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Background Injury is a leading health burden in children yet relatively little is reported about the contemporary risks they face. Current national registry data may under-represent the true burden of injury to children. We aim to analyse contemporary patterns of paediatric trauma and identify current factors putting children at risk of injury.Methods A 3-month prospective multicentre cohort evaluation of injured children across the London Major Trauma System was performed. All children receiving a trauma team activation; meeting National Institute for Health and Care Excellence CT head criteria; or admitted/transferred out due to trauma were included. Data were collected on demographics, mechanism and location of injury, and body region injured. The primary outcome was in-hospital mortality and secondary outcome was safeguarding concerns.Results 659 children were included. Young children were more likely to be injured at home (0–5 years old: 70.8%, n=167 vs adolescents: 15.6%, n=31). Adolescents were more likely to be injured in the street (42.7%, n=85). Head trauma caused over half of injuries in 0–5 years old (51.9%, n=121). Falls were common and increasingly prevalent in younger children, causing 56.6% (n=372) of injuries. In adolescents, penetrating violence caused more than one in five injuries (21.9%, n=50). Most injured children survived (99.8%, n=658), however, one in four (26.1%, n=172) had safeguarding concerns and a quarter of adolescents had police, third sector or external agency involvement (23.2%, n=53).Conclusions This study describes modern-day paediatric trauma and highlights the variance in injury patterns in young children and adolescents. Importantly, it highlights differences in actual rates of injuries compared with those reported from current national registry data. We must understand real risks facing 21st century children to effectively safeguard future generations. The results provide an opportunity to reassess the current approach to injury prevention, child and adolescent safeguarding, and public health campaigns for child safety.

This paper examines ways in which Aboriginal residents of Taloyoak, Nunavut and Tuktoyaktuk, Northwest Territories perceive aquatic-based risk communication, and how this information could be used to improve water safety. We argue that aquatic risk communication with northern Aboriginal populations can be improved by identifying and accounting for the consequences of colonialism in the context of aquatic risk communication and, in turn, decolonizing water safety programs north of the 60th parallel-Canada's North. [ABSTRACT FROM AUTHOR]

Introduction: Physician recruitment to rural and remote communities poses a major challenge to health care delivery in Canada. Rather than focusing solely on the politics and policies that contribute to the shortage of family physicians in Canada's North, we argue that more attention should be paid to the reasons that lead, and have led, family physicians to the North, and also to the factors that contribute to physician retention. Methods: We used archival research and semi- and unstructured interviews to provide a history of medicine in Liidlii Kue/Fort Simpson, NWT, and to describe the features of physicians who have served and continue to serve this Northern community. Results: Results show that medicine in Liidlii Kue/Fort Simpson can be divided into 4 distinct eras: the prehospital era (1848-1916), the early hospital era (1917-1925), the middle era (1926-1972) and the government era (1973-present). Thirty-eight physicians were identified as having worked in Liidlii Kue/Fort Simpson. Of those, 19 were contacted. Nine physicians and the offspring of 1 deceased physician were interviewed. We found physicians fell into 1 of 4 categories: new graduates, those seeking midcareer (or midlife) change, those about to retire and international medical graduates. Conclusion: By examining Liidlii Kue/Fort Simpson as a case study, this research fills the dearth of knowledge in the factors that contribute to physician recruitment and retention in Canada's North. [ABSTRACT FROM AUTHOR]

Mesial temporal lobe epilepsy (mTLE) is the most prevalent type of epilepsy in adults. First and subsequent generations of anti-epileptic therapy regimens fail to decrease seizures in a large number of patients suffering from mTLE, leaving surgical ablation of part of the hippocampus as the only therapeutic option to potentially reach seizure freedom. GluK2 has recently been identified as a promising target for the treatment of mTLE using gene therapy. Here, we engineered an adeno-associated virus serotype 9 vector expressing a cluster of two synthetic microRNAs (miRNAs), expressed from the human synapsin promoter, that target GRIK2 mRNA. Intra-hippocampal delivery of this vector in a mouse model of mTLE significantly reduced GRIK2 expression and daily seizure frequency. This treatment also improved the animals' health, reduced their anxiety, and restored working memory. Focal administration of the vector to the hippocampus of cynomolgus monkeys in GLP toxicology studies led to the selective transduction of hippocampal neurons with little exposure elsewhere in the brain and no transduction outside the central nervous system. Expression of miRNAs in hippocampal neurons resulted in substantially decreased GRIK2 mRNA expression. These data suggest that the intra-hippocampal delivery of a GMP-grade AAV9 encoding a synthetic miRNAs targeting GRIK2 is a promising treatment strategy for mTLE., Competing Interests: A patent application has been filed relating to this work. S.J.B., N.Pearson, C.H., N.Partouche, J.G., and R.P. declare an association with uniQure/Corlieve Therapeutics. M.W. and I.B. declare an association with uniQure B.V. A.G., J.S., A.M., and O.D. declare association with Regenxbio Inc., (© 2024 uniQure biopharma B.V.)

The significant burden of home injuries has become a growing concern that affect thousands of people every year across Canada. This study examined the relationship between neighbourhood deprivation and unintentional injuries occurring at home leading to hospitalizations in British Columbia (BC) between 2015 and 2019. This study used de-identified hospitalization data on unintentional home-related injuries from the Discharge Abstract Database (DAD) and population data for each dissemination area from Statistics Canada's 2016 Census Profiles. Hospitalization rates were computed for unintentional home-related injuries across four dimensions specified in the Canadian Index of Multiple Deprivation (CIMD) for BC. For three CIMD dimensions (situational vulnerability, economic dependency, and residential instability), unintentional home injury rates were higher in areas with higher deprivation, while the inverse was observed for ethno-cultural diversity. Understanding socio-economic disparities within neighbourhoods enables injury prevention partners to identify vulnerable populations and prioritize the development and implementation of evidence-based injury prevention interventions.

Introduction: Improving sustainable transportation options will help cities tackle growing challenges related to population health, congestion, climate change and inequity. Interventions supporting active transportation face many practical and political hurdles. Implementation science aims to understand how interventions or policies arise, how they can be translated to new contexts or scales and who benefits. Sustainable transportation interventions are complex, and existing implementation science frameworks may not be suitable. To apply and adapt implementation science for healthy cities, we have launched our mixed-methods research programme, CapaCITY/É. We aim to understand how, why and for whom sustainable transportation interventions are successful and when they are not., Methods and Analysis: Across nine Canadian municipalities and the State of Victoria (Australia), our research will focus on two types of sustainable transportation interventions: all ages and abilities bicycle networks and motor vehicle speed management interventions. We will (1) document the implementation process and outcomes of both types of sustainable transportation interventions; (2) examine equity, health and mobility impacts of these interventions; (3) advance implementation science by developing a novel sustainable transportation implementation science framework and (4) develop tools for scaling up and scaling out sustainable transportation interventions. Training activities will develop interdisciplinary scholars and practitioners able to work at the nexus of academia and sustainable cities., Ethics and Dissemination: This study received approval from the Simon Fraser University Office of Ethics Research (H22-03469). A Knowledge Mobilization Hub will coordinate dissemination of findings via a website; presentations to academic, community organisations and practitioner audiences; and through peer-reviewed articles., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

This study contributes to a growing body of scholarly discussions around the many aspects and challenges of combining parenthood with elite-level sport, with a particular focus on the experiences of male elite athletes who are fathers. We used a caring masculinities theoretical framework, community-based participatory research, and semi-structured interviews to explore the experiences of 10 elite/international and world-class athletes ( n = 9 fathers, n = 1 expectant father). Through reflexive thematic analysis, we identified three main themes: fatherhood can (1) improve and (2) impede elite athlete-fathers' athletic performance; and (3) athlete-fathers experience a trade-off between athletic performance and fatherhood responsibilities. Our findings underscore the ways in which male athletes' experiences with parenthood reflect the new era of involved fatherhood and are analogous to some of the identity tensions that have been reported with regard to the experiences of elite female athletes who are pregnant and/or mothers. Recognizing the impact of children on male athletes' athletic careers and the parallels between fatherhood, motherhood, and elite sport may lead to better support for athlete-fathers while also contributing to diminishing the expectation that women are primary caregivers to children., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© 2023 SAGE Publications.)

In Canada, the Truth and Reconciliation Commission (TRC) released its list of Calls to Action (CTA) in 2015, and five Calls were directly related to reconciliation and sport. Within these five sport-related CTA, there was no specific reference to gender. Lacrosse, as an Indigenous cultural practice that has been culturally appropriated by white settlers, is a complex site to investigate how the TRC's CTA is (or are not) being implemented and the ways in which these efforts are gendered. In this paper, we examined how staff at Canadian lacrosse organizations address the CTA and Indigenous women's and girls' participation in lacrosse. Through the use of Indigenous feminist theory, feminist methodologies informed by the tenets of Indigenous methodologies, semi-structured interviews and reflexive thematic analysis, our findings demonstrate that Indigenous women and girls are commonly overlooked, and gender is typically an afterthought within the implementation of sport-related CTA by lacrosse organizing bodies in Canada - if they are implemented at all. As a result, we argue that there is a need to make gender a central organizing principle when lacrosse organizations within Canada implement the TRC's CTA., 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) 2023.)

Eekeeluak Avalak, an 18-year-old Inuk wrestler who won the first-ever gold medal for Nunavut at the Canada Summer Games in 2022, dedicated his win to his late brother who died by suicide in 2015. Avalak openly attributed sport - specifically wrestling - to saving his own life. This story raises important questions about the role of sport and traditional games in Inuit suicide prevention strategies. Few studies have examined the role of sport or traditional games in Inuit suicide prevention strategies. In an attempt to reduce Inuit suicide rates, in addition to the National Inuit Prevention Strategy, three of the four land claim regions that constitute Inuit Nunangat have suicide prevention strategies. In this study, we used settler colonial theory, critical Inuit studies, and content analysis to examine if and how sport and Inuit traditional games are identified as prevention tools in these Inuit suicide prevention strategies. The results demonstrate that sport and traditional games have largely been overlooked as protective factors in current Inuit-wide and land-claim specific suicide prevention strategies. Moving forward, evidence-based and community-driven approaches could be funded, created, implemented, and evaluated as culturally-safe Inuit mental health intervention models to address the disproportionately high suicide rates among Inuit in Inuit Nunangat.

Recently, motherhood and pregnancy in elite sport have received increased attention in sport media. Through a comprehensive news media search across Factiva as well as a gray literature search using Google search engine, we analyzed 115 articles using feminist framing analysis. We developed two primary frames: 1) empowerment versus exploitation, and 2) proactivity versus reactivity. Our results show that many pregnant and parenting athletes frame their respective sponsors as exploitative for recognizing and capitalizing upon their unique marketing value, while these same corporate sponsors frame themselves as industry leaders who empower pregnant and parenting athletes. These two frames show that pregnant/parenting elite athletes commonly face discriminatory policies and practices and that there is often a lack of congruence between marketing and actual corporate practices and policies. These findings arguably reflect larger societal issues related to gender equity and highlight the importance of action over rhetoric to ensure motherhood is supported-rather than marketed-for elite athletes., 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) 2022.)

Importance: The use of adeno-associated viruses (AAVs) as gene delivery vectors has vast potential for the treatment of many severe human diseases. Over one hundred naturally existing AAV capsid variants have been described and classified into phylogenetic clades based on their sequences. AAV8, AAV9, AAVrh.10, and other intensively studied capsids have been propelled into pre-clinical and clinical use, and more recently, marketed products; however, less-studied capsids may also have desirable properties (e.g., potency differences, tissue tropism, reduced immunogenicity, etc.) that have yet to be thoroughly described. These data will help build a broader structure-function knowledge base in the field, present capsid engineering opportunities, and enable the use of novel capsids with unique properties., Competing Interests: All REGENXBIO employees earn salary and own stock in REGENXBIO, Inc. All Invicro employees earn salary from Invicro.

The primary objective of this community-based participatory research is to explore the impacts of COVID-19 and the delayed Tokyo 2020 Olympic Games on world-class and elite/international-class parenting and pregnant athletes. Participants in this study include 11 female and 10 male parenting and/or pregnant middle and distance runners. Combined, the participants have competed at 26 Olympic Games and 31 World Championships. Drawing on the general concepts of stressors and psychological resilience, we use thematic analysis to develop four themes to understand the stressors for world-class and elite/international-class parenting and pregnant athletes due to COVID-19 and the delayed Tokyo 2020 Olympic Games: (1) lack of childcare support, (2) family planning, and (3) needing to stay away from sources of COVID-including their children. Despite the stressors identified in the aforementioned themes, we identified a fourth theme: (4) participants demonstrated adaptability to stress in spite of-or due to-their athlete-parent identities., Competing Interests: DW was affiliated with Mile2Marathon Inc. during this study. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Darroch, Smith, Sheppard-Perkins, Giles and Wykes.)

Parenting education interventions and parenting programs are important for health promotion efforts among children and families; however, the majority of parenting programs are directed towards and attended by mothers. This is problematic because research has consistently demonstrated that fathers' active participation in the family can have a positive influence on mothers' well-being, children's self-esteem, success in school, and interpersonal relationships. In this paper, using an intersectional poststructuralist framework, document analysis, and Bacchi and Goodwin's "What's the problem represented to be" approach (WPR), we analyzed the program policies of 12 organizations that provide family-centred services in the Downtown Eastside of Vancouver, British Columbia, Canada. We identified the following three discourses: organizations strive to be client-centred and provide choices; organizations want to empower their participants; and women need safe place to raise their families. Our analysis revealed that fathers are absent or represented as problems in program policies, and that this has consequences for not only fathers but also mothers and children., Competing Interests: Conflict of InterestThe authors declare no competing interests., (© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2022. Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Purpose: The International Olympic Committee expert group on pregnancy has identified a paucity of information regarding training and performance in truly elite athletes. Thus, the purpose of this study was to quantify elite runners' training volume throughout pregnancy and postpartum competition performance outcomes., Methods: Forty-two elite (>50% competed at the World Championships/Olympic) middle-/long-distance runners' training before, during, and after pregnancy (quality/quantity/type) data (retrospective questionnaire) and competition data (published online) were collected., Results: Running volume decreased significantly ( P < 0.01) from the first trimester (63 ± 34 km·wk -1 ) to the third trimester (30 ± 30 km·wk -1 ). Participants returned to activity/exercise at ~6 wk postpartum and to 80% of prepregnancy training volumes by 3 months. Participants who intended to return to equivalent performance levels postpregnancy, there was no statistical decrease in performance in the 1 to 3 yr postpregnancy compared with prepregnancy, and ~56% improved performances postpregnancy., Conclusions: This study features the largest cohort of elite runners training and competition outcomes assessed throughout pregnancy, with training volumes being approximately two to four times greater than current guidelines. For the first time, performance was directly assessed (due to the quantifiable nature of elite running), and study participants who intended to return to high-level competition did so at a statistically similar level of performance in the 1- to 3-yr period postpregnancy. Taken together, this article provides much needed insights into current training practices and performance of elite pregnant runners, which should help to inform future training guidelines as well as sport policy and sponsor expectations around return to training timelines and performance., (Copyright © 2022 by the American College of Sports Medicine.)

Understanding the kinetics and durability of AAV-mediated transgene expression in the brain is essential for conducting basic neuroscience studies as well as for developing gene therapy approaches for CNS diseases. Here, we characterize and compare the temporal profile of transgene expression after bilateral injections into the mouse striatum of rAAV9 encoding GFP under the control of either a ubiquitous promoter (CAG), or the neuron-specific human synapsin (hSyn) and CamKII promoters. GFP protein expression with the CAG promoter was highest at 3 weeks, and then decreased to stable levels at 3 and 6 months. Surprisingly, GFP mRNA levels continued to increase from 3 weeks to 3 months, despite GFP protein expression decreasing during this time. GFP protein expression with hSyn increased more slowly, reaching a maximum at 3 months, which was equivalent to protein expression levels from CAG at that time point. Importantly, transgene expression driven by the hSyn promoter at 6 months was not silenced as previously reported, and GFP mRNA was continuing to rise even at the final 6-month time point. Thus, hSyn as a promoter for transgene expression demonstrates long-term durability but may require more time after vector administration to achieve steady-state levels. Because CAG had the highest GFP protein expression in our comparison, which was at 3 weeks post administration, the early kinetics of transgene expression from CAG was examined (1, 2, 5, and 10 days after injection). This analysis showed that GFP protein expression and GFP mRNA increased during the first 3 weeks after administration. Interestingly, vector DNA rapidly decreased 10-fold over the first 3 weeks following injection as it assembled into stable circular episomes and concatemers. Surprisingly, the processing of vector genomes into circular episomes and concatemers was continually dynamic up to 3 months after injection. These results provide novel insight into the dynamic processing of vector genomes and promoter-specific temporal patterns of transgene expression in the brain., Competing Interests: This study received funding from REGENXBIO Inc. The funder had the following involvement in the study. All authors are employees of REGENXBIO Inc. and thus designed the studies, performed the experiments, analyzed the data, generated the figures, and wrote the manuscript., (Copyright © 2022 Hollidge, Carroll, Qian, Fuller, Giles, Mercer, Danos, Liu, Bruder and Smith.)

Boating-related fatalities in the Northwest Territories (NWT) are well above the national average. These fatalities are exacerbated by very cold water, and water and boating safety resources that lack relevance to residents of northern communities. We utilised an iterative, participatory approach to create a plain language, culturally and geographically adapted version of a cold water survival course, "Beyond Cold Water Bootcamp". The purpose of this research was to determine what adaptations are necessary to create appealing and pertinent boating safety interventions for Inuvialuit communities in the NWT and to demonstrate the value of generating such interventions. First, we conducted a focus group with boating safety experts to gain feedback on the first draft of the adapted course. We then subsequently completed a pilot of the course with community members in Tuktoyaktuk, NWT, and we obtained their feedback and suggestions. We then trained a local community member to deliver the course and conducted another focus group with residents. Using reflexive thematic analysis, our results demonstrated the value of culturally and geographically adapted boating safety interventions for Inuvialuit communities and the importance of relinquishing colonial power structures and enabling community members to independently adapt and disseminate knowledge.

With the advent of single B-cell cloning technology, we can isolate antibodies against virtually any antigen to study the interaction of a given pathogen with the immune system and develop novel therapeutic strategies. Antibodies directed against the capsid of adeno-associated viruses (AAV) are a significant obstacle to effectively leveraging AAV as a gene-delivery vector in seropositive individuals. In order to design next-generation vectors that can evade neutralization by these antibodies, studies have mapped the epitopes of mouse monoclonal antibodies generated by immunization with AAV. Although these studies provide critical information regarding capsid immunogenicity, they cannot address (1) differences in the antibody repertoire generated in humans following AAV natural infection; or (2) how reactions can vary when generated in response to vector administration. Here, we isolated and evaluated a panel of novel, fully human anti-AAV antibodies by cloning single memory B cells from a seropositive normal donor. We have validated the utility of this approach to study AAV immunology. Our goal is to leverage this knowledge to design novel AAV variants that can effectively transduce target tissues in individuals with AAV-neutralizing antibodies., (Copyright © 2020 Giles, Calcedo, Tretiakova and Wilson.)

Background: There is inconsistency across child development and care literature in operationalizing serious play-related injury and also a lack of understanding of how mothers and fathers conceptualize serious play-related injury. The current study explores parents' perspectives of their 2- to 7-year-old children's serious play-related injuries in urban and rural areas of British Columbia and Québec, Canada, and provides an urban/rural and gender analysis of the results., Methods: We conducted semistructured interviews with 41 mothers and 63 fathers from 57 families, a total of 104 participants, in urban and rural locations in British Columbia and Québec, Canada. We used a social constructionist approach to the research and reflexive thematic analysis to construct themes from participant responses and to inform the consequent categorizations of serious play-related injury., Results: The results indicate four categories of parents' conceptualizations of serious play-related injury: (a) injury requiring medical intervention, (b) injury resulting in head trauma, (c) injury resulting in debilitation, and (d) broken bones., Conclusions: Child development and care advocates can use these categories to strengthen their communications with parents and to improve understanding of parents' conceptualizations of children's serious play-related injury., (© 2020 John Wiley & Sons Ltd.)

Unintentional injuries are one of the leading causes of death worldwide, yet they are predictable and avoidable events. Community-based approaches to injury prevention are those where researchers and/or injury prevention specialists work alongside the target population to identify injury prevention issues and then co-create strategies that are relevant to the population. Community-based strategies differ from other approaches as they strive to conduct research with, rather than on marginalized groups. A community-based approach to social marketing, injury prevention and risk messaging was applied in Inuvik, Northwest Territories, Canada, to examine and address men's boating safety behaviours. Community participants identified the need for northern-based safety resources and a community-wide education campaign. As demonstrated through this example, community-based strategies should be considered for injury prevention, as the involvement of local community members may lead to more effective risk messaging that reflects the needs, culture, and experiences of the target group, while promoting healthy behaviours., (© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

An ongoing concern of in vivo gene therapy is adaptive immune responses against the protein product of a transgene, particularly for recessive diseases in which antigens are not presented to lymphocytes during central tolerance induction. Here we show that Toll-like receptor 9 (TLR9) signaling activates T cells against an epitope tagged mitochondria-targeted ornithine transcarbamylase (OTC) following the administration of a systemic adeno-associated virus (AAV) vector. Using a transgenic mouse model system, we demonstrate that TLR9 signaling extrinsic to T cells induces a robust cytotoxic T-cell response against the transgene and results in transgene expression loss. Overall, our results suggest that inflammation mediated by TLR9 signaling and the presence of high affinity transgene-specific T cells is important for the development of adaptive immune responses to transgene products following AAV gene therapy., (Copyright © 2019 Elsevier Inc. All rights reserved.)

First Nations women who live on rural and remote reserves in Canada leave their communities between 36 and 38 weeks gestational age to receive labor and birthing services in large urban centers. The process and administrative details of this process are undocumented despite decades of relocation as a routine component of maternity care. Using data from 32 semistructured interviews and information from peer-reviewed literature, grey literature, and public documents, I constructed a descriptive map and a visual representation of the policy. I present new and detailed information about Canada's health policy as well as recommendations to address the health care gaps identified.

Background and Purpose Child safety campaigns play an important role in disseminating injury prevention information to families. A critical discourse analysis of gender bias in child safety campaign marketing materials can offer important insights into how families are represented and the potential influence that gender bias may have on uptake of injury prevention information. Methods Our approach was informed by poststructural feminist theory, and we used critical discourse analysis to identify discourses within the poster materials. We examined the national Safe Kids Canada Safe Kids Week campaign poster material spanning twenty years (1997-2016). Specifically, we analyzed the posters' typeface, colour, images, and language to identify gender bias in relation to discourses surrounding parenting, safety, and societal perceptions of gender. Results The findings show that there is gender bias present in the Safe Kids Week poster material. The posters represent gender as binary, mothers as primary caregivers, and showcase stereotypically masculine sporting equipment among boys and stereotypically feminine equipment among girls. Interestingly, we found that the colour and typeface of the text both challenge and perpetuate the feminization of safety. Discussion It is recommended that future child safety campaigns represent changing family dynamics, include representations of children with non-traditionally gendered sporting equipment, and avoid the representation of gender as binary. This analysis contributes to the discussion of the feminization of safety in injury prevention research and challenges the ways in which gender is represented in child safety campaigns., Competing Interests: Competing interests: None declared, (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2019. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Despite the proliferation of age-friendly cities in Canada that are intended to support older adults to age well, there are still many inequalities between groups of older adults, particularly, and of concern for this paper, between Indigenous older adults, who experience colonialism's ongoing impacts, and non-Indigenous older adults. A better understanding of factors that inform these inequalities will help in the development of policies and programs that better support Indigenous older adults to age well and, thus, will contribute to ameliorating the inequalities that they face. Using a community-based participatory research approach, informed by a postcolonial theoretical lens, in this paper we addressed the question, "what community-level factors contribute to Indigenous older adults (aged 55 years and over) feeling supported to age well in the city of Ottawa?" We specifically examined this question in relation to the age-friendly communities framework, which guides the City of Ottawa's Older Adult Plan. Thematic analysis of semi-structured interviews, focus groups, and photovoice with 32 First Nations and Inuit older adults revealed that the participants felt both supported and unsupported to age well. More specifically, there were two main areas in which they felt they could be better supported to age well: the social environment and physical environment. There were three subthemes within the social environment theme: responsive health and community support services, respect and recognition, and communication and information. Within the physical environment theme there were four subthemes: transportation, housing, accessibility, and gathering space. The results demonstrate that despite there being similarities in the areas that the participants felt they needed support and the areas on which the Older Adult Plan focuses, if the domains of aging well initiatives do not better account for the impacts of colonialism, it is unlikely that they will be effective in supporting Indigenous older adults' health and well-being., (Copyright © 2019 Elsevier Inc. All rights reserved.)

This paper used netnography and thematic analysis of the comments made in online news articles to understand better the public response to the closure of the only KFC restaurant in Yellowknife, Northwest Territories, Canada, in 2015. While the popular media often cover fast-food restaurant closures, past academic research has not examined the public response to these closures. To begin to fill this gap, we examined the comments sections of five online news articles from the Canadian news outlet, CBC.ca, and reactions shared on Facebook. 239 commenters made 308 publicly available online comments addressing the closure. Key themes in commenter perceptions included pro-closure reactions, which were based on the perceived public health benefits of reduced fast-food consumption, and anti-closure reactions to such factors as the loss of a local landmark and a source of positive memories. The unfavorable reactions appeared to pose a significant barrier to public acceptance of the KFC closure. This paper argues that it is important to examine public perceptions of fast-food closures to understand better what these restaurants mean to individuals and communities. This information, in turn, can be used to promote healthier restaurant-eating in ways that will complement efforts to encourage healthier food choices.

Post-translational modification of the adeno-associated virus capsids is a poorly understood factor in the development of these viral vectors into pharmaceutical products. Here we report the extensive capsid deamidation of adeno-associated virus serotype 8 and seven other diverse adeno-associated virus serotypes, with supporting evidence from structural, biochemical, and mass spectrometry approaches. The extent of deamidation at each site depended on the vector's age and multiple primary-sequence and three-dimensional structural factors. However, the extent of deamidation was largely independent of the vector recovery and purification conditions. We demonstrate the potential for deamidation to impact transduction activity and, moreover, correlate an early time point loss in vector activity to rapidly progressing spontaneous deamidation at several adeno-associated virus 8 asparagines. We explore mutational strategies that stabilize side-chain amides, improving vector transduction and reducing the lot-to-lot molecular variability that presents a key concern in biologics manufacturing. This study illuminates a previously unknown aspect of adeno-associated virus capsid heterogeneity and highlights its importance in the development of these vectors for gene therapy., (Copyright © 2018 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.)

Background: Aboriginal peoples in Canada are comprised of First Nations, Métis, and Inuit. Health care services for First Nations who live on rural and remote reserves are mostly provided by the Government of Canada through the federal department, Health Canada. One Health Canada policy, the evacuation policy, requires all First Nations women living on rural and remote reserves to leave their communities between 36 and 38 weeks gestational age and travel to urban centres to await labour and birth. Although there are a few First Nations communities in Canada that have re-established community birthing and Aboriginal midwifery is growing, most First Nations communities are still reliant on the evacuation policy for labour and birthing services. In one Canadian province, Manitoba, First Nations women are evacuated to The Pas, Thompson, or Winnipeg but most - including all women with high-risk pregnancies - go to Winnipeg., Aim: To contribute scholarship that describes First Nations women's and community members' experiences and perspectives of Health Canada's evacuation policy in Manitoba., Methods: Applying intersectional theory to data collected through 12 semi-structured interviews with seven women and five community members (four females, one male) in Manitoba who had experienced the evacuation policy. The data were analyzed thematically, which revealed three themes: resignation, resilience, and resistance., Findings: The theme of resignation was epitomized by the quote, "Nobody has a choice." The ability to withstand and endure the evacuation policy despite poor or absent communication and loneliness informed of resilience. Resistance was demonstrated by women who questioned the necessity and requirement of evacuation for labour and birth. In one instance, resistance took the form of a planned homebirth with Aboriginal registered midwives., Conclusion: There is a pressing need to improve the maternity care services that First Nations women receive when they are evacuated out of their communities, particularly when understood from the specific legal and constitutional position of First Nations women in Manitoba., (Copyright © 2018 Australian College of Midwives. Published by Elsevier Ltd. All rights reserved.)

Recent clinical trials have demonstrated the potential of adeno-associated virus (AAV)-based vectors for treating rare diseases. However, significant barriers remain for the translation of these vectors into widely available therapies. In particular, exposure to the AAV capsid can generate an immune response of neutralizing antibodies. One approach to overcome this response is to map the AAV-specific neutralizing epitopes and rationally design an AAV capsid able to evade neutralization. To accomplish this, we isolated a monoclonal antibody against AAV9 following immunization of BALB/c mice and hybridoma screening. This antibody, PAV9.1, is specific for intact AAV9 capsids and has a high neutralizing titer of >1:160,000. We used cryo-electron microscopy to reconstruct PAV9.1 in complex with AAV9. We then mapped its epitope to the 3-fold axis of symmetry on the capsid, specifically to residues 496-NNN-498 and 588-QAQAQT-592. Capsid mutagenesis demonstrated that even a single amino acid substitution within this epitope markedly reduced binding and neutralization by PAV9.1. In addition, in vivo studies showed that mutations in the PAV9.1 epitope conferred a "liver-detargeting" phenotype to the mutant vectors, unlike AAV9, indicating that the residues involved in PAV9.1 interactions are also responsible for AAV9 tropism. However, we observed minimal changes in binding and neutralizing titer when we tested these mutant vectors for evasion of polyclonal sera from mice, macaques, or humans previously exposed to AAV. Taken together, these studies demonstrate the complexity of incorporating mapped neutralizing epitopes and previously identified functional motifs into the design of novel capsids able to evade immune response. IMPORTANCE Gene therapy utilizing viral vectors has experienced recent success, culminating in U.S. Food and Drug Administration approval of the first adeno-associated virus vector gene therapy product in the United States: Luxturna for inherited retinal dystrophy. However, application of this approach to other tissues faces significant barriers. One challenge is the immune response to viral infection or vector administration, precluding patients from receiving an initial or readministered dose of vector, respectively. Here, we mapped the epitope of a novel neutralizing antibody generated in response to this viral vector to design a next-generation capsid to evade immune responses. Epitope-based mutations in the capsid interfered with the binding and neutralizing ability of the antibody but not when tested against polyclonal samples from various sources. Our results suggest that targeted mutation of a greater breadth of neutralizing epitopes will be required to evade the repertoire of neutralizing antibodies responsible for blocking viral vector transduction., (Copyright © 2018 American Society for Microbiology.)

The Kivalliq Inuit Centre (KIC), a boarding home in Winnipeg, Manitoba, is unique in its provision of a pilot prenatal education class and public health nursing services for Nunavummiut who are beneficiaries of the Nunavut Land Claim Agreement. Through a critical review of literature, policies and interviews related to evacuation for birth, we argue that the pilot at the KIC has the potential to play an important role in improving maternal child health for residents of Nunavut., Competing Interests: and funding The authors have not received any funding or benefits from industry or elsewhere to conduct this study.

The 2011 National Household Survey found that the number of Aboriginal peoples in Canada aged 65 and over has increased by over 46 % since the 2006 Canadian Census (Statistics Canada 2011). Despite this dramatic increase in older Aboriginal peoples, there is a dearth of research concerning this cohort, especially regarding their engagement with physical activity. Using a case study methodology, this research sought to examine if the Northwest Territories (NWT) Recreation and Parks Association's (NWTRPA) Elders in Motion (EIM) program is culturally relevant for the participants. For this research we used a postcolonial theoretical framework since many of the participants in EIM are Aboriginal older adults and have experienced, and continue to experience, the effects of colonialism. To address this aim we conducted nine semi-structured interviews with EIM program leaders and NWTRPA staff, and supplemented these with archival research of EIM program documents. The findings show that the NWTRPA has adapted many EIM program documents for the participants and thus attempts to be culturally relevant for the participants. There are, however, aspects of the program that are not culturally relevant and actually reinforce colonialism, specifically with the program content (i.e. activities that are a part of EIM). In light of these findings, recommendations are offered for the NWTRPA on how the EIM program can become more culturally relevant for its Aboriginal participants.

Background: Elite female distance runners lack guidelines regarding breastfeeding while training at a high intensity., Objectives: The purpose of this research was to understand how elite female distance runners manage breastfeeding., Methods: Semistructured interviews were conducted with 14 women who had had at least one pregnancy within the past 5 years and had achieved a minimum of the USA Track and Field 2012 Olympic Trials "B" entry standard for running for the marathon or equivalent performance for 1,500 m or longer., Results: Using thematic analysis, we identified the following themes: breastfeeding as a barrier to training and competition, limited access to relevant breastfeeding information, and concerns for the baby's health. Our findings show that despite the considerable barriers with which these women contend, they breastfed at higher rates and for longer duration than members of the general public., Conclusion: Based on our findings, we argue that elite female distance runners' experiences of breastfeeding would be enhanced if more research were conducted on breastfeeding practices while training and competing at an elite level.

Problem: Excessive weight gain and physical inactivity in pregnancy have been identified as risk factors for negative health outcomes for mothers and fetuses, particularly among Aboriginal women., Question: In this paper we engage with postcolonial feminist theory and critical discourse analysis to examine the question, "how do urban Aboriginal women understand pregnancy-related weight gain and physical activity.", Methods: We conducted focus groups and semi-structured interviews with 25 urban Aboriginal pregnant or postpartum women between the ages of 16 and 39 in Ottawa, Canada., Findings: Three prominent discourses emerged: Aboriginal women have different pregnancies than non-Aboriginal women because Aboriginal women gain more weight and are more likely to develop gestational diabetes; Aboriginal women feel personally responsible for and shameful about excessive weight gain; finally, Aboriginal women need culturally safe pregnancy resources., Discussion: Our results illuminate the complex and often paradoxical ways in which discourses around weight gain and physical activity are produced and taken-up by Aboriginal women and their healthcare providers., Conclusion: Based on these findings, we argue there is a lack of accessible and culturally safe resources for urban Aboriginal women, specifically concerning weight gain and physical activity in pregnancy. We recommend the development of resources that are created for/by/with Aboriginal women to better address that issues that urban Aboriginal women themselves identify as being of key importance., (Copyright © 2015 Australian College of Midwives. Published by Elsevier Ltd. All rights reserved.)

The purpose of this article is to examine health/service providers' perspectives of barriers to healthy weight gain and physical activity for urban, pregnant First Nations women in Ottawa, Canada. Through the use of semi-structured interviews, we explored 15 health/service providers' perspectives on the complex barriers their clients face. By using a postcolonial feminist lens and a social determinants of health framework, we identified three social determinants of health that the health/service providers believed to have the greatest influence on their clients' weight gain and physical activity during pregnancy: poverty, education, and colonialism. Our findings are then contextualized within existing Statistics Canada and the Ottawa Neighbourhood Study data. We found that health/service providers are in a position to challenge colonial relations of power. We conclude by urging health/service providers, researchers, and policymakers alike to take into consideration the ways in which these social determinants of health and their often synergistic effects affect urban First Nations women during pregnancy., (© The Author(s) 2015.)

Public health nurses are on the front line of injury prevention initiatives. However, within injury prevention interventions and research, issues pertaining to culture are often addressed through the employment of one of the three approaches: cultural competency, cultural appropriateness, and/or cultural sensitivity. When using these approaches, it is often suggested that it is only those who are the recipients of an intervention or the focus of research that "have" culture. The injury prevention designer's/provider's/researcher's own culture, as well as the ways in which it may influence the interventions or research, is typically rendered invisible. In this paper, we provide an overview and illustrations of the use of cultural competency, cultural appropriateness, and cultural sensitivity in injury prevention initiatives, as well as each approach's shortcomings. We then introduce cultural safety, an approach that has not yet gained traction in injury prevention but has had significant uptake within nursing in general, and argue that it has the potential to overcome many other approaches' shortcomings and thus may lead to more effective and socially just injury prevention initiatives., (© 2015 Wiley Periodicals, Inc.)

Adeno-associated virus (AAV) vectors often undergo long-distance axonal transport after brain injection. This leads to transduction of brain regions distal to the injection site, although the extent of axonal transport and distal transduction varies widely among AAV serotypes. The mechanisms driving this variability are poorly understood. This is a critical problem for applications that require focal gene expression within a specific brain region, and also impedes the utilization of vector transport for applications requiring widespread delivery of transgene to the brain. Here, we compared AAV serotypes 1 and 9, which frequently demonstrate distal transduction, with serotype 8, which rarely spreads beyond the injection site. To examine directional AAV transport in vitro, we used a microfluidic chamber to apply dye-labeled AAV to the axon termini or to the cell bodies of primary rat embryonic cortical neurons. All three serotypes were actively transported along axons, with transport characterized by high velocities and prolonged runs in both the anterograde and retrograde directions. Coinfection with pairs of serotypes indicated that AAV1, 8, and 9 share the same intracellular compartments for axonal transport. In vivo, both AAV8 and 9 demonstrated anterograde and retrograde transport within a nonreciprocal circuit after injection into adult mouse brain, with highly similar distributions of distal transduction. However, in mass-cultured neurons, we found that AAV1 was more frequently transported than AAV8 or 9, and that the frequency of AAV9 transport could be enhanced by increasing receptor availability. Thus, while these serotypes share conserved mechanisms for axonal transport both in vitro and in vivo, the frequency of transport can vary among serotypes, and axonal transport can be markedly increased by enhancing vector uptake. This suggests that variability in distal transduction in vivo likely results from differential uptake at the plasma membrane, rather than fundamental differences in transport mechanisms among AAV serotypes.

Cultural safety is an approach currently used in health care that is meant to address health disparities between Indigenous and non-Indigenous peoples and colonizing practices in health care. It has been found to empower patient decision-making and result in a relationship where patients and providers work together towards effective care. In this commentary, we argue that such an approach needs to be employed in physical activity promotion and programs as another way of addressing health disparities that continue to exist between Indigenous and non-Indigenous peoples in Canada. Further, we assert that cultural safety can address the critiques that have been made of attempts to use cultural sensitivity, cultural relevancy, and cultural competency training for physical activity providers and in implementing physical activity programs. Cultural safety in physical activity promotion and programs is not only an ethical practice, but also one that has the potential to significantly improve the health of Indigenous peoples, which could lead to related improvements in quality of life, lowering rates of morbidity and mortality, and resulting in considerable savings to the health care sector.