High-'n'-dry? A comparison of cannabis and alcohol use in drivers presenting to hospital after a vehicular collision.

DESIGN: This was a prospective observational study. BACKGROUND AND AIMS: The characteristics of cannabis-involved motor vehicle collisions are poorly understood. This study of injured drivers identifies demographic and collision characteristics associated with high tetrahydrocannabinol (THC) concentrations. SETTING: The study was conducted in 15 Canadian trauma centres between January 2018 and December 2021. CASES: The cases (n = 6956) comprised injured drivers who required blood testing as part of routine trauma care. MEASUREMENTS: We quantified whole blood THC and blood alcohol concentration (BAC) and recorded driver sex, age and postal code, time of crash, crash type and injury severity. We defined three driver groups: high THC (THC ≥ 5 ng/ml and BAC = 0), high alcohol (BAC ≥ 0.08% and THC = 0) and THC/BAC-negative (THC = 0 = BAC). We used logistic regression techniques to identify factors associated with group membership. FINDINGS: Most injured drivers (70.2%) were THC/BAC-negative; 1274 (18.3%) had THC > 0, including 186 (2.7%) in the high THC group; 1161 (16.7%) had BAC > 0, including 606 (8.7%) in the high BAC group. Males and drivers aged less than 45 years had higher adjusted odds of being in the high THC group (versus the THC/BAC-negative group). Importantly, 4.6% of drivers aged less than 19 years had THC ≥ 5 ng/ml, and drivers aged less than 19 years had higher unadjusted odds of being in the high THC group than drivers aged 45-54 years. Males, drivers aged 19-44 years, rural drivers, seriously injured drivers and drivers injured in single-vehicle, night-time or weekend collisions had higher adjusted odds ratios (aORs) for being in the high alcohol group (versus THC/BAC-negative). Drivers aged less than 35 or more than 65 years and drivers involved in multi-vehicle, daytime or weekday collisions had higher adjusted odds for being in the high THC group (versus the high BAC group). CONCLUSIONS: In Canada, risk factors for cannabis-related motor vehicle collisions appear to differ from those for alcohol-related motor vehicle collisions. The collision factors associated with alcohol (single-vehicle, night-time, weekend, rural, serious injury) are not associated with cannabis-related collisions. Demographic factors (young drivers, male drivers) are associated with both alcohol and cannabis-related collisions, but are more strongly associated with cannabis-related collisions.

The probability of parallel genetic evolution from standing genetic variation.

Parallel evolution is often assumed to result from repeated adaptation to novel, yet ecologically similar, environments. Here, we develop and analyse a mathematical model that predicts the probability of parallel genetic evolution from standing genetic variation as a function of the strength of phenotypic selection and constraints imposed by genetic architecture. Our results show that the probability of parallel genetic evolution increases with the strength of natural selection and effective population size and is particularly likely to occur for genes with large phenotypic effects. Building on these results, we develop a Bayesian framework for estimating the strength of parallel phenotypic selection from genetic data. Using extensive individual-based simulations, we show that our estimator is robust across a wide range of genetic and evolutionary scenarios and provides a useful tool for rigorously testing the hypothesis that parallel genetic evolution is the result of adaptive evolution. An important result that emerges from our analyses is that existing studies of parallel genetic evolution frequently rely on data that is insufficient for distinguishing between adaptive evolution and neutral evolution driven by random genetic drift. Overcoming this challenge will require sampling more populations and the inclusion of larger numbers of loci.

The association between obesity and self-reported sinus infection in non-smoking adults: a cross-sectional study.

The aim of this article was to examine the associations between having had a sinus infection (SI) and BMI and physical activity (PA), diet quality, stress and/or sleep. A total of 2915 adults from the National Health and Nutrition Examination Survey 2005-2006 were examined. Logistic regression analysis was used to examine the association between having had an SI with BMI and PA, diet quality, stress or sleep. As these factors are known to influence one another, a fully adjusted model with PA, diet quality, stress and sleep was also constructed to examine their independent associations with having had an SI. Overall, 15.5 ± 1.2% of the population report having had an SI in the past year. In all models, individuals with obesity were approximately twice as likely to have had an SI compared to those of normal weight (P < 0.05). While PA and diet quality were not significantly associated with having had an SI (P > 0.05), individuals with stress and sleep troubles were also twice as likely to have had an SI (P < 0.05) independent of BMI. In the fully adjusted model, only the associations for BMI and sleep troubles remained significant (P < 0.05). Results from this study suggest that obesity and sleep troubles, but not PA, quality of diet and stress, are associated with having had an SI. As interactions exist between obesity, immune system factors and exposure to infectious disease(s), more research is necessary to understand the directionality of these relationships.

CD4 T cells are required for both development and maintenance of disease in a new mouse model of reversible colitis.

Current therapies to treat inflammatory bowel diseases have limited efficacy, significant side effects, and often wane over time. Little is known about the cellular and molecular mechanisms operative in the process of mucosal healing from colitis. To study such events, we developed a new model of reversible colitis in which adoptive transfer of CD4(+)CD45RB(hi) T cells into Helicobacter typhlonius-colonized lymphopenic mice resulted in a rapid onset of colonic inflammation that was reversible through depletion of colitogenic T cells. Remission was associated with an improved clinical and histopathological score, reduced immune cell infiltration to the intestinal mucosa, altered intestinal gene expression profiles, regeneration of the colonic mucus layer, and the restoration of epithelial barrier integrity. Notably, colitogenic T cells were not only critical for induction of colitis but also for maintenance of disease. Depletion of colitogenic T cells resulted in a rapid drop in tumor necrosis factor α (TNFα) levels associated with reduced infiltration of inflammatory immune cells to sites of inflammation. Although neutralization of TNFα prevented the onset of colitis, anti-TNFα treatment of mice with established disease failed to resolve colonic inflammation. Collectively, this new model of reversible colitis provides an important research tool to study the dynamics of mucosal healing in chronic intestinal remitting-relapsing disorders.

Standardised animal models of host microbial mutualism.

An appreciation of the importance of interactions between microbes and multicellular organisms is currently driving research in biology and biomedicine. Many human diseases involve interactions between the host and the microbiota, so investigating the mechanisms involved is important for human health. Although microbial ecology measurements capture considerable diversity of the communities between individuals, this diversity is highly problematic for reproducible experimental animal models that seek to establish the mechanistic basis for interactions within the overall host-microbial superorganism. Conflicting experimental results may be explained away through unknown differences in the microbiota composition between vivaria or between the microenvironment of different isolated cages. In this position paper, we propose standardised criteria for stabilised and defined experimental animal microbiotas to generate reproducible models of human disease that are suitable for systematic experimentation and are reproducible across different institutions.

Developing injury indicators for First Nations and Inuit children and youth in Canada: a modified Delphi approach.

INTRODUCTION: The purpose of this research was to take the initial step in developing valid indicators that reflect the injury issues facing First Nations and Inuit children and youth in Canada. METHODS: Using a modified-Delphi process, relevant expert and community stakeholders rated each indicator on its perceived usefulness and ability to prompt action to reduce injury among children and youth in indigenous communities. The Delphi process included 5 phases and resulted in a refined set of 27 indicators. RESULTS: Indicators related to motorized vehicle collisions, mortality and hospitalization rates were rated the most useful and most likely to prompt action. These were followed by indicators for community injury prevention training and response systems, violent and inflicted injury, burns and falls, and suicide. CONCLUSION: The results suggest that a broad-based modified-Delphi process is a practical and appropriate method, within the OCAP™ (Ownership, Control, Access and Possession) principles, for developing a proposed set of indicators for injury prevention activity focused on First Nations and Inuit children and youth. Following additional work to validate and populate the indicators, it is anticipated that communities will utilize them to monitor injury and prompt decisions and action to reduce injuries among children and youth.

TITRE: Élaboration d'indicateurs de blessures chez les enfants et les jeunes des Premières nations et inuits au Canada grâce à une méthode de Delphes modifiée. INTRODUCTION: Le but de cette recherche était de franchir la première étape de l'élaboration d'indicateurs valides et représentatifs des blessures chez les enfants et les jeunes des Premières nations et Inuits du Canada. MÉTHODOLOGIE: À l'aide d'une méthode de Delphes modifiée, des intervenants des collectivités et des experts ont évalué chaque indicateur en fonction de son utilité perçue et de sa capacité à inciter à l'action dans le but de réduire les blessures chez les enfants et les jeunes des collectivités autochtones. Le processus s'est déroulé en 5 étapes et a permis d'obtenir un ensemble de 27 indicateurs. RÉSULTATS: Les indicateurs évalués comme étant les plus utiles et les plus susceptibles d'inciter à l'action ont été ceux liés au taux de collision de véhicules à moteur, au taux de mortalité et au taux d'hospitalisation. Ont été sélectionnés ensuite les indicateurs de la formation en prévention des blessures et programmes communautaires d'intervention, ceux des blessures intentionnelles, ceux des brûlures et des chutes et enfin ceux du suicide. CONCLUSION: Les résultats indiquent qu'utiliser une méthode de Delphes modifiée avec participation élargie est efficace et pertinent pour élaborer un ensemble d'indicateurs visant à guider les activités de prévention des blessures chez les enfants et les jeunes des Premières nations et Inuits, tout en respectant les principes PCAP™ (propriété, contrôle, accès et possession). Une fois achevés les travaux complémentaires de validation des indicateurs et la collecte des données associées, ces indicateurs vont pouvoir servir aux collectivités pour la surveillance des blessures et pour la prise de décisions et de mesures efficaces de réduction des blessures chez les enfants et les jeunes.

Canadian parents' attitudes and beliefs about bicycle helmet legislation in provinces with and without legislation.

INTRODUCTION: The objective of this study was to survey Canadian parents on their attitudes and beliefs about bicycle helmet legislation and to compare responses from parents living in provinces with and without legislation. METHODS: A national survey of 1002 parents of children aged under 18 years was conducted. Chi-square tests were used to compare responses from the surveyed parents in the different jurisdictions. RESULTS: Responses from parents living in provinces with legislation (n = 640) and without legislation (n = 362) were as follows: concern for injury (63% vs. 68%, nonsignificant [NS]); believe helmets are effective (98% vs. 98%, NS); child always wears a helmet (74% vs. 69%, NS); support legislation for children (95% vs. 83%, p < .001); support legislation for all ages (85% vs. 75%, p < .001); support police enforcement (83% vs. 76%, p = .003); believe legislation decreases the amount of time their child bicycles (5% vs. 8%, NS). CONCLUSION: Parents are highly supportive of bicycle helmet legislation in Canada. They believe that bicycle helmets are effective and that legislation does not decrease the amount of time a child spends bicycling. There was also a high level of support for legislation across all ages, and for police enforcement.

TITRE: Attitudes et croyances des parents au sujet du port obligatoire du casque de vélo : comparaison entre provinces avec et sans législation. INTRODUCTION: L'objectif de l'étude était d'effectuer un sondage auprès de parents canadiens sur leurs attitudes et leurs croyances au sujet de la législation du port du casque chez les cyclistes et de comparer les réponses des parents vivant dans une province ayant légiféré dans ce domaine et celles de ceux vivant dans une province n'ayant pas légiféré. MÉTHODOLOGIE: Un sondage national a été réalisé auprès de 1 002 parents d'enfants âgés de moins de 18 ans. Des tests du chi-carré ont été utilisés pour comparer les réponses des parents dans les différentes provinces. RÉSULTATS: Les réponses des parents vivant dans une province ayant légiféré (n = 640) ou ne l'ayant pas fait (n = 362) s'établissent respectivement comme suit : sont préoccupés par les accidents de vélo (63 % et 68 %, non significatif [NS]); croient que le port du casque de vélo est une mesure efficace (98 % et 98 %, NS); l'enfant porte toujours un casque de vélo (74 % et 69 %, NS); sont favorables à une loi visant les enfants (95 % et 83 %, p < 0,001); sont favorables à une loi visant les cyclistes de tous âges (85 % et 75 %, p < 0,001); sont favorables à l'application de la loi par les services de police (83 % et 76 %, p = 0,003); croient que la loi réduit la durée d'utilisation de la bicyclette par leur enfant (5 % et 8 %, NS). CONCLUSION: Les parents sont largement favorables à la législation du port du casque chez les cyclistes au Canada. Ils croient que le casque de vélo est une mesure efficace et que la loi n'a pas pour effet de réduire la durée d'utilisation de la bicyclette par leur enfant. Ils sont également largement favorables à une loi visant les cyclistes de tous âges et à l'application de la loi par les services de police.

Reaction time-monitored patient-maintained propofol sedation: a pilot study in oral surgery patients.

Previous volunteer studies of an effect-site controlled patient-maintained sedation system using propofol have demonstrated a risk of oversedation. We have incorporated a reaction time monitor into the handset to add an individualised patient-feedback mechanism. This pilot study assessed if the reaction time-feedback modification would prove safe and effective in 20 healthy patients receiving sedation while undergoing oral surgery. All patients successfully sedated themselves without reaching any unsafe endpoints. All 20 maintained verbal contact throughout. The mean (SD) lowest peripheral blood oxygen saturation was 98.0 (2.1)% breathing room air. No patient required supplementary oxygen. The mean (SD) maximum effect-site propofol concentration reached was 1.6 (0.5) µg.ml(-1). The present system was found to be safe and effective, allowing oral surgery treatment under conscious sedation, but preventing oversedation.

Crossing the threshold: gene flow, dominance and the critical level of standing genetic variation required for adaptation to novel environments.

Genetic architecture plays an important role in the process of adaptation to novel environments. One example is the role of allelic dominance, where advantageous recessive mutations have a lower probability of fixation than advantageous dominant mutations. This classic observation, termed 'Haldane's sieve', has been well explored theoretically for single isolated populations adapting to new selective regimes. However, the role of dominance is less well understood for peripheral populations adapting to novel environments in the face of recurrent and maladaptive gene flow. Here, we use a combination of analytical approximations and individual-based simulations to explore how dominance influences the likelihood of adaptation to novel peripheral environments. We demonstrate that in the face of recurrent maladaptive gene flow, recessive alleles can fuel adaptation only when their frequency exceeds a critical threshold within the ancestral range.

The function of secretory IgA in the context of the intestinal continuum of adaptive immune responses in host-microbial mutualism.

The large production of immunoglobulin (Ig)A is energetically costly. The fact that evolution retained this apparent luxury of intestinal class switch recombination to IgA within the human population strongly indicates that there must be a critical specific function of IgA for survival of the species. The function of IgA has been investigated in a series of different models that will be discussed here. While IgA has clear protective functions against toxins or in the context of intestinal viral infections, the function of IgA specific for non-pathogenic commensal bacteria remains unclear. In the context of the current literature we present a hypothesis where secretory IgA integrates as an additional layer of immune function into the continuum of intestinal CD4 T cell responses, to achieve a mutualistic relationship between the intestinal commensal microbiota and the host.

Hypersensitivity and oral tolerance in the absence of a secretory immune system.

BACKGROUND: Mucosal immunity protects the epithelial barrier by immune exclusion of foreign antigens and by anti-inflammatory tolerance mechanisms, but there is a continuing debate about the role of secretory immunoglobulins (SIgs), particularly SIgA, in the protection against allergy and other inflammatory diseases. Lack of secretory antibodies may cause immune dysfunction and affect mucosally induced (oral) tolerance against food antigens. METHODS: We used polymeric Ig receptor (pIgR) knockout (KO) mice, which cannot export SIgA or SIgM, to study oral tolerance induction by ovalbumin (OVA) feeding and for parenteral antigen sensitization in the same animal. RESULTS: Remarkable systemic hyperreactivity was observed in pIgR KO mice, as 50% died after intradermal OVA challenge, which was not seen in similarly sensitized and challenged wild-type (WT) mice. Oral tolerance induced by OVA completely protected the sensitized pIgR KO mice against anaphylaxis and suppressed antibody levels (particularly IgG1) as well as delayed-type hypersensitivity (DTH) to OVA. Delayed-type hypersensitivity to a bystander antigen, human serum albumin, was also suppressed and T-cell proliferation against OVA in vitro was reduced in tolerized compared with non-tolerized pIgR KO mice. This effect was largely mediated by CD25+ T cells. Adoptive transfer of splenic putative regulatory T cells (CD4+ CD25+) obtained from OVA-fed pIgR KO mice to naïve WT mice mediated suppression of DTH against OVA after sensitization of the recipients. CONCLUSION: Compensatory regulatory T-cell function becomes critical in pIgR-deficient mice to avoid the potentially catastrophic effects of systemic immune hyperreactivity, presumably resulting from defective secretory antibody-mediated immune exclusion of microbial components.

Booster seat laws and child fatalities: a case-control study.

A case-control study examined, primarily, the association between booster seat laws and fatalities among children in frontal collisions and, secondarily, the association between booster seat laws and reported restraint use, and restraint use and child fatalities. Children who died in a crash in the US were cases, and children who survived a fatal crash were controls. Subjects were child passengers (4-8 years old) in the Fatality Analysis Reporting System Database, 1995-2005. In states with a booster seat law, children were less likely to die than in states without a law (OR 0.80; 95% CI 0.66 to 0.98). They were also more likely to be restrained (adjusted OR 1.59; 95% CI 1.21 to 2.09) and were more likely to be correctly restrained (adjusted OR 4.44; 95% CI 3.18 to 6.20). It is concluded that booster seat laws are associated with a decrease in child deaths and an increase in correct restraint use among children involved in a fatal crash in the USA.

The immune geography of IgA induction and function.

The production of immunoglobulin A (IgA) in mammals exceeds all other isotypes, and it is mostly exported across mucous membranes. The discovery of IgA and the realization that it dominates humoral mucosal immunity, in contrast to the IgG dominance of the systemic immune system, was early evidence for the distinct nature of mucosal immunology. It is now clear that IgA can function in high-affinity modes for neutralization of toxins and pathogenic microbes, and as a low-affinity system to contain the dense commensal microbiota within the intestinal lumen. The basic map of induction of IgA B cells in the Peyer's patches, which then circulate through the lymph and bloodstream to seed the mucosa with precursors of plasma cells that produce dimeric IgA for export through the intestinal epithelium, has been known for more than 30 years. In this review, we discuss the mechanisms underlying selective IgA induction of mucosal B cells for IgA production and the immune geography of their homing characteristics. We also review the functionality of secretory IgA directed against both commensal organisms and pathogens.

Examining the sensitivity of an injury surveillance program using population-based estimates.

This study uses population-based estimates to assess the sensitivity and representativeness of an injury surveillance system using a 1-year population-based approach. Data from the Ottawa Canadian Hospitals Injury Reporting and Prevention Program (CHIRPP) site (Children's Hospital of Eastern Ontario) were compared with those from six expansion sites. The overall sensitivity of CHIRPP was 43% of all treated injuries and 57% of injuries treated at emergency departments. CHIRPP was less likely to be representative for older children and more likely to capture children with more severe injuries. The limitations related to using CHIRPP for representing population-based injury remain fairly stable over time. A one-time population-based sample can provide useful information to add to routinely collected injury surveillance.

Bicycle helmet legislation for the uptake of helmet use and prevention of head injuries.

BACKGROUND: Evidence exists to suggest that bicycle helmets may reduce the risk of head injuries to cyclists, however helmets are not uniformly worn by all bicycle users. Legislation has been enacted in some countries to mandate helmet use by cyclists, however the issue remains controversial with opponents arguing that this may inhibit people from bicycle riding and thus from gaining the associated health benefits, or that other countermeasures may have been responsible for decline in head injuries. OBJECTIVES: To assess the effects of bicycle helmet legislation on bicycle-related head injuries and helmet use, and the occurrence of unintended adverse consequences. SEARCH STRATEGY: We searched CENTRAL, the Cochrane Injuries Group's specialised register, MEDLINE, EMBASE, TRANSPORT and other specialist electronic databases, up to February 2006. In addition we searched government websites, handsearched selected journals and examined the reference lists of selected publications. SELECTION CRITERIA: We included studies that reported changes in either the number of head injuries, helmet use or bicycle use post- versus pre-legislation. Only studies that included a concurrent control group and which reported on the effect of legislation implemented at either the country, state or province wide level were included. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data and assessed methodological quality. The data were not appropriate for meta-analysis, thus the results of the included studies have been reviewed narratively. MAIN RESULTS: Five studies, all from North America, met the inclusion criteria. For each of the studies, bicycle helmet legislation had been enacted for children only. Adults were used as controls in four of the studies, whilst jurisdictions with no helmet legislation were used as controls in the fifth. Three of the studies reported on changes in head injury rates and three reported on changes in helmet use. There were no included studies reporting change in bicycle use or other adverse consequences of legislation. In two studies, statistically significant decreases in head injuries were reported following the implementation of helmet legislation compared with controls, whilst one reported a non-statistically significant decline. Bicycle helmet use increased statistically significantly post-legislation in all three of the studies reporting on helmet use. AUTHORS' CONCLUSIONS: Bicycle helmet legislation appears to be effective in increasing helmet use and decreasing head injury rates in the populations for which it is implemented. However, there are very few high quality evaluative studies that measure these outcomes, and none that reported data on an possible declines in bicycle use.

Injury risk from popular childhood physical activities: results from an Australian primary school cohort.

BACKGROUND: Children engage in various physical activities that pose different injury risks. However, the lack of adequate data on exposure has meant that these risks have not been quantified or compared in young children aged 5-12 years. OBJECTIVES: To measure exposure to popular activities among Australian primary school children and to quantify the associated injury risks. METHOD: The Childhood Injury Prevention Study prospectively followed up a cohort of randomly selected Australian primary and preschool children aged 5-12 years. Time (min) engaged in various physical activities was measured using a parent-completed 7-day diary. All injuries over 12 months were reported to the study. All data on exposure and injuries were coded using the International classification of external causes of injury. Injury rates per 1000 h of exposure were calculated for the most popular activities. RESULTS: Complete diaries and data on injuries were available for 744 children. Over 12 months, 314 injuries relating to physical activity outside of school were reported. The highest injury risks per exposure time occurred for tackle-style football (2.18/1000 h), wheeled activities (1.72/1000 h) and tennis (1.19/1000 h). Overall, boys were injured more often than girls; however, the differences were non-significant or reversed for some activities including soccer, trampolining and team ball sports. CONCLUSION: Although the overall injury rate was low in this prospective cohort, the safety of some popular childhood activities can be improved so that the benefits may be enjoyed with fewer negative consequences.

IgA adaptation to the presence of commensal bacteria in the intestine.

The lower intestine of mammals is colonised by a dense flora composed mainly of non-pathogenic commensal bacteria. These intestinal bacteria have a wide-ranging impact on host immunity and physiology. One adaptation following intestinal colonisation is increased production and secretion of polyspecific intestinal IgA. In contrast to the strong mucosal immune response to bacterial colonisation, the systemic immune system remains ignorant of these organisms in pathogen-free mice. Small numbers of bacteria can penetrate the epithelial surface overlying Peyer's patches and survive in dendritic cells to induce IgA by T-dependent and T-independent mechanisms. These dendritic cells loaded with live commensal organisms can home to the mesenteric lymph nodes but do not reach systemic secondary lymphoid structures, so induction of mucosal responses is focused in mucosal lymphoid tissues. The secretion of antibodies across the intestinal epithelial surface in turn limits the penetration of commensal organisms, but this is one of many mechanisms which adapt the intestinal mucosa to co-existence with commensal bacteria.