occurred, albeit 2-10-fold less efficiently than measles virus. Importantly, MBaMV is restricted by cross-neutralizing human sera elicited by measles, mumps and rubella vaccination and is inhibited by orally bioavailable polymerase inhibitors in vitro. MBaMV-encoded P/V genes did not antagonize human interferon induction. Finally, we show that MBaMV does not cause disease in Jamaican fruit bats. We conclude that, while zoonotic spillover into humans may theoretically be plausible, MBaMV replication would probably be controlled by the human immune system., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: The number of pediatric SOT recipients surviving into adulthood is increasing. Thus, understanding their psychosocial and QoL outcomes is important. We conducted a systematic review to collate existing literature examining QoL outcomes (physical functioning, psychological functioning, social functioning), as well as risk and protective factors associated with QoL, among adults who underwent SOT during childhood., Methods: A systematic search of five databases, from inception to January 6, 2021, was conducted to identify articles that reported on QoL outcomes for adults (≥18-year of age) who received a SOT during childhood (<19-year of age)., Results: Twenty-five articles met inclusion criteria. Studies examined QoL across a range of SOT populations (liver, kidney, heart). QoL and psychosocial outcomes were variable; however, the majority of studies indicated QoL in this population to be similar to the general population, or at least similar to other chronic illness groups, with the exception of physical and social functioning. Factors related to a more optimal medical course, younger age at transplant and follow-up, and positive psychosocial functioning, were found to be predictive of better QoL outcomes., Conclusions: While several studies indicated QoL to be similar to the general population, the literature is limited in both quantity and quality. No study employed prospective, longitudinal methodologies to systematically evaluate QoL over time and few studies utilized normative-based measures of QoL. Furthermore, several SOT groups were under-represented in the literature (e.g., lung, intestine, multi-visceral). Nonetheless, findings have implications for intervention and clinical decision-making., (© 2022 Wiley Periodicals LLC.)

Background: Despite heart and lung transplantation being life-saving therapies for children and adolescents, little research has focused on recipients' lived experience post-transplant. This study captures the subjective experiences of adolescent thoracic transplant recipients, providing insight into the impact of life changes following transplantation in this population., Methods: A grounded theory approach guided an iterative process of data collection and data analysis. Adolescent heart and lung transplant recipients were recruited from a large Canadian pediatric teaching hospital to participate in one-on-one semi-structured interviews. Analysis using line-by-line coding and constant comparison methods facilitated reflection and agreement on categories and emergent themes., Results: A total of 27 heart and 5 lung transplant recipients (66% female) participated at a median age of 15.9 years and a median time post-transplant of 2.7 years. Participant narratives illuminated three themes describing (1) personal growth - an awareness of personal strengths and coping abilities, (2) relationship growth - a greater appreciation for family and friends, and (3) introspective growth - a developing life philosophy. Findings suggest that adolescents experience an emergent 'transplanted self', positioning thoracic transplantation as a potential catalyst for positive growth and personal change., Conclusions: The study findings describe pediatric thoracic transplantation as potentially transformative in nature and sheds light on the application of post-traumatic growth theory. Practitioners and researchers are encouraged to acknowledge the possibility of growth, transformation, and positive change that may be possible within the adolescent thoracic transplant experience and leverage such strengths in clinical care., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Importance: Wearing a face mask in school can reduce SARS-CoV-2 transmission but it may also lead to increased hand-to-face contact, which in turn could increase infection risk through self-inoculation., Objective: To evaluate the effect of wearing a face mask on hand-to-face contact by children while at school., Design, Setting, and Participants: This prospective randomized clinical trial randomized students from junior kindergarten to grade 12 at 2 schools in Toronto, Ontario, Canada, during August 2020 in a 1:1 ratio to either a mask or control class during a 2-day school simulation. Classes were video recorded from 4 angles to accurately capture outcomes., Interventions: Participants in the mask arm were instructed to bring their own mask and wear it at all times. Students assigned to control classes were not required to mask at any time (grade 4 and lower) or in the classroom where physical distancing could be maintained (grade 5 and up)., Main Outcomes and Measures: The primary outcome was the number of hand-to-face contacts per student per hour on day 2 of the simulation. Secondary outcomes included hand-to-mucosa contacts and hand-to-nonmucosa contacts. A mixed Poisson regression model was used to derive rate ratios (RRs), adjusted for age and sex with a random intercept for class with bootstrapped 95% CIs., Results: A total of 174 students underwent randomization and 171 students (mask group, 50.6% male; control group, 52.4% male) attended school on day 2. The rate of hand-to-face contacts did not differ significantly between the mask and the control groups (88.2 vs 88.7 events per student per hour; RR, 1.00; 95% CI, 0.78-1.28; P = >.99). When compared with the control group, the rate of hand-to-mucosa contacts was significantly lower in the mask group (RR, 0.12; 95% CI, 0.07-0.21), while the rate of hand-to-nonmucosa contacts was higher (RR, 1.40; 95% CI, 1.08-1.82)., Conclusions and Relevance: In this clinical trial of simulated school attendance, hand-to-face contacts did not differ among students required to wear face masks vs students not required to wear face masks; however, hand-to-mucosa contracts were lower in the face mask group. This suggests that mask wearing is unlikely to increase infection risk through self-inoculation., Trial Registration: ClinicalTrials.gov Identifier: NCT04531254.

As part of a broad One Health surveillance effort to detect novel viruses in wildlife and people, we report several paramyxovirus sequences sampled primarily from bats during 2013 and 2014 in Brazil and Malaysia, including seven from which we recovered full-length genomes. Of these, six represent the first full-length paramyxovirid genomes sequenced from the Americas, including two that are the first full-length bat morbillivirus genome sequences published to date. Our findings add to the vast number of viral sequences in public repositories, which have been increasing considerably in recent years due to the rising accessibility of metagenomics. Taxonomic classification of these sequences in the absence of phenotypic data has been a significant challenge, particularly in the subfamily Orthoparamyxovirinae, where the rate of discovery of novel sequences has been substantial. Using pairwise amino acid sequence classification (PAASC), we propose that five of these sequences belong to members of the genus Jeilongvirus and two belong to members of the genus Morbillivirus. We also highlight inconsistencies in the classification of Tupaia virus and Mòjiāng virus using the same demarcation criteria and suggest reclassification of these viruses into new genera. Importantly, this study underscores the critical importance of sequence length in PAASC analysis as well as the importance of biological characteristics such as genome organization in the taxonomic classification of viral sequences., (© 2022. The Author(s).)

Host-virus associations have co-evolved under ecological and evolutionary selection pressures that shape cross-species transmission and spillover to humans. Observed virus-host associations provide relevant context for newly discovered wildlife viruses to assess knowledge gaps in host-range and estimate pathways for potential human infection. Using models to predict virus-host networks, we predicted the likelihood of humans as hosts for 513 newly discovered viruses detected by large-scale wildlife surveillance at high-risk animal-human interfaces in Africa, Asia, and Latin America. Predictions indicated that novel coronaviruses are likely to infect a greater number of host species than viruses from other families. Our models further characterize novel viruses through prioritization scores and directly inform surveillance targets to identify host ranges for newly discovered viruses., (© 2022. The Author(s).)

Background: Pediatric patients with neurological disorders often require lifelong management of symptoms and behaviours that can result in enduring emotional burden, stress and impacted health-related quality of life. Single session therapy (SST) draws upon patients' existing skills and knowledge and has emerged as a therapeutic approach to address pediatric patient and family needs in a timely manner. This study aimed to assess the clinical effectiveness of SST for pediatric patients with neurological disorders and their families, considering self-efficacy, distress, anxiety, therapeutic alliance and client satisfaction, as well as perceptions of whether SST met their pressing needs., Methods: A convergent parallel mixed-methods design included quantitative data collection via five standardized questionnaires across three time points and qualitative data collection through semi-structured interviews. Quantitative and qualitative data were analyzed independently and then integrated., Results: The study comprised of 135 participants, including patients, parents and siblings across diverse neurological conditions. Scores of self-efficacy and anxiety in children, and distress and anxiety in adults, improved significantly after the SST. Notably, changes in anxiety in adults remained significant five to seven weeks after the SST. Seventeen participants participated in 12 semi-structured interviews. Participants described that SST (1) was a missing piece in ongoing clinical care, (2) illuminated existing strengths and resilience, and (3) effected a lasting impact beyond the single session., Conclusions: SST may be a promising initial, strengths-based treatment to support the short-term and potentially long-term needs of pediatric patients with neurological disorders and their families by emphasizing existing strengths, supporting therapeutic alliance and cultivating hope., (© 2022. The Author(s).)

Introduction: Mothers are often the primary caregivers for children requiring heart transplantation. Given that a mother's ability to successfully cope with the demands of her caregiving role may be predictive of positive familial psychosocial outcomes, it is critical that maternal coping is assessed and supported in paediatric healthcare. Mindfulness-based programmes are proposed as one intervention that may enhance quality of life, improve distress tolerance and coping and reduce social isolation in caregiving populations. This pilot study aims to investigate: (1) the implementation success of a mindfulness-based retreat (MBR), and (2) the effectiveness of a MBR at improving quality of life, distress tolerance, coping and perceived social support for mothers of paediatric heart transplant recipients., Methods and Analysis: A convergent parallel, mixed-method design is proposed for this pilot, exploratory study. Twenty mothers will participate in this pilot MBR held at a resort in Ontario, Canada. Quantitative data will be obtained using five standardised instruments completed at three time points: (T1) 24-hours prior to the intervention, (T2) immediately on completion of the intervention, and (T3) three months post-intervention. Qualitative data will be collected from all participants both through semi-structured focus groups at T2 and individual telephone interviews at T3. Focus groups and individual interviews will be transcribed verbatim for thematic analysis. Quantitative and qualitative data will be merged and compared during interpretation to ensure that the intervention implementation and effectiveness of the MBR retreat are described with comprehensive accuracy. The primary outcomes will be feasibility in relation to implementation effectiveness and participants' perception of social support for efficacy of the MBR intervention., Ethics and Dissemination: This study received Institutional Research Ethics Board approval from The Hospital for Sick Children (Number: 1000064719). Informed consent will be obtained prior to participant enrolment. Findings will be disseminated via conference presentations and submitted for publication in a peer-reviewed journal., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Bats are important hosts of zoonotic viruses with pandemic potential, including filoviruses, MERS-Coronavirus (CoV), SARS-CoV -1, and likely SARS-CoV-2. Viral infection and transmission among wildlife are dependent on a combination of factors that include host ecology and immunology, life history traits, roosting habitats, biogeography, and external stressors. Between 2016 and 2018, four species of insectivorous bats from a readily accessed roadside cave and buildings in Ethiopia were sampled and tested for viruses using consensus PCR assays for five viral families/genera. Previously identified and novel coronaviruses and paramyxoviruses were identified in 99 of the 589 sampled bats. Bats sampled from the cave site were more likely to test positive for a CoV than bats sampled from buildings; viral shedding was more common in the wet season; and rectal swabs were the most common sample type to test positive. A previously undescribed alphacoronavirus was detected in two bat species from different taxonomic families, sampling interfaces, geographic locations, and years. These findings expand knowledge of the range and diversity of coronaviruses and paramyxoviruses in insectivorous bats in Ethiopia and reinforce that an improved understanding of viral diversity and species-specific shedding dynamics is important for designing informed zoonotic disease surveillance and spillover risk reduction efforts., (© 2022. The Author(s).)

Background: Aging-related disease risk is exacerbated by obesity and physical inactivity. It is unclear how weight loss and increased activity improve risk in older adults. We aimed to determine the effects of diet-induced weight loss with and without exercise on insulin sensitivity, VO2peak, body composition, and physical function in older obese adults., Methods: Physically inactive older (68.6 ± 4.5 years) obese (body mass index 37.4 ± 4.9 kg/m2) adults were randomized to health education control (HEC; n = 25); diet-induced weight loss (WL; n = 31); or weight loss and exercise (WLEX; n = 28) for 6 months. Insulin sensitivity was measured by hyperinsulinemic-euglycemic clamp, body composition by dual-energy X-ray absorptiometry and MRI, strength by isokinetic dynamometry, and VO2peak by graded exercise test., Results: WLEX improved (p < .05) peripheral insulin sensitivity (+75 ± 103%) versus HEC (+12 ± 67%); WL (+36 ± 47%) versus HEC did not reach statistical significance. WLEX increased VO2peak (+7 ± 12%) versus WL (-2 ± 24%) and prevented reductions in strength and lean mass induced by WL (p < .05). WLEX decreased abdominal adipose tissue (-16 ± 9%) versus HEC (-3 ± 8%) and intermuscular adipose tissue (-15 ± 13%) versus both HEC (+9 ± 15%) and WL (+2 ± 11%; p < .01)., Conclusions: Exercise with weight loss improved insulin sensitivity and VO2peak, decreased ectopic fat, and preserved lean mass and strength. Weight loss alone decreased lean mass and strength. Older adults intending to lose weight should perform regular exercise to promote cardiometabolic and functional benefits, which may not occur with calorie restriction-induced weight loss alone., (© The Author(s) 2021. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: This study examined children's perspectives about returning to in-person school following lockdown due to the pandemic and about mask-wearing in class, as well as the mental health of children and parents during the pandemic., Methods: This cross-sectional study was part of a 2-day school simulation exercise that randomized students to different masking recommendations. Parent-report of mental health and post-simulation child-report of COVID-19-related anxiety and mask-wearing were analyzed using descriptive and multiple regression analyses. Semi-structured focus groups were conducted with older students to supplement questionnaire data., Results: Of 190 students in this study, 31% were in grade 4 or lower 95% looked forward to returning to in-person school. Greater child anxiety about COVID-19 was predicted by increased parent/caregiver anxiety (β=0.67; P<0.001), and lower parental educational attainment (β=1.86; P<0.002). Older students were more likely than younger students to report that mask-wearing interfered with their abilities to interact with peers (χ 2 (1)=31.16; P<0.001) and understand the teacher (χ 2 (1)=13.97; P<0.001). Students in the group that did not require masks were more likely than students in the masking group to report worries about contracting COVID-19 at school (χ 2 (1)=10.07; P<0.05), and anticipated difficulty wearing a mask (χ 2 (1)=18.95; P<0.001)., Conclusions: For children anxious about COVID-19, parental anxiety and education about COVID-19 may be targets for intervention. Future research should examine the impact of prolonged implementation of public health mitigation strategies in school on academic achievement and children's mental health., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Canadian Paediatric Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: As a result of the COVID-19 pandemic, public health agencies and school boards across Canada enacted new protocols, including face masks, physical distancing and enhanced hygiene, to support the safe reopening of in-person school. This study explored the experiences and perceptions of teachers instructing children and adolescents in person during a two-day school simulation., Method: This study was part of a large school simulation exercise conducted in Toronto, Ontario. Kindergarten to grade 12 teachers taught in classrooms with either masked students, or students who were un-masked or only masked when physical distancing was not possible. A qualitative descriptive phenomenology approach was utilized, and data were collected via virtual focus groups. Qualitative data analysis involved multiple rounds of inductive coding to generate themes., Results: The sample included 14 teachers (92.9% female; 85.7% White), with a median of 9.5 years teaching experience. Three primary themes emerged: 1) learning to navigate public health measures , 2 ) needing to adapt teaching strategies and 3) striving to manage conflicting priorities . The majority of teachers reported that mask-wearing and physical distancing impacted their classroom teaching, communication and connection with students., Conclusions: As schools transition to in-person instruction, teachers will be required to play dual roles in education and public health, with implications on safety, teaching and professional identity. Public health agencies and school boards are encouraged to engage teachers in ongoing conversations regarding in-person school planning and operations. Furthermore, evidence-based interventions, including increased teaching development programs, are recommended to support teachers during the COVID-19 pandemic., Competing Interests: Conflicts of Interest The authors have no financial relationships to disclose., (Copyright © 2022 Canadian Academy of Child and Adolescent Psychiatry.)

Purpose: Trust in the deceased organ donation process relies on the expectation that the diagnosis of death by neurologic criteria (DNC) is accurate and reliable. The objective of this study was to assess the perceptions and approaches to DNC diagnosis among Canadian intensivists., Methods: We conducted a self-administered, online, cross-sectional survey of Canadian intensivists. Our sampling frame included all intensivists practicing in Canadian institutions. Results are reported using descriptive statistics., Results: Among 550 identified intensivists, 249 (45%) completed the survey. Respondents indicated they would be comfortable diagnosing DNC based on clinical criteria alone in cases where there is movement in response to stimulation (119/248; 48%); inability to evaluate upper/lower extremity responses (84/249; 34%); spontaneous peripheral movement (76/249; 31%); inability to evaluate both oculocephalic and oculo-caloric reflexes (40/249; 16%); presence of high cervical spinal cord injury (40/249; 16%); and within 24 hr of hypoxemic-ischemic brain injury (38/247; 15%). Most respondents agreed that an ancillary test should always be conducted when a complete clinical evaluation is impossible (225/241; 93%); when there is possibility of a residual sedative effect (216/242; 89%); when the mechanism for brain injury is unclear (172/241; 71%); and if isolated brainstem injury is suspected (142/242; 59%). Sixty-six percent (158/241) believed that ancillary tests are sensitive and 55% (132/241) that they are specific for DNC. Respondents considered the following ancillary tests useful for DNC: four-vessel conventional angiography (211/241; 88%), nuclear imaging (179/240; 75%), computed tomography (CT) angiography (156/240; 65%), and CT perfusion (134/240; 56%)., Conclusion: There is variability in perceptions and approaches to DNC diagnosis among Canadian intensivists, and some practices are inconsistent with national recommendations., (© 2021. Canadian Anesthesiologists' Society.)

Introduction: Patient-reported outcome measures (PROMs) provide an opportunity for meaningful patient engagement and shared decision-making. The objective of this research programme is to improve health outcomes for paediatric solid organ transplant patients by implementing PROMs into clinical care. The current study aims to create Voxe, a paediatric user-centred electronic PROM platform, by engaging patients and healthcare providers throughout the design and development process., Methods and Analysis: The creation of Voxe will occur over two phases that build on previous research. The user interface design phase employs a 'user-centric' approach to identify end-users' needs and iteratively refine the look and layout of Voxe to meet these needs. Transplant recipients, aged 10-17, and healthcare providers will participate in three rounds of testing (24 participants total). Participants will: (1) complete task-based activities (outcomes-effectiveness and efficiency), (2) complete questionnaires (outcome-satisfaction) and (3) participate in a semi-structured interview. The following phase involves software development and Voxe usability testing. Transplant recipients, aged 8-17, and healthcare providers will participate in four rounds of iterative testing (24-40 participants total). The think-aloud technique will be employed, and participants will describe their thoughts and feelings while interacting with a Voxe prototype. Participants will: (1) log into Voxe and complete tasks (outcomes-time on task, successful task completion, frequency of critical and non-critical errors and error-free rate), (2) complete questionnaires (outcome-satisfaction) and (3) participate in a semi-structured interview. Findings will result in the creation and launch of a user-centred electronic PROM platform., Ethics and Dissemination: Research ethics board approval has been provided by The Hospital for Sick Children. This research is critical to answering methodological and operational questions to inform Voxe implementation in paediatric clinical settings and facilitate PROM data collection. Future investigations will include an implementation-effectiveness evaluation., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Since the first reports of a novel severe acute respiratory syndrome (SARS)-like coronavirus in December 2019 in Wuhan, China, there has been intense interest in understanding how severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in the human population. Recent debate has coalesced around two competing ideas: a "laboratory escape" scenario and zoonotic emergence. Here, we critically review the current scientific evidence that may help clarify the origin of SARS-CoV-2., Competing Interests: Declaration of interests E.C.H. is an honorary visiting professor at Fudan University (Shanghai Public Health Clinical Center), Shanghai, China and, from 2014–2020, was a guest professor at the Chinese Center for Disease Control and Prevention, Beijing, China. These affiliations are only used in papers co-authored with Prof. Yong-Zhen Zhang (Shanghai Public Health Clinical Center) and involve no formal appointment, no duties, and no remuneration nor research funding. J.O.W. receives funding from the U.S. Centers for Disease Control and Prevention (ongoing) via grants and contracts to his institution unrelated to this research. S.R.W. consults for Immunome and Ocugen. A.R., A.L.R., M.F.B., S.A.G., and K.G.A. have received consulting fees and compensation for expert testimony on SARS-CoV-2 and the COVID-19 pandemic. R.F.G. is co-founder of Zalgen Labs., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: To understand the effectiveness of a nurse-led transition intervention by analyzing qualitative data generated in the context of a clinical trial., Design & Methods: Qualitative study of a two-session transition intervention conducted by registered nurses at two sites. Adolescents aged 16-17 years with moderate or complex congenital heart disease (CHD) had been randomized to a two-session transition intervention or usual care. Session 1 emphasized patient education including creation of a health passport and goal setting. Session 2, two months later, emphasized self-management. Qualitative data extracted from intervention logs, field notes and audio recordings of the sessions were analyzed for content and themes., Results: Data from 111 transition intervention sessions with 57 adolescents were analyzed. Creating a health passport, goal setting, and role-plays were the elements of the intervention most valued by participants. A typology of transition readiness was identified: 1) the independent adolescent (5%), already managing their own care; 2) the ready adolescent who was prepared for transition after completing the intervention (46%); 3) the follow-up needed adolescent who was still in need of extra coaching (26%), and 4) the at-risk adolescent who warranted immediate follow-up (14%). Baseline knowledge and transition surveys scores validated the typology., Conclusions: A two-session nursing intervention met the transition needs of approximately half of adolescents with CHD. However, additional transition-focused care was needed by 40% of participants (groups 3 and 4)., Practice Implications: These findings will guide pediatric nurses and other healthcare professionals to optimize an individualized approach for ensuring transition readiness for adolescents with CHD., Competing Interests: Declaration of Competing Interest The authors have no conflict of interests to disclose., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: Self-management for patients who have undergone solid organ transplantation is demanding and a challenge for adolescents transitioning into adult-oriented healthcare systems. This study explores whether adolescent and young adult solid organ transplant patients support the use of online peer support programs that encourage peer mentorship as an approach to improve disease self-management., Methods: A qualitative descriptive design comprised of semi-structured interviews with adolescent and young adult transplant patients. Individual interviews were audio-recorded, transcribed verbatim, and subject to content analysis. Emergent categories and themes were refined through member checking and team consensus following saturation., Results: Interviews were conducted across organ groups with 15 participants (60% female) ages 14 to 22 years. Participants expressed unanimous support for an online peer support mentorship program to aid disease self-management in the pediatric transplant patient population. Three themes emerged from the interviews: (a) self-management care can be "taxing"; (b) there would be value in peer mentorship for adolescent transplant patients; and (c) online peer mentorship is the "best" option but still requires relationship building. Logistical preferences of an online peer mentorship program were solicited. The preferred peer "match" was someone of the same organ transplant group and gender who was able to have weekly contact via texting., Conclusions: Creating tailored, online peer mentorship programs is gaining evidence to justify further development. Findings from this study will support program modifications for adolescent and young adult solid organ transplant patients. Next steps will involve usability and feasibility testing of an adapted online program for this patient group., (© 2020 Wiley Periodicals LLC.)

Purpose: Patient-reported outcome measures (PROMs) are standardized instruments used to collect data about the subjective assessment of medical care from the patient perspective. Implementing PROMs within pediatric clinical settings has gained increasing importance as health services prioritize patient-centred pediatric care. This study explores the perspectives of pediatric solid organ transplant patients, caregivers, and healthcare practitioners (HCPs) on implementing PROMs into clinical practice., Methods: Qualitative description methods were used to elicit stakeholder perspectives. Semi-structured interviews were conducted across five Canadian transplant centres. Purposive sampling was used to obtain maximum variation across age, gender, and transplant program for all participants, as well as discipline for HCPs., Results: The study included a total of 63 participants [patients (n = 20), caregivers (n = 22) and HCPs (n = 21)]. Nearly all participants endorsed the implementation of PROMs to enhance pediatric transplant clinical care. Three primary roles for PROMs emerged: (1) to bring a transplant patient's overall well-being into the clinical care conversation; (2) to improve patient communication and engagement; and, (3) to inform the practice of clinical pediatric transplant care. Insights for effective implementation included completing electronic PROMs remotely and prior to clinical appointments by patients who are eight to 10 years of age or older., Conclusions: This study contributes to current research that supports the use of PROMs in clinical pediatric care and guides their effective implementation into practice. Future directions include the development, usability testing, and evaluation of a proposed electronic PROM platform that will inform future research initiatives.

Purpose: In Ontario, an individual's registered wish for organ donation is legally valid consent following death. Family veto occurs when the deceased donor's substitute decision-maker (SDM) overrides this consent to donate, evoking a legal and ethical conflict. The objective of this study was to examine the experiences of Organ and Tissue Donation Coordinators (OTDCs) working with SDMs who vetoed a deceased donor's consent for organ donation., Methods: Qualitative focus groups were conducted with ten OTDCs in Ontario, Canada who reported experience with family veto. An interpretative phenomenological approach informed data analysis. Themes emerged through team consensus and were further refined through collaborative and reflexive engagement., Results: Four themes emerged regarding family veto: 1) the significance of the OTDC role, 2) emotional distress and the "understandable" family veto, 3) barriers contributing to family veto, and 4) strategies towards a culture of organ donation. Findings highlighted the importance of patient advocacy in the OTDC role, while revealing the emotional distress of experiencing family veto. OTDCs identified timing and healthcare providers' perceived ambivalence toward organ donation as critical barriers to family authorization. Value-positive language, role reframing, and increased education were offered as strategies to address these barriers and reduce family veto., Conclusion: This study highlights important considerations about organ donation authorization processes in Ontario. Findings support practice changes towards reducing family veto and further research nationally. Collaborations with key stakeholders are warranted to align healthcare practices, donation policies, and education initiatives towards a shared goal of increasing organ donation.

Coronavirus (CoV) spillover events from wildlife reservoirs can result in mild to severe human respiratory illness. These spillover events underlie the importance of detecting known and novel CoVs circulating in reservoir host species and determining CoV prevalence and distribution, allowing improved prediction of spillover events or where a human-reservoir interface should be closely monitored. To increase the likelihood of detecting all circulating genera and strains, we have modified primers published by Watanabe et al. in 2010 to generate a semi-nested pan-CoV PCR assay. Representatives from the four coronavirus genera (α-CoVs, β-CoVs, γ-CoVs and δ-CoVs) were tested and all of the in-house CoVs were detected using this assay. After comparing both assays, we found that the updated assay reliably detected viruses in all genera of CoVs with high sensitivity, whereas the sensitivity of the original assay was lower. Our updated PCR assay is an important tool to detect, monitor and track CoVs to enhance viral surveillance in reservoir hosts.

Study Design: Pilot nonrandomized clinical trial., Objectives: To examine the feasibility, acceptability, and preliminary efficacy of performing handcycling high-intensity interval training (HIIT) for 6 weeks in wheelchair users with spinal cord injury., Setting: Participant's home., Methods: Participants completed pre- and postgraded exercise stress tests, exercise surveys and 6 weeks of handcycling HIIT. The HIIT program consisted of two weekly, 25 min supervised at-home sessions (2-3 min warm-up, then ten intervals of cycling with a ratio of 1 min work at 90% peak power output (PPO) to 1 min recovery at 0-20% PPO, then 2-3 min cool down). Real-time power output and heart rate were recorded via sensors and a bike computer. The sensor data were analyzed to evaluate training efficacy., Results: Seven of the ten enrolled participants (70%) completed the study. All but one completed the required 12 sessions. The participants met at least 1 of the HIIT target intensity criteria in 76 out of 89 total sessions (85.4%) performed. Participants expressed a high level of enjoyment on the Physical Activity Enjoyment Scale, mean (SD) = 114.8 (11.3), and satisfaction with the overall experience. Five of the seven participants (71%) who completed the study felt an increase in endurance, function, and health. Objective physiological changes showed mixed results., Conclusions: Six weeks of handcycling HIIT appears to be safe, feasible and acceptable. A longer HIIT work interval may be needed to elicit significant physiological responses. Future investigation of the feasibility and efficacy of differing HIIT parameters is needed.

Nipah virus (NiV) is an emerging bat-borne zoonotic virus that causes near-annual outbreaks of fatal encephalitis in South Asia-one of the most populous regions on Earth. In Bangladesh, infection occurs when people drink date-palm sap contaminated with bat excreta. Outbreaks are sporadic, and the influence of viral dynamics in bats on their temporal and spatial distribution is poorly understood. We analyzed data on host ecology, molecular epidemiology, serological dynamics, and viral genetics to characterize spatiotemporal patterns of NiV dynamics in its wildlife reservoir, Pteropus medius bats, in Bangladesh. We found that NiV transmission occurred throughout the country and throughout the year. Model results indicated that local transmission dynamics were modulated by density-dependent transmission, acquired immunity that is lost over time, and recrudescence. Increased transmission followed multiyear periods of declining seroprevalence due to bat-population turnover and individual loss of humoral immunity. Individual bats had smaller host ranges than other Pteropus species (spp.), although movement data and the discovery of a Malaysia-clade NiV strain in eastern Bangladesh suggest connectivity with bats east of Bangladesh. These data suggest that discrete multiannual local epizootics in bat populations contribute to the sporadic nature of NiV outbreaks in South Asia. At the same time, the broad spatial and temporal extent of NiV transmission, including the recent outbreak in Kerala, India, highlights the continued risk of spillover to humans wherever they may interact with pteropid bats and the importance of limiting opportunities for spillover throughout Pteropus 's range., Competing Interests: The authors declare no competing interest., (Copyright © 2020 the Author(s). Published by PNAS.)

Purpose: We surveyed Canadian critical care physicians who may care for patients who are potential organ donors to understand their attitudes and knowledge of legislation governing the deceased organ donation system., Methods: We used a web-based, self-administered survey that included questions related to opt-out consent and mandatory referral legislation. Potential participants were identified through membership lists of professional societies and manual searches. We designed our survey using standardized methods and administered it in February and March 2018., Results: Fifty percent (263/529) of potential participants completed the questionnaire. A majority (61%; 144/235) supported a change towards an opt-out consent model, and 77% (181/235) stated they believe it would increase donation rates. Asked if opt-out consent would change their practices, 71% (166/235) stated an opt-out model would not change how or if they approach families to discuss donation. Fifty-six percent (139/249) supported mandatory referral laws, while only 42% (93/219) of those working in provinces with mandatory referral correctly stated that such laws exist in their province. Respondents gave variable responses on who should be accountable when patients are not referred, and 16% (40/249) believed no one should be held accountable., Conclusions: While a majority of critical care physicians supported opt-out consent and mandatory referral, many were neutral or against it. Many were unaware of existing laws and had variable opinions on how to ensure accountability. Efforts to increase understanding of how legislative models influence practice are required for any law to achieve its desired effect.

Ebola virus (EBOV) entry into cells is mediated by its spike glycoprotein (GP). Following attachment and internalization, virions traffic to late endosomes where GP is cleaved by host cysteine proteases. Cleaved GP then binds its cellular receptor, Niemann-Pick C1. In response to an unknown cellular trigger, GP undergoes conformational rearrangements that drive fusion of viral and endosomal membranes. The temperature-dependent stability (thermostability) of the prefusion conformers of class I viral fusion glycoproteins, including those of filovirus GPs, has provided insights into their propensity to undergo fusion-related rearrangements. However, previously described assays have relied on soluble glycoprotein ectodomains. Here, we developed a simple enzyme-linked immunosorbent assay (ELISA)-based assay that uses the temperature-dependent loss of conformational epitopes to measure thermostability of GP embedded in viral membranes. The base and glycan cap subdomains of all filovirus GPs tested suffered a concerted loss of prefusion conformation at elevated temperatures but did so at different temperature ranges, indicating virus-specific differences in thermostability. Despite these differences, all of these GPs displayed reduced thermostability upon cleavage to GP conformers (GP CL ). Surprisingly, acid pH enhanced, rather than decreased, GP thermostability, suggesting it could enhance viral survival in hostile endo/lysosomal compartments. Finally, we confirmed and extended previous findings that some small-molecule inhibitors of filovirus entry destabilize EBOV GP and uncovered evidence that the most potent inhibitors act through multiple mechanisms. We establish the epitope-loss ELISA as a useful tool for studies of filovirus entry, engineering of GP variants with enhanced stability for use in vaccine development, and discovery of new stability-modulating antivirals. IMPORTANCE The development of Ebola virus countermeasures is challenged by our limited understanding of cell entry, especially at the step of membrane fusion. The surface-exposed viral protein, GP, mediates membrane fusion and undergoes major structural rearrangements during this process. The stability of GP at elevated temperatures (thermostability) can provide insights into its capacity to undergo these rearrangements. Here, we describe a new assay that uses GP-specific antibodies to measure GP thermostability under a variety of conditions relevant to viral entry. We show that proteolytic cleavage and acid pH have significant effects on GP thermostability that shed light on their respective roles in viral entry. We also show that the assay can be used to study how small-molecule entry inhibitors affect GP stability. This work provides a simple and readily accessible assay to engineer stabilized GP variants for antiviral vaccines and to discover and improve drugs that act by modulating GP stability., (Copyright © 2020 American Society for Microbiology.)

Bat-borne zoonotic pathogens belonging to the family Paramxyoviridae, including Nipah and Hendra viruses, and the family Filoviridae, including Ebola and Marburg viruses, can cause severe disease and high mortality rates on spillover into human populations. Surveillance efforts for henipaviruses and filoviruses have been largely restricted to the Old World; however, recent studies suggest a potentially broader distribution for henipaviruses and filoviruses than previously recognized. In the current study, we screened for henipaviruses and filoviruses in New World bats collected across 4 locations in Trinidad near the coast of Venezuela. Bat tissue samples were screened using previously established reverse-transcription polymerase chain reaction assays. Serum were screened using a multiplex immunoassay to detect antibodies reactive with the envelope glycoprotein of viruses in the genus Henipavirus and the family Filoviridae. Serum samples were also screened by means of enzyme-linked immunosorbent assay for antibodies reactive with Nipah G and F glycoproteins. Of 84 serum samples, 28 were reactive with ≥1 henipavirus glycoprotein by ≥1 serological method, and 6 serum samples were reactive against ≥1 filovirus glycoproteins. These data provide evidence of potential circulation of viruses related to the henipaviruses and filoviruses in New World bats., (Published by Oxford University Press for the Infectious Diseases Society of America 2020.)