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Wood is commonly used in construction, but often perceived as being less safe than structures made from non-combustible materials. With the advancement of wood products and treatment, construction techniques, and protective systems, this may not be the case any longer. Using retrospective data from fire departments across Canada, this study aimed to determine whether the type of construction material (combustible or non-combustible) affected the fire severity outcome of a one to six storey apartment building fire, after accounting for protective systems (smoke alarms and sprinklers). The study found that, after adjusting for the presence of smoke alarms and sprinklers, structures constructed from non-combustible construction materials did not perform better in terms of injuries, requiring extinguishment by fire department, or the fire spreading beyond the room of origin. The presence of working smoke alarms and sprinklers played a central role in reducing the severity outcome of a fire. Smoke alarms and sprinklers both reduced the odds of extinguishment by the fire department and the fire spreading beyond the room of origin. Sprinklers also reduced the injury rate. Overall, this study highlighted the importance of protective systems in reducing fire severity outcomes.

Background: The rare A673T variant was the first variant found within the amyloid precursor protein (APP) gene conferring protection against Alzheimer’s disease (AD). Thereafter, different studies have discovered that the carriers of the APP A673T variant show reduced levels of amyloid beta (Aβ)in the plasma and better cognitive performance at high age. Methods: Cerebrospinal fluid (CSF) and plasma of APP A673T carriers and control individuals were analyzed using a mass spectrometry-based proteomics approach to identify differentially regulated targets in an unbiased manner. Furthermore, the APP A673T variant was introduced into 2D and 3D neuronal cell culture models together with the pathogenic APP Swedish and London mutations. Results: Here, we report for the first time the protective effect of the APP A673T variant against AD-related alterations in the CSF, plasma, and brain biopsy samples from the frontal cortex. Levels of both soluble APPβ (sAPPβ) and Aβ42 were lower in the CSF of APP A673T carriers than in the CSF of controls not carrying the protective variant. Consistent with these CSF findings, immunohistochemical assessment of cortical biopsy samples from the same APP A673T carriers did not reveal Aβ, phospho-tau, or p62 pathologies. We identified differentially regulated targets involved in protein phosphorylation, inflammation, and mitochondrial function in the CSF and plasma samples of APP A673T carriers. Some of the identified targets showed inverse levels in AD brain tissue with respect to increased AD-associated neurofibrillary pathology. In 2D and 3D neuronal cell culture models expressing APP with the Swedish and London mutations, the introduction of the APP A673T variant led to lower sAPPβ levels. Concomitantly, the levels of sAPPα were increased, while decreased levels of CTFβ and Aβ42 were detected in some of these models. Conclusions: Our findings emphasize the important role of APP-derived peptides in the pathogenesis of AD and demonstrate the effectiveness of the protective APP A673T variant to shift APP processing toward the non-amyloidogenic pathway in vitro even in the presence of two pathogenic mutations.

The development of the TMTpro-16plex series expanded the breadth of commercial isobaric tagging reagents by nearly 50% over classic TMT-11plex. In addition to the described 16plex reagents, the proline-based TMTpro molecule can accommodate two additional combinations of heavy carbon and nitrogen isotopes. Here, we introduce the final two labeling reagents, TMTpro-134C and TMTpro-135N, which permit the simultaneous global protein profiling of 18 samples with essentially no missing values. For example, six conditions with three biological replicates can now be perfectly accommodated. We showcase the 18plex reagent set by profiling the proteome and phosphoproteome of a pair of isogenic mammary epithelial cell lines under three conditions in triplicate. We compare the depth and quantitative performance of this data set with a TMTpro-16plex experiment in which two samples were omitted. Our analysis revealed similar numbers of quantified peptides and proteins, with high quantitative correlation. We interrogated further the TMTpro-18plex data set by highlighting changes in protein abundance profiles under different conditions in the isogenic cell lines. We conclude that TMTpro-18plex further expands the sample multiplexing landscape, allowing for complex and innovative experimental designs.

Tryptophan (Trp)-catabolic enzymes (TCEs) produce metabolites that activate the aryl hydrocarbon receptor (AHR) and promote tumor progression and immunosuppression in glioblastoma. As therapies targeting TCEs or AHR become available, a better understanding of Trp metabolism is required. Methods: The combination of LC-MS/MS with chemical isobaric labeling enabled the simultaneous quantitative comparison of Trp and its amino group-bearing metabolites in multiple samples. We applied this method to the sera of a cohort of 43 recurrent glioblastoma patients and 43 age- and sex-matched healthy controls. Tumor volumes were measured in MRI data using an artificial neural network-based approach. MALDI MSI visualized Trp and its direct metabolite N-formylkynurenine (FK) in glioblastoma tissue. Analysis of scRNA-seq data was used to detect the presence of Trp metabolism and AHR activity in different cell types in glioblastoma. Results: Compared to healthy controls, glioblastoma patients showed decreased serum Trp levels. Surprisingly, the levels of Trp metabolites were also reduced. The decrease became smaller with more enzymatic steps between Trp and its metabolites, suggesting that Trp availability controls the levels of its systemic metabolites. High tumor volume associated with low systemic metabolite levels and low systemic kynurenine levels associated with worse overall survival. MALDI MSI demonstrated heterogeneity of Trp catabolism across glioblastoma tissues. Analysis of scRNA-seq data revealed that genes involved in Trp metabolism were expressed in almost all the cell types in glioblastoma and that most cell types, in particular macrophages and T cells, exhibited AHR activation. Moreover, high AHR activity associated with reduced overall survival in the glioblastoma TCGA dataset.Conclusion: The novel techniques we developed could support the identification of patients that may benefit from therapies targeting TCEs or AHR activation

Background Lebanon, an Eastern Mediterranean country, suffers a large burden of injury as a consequence of conflict and war, political instability, and the lack of policies and safety regulations. This article aims to systematically map and comprehensively describe the injury research literature in Lebanon and, to identify gaps for future research. Methods MEDLINE, Embase, Eric and SafetyLit, and the grey literature, including conference proceedings, theses and dissertations, government and media reports, were searched without any date or language limits. Data were extracted from 467 documents using REDCap. Results War-related injuries were the most prevalent type of injury in Lebanon, followed by homicide and other forms of violence. While existing literature targeted vulnerable and at-risk populations, the vast majority focused solely on reporting the prevalence of injuries and associated risk factors. There are considerable gaps in the literature dealing with the integration of preventive programs and interventions across all populations. Conclusions Lebanon, historically and currently, experiences a high number of injuries from many different external causes. To date, efforts have focused on reporting the prevalence of injuries and making recommendations, rather than implementing and evaluating interventions and programs to inform policies. Future injury related work should prioritize interventions and prevention programs.

Isobaric labeling empowers proteome-wide expression measurements simultaneously across multiple samples. Here an expanded set of 16 isobaric reagents based on an isobutyl-proline immonium ion reporter structure (TMTpro) is presented. These reagents have similar characteristics to existing tandem mass tag reagents but with increased fragmentation efficiency and signal. In a proteome-scale example dataset, we compared eight common cell lines with and without Torin1 treatment with three replicates, quantifying more than 8,800 proteins (mean of 7.5 peptides per protein) per replicate with an analysis time of only 1.1 h per proteome. Finally, we modified the thermal stability assay to examine proteome-wide melting shifts after treatment with DMSO, 1 or 20 µM staurosporine with five replicates. This assay identified and dose-stratified staurosporine binding to 228 cellular kinases in just one, 18-h experiment. TMTpro reagents allow complex experimental designs—all with essentially no missing values across the 16 samples and no loss in quantitative integrity. A set of isobaric labeling reagents called TMTpro enables deep quantitative comparisons of proteome measurements across 16 samples.

IntroductionEvidence suggests the presence of deficiencies in the quality of care provided to up to half of all paediatric trauma patients in Canada, the USA and Australia. Lack of adherence to evidence-based recommendations may be driven by lack of knowledge of clinical practice guidelines (CPGs), heterogeneity in recommendations or concerns about their quality. We aim to systematically review CPG recommendations for paediatric injury care and appraise their quality.Methods and analysisWe will identify CPG recommendations through a comprehensive search strategy including Medical Literature Analysis and Retrieval System Online, Excerpta Medica dataBASE, Cochrane library, Web of Science, ClinicalTrials and websites of organisations publishing recommendations on paediatric injury care. We will consider CPGs including at least one recommendation targeting paediatric injury populations on any diagnostic or therapeutic intervention from the acute phase of care with any comparator developed in high-income countries in the last 15 years (January 2007 to a maximum of 6 months prior to submission). Pairs of reviewers will independently screen titles, abstracts and full text of eligible articles, extract data and evaluate the quality of CPGs and their recommendations using Appraisal of Guidelines Research and Evaluation (AGREE) II and AGREE Recommendations Excellence instruments, respectively. We will synthesise evidence on recommendations using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) Evidence-to-Decision framework and present results within a recommendations matrix.Ethics and disseminationEthics approval is not a requirement as this study is based on available published data. The results of this systematic review will be published in a peer-reviewed journal, presented at international scientific meetings and distributed to healthcare providers.PROSPERO registration numberInternational Prospective Register of Systematic Reviews (CRD42021226934).

Globally, residential fires constitute a substantial public health problem, causing major fire-related injury morbidity and mortality. This review examined the literature on residential fire prevention interventions relevant to Indigenous communities and assessed their effectiveness on mitigating fire incidents and their associated human and economic burden. Electronic databases including MEDLINE, EMBASE, CENTRAL, and Web of Science Core Collection were reviewed for studies on fire prevention interventions published after 1990 and based on the 4E’s of injury prevention approaches (Education, Enforcement, Engineering, and Engagement). The grey literature and sources including indigenous organizational websites were also searched for eligible studies. Two authors independently screened, selected, and extracted data, in consultation with experts in the field. Outcomes measured included enhanced safety knowledge and practices, decreased residential fires incidents, reduced fire-related injuries and deaths, and lowered costs for healthcare needs. After removing duplicates, screening titles and abstracts, and assessing full texts, 81 articles were included in this review. Of the included studies, 29.1% implemented educational interventions within a variety of settings, including schools, community centres and homes, and included healthcare professionals and firefighters to raise awareness and the acquisition of fire safety skills. Engineering and environmental modifications were adopted in 20.2% of the studies with increased smoke alarm installations being the leading effective intervention followed by sprinkler inspections. Moreover, engagement of household members in hands-on safety training proved to be effective in enhancing household knowledge, fire safety decisions and practices. More importantly, effective outcomes were obtained when multi-faceted fire safety interventions were adopted, e.g., environmental modification and educational interventions, which together markedly reduced fire incidents and associated injuries. This review reveals the dearth of fire prevention evidence gathered directly within Indigenous communities. Nonetheless, relevant fire prevention recommendations can be made, calling for the adoption of combined and context-sensitive fire prevention interventions tailored to targeted Indigenous and vulnerable communities through multiple approaches and measures. Follow-ups and longitudinal studies are critical for accurate evaluation of the long-term outcomes and impacts on preventing residential fires.

There has been increasing scrutiny of opioid prescribing following injury because of concerns that prescribed opioids may contribute to addiction and overdose. This study aimed to better understand the relationship between injury, opioids prescribed before and after injury, and non-medical drug poisoning.Working age (15 to 65 years old) residents of British Columbia's Fraser Health region with an injury that involved an emergency department visit were included. Factors examined included the prescription of opioid and opioid agonist therapy (OAT) medications before and after injury, age, sex, work-related injuries, and socioeconomic status, as well as how they were associated with non-medical drug poisoning risk and post-injury prescriptions.Opioid-naive individuals (those without an opioid prescription captured before their injury) who were prescribed OAT medication-a marker of opioid use disorder-following their injury had a higher risk of subsequent non-medical drug poisoning (Hazard ratio (HR): 21.4 to 22.4 compared with opioid-naive individuals without an opioid or OAT prescription). Post-injury opioid prescription in these individuals increased poisoning risk (HR: 1.27 compared with those without a prescription). Being of male sex (HR: 1.80), being younger (HR: 0.76 for every 10-year increase in age) and living in the lowest-income neighbourhoods (HR: 1.44 compared with the middle quintile) increased poisoning risk. Compared with injuries sustained outside of work, work-related injuries reduced risk (HR: 0.62).Among a cohort of British Columbians visiting emergency departments following an injury, opioid prescribing in patients who were opioid-naive appears to be a minor contributor to non-medical drug poisoning, particularly when compared with other patient factors, such as being male, being younger and having a low socioeconomic status.

Injuries and deaths from motor vehicle collisions are a significant public health issue. As public health researchers and practitioners, we must support the work of municipalities by advocating for effective interventions to reduce this burden. This requires an evidence-based approach; however, many interventions embedded in existing road safety policies in Canada are not supported by evidence. The objective of this work was to review the built environment (BE) interventions in road safety policies in five, urban municipalities in Canada and summarize the peer-reviewed literature to support them. A low proportion of included studies specific to the existing road safety policies in urban areas in Canada demonstrated a reduction in collisions. Further, significant variability in the level of effectiveness across interventions exists. Information specific to the effectiveness of interventions should be an integral part of the decision making process for BE change; however, more work is needed to better understand critical decision making factors.

Road traffic injury and death continue to be a concern in Canada. The built environment (BE) is a contributing factor affecting the health of road users, yet there are significant challenges to making injury-reducing BE changes. This research increases our knowledge of these challenges by investigating the opinions of injury prevention and road safety professionals working in Canada about the barriers and facilitators to BE change. Cross-referencing themes with the CFIR situated our findings within the scope of implementation science, which demonstrated how barriers and facilitators influence BE change project implementation. The prioritization of motor vehicles results in disproportionate injury and health risks for VRUs. Collaboration across sectors, with the support of champions and advocates, can facilitate sharing of resources, data, and expertise, which results in more opportunities to enact BE change. Knowledge of these barriers and facilitators, contextualized by the CFIR, makes a case for policy/decision-makers in Canada to approve BE projects that reduce risk of road traffic injury and death.

Background: Refugees are susceptible to various types of injury mechanisms associated with their dire living conditions and settlements. This study aims to compare and characterize the emergency department admissions due to physical trauma and injuries among local residents and refugees in greater Beirut. Methods: This epidemiological study analyzes injury incidence and characteristics of patients presenting to Emergency Departments of 5 sentinel hospitals between 2017 and 2019. Using the WHO Injury Surveillance Guidelines and Pan-Asia Trauma Outcomes Study form, an injury data surveillance form was designed and used in hospital settings to collect data on injuries. Chi-square test analysis was performed to compare differences in injury characteristics between local residents and refugees. Regression models were constructed to assess the effect of being a refugee on the characteristics of injuries and outcomes of interest. Results: A total of 4847 injuries (3933 local residents and 914 refugees)were reported. 87.4% of the total injuries among refugees were sustained by the younger age groups 0-45 years compared to 68.8% among local residents. The most prevalent injury mechanism was fall (39.4%) for locals and road traffic injury (31.5%) for refugees. The most injured body part was extremities for both populations (78.2% and 80.1%). Injuries mostly occurred at home or its vicinity (garden or inside the camp) for both populations (29.3% and 23.1%). Refugees sustained a higher proportion of injuries at work (6%) compared to locals (1.3%). On multivariate analysis, refugee status was associated with higher odds of having an injury due to a stab/gunshot (odds ratio (OR) = 3.392, 95% confidence interval (CI) = 2.605-4.416), having a concussion injury (OR = 1.718, 95% CI = 1.151-2.565), and being injured at work (OR = 4.147, 95% CI = 2.74-6.278). Refugee status was associated with increased odds of leaving the hospital with injury-related disability (OR = 2.271, 95% CI = 1.891-2.728)] Conclusions: Injury remains a major public health problem among resident and refugee communities in Beirut, Lebanon. Refugees face several injury-related vulnerabilities, which adversely affect their treatment outcomes and long-term disabilities. The high prevalence of occupational and violence-related injuries among refugees necessitates the introduction of targeted occupational safety and financial security interventions, aiming at reducing injuries while enhancing social justice among residents.

The design and synthesis of a proline-based reporter isobaric Tandem Mass Tag structure (TMTpro) is presented. An analysis is made of the performance of the new TMTpro tags in comparison with the current commercially available dimethylpiperidine-reporter-based TMT10/11 reagents. The new reporter structure provides a set of 16 tags for use with resolution of 6.3 mDa mass differences in high resolution mass spectrometers and a set of 9 reagents with 1 Da spacing between reporter ions for single dalton analysis using 9 heavy nuclei per tag. We show similar performance in terms of peptide identification rates and quantification between the TMTpro 16-plex and TMT10/11-plex reagents. We also demonstrate the suitability of the TMTpro reagents for phosphopeptide analysis. The ability to pool 16 samples reduces the overall amount of sample required for each channel, and we anticipate that TMTpro reagents will be a useful enhancement for any protocol that benefits from sample pooling and should reduce missing data.

Burn-related injury is a global public health problem with significant rates of morbidity and mortality. The adverse effect of burn leads to substantial functional, psychological, and economic repercussions. Low- and middle-income countries, including Lebanon, carry a disproportionately greater burden of burn injuries. This study adopted a mixed method approach to explore burn-related injuries in a sample (n = 347) of refugee children settling in Lebanon. We reviewed 179 cases of patients records that met the criteria of a child aged 0 to 19 years and has sustained a burn due to living conditions. War-related burn injuries were excluded. The findings demonstrate that there is a significantly higher proportion of 0- to 4-year-olds with burn injuries (53.6%) compared with the older age groups. Scald burns, caused by boiling liquid, were the most common cause of burns (58.6%), followed by fire/open flame (12.8%) and heat contact (6.7%). Upper trunk and arm burns were significantly higher than other body parts (35.2%), females were among the potential at-risk group with due to boiling liquids caused by food preparation and serving. Fifteen to nineteen years showed a high proportion of fire/flame burn caused by labor accident. Qualitative analysis of case reports further confirmed our findings and emphasized the impact of low socioeconomic status, overcrowded living conditions and open floor cooking and heating on increasing risk of pediatric burns. Additional research is needed to increase understanding on risk factors pertaining to pediatric burns in the refugee community with a view to integrating appropriate preventive measures and informing evidence-based policies and programs.

Introduction Sachant que l’association entre l'état de santé et le statut socioéconomique (SSE) est largement documentée et que les blessures non intentionnelles continuent de se classer parmi les principales causes de décès chez les Britanno-Colombiens, nous avons voulu quantifier les disparités liées au SSE dans les taux de mortalité associés à trois secteurs prioritaires pour la Colombie-Britannique en matière de prévention des blessures : le suicide chez les jeunes, les blessures liées aux chutes chez les aînés et les blessures liées au transport. Méthodologie Nous avons jumelé les données liées aux décès (2009 à 2013) tirées des statistiques de l’état civil et des données socioéconomiques de CensusPlus de 2011 à l’échelle de l’aire de diffusion ou de la circonscription sanitaire afin d'étudier les taux de mortalité normalisés selon l’âge (TMNA) et les disparités des TMNA concernant les blessures non intentionnelles et leurs sous-types, notamment les blessures liées aux chutes chez les aînés (65 ans et plus) et les blessures liées au transport, ainsi que le suicide chez les jeunes (15 à 24 ans), ce dernier étant considéré comme une forme de blessure intentionnelle. Nous avons étudié les disparités spatiales et les disparités selon le sexe et nous avons mesuré les disparités relatives et absolues entre les zones moins favorisées et les zones plus favorisées en fonction des quintiles de revenu, de scolarité, d’emploi, de défavorisation matérielle et de défavorisation sociale. Résultats Notre étude a mis en évidence d’importantes différences entre les sexes en matière de taux de mortalité attribuable au suicide chez les jeunes, à des blessures liées aux chutes chez les aînés et à des blessures liées au transport, les hommes affichant des taux de mortalité beaucoup plus élevés que les femmes. Nous avons également observé des variations spatiales notables dans les TMNA pour l’ensemble des blessures non intentionnelles à l’échelle de la province. En général, la population vivant dans des zones où les revenus étaient faibles et où la défavorisation matérielle était importante a affiché des taux de mortalité plus élevés que la population vivant dans des zones favorisées. Conclusion Le repérage de différences importantes dans les taux de mortalité liée à des blessures intentionnelles et non intentionnelles entre les sexes et en fonction du SSE ouvre des possibilités quant à l’élaboration de stratégies de prévention ciblées pour réduire ces disparités.

Although automated speed enforcement (ASE) technologies have broad potential to reduce the societal and economic impacts of transport injuries, perceptions of poor public support have thwarted their widespread deployment in British Columbia (B.C.), Canada. This study in-vestigates the levels of acceptance and support for different types of speed enforcement, partic-ularly ASE, and the influence of informative statements or suggested ASE policies on levels of acceptance and support among a representative sample of British Columbians. The online survey was conducted by Insights West, a public opinion research firm, in March 2018. The majority of British Columbians polled demonstrated acceptance and support for the use of ASE technologies in B.C., and strategies designed to foster strong public buy-in for implementation and expansion of ASE technologies were delineated. This survey highlighted the areas which need to be strengthened in order to garner and maintain sufficient community acceptance and support for the ASE program. The findings would be instructive for any jurisdiction that aims to deploy ASE technologies to reduce the burden of preventable transport injuries and deaths.

BackgroundIn 2010 in British Columbia (BC), Canada, total injury costs per capita were higher among youth aged 15–24 years than in any other age group. Injury prevention efforts have targeted injuries with high mortality (transportation injuries) or morbidity (concussions). However, the profile and health costs of common youth injuries (types, locations, treatment choices and prevention strategies) and how these change from adolescence to young adulthood is not known.MethodsParticipants (n=662) were a randomly recruited cohort of BC youth, aged 12–18, in 2003. They were followed biennially across a decade (six assessments).ResultsSerious injuries (defined as serious enough to limit normal daily activities) in the last year were reported by 27%–41% of participants at each assessment. Most common injuries were sprains or strains, broken bones, cuts, punctures or animal bites, and severe bruises. Most occurred when playing a sport or from falling. Estimated total direct cost of treatment per injury was approximately $2500. In addition, 25% experienced serious injuries at three or more assessments, indicating possible differences that warrents further investigation.ConclusionsThe occurence and health cost of common injuries to youth and young adults are underestimated in this study but are nevertheless substantial. Ongoing surveillence, awareness raising, and prevention efforts may be needed to reduce these costs.

ObjectivesAn online, evidence-based resource was created to support the development of sport and recreational injury prevention programmes. The resource, called Active & Safe Central (www.activesafe.ca), provides evidence-based information across the public health approach for a number of sport and recreational activities. The objective of this project was to evaluate the perceived usefulness of Active & Safe Central as an educational tool.DesignA mixed-methods study design, guided by the RE-AIM (reach, effectiveness, adoption, implementation and maintenance) framework, was used to evaluate Active & Safe Central.SettingData were collected using an online survey, available to all users of the site, and focus groups (n=2) that took place in Vancouver and Toronto, Canada.ParticipantsSurvey respondents (n=87) were recruited online, including parents, coaches, youth and adult athletes, and teachers. Focus group participants (n=16) were key stakeholders and end users, recruited from academia, local health sectors, sport and recreational organisations, and not-for-profit injury prevention organisations.ResultsPost launch, there were 1712 users visiting the website 2306 times (sessions), with the majority representing new users, over returning users (87.5% and 12.5%, respectively). There were 6340 page visits, with the most popular pages including soccer, playgrounds and ice hockey. Active & Safe Central was reported as a credible source of evidence-based sport and recreational information and that the site would be recommended to others. Information collected from focus group participants was used to inform necessary adaptations to the online platform, including critical navigation issues, visualisations and interactivity. The major themes that emerged from focus group and survey data included increased awareness of injury prevention recommendations and that the recommendations would be used in one’s own sporting activity and/or practice.ConclusionsThe results of the evaluation suggest the tool is a useful resource for sport and recreational injury information that has significant potential to impact prevention practice.

Plasma proteome composition reflects the inflammatory and metabolic state of the organism and can be predictive of system-level and organ-specific pathologies. Circulating protein aggregates are enriched with neurofilament heavy chain—axonal proteins involved in brain aggregate formation and recently identified as biomarkers of the fatal neuromuscular disorder amyotrophic lateral sclerosis. Using unbiased proteomic methods, we have fully characterized the content in neuronal proteins of circulating protein aggregates from amyotrophic lateral sclerosis patients and healthy controls, with reference to brain protein aggregate composition. We also investigated circulating protein aggregate protein aggregation propensity, stability to proteolytic digestion and toxicity for neuronal and endothelial cell lines. Circulating protein aggregates separated by ultracentrifugation are visible as electron-dense macromolecular particles appearing as either large globular or as small filamentous formations. Analysis by mass spectrometry revealed that circulating protein aggregates obtained from patients are enriched with proteins involved in the proteasome system, possibly reflecting the underlying basis of dysregulated proteostasis seen in the disease, while those from healthy controls show enrichment of proteins involved in metabolism. Compared to the whole human proteome, proteins within circulating protein aggregates and brain aggregates show distinct chemical features of aggregation propensity, which appear dependent on the tissue or fluid of origin and not on the health status. Neurofilaments’ two high-mass isoforms (460 and 268 kDa) showed a strong differential expression in amyotrophic lateral sclerosis compared to healthy control circulating protein aggregates, while aggregated neurofilament heavy chain was also partially resistant to enterokinase proteolysis in patients, demonstrated by immunoreactive bands at 171 and 31 kDa fragments not seen in digested healthy controls samples. Unbiased proteomics revealed that a total of 4973 proteins were commonly detected in circulating protein aggregates and brain, including 24 expressed from genes associated with amyotrophic lateral sclerosis. Interestingly, 285 circulating protein aggregate proteins (5.7%) were regulated (P, Circulating protein aggregates in blood contain 4973 brain peptides including heavy chain neurofilaments and 24 amyotrophic lateral sclerosis-associated proteins. In amyotrophic lateral sclerosis, circulating protein aggregates express proteins involved in metabolism and proteosome and may be biologically active on endothelial cells., Graphical Abstract Graphical Abstract

Children under the age of 5 years have the highest rate of hospitalization and mortality from burns. Studies of costs associated with pediatric burns have included a limited number of patients and focused on inpatient and complication costs, limiting our understanding of the full economic burden of pediatric burns. This study aimed to develop a costing model for burn injuries among children to estimate the economic burden of child burns in British Columbia, Canada. Costs of services and resources used by children aged 0 to 4 years old who were treated at BC Children’s Hospital (BCCH) between January 1, 2014 and March 15, 2018 for a burn injury were estimated and summed, using a micro-costing approach. The average cost of burn injuries per percentage of total body surface area (%TBSA) was then applied to the number of 0 to 4 years old children treated for a burn injury across British Columbia between January 1 and December 31, 2016. Based on 342 included children, a 1–5%, 6–10%, 11–20%, and >20% burn, respectively cost an average of $3338.80, $13,460.00, $20,228.80, and $109,881.00 to society. The societal cost of child burns in BC in 2016 totaled $2,711,255.01. In conclusion, pediatric burn injuries place an important, yet preventable economic burden on society. Preventing even a small number of severe pediatric burns or multiple small burns may have considerable economic impacts on society and allow for the reallocation of healthcare funds toward other clinical priorities.

BACKGROUND Outdoor risky play, such as climbing, racing, and independent exploration, is an important part of childhood and is associated with various positive physical, mental, and developmental outcomes for children. Parental attitudes and fears, particularly mothers’, are a major deterrent to children’s opportunities for outdoor risky play. OBJECTIVE The aim of this study was to evaluate the efficacy of 2 versions of an intervention to reframe mothers’ perceptions of risk and change parenting behaviors: a web-based intervention or an in-person workshop, compared with the control condition. METHODS The Go Play Outside! randomized controlled trial was conducted in Canada from 2017 to 2018. Participants were recruited through social media, snowball sampling, and community notices. Mothers of children aged 6-12 years were self-assessed through eligibility questions, and those eligible and consented to participate in the study were randomized into a fully automated web-based intervention, the in-person workshop, or the control condition. The intervention was underpinned by social cognitive theory, incorporating behavior change techniques. Participants progressed through a series of self-reflection exercises and developed a goal for change. Control participants received the Position Statement on Active Outdoor Play. The primary outcome was increase in tolerance of risky play and the secondary outcome was goal attainment. Data were collected online via REDCap at baseline, 1 week, and 3 months after the intervention. Randomization was conducted using sealed envelope. Allocations were concealed to researchers at assignment and data analysis. We conducted mediation analyses to examine whether the intervention influenced elements of social cognitive theory, as hypothesized. RESULTS A total of 451 mothers were randomized and completed baseline sociodemographic assessments: 150 in the web-based intervention, 153 in the in-person workshop, and 148 in the control condition. Among these, a total of 351 mothers completed the intervention. At 1 week after the intervention, 113, 85, and 135 mothers completed assessments for each condition, respectively, and at 3 months after the intervention, 105, 84, and 123 completed the assessments, respectively. Compared with mothers in the control condition, mothers in the web-based intervention had significantly higher tolerance of risky play at 1 week (P=.004) and 3 months after the intervention (P=.007); and mothers in the in-person workshop had significantly higher tolerance of risky play at 1 week after the intervention (P=.02). No other significant outcomes were found. None of the potential mediators were found to significantly mediate the outcomes. CONCLUSIONS The trial demonstrates that the web-based intervention was effective in increasing mothers’ tolerance for risk in play. CLINICALTRIAL ClinicalTrials.gov NCT03374683; https://clinicaltrials.gov/ct2/show/NCT03374683 INTERNATIONAL REGISTERED REPORT RR2-10.1186/s13063-018-2552-4

Background: plasma proteins composition reflects the inflammatory and metabolic state of an organism and can be predictive of system-level and organ-specific pathologies. Circulating protein aggregates (CPA) are enriched with heavy chain neurofilaments (NfH), axonal proteins involved in brain protein aggregates (BPA) formation and recently identified as biomarkers of the fatal neuromuscular disorder amyotrophic lateral sclerosis (ALS). Methods: here we use mass spectrometry and brain-enhanced TMTcalibrator™-based proteomics to evaluate the composition and the brain-derived protein component of CPA extracted from ALS and healthy controls (HC) plasma samples using high-performance ultracentrifugation. We also test CPA and BPA proteins aggregation propensity and the resistance to proteases digestion by trypsin, chymotrypsin, calpain and enterokinase of NFH within aggregates. Finally, we study CPA biological effects on neuronal and endothelial cell lines. Results: electron microscopy confirms the presence in CPA of electron-dense macromolecular particles appearing as either large globular or as small filamentous formations. CPA from ALS are enriched with proteasome system proteins while HC CPA show a prominent expression of proteins involved in metabolism. CPA enterokinase digestion in ALS generates 171 and 31 KDa NfH fragments not seen in HC samples. Compared to the whole human proteome, proteins within CPA and BPA show distinct chemical features of aggregation propensity, which appear dependent on the tissue or fluid of origin and not on the healthy or pathological source of plasma. The use of a TMTcalibrator™ proteomics workflow reveals 4973 brain-derived low-abundance proteins in CPA, including products of translation of 24 ALS risk genes. 285 (5.7%) are regulated in ALS (p < 0.05) and belong to biochemical pathways previously linked to ALS pathogenesis and aggregates formation. CPA from both ALS and HC have a higher effect on hCMEC/D3 endothelial and PC12 neuronal cells viability than immunoglobulins extracted from the same plasma samples. Compared to HC, CPA from ALS plasma samples exert a higher toxic effect on both cell lines at lower concentrations.Conclusions: this study demonstrates that CPA are significantly enriched with brain proteins which are representative of ALS pathology and a potential source of biomarkers and therapeutic targets for this incurable disorder.

Education is a common strategy used to prevent occupational injuries. However, its effectiveness is often measured using surrogate measures instead of true injury outcomes. To evaluate the effectiveness of workplace educational interventions, we selectively analyzed studies that reported injury outcomes (PROSPERO ID: CRD42019140631). We searched databases for peer-reviewed journal articles and sources of grey literature such as abstracts, registered trials, and theses published between 2000 and 2019. Studies on educational interventions that reported fatal or non-fatal occupational injury outcomes were selected. Two reviewers independently and in duplicate screened the studies, extracted data, and assessed risk of bias. Heterogeneity in the data precluded meta-analysis, and the results were reviewed narratively. In total, 35 studies were included. Of which, 17 found a significant reduction in injuries, most of which featured a multifaceted approach or non-didactic education. The remaining studies either described equivocal results or did not report statistical significance. Overall, interventions in the manufacturing industry were more effective than those in the construction sector. Risk of bias among included studies was moderate to high. In conclusion, educational interventions could be an effective part of multifaceted injury prevention programs. However, over-reliance on didactic education alone is not advised.

Background Outdoor play and risk-taking behaviors, including play at heights, are important to children’s physical, social, and cognitive development. These aspects of play are important to consider when informing prevention policies for serious injuries that commonly occur on play structures. Supracondylar fractures of the humerus (SCH) are the most common type of elbow fractures that result from falls on an outstretched hand among healthy children. Despite being one of the leading causes of admission to the hospital and surgical intervention, the details surrounding the cause of these injuries are often not recorded. Previous research has correlated decreased overall playground safety with higher rates of SCH fractures. Play structure height and the type of undersurface have been identified as potential risk factors for severe injuries, including SCH fractures, in part due to low compliance with safety standards. This paper explores the challenges we encountered designing the study and the resulting insights and methodological modifications we made. Objective The aim of this paper is to discuss the challenges related specifically to clinical research in pediatrics and strategies developed to conduct a study that prioritizes the engagement and perspective of children and their families. Methods To explore the link between the severity of SCH fractures and children’s behavioral, environmental, and mechanistic factors, we conducted a mixed-methods study. Results During phase 1 (the original methodology) from April 2017 to July 2018, there were 58 eligible study participants and 17 were recruited. For phase 2 (the revised methodology) between October 2018 and October 2019, there were 116 eligible participants and 47 were recruited. Conclusions The changes in methodology made following the first phase of data collection were effective in our ability to recruit participants. By identifying and addressing challenges pertaining to recruitment and resource limitations, we were able to collect data in a concise manner while not compromising the quality of the data and make for an easily adoptable methodology for other sites interested in participating in the study. We hope that future studies that plan to employ a similar methodology can gain insight through the methodological challenges we have encountered and the way we adapted the methodology to build a more pragmatic approach. International Registered Report Identifier (IRRID) DERR1-10.2196/21816

BACKGROUND Outdoor play and risk-taking behaviors, including play at heights, are important to children’s physical, social, and cognitive development. These aspects of play are important to consider when informing prevention policies for serious injuries that commonly occur on play structures. Supracondylar fractures of the humerus (SCH) are the most common type of elbow fractures that result from falls on an outstretched hand among healthy children. Despite being one of the leading causes of admission to the hospital and surgical intervention, the details surrounding the cause of these injuries are often not recorded. Previous research has correlated decreased overall playground safety with higher rates of SCH fractures. Play structure height and the type of undersurface have been identified as potential risk factors for severe injuries, including SCH fractures, in part due to low compliance with safety standards. This paper explores the challenges we encountered designing the study and the resulting insights and methodological modifications we made. OBJECTIVE The aim of this paper is to discuss the challenges related specifically to clinical research in pediatrics and strategies developed to conduct a study that prioritizes the engagement and perspective of children and their families. METHODS To explore the link between the severity of SCH fractures and children’s behavioral, environmental, and mechanistic factors, we conducted a mixed-methods study. RESULTS During phase 1 (the original methodology) from April 2017 to July 2018, there were 58 eligible study participants and 17 were recruited. For phase 2 (the revised methodology) between October 2018 and October 2019, there were 116 eligible participants and 47 were recruited. CONCLUSIONS The changes in methodology made following the first phase of data collection were effective in our ability to recruit participants. By identifying and addressing challenges pertaining to recruitment and resource limitations, we were able to collect data in a concise manner while not compromising the quality of the data and make for an easily adoptable methodology for other sites interested in participating in the study. We hope that future studies that plan to employ a similar methodology can gain insight through the methodological challenges we have encountered and the way we adapted the methodology to build a more pragmatic approach. INTERNATIONAL REGISTERED REPORT DERR1-10.2196/21816

This case study describes a participatory research project that engaged young people (ages 11 to 13) in examining the play-friendliness of their local neighborhoods. Part of a larger study related to the city’s ‘Child and Youth Friendly Community Strategy,’ the project involved youth in creating and sharing knowledge about their neighborhood play environments. University researchers, a youth leadership group, city staff, and school personnel collaborated in designing and carrying out the project. Through regular in-school sessions over 3 months, 51 youth participants engaged in activities related to children’s rights, child-friendly cities, outdoor play, photography, and municipal decision making. They also went on a neighborhood walk and took photographs of places and things they perceived as ‘friendly’ and ‘not friendly’ for play. These photographs—and accompanying narratives—were displayed at City Hall and the School Board office. A number of youth participants also delivered presentations and recommendations to City Council and the Board of Education about making the city better for young people. This case study outlines the process of carrying out the research project and identifies impacts of such a project on youth participants, the city’s Child and Youth Friendly Community Strategy, and the local community.

Soccer is the most popular sport in the world. Expectedly, the incidence of soccer-related injuries is high and these injuries exert a significant burden on individuals and families, including health and financial burdens, and on the socioeconomic and healthcare systems. Using established injury prevention frameworks, we present a concise synthesis of the most recent scientific evidence regarding injury rates, characteristics, mechanisms, risk and protective factors, interventions for prevention, and implementation of interventions in soccer. In this umbrella review, we elucidate the most recent available evidence gleaned primarily from systematic reviews and meta-analyses. Further, we express the exigent need to move current soccer injury prevention research evidence into action for improved player outcomes and widespread impact through increased attention to dissemination and implementation research. Additionally, we highlight the importance of an enabling context and effective implementation strategies for the successful integration of evidence-based injury prevention programs into real-world soccer settings. This narrative umbrella review provides guidance to inform future research, practice, and policy towards reducing injuries among soccer players.

The purpose of this commentary is to discuss how legalization of non-medical marijuana (LNMM) in Canada can potentially influence child and adolescent unintentional injuries based on evidence from states (American) and jurisdictions that have already legalized cannabis for recreational purposes. Although the evidence is still not conclusive, LNMM can bring about higher exposure, lower perceived harms, and higher prevalence of cannabis use by minors through role modeling and normalization of behaviour within the household and the community, and higher rates of driving under the influence of cannabis, which can contribute to a higher burden of road traffic injuries. Experience of American states with LNMM shows higher rates of emergency visits for pediatric poisoning due to unintentional ingestion of cannabis-containing foods and severe burns due to explosions during the course of home-based cannabis extraction. While the justification for legalization has created a strict legal framework for improved control of cannabis in Canada, the implications for health and safety of children and adolescents necessitate further study, communication with policy-makers and public health practitioners, and evidence-based education of parents, caregivers, and youth.

Introduction Malgré la protection juridique dont les jeunes travailleurs au Canada font l’objet, les jeunes de 15 à 24 ans sont exposés à un risque élevé de blessures traumatiques au travail. Étant donné que de nombreuses initiatives de prévention des blessures ciblant les jeunes travailleurs existent, les défenseurs des droits des jeunes et les employeurs doivent relever le défi de choisir quels aspects de la prévention vont être les plus efficaces afin d’y consacrer leurs efforts. Une analyse de la littérature universitaire et de la littérature grise a été entreprise afin de compiler les paramètres (indicateurs évalués et méthodes de mesure) couramment utilisés pour évaluer les programmes de prévention des blessures auprès des jeunes travailleurs. Les paramètres constituent des références de mesure permettant d’évaluer l’efficacité, le rendement, le progrès ou la qualité d’un projet, d’un procédé ou d’un produit. Méthodologie Nous avons utilisé le modèle PICO pour définir les termes de recherche. Des recherches ont été effectuées dans Medline, PubMed, OVID, EMBASE, CCOHS, PsychINFO, CINAHL, NIOSHTIC, Google Scholar et dans la littérature grise afin de trouver des articles en anglais publiés entre 1975 et 2015. Deux lecteurs critiques indépendants ont examiné la liste des articles et ont classé les paramètres en trois catégories de prévention des blessures : l’éducation, l’environnement et l’application de règlements. Résultats Sur les 174 articles ayant répondu aux critères d’inclusion, 21 décrivaient et évaluaient une intervention. Parmi ceux-ci, la moitié (n=11) étaient à caractère éducatif. Les paramètres couramment évalués étaient : les connaissances, les perceptions, les comportements ou les intentions autodéclarées, l’exposition aux dangers, les demandes d’indemnisation pour blessures et le taux d’accidents de travail. Une étude présentait une méthode destinée à élaborer des paramètres permettant de prédire les taux de blessure. Conclusion Des paramètres spécifiques à l’évaluation des programmes de prévention des blessures chez les jeunes travailleurs sont nécessaires, car les paramètres actuels sont insuffisants pour prévoir la diminution du nombre de blessures en lien avec la mise en place de programmes. De notre analyse ressort une étude apte à constituer un modèle pertinent pour les recherches futures visant à élaborer des paramètres de base valides destinés aux jeunes travailleurs, afin de les appliquer ensuite aux programmes de prévention des blessures chez les jeunes.

BackgroundInjury prevention report cards that raise awareness about the preventability of childhood injuries have been published by the European Child Safety Alliance and the WHO. These report cards highlight the variance in injury prevention practices around the world. Policymakers and stakeholders have identified research evidence as an important enabler to the enactment of injury legislation. In Canada, there is currently no childhood injury report card that ranks provinces on injury rates or evidence-based prevention policies.MethodsThree key measures, with five metrics, were used to compare provinces on childhood injury prevention rates and strategies, including morbidity, mortality and policy indicators over time (2006–2012). Nine provinces were ranked on five metrics: (1) population-based hospitalisation rate/100 000; (2) per cent change in hospitalisation rate/100 000; (3) population-based mortality rate/100 000; (4) per cent change in mortality rate/100 000; (5) evidence-based policy assessment.ResultsOf the nine provinces analysed, British Columbia ranked highest in Canada and Saskatchewan lowest. British Columbia had a morbidity and mortality rate that was close to the Canadian average and decreased over the study period. British Columbia also had a number of injury prevention policies and legislation in place that followed best practice guidelines. Saskatchewan had a higher rate of injury hospitalisation and death; however, Saskatchewan’s rate decreased over time. Saskatchewan had a number of prevention policies in place but had not enacted bicycle helmet legislation.ConclusionsFuture preventative efforts should focus on harmonising policies across all provinces in Canada that reflect evidence-based best practices.

A subset of C9orf72 repeat expansion-carrying frontotemporal dementia patients display an Alzheimer-like decrease in cerebrospinal fluid amyloid-β (Aβ) biomarker levels. We report that downregulation of C9orf72 in non-neuronal human cells overexpressing amyloid-β protein precursor (AβPP) resulted in increased levels of secreted AβPP fragments and Aβ, while levels of AβPP or its C-terminal fragments (CTFs) remained unchanged. In neuronal cells, AβPP and C83 CTF levels were decreased upon C9orf72 knockdown, but those of secreted AβPP fragments or Aβ remained unchanged. C9orf72 protein levels significantly increased in human brain with advancing neurofibrillary pathology and positively correlated with brain Aβ42 levels. Our data suggest that altered C9orf72 levels may lead to cell-type specific alterations in AβPP processing, but warrant further studies to clarify the underlying mechanisms.

OBJECTIVES: The primary objectives of this work were to (1) identify the risk and/or protective factors associated with playground injuries among children less than 18 years of age and (2) identify interventions/programs/policies aimed at preventing playground-related injuries among children less than 18 years of age. Secondary objectives include a summary of the data that reflect alignment with current playground standards. METHODS: For the primary outcome, 4 databases and 12 online resources were systematically searched to include observational and experimental studies examining risk and/or protective factors or interventions associated with playground injury or outcomes related to playground injury (e.g., risky playground behaviour). Data extraction included study design, participants, outcome, exposure or intervention, data analysis, and effect estimates. The quality of evidence for all studies was assessed using the Downs and Black criteria. RESULTS: This review included studies of moderate quality, revealing a number of risk factors and effective interventions for playground injury. Risk factors included absence of handrails and guardrails on playground equipment, non-impact-absorbing surfacing, and critical fall heights. Effective interventions included modifying playground surfacing and reducing equipment height to less than 1.5 m. CONCLUSION: Equipment- and structure-based playgrounds should adhere to and maintain playground standards in order to reduce the risk of serious injury. Organizations responsible for installing and maintaining playgrounds should consider alternative play spaces that allow children to play outdoors, in a natural environment that supports healthy child development and promotes physical activity.

Objectives: To explore the relationship between neighborhood social and material deprivation and the rates of abusive head trauma (AHT), and whether it differs according to sex, and following the implementation of the Period of PURPLE Crying ( PURPLE) program. Method: A cross-sectional study design was applied to data from children 0 to 24 months old with a confirmed AHT diagnosis between 2005 and 2017 in British Columbia. Dissemination area–based social and material deprivation scores were assigned to residential areas, where AHT cases were recorded. Poisson regression models tested the relationship between deprivation scores and AHT rates, adding sex and pre–post program implementation as interaction terms. Results: With each increase in material and social deprivation quintiles, AHT rates increased by 42% (95% CI [1.18, 1.72]) and 25% (95% CI [1.06, 1.51]), respectively, following a social gradient. AHT rate disparities between neighborhoods did not change following the PURPLE program implementation. Conclusions: This study stresses the need to provide additional AHT prevention services proportionately to the levels of neighborhood disadvantage, in addition to universal AHT programs, to successfully protect all children.

ObjectivesThe objective of this study was to explore parent perspectives of and interest in an interactive knowledge translation platform called Child-Sized KT that proposes to catalyse the collaboration of patients, families, practitioners and researchers in patient-oriented research at British Columbia Children’s Hospital (BCCH).MethodsAn explanatory sequential mixed methods design was used over 1 year. Over 500 parents across BC completed an online survey, including a subsample of 102 parents who had accessed care at BCCH within the past 2 years. The survey explored parent perspectives about the value of their engagement at all stages of the research process and their interest in and concerns with using an online platform. Following the online survey, two focus groups were held with parents in the Vancouver area to explore themes emerging from the survey.ResultsParents expressed keen interest in engaging in research at BCCH. Parents perceived benefit from their input at all stages of the research process; however, they were most interested in helping to identify the problem, develop the research question and share the results. Although parents preferred online participation, they had concerns about protecting the privacy of their child’s information.ConclusionsParents see value in their involvement in all stages of child health research at BCCH. Their input suggests that Child-Sized KT, a hypothetical online platform, would facilitate meaningful stakeholder engagement in child health research, but should offer a customised experience and ensure the highest standard of data privacy and protection.

The lack of biomarkers for early diagnosis, clinical stratification and to monitor treatment response has hampered the development of new therapies for amyotrophic lateral sclerosis (ALS), a clinically heterogeneous neurodegenerative disorder with a variable site of disease initiation and rate of progression. To identify new biomarkers and therapeutic targets, two separate proteomic workflows were applied to study the immunological response and the plasma/brain proteome in phenotypic variants of ALS. Conventional multiplex (TMT) proteomic analysis of peripheral blood mononuclear cells (PBMCs) was performed alongside a recently introduced method to profile neuronal-derived proteins in plasma using brain tissue-enhanced isobaric tagging (TMTcalibrator). The combined proteomic analysis allowed the detection of regulated proteins linked to ALS pathogenesis (RNA-binding protein FUS, superoxide dismutase Cu-Zn and neurofilaments light polypeptide) alongside newly identified candidate biomarkers (myosin-9, fructose-bisphosphate aldolase and plectin). In line with the proteomic results, orthogonal immunodetection showed changes in neurofilaments and ApoE in bulbar versus limb onset fast progressing ALS. Functional analysis of significantly regulated features showed enrichment of pathways involved in regulation of the immune response, Rho family GTPases, semaphorin and integrin signalling. Our cross-phenotype investigation of PBMCs and plasma/brain proteins provides a more sensitive biomarker exploratory platform than conventional case-control studies in a single matrix. The reported regulated proteins may represent novel biomarker candidates and potentially druggable targets.

The purpose of this research paper is to assess the response on Facebook to a social marketing campaign for recreational boating safety. The campaign ran for the 2018 and 2019 boating seasons in British Columbia, Canada. Messages related to boating safety were delivered in multi-media formats, including ten Facebook posts. All public comments on the campaign Facebook page in response to the ads were included in the analysis. Comments were reviewed for tone and subject, those that related directly to the campaign or boating safety-related topics, such as alcohol use or enforcement, were labeled positive, negative or neutral in tone. Metrics such as likes and shares were also noted. The overall engagement rate (defined as engagements over people reached) was 4.1%. The posts were liked &gt, 7000 times and received 901 shares. A total of 219 comments were analysed. Almost half of the comments were positive (n = 106, 48.4%). Fifty comments were off-topic (22.8%), 45 were neutral (20.5%) and 18 were negative (8.2%). The majority of comments were positive, indicating that the campaign performed as planned and was generally well received by the people for whom it was intended. Comments illuminated prevailing attitudes towards risks, injuries and safety practices related to recreational boating. Positive comments valued safety as an aspect of having a pleasant experience, rather than a barrier. Negative comments were about perceiving reduced fun of boating, rather than objecting to the campaign itself. As a component of a multi-media social marketing strategy, Facebook can be a source of instant feedback from the campaign audience.

Background Outdoor risky play, such as climbing, racing, and independent exploration, is an important part of childhood and is associated with various positive physical, mental, and developmental outcomes for children. Parental attitudes and fears, particularly mothers’, are a major deterrent to children’s opportunities for outdoor risky play. Objective The aim of this study was to evaluate the efficacy of 2 versions of an intervention to reframe mothers’ perceptions of risk and change parenting behaviors: a web-based intervention or an in-person workshop, compared with the control condition. Methods The Go Play Outside! randomized controlled trial was conducted in Canada from 2017 to 2018. Participants were recruited through social media, snowball sampling, and community notices. Mothers of children aged 6-12 years were self-assessed through eligibility questions, and those eligible and consented to participate in the study were randomized into a fully automated web-based intervention, the in-person workshop, or the control condition. The intervention was underpinned by social cognitive theory, incorporating behavior change techniques. Participants progressed through a series of self-reflection exercises and developed a goal for change. Control participants received the Position Statement on Active Outdoor Play. The primary outcome was increase in tolerance of risky play and the secondary outcome was goal attainment. Data were collected online via REDCap at baseline, 1 week, and 3 months after the intervention. Randomization was conducted using sealed envelope. Allocations were concealed to researchers at assignment and data analysis. We conducted mediation analyses to examine whether the intervention influenced elements of social cognitive theory, as hypothesized. Results A total of 451 mothers were randomized and completed baseline sociodemographic assessments: 150 in the web-based intervention, 153 in the in-person workshop, and 148 in the control condition. Among these, a total of 351 mothers completed the intervention. At 1 week after the intervention, 113, 85, and 135 mothers completed assessments for each condition, respectively, and at 3 months after the intervention, 105, 84, and 123 completed the assessments, respectively. Compared with mothers in the control condition, mothers in the web-based intervention had significantly higher tolerance of risky play at 1 week (P=.004) and 3 months after the intervention (P=.007); and mothers in the in-person workshop had significantly higher tolerance of risky play at 1 week after the intervention (P=.02). No other significant outcomes were found. None of the potential mediators were found to significantly mediate the outcomes. Conclusions The trial demonstrates that the web-based intervention was effective in increasing mothers’ tolerance for risk in play. Trial Registration ClinicalTrials.gov NCT03374683; https://clinicaltrials.gov/ct2/show/NCT03374683 International Registered Report Identifier (IRRID) RR2-10.1186/s13063-018-2552-4

RATIONALE: Ideal biomarkers are present in readily accessible samples including plasma and cerebrospinal fluid (CSF), and are directly derived from diseased tissue, therefore likely to be of relatively low abundance. Traditional unbiased proteomic approaches for biomarker discovery have struggled to detect low-abundance markers due to the high dynamic range of proteins, the predominance of hyper-abundant proteins, and the use of data-dependent acquisition mass spectrometry (MS). To overcome these limitations and improve biomarker discovery in peripheral fluids, we have developed TMTcalibrator™; a novel MS workflow combining isobarically labelled diseased tissue digests in parallel with an appropriate set of labelled body fluids to increase the chance of identifying low-abundance, tissue-derived biomarkers. METHODS: A disease relevant cell line was labelled with TMT® in a range of concentrations generating a multi-point calibration curve. Peripheral biofluid samples were labelled with the remaining tags and quantitative analysis was performed using an Orbitrap Fusion Tribrid mass spectrometer with a Top10 CID-HCD MS3 synchronous precursor selection (SPS) method. SPS allowed direct analysis of non-depleted, unfractionated CSF samples with complete profiling of six individual samples requiring only 15 hours of MS time, equivalent to 1.5 h per sample. RESULTS: Using the TMTcalibrator™ workflow allowed the identification of several markers of microglia activation that are differentially quantified in the CSF of patients with Alzheimer's disease (AD). We report peptides from 41 proteins that have not previously been detected in the CSF, that appear to be regulated by at least 60% in AD. CONCLUSIONS: This study has demonstrated the benefits of the new TMTcalibrator™ workflow and the results suggest this is a suitable and efficient method of detecting low-abundance peptides within biological fluids. The use of TMTcalibrator™ in further biomarker discovery studies should be considered to overcome some of the limitations commonly associated with more conventional approaches.

Introduction In 2010, British Columbia (BC) introduced new traffic laws designed to deter impaired driving, speeding, and distracted driving. These laws generated significant media attention and were associated with reductions in fatal crashes and in ambulance calls and hospital admissions for road trauma. Objective To understand the extent and type of media coverage of the new traffic laws and to identify how the laws were framed by the media. Methods We reviewed a database of injury related news coverage (May 2010–December 2012) and extracted reports that mentioned distracted driving, impaired driving, or speeding. Articles were classified according to: (i) Type, (ii) Issue discussed, (iii) ‘Reference to new laws’, and (iv) ‘Pro/anti traffic law’. Articles mentioning the new laws were reread and common themes in how the laws were framed were identified and discussed. Results Over the course of the study, 1848 articles mentioned distraction, impairment, or speeding and 597 reports mentioned the new laws: 65 against, 227 neutral, and 305 supportive. Reports against the new laws framed them as unfair or as causing economic damage to the entertainment industry. Reports in favor of the new laws framed them in terms of preventing impaired driving and related trauma or of bringing justice to drinking drivers. Growing evidence of the effectiveness of the new laws generated media support. Conclusions BC's new traffic laws generated considerable media attention both pro and con. We believe that this media attention helped inform the public of the new laws and enhanced their deterrent effect.

Aberrant tau phosphorylation is a hallmark in Alzheimer's disease (AD), believed to promote formation of paired helical filaments, the main constituent of neurofibrillary tangles in the brain. While cerebrospinal fluid (CSF) levels of total tau and tau phosphorylated at threonine residue 181 (pThr181) are established core biomarkers for AD, the value of alternative phosphorylation sites, which may have more direct relevance to pathology, for early diagnosis is not yet known, largely due to their low levels in CSF and lack of standardized detection methods. To overcome sensitivity limitations for analysis of phosphorylated tau in CSF, we have applied an innovative mass spectrometry (MS) workflow, TMTcalibratortrademark, to enrich and enhance the detection of phosphoproteome components of AD brain tissue in CSF, and enable the quantitation of these analytes. We aimed to identify which tau species present in the AD brain are also detectable in CSF and which, if any, are differentially regulated with disease. Over 75% coverage of full-length (2N4R) tau was detected in the CSF with 47 phosphopeptides covering 31 different phosphorylation sites. Of these, 11 phosphopeptides were upregulated by at least 40%, along with an overall increase in tau levels in the CSF of AD patients relative to controls. Use of the TMTcalibratortrademark workflow dramatically improved our ability to detect tau-derived peptides that are directly related to human AD pathology. Further validation of regulated tau peptides as early biomarkers of AD is warranted and is currently being undertaken.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Analysis of tyrosine kinase signaling is critical for the development of targeted cancer therapy. Currently, immunoprecipitation of phosphotyrosine (pY) peptides prior to liquid chromatography-tandem mass spectrometry (LC-MS/MS) is used to profile tyrosine kinase substrates. A typical protocol requests 10 mg of total protein from ≈10(8) cells or 50–100 mg of tissue. Large sample requirements can be cost prohibitive or not feasible for certain experiments. Sample multiplexing using chemical labeling reduces the protein amount required for each sample, and newer approaches use a material-rich reference channel as a calibrator to trigger detection and quantification for smaller samples. Here, it is demonstrated that the tandem mass tag (TMT) calibrator approach reduces the sample input for pY profiling tenfold (to ≈1 mg total protein per sample from 10(7) cells grown in one plate), while maintaining the depth of pY proteome sampling and the biological content of the experiment. Data are available through PRIDE (PXD019764 for label-free and PXD018952 for TMT). This strategy opens more opportunities for pY profiling of large sample cohorts and samples with limited protein quantity such as immune cells, xenograft models, and human tumors.

BackgroundSchool-based injuries represent a sizeable portion of child injuries. This study investigated the rates of school-based injuries in Lebanon, examining injury mechanisms, outcomes and associated risk factors.MethodsData were prospectively collected by intern school nurses at 11 private schools for the 2018-2019 academic year. Descriptive and inferential analyses were performed. Chi-square comparisons were conducted to determine the significance of any differences in injury rates between boys and girls for each category of school.Results4,619 injury cases were collected. The yearly rate for school injuries was 419.1 per 1,000 children for the year 2018-2019. Boys demonstrated a significantly higher injury rate for all mechanisms of injuries, with the exception of being injured while walking, injured in the gym/sports areas, and other areas outside the playground and classroom. Elementary school children had the highest rate of injuries, nearly 2.4 times higher than kindergarten, 2.8 times higher than middle school, and 14.5 times higher than high school. Injuries to the face, upper extremities, and lower extremities were nearly 3 times more common than injuries to other areas of the body. Bumps/hits and bruises were most common-almost 3 times more likely than all other injury types. Injuries were mainly minor or moderate in severity-severe injuries were about 10 times less likely. Most injuries were unintentional, with rates nearly 5 times higher than those with unclear intent and 12 times higher than intentional injuries.ConclusionsSchool injuries represent a relatively common problem. Compliance with playground safety standards coupled with the implementation of injury prevention strategies and active supervision at schools can curtail child injuries and ensure a safe and injury-free school environment.

BackgroundSport and recreation related injuries exert a significant cost on the healthcare system. As prevention researchers and practitioners, we have a responsibility to provide guidance towards prevention to those who participate in sport and recreation, and those that coach, treat and parent children that participate. The objective of this project was to use an integrated knowledge translation approach to develop an end user-driven digital platform that provides injury prevention information and resources across 51 sport and recreational activities.DesignWe used an integrated knowledge translation approach to scope and develop an online sport and recreational injury prevention resource. A project team was formed that included end users—coaches, parents and athletes, injury researchers and practitioners, as well as members of a digital design team. All members of the project team informed the development process, including a review of literature and existing resources, the translation of evidence and development of the platform. At all stages of development, members of the project team cocreated knowledge for the tool, including forming the research questions, the approach, feasibility and development of outcomes.ConclusionThe ‘Active & Safe Central’ (https://activesafe.ca/) platform provides web-based sport injury and prevention information. This user-friendly, web and mobile accessible platform can increase the reach, awareness and implementation of prevention programming in sport and recreational activity.

Introduction Children under the age of five years are particularly vulnerable to scalds and contact burns and have the highest rate of hospitalization and mortality from burns. Studies of costs associated with pediatric burns have included a limited number of patients and focused on inpatient and complication costs, limiting our understanding of the full economic burden of pediatric burns, including costs incurred through outpatient care and caregivers’ productivity loss. This study aimed to develop a societal costing model for burn injuries among children aged 0 to 4 years. Methods Children aged 0 to 4 years identified through the local Burn Registry with a burn injury between January 1, 2014 and March 15, 2018 were included in this study. Patients with inhalation injury, electrical, chemical and friction burns were excluded. An incidence-based cost-of-illness analysis with a human capital approach was used to quantify the cost of partial and full-thickness burns according to the percentage of total body surface area (%TBSA) involved. The cost of a burn injury was assessed from a societal perspective through the following cost categories: emergency department visits, inpatient, outpatient dressing changes, outpatient burnbaths, day surgeries, clinic visits and caregiver productivity losses. A list of resource items for each category were extracted from patient chart review, the local Burn Registry, and the local Hospital Finance Database, and assigned unit prices. Costs were discounted to a present value in 2017 dollars at 1.5% per annum. Results Burn injuries were observed for 342 children, of which 249 (73%) had their burn severity classified (%TBSA and partial/full thickness) and were included in this study. Burn severity categories (1–5%, 6–10%, 11–20%, and >20%) were developed based on the differential distribution of the costs allocated to each burn incident. The majority of children (60.8%) suffered from a 1–5% burn. A 1–5%, 6–10%, 11–20%, and >20% burn respectively cost an average of $2,229, $8,653, $13,663, and $98,634 to society. Costs incurred by the 1–5% burns were related mostly to emergency department visits and dressing changes, while costs incurred by the >20% were related mostly to inpatient and clinic visits (garments) costs. Conclusions This costing approach raises awareness about the important, yet preventable economic burden that pediatric burn injuries place on society. Applicability of Research to Practice This evidence may persuade policymakers and clinicians to invest in pediatric burns prevention programs in order to decrease pediatric burns costs allowing for the allocation of funds towards other clinical initiatives. This costing model may also facilitate cost-effectiveness analyses of burn prevention programs in the coming years.