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Objective To examine the relationship between schizophrenia, antipsychotic medication adherence and driver responsibility for motor vehicle crash.Design Retrospective observational cohort study using 20 years of population-based administrative health and driving data.Setting British Columbia, Canada.Participants Licensed drivers who were involved in a police-attended motor vehicle crash in British Columbia over a 17-year study interval (2000–16).Exposures Incident schizophrenia was identified using hospitalisation and physician services data. Antipsychotic adherence was estimated using prescription fill data to calculate the ‘medication possession ratio’ (MPR) in the 30 days prior to crash.Primary outcome measures We deemed drivers ‘responsible’ or ‘non-responsible’ for their crash by applying a validated scoring tool to police-reported crash data. We used logistic regression to evaluate the association between crash responsibility and exposures of interest.Results Our cohort included 808 432 drivers involved in a police-attended crash and for whom crash responsibility could be established. In total, 1689 of the 2551 drivers with schizophrenia and 432 430 of the 805 881 drivers without schizophrenia were deemed responsible for their crash, corresponding to a significant association between schizophrenia and crash responsibility (66.2% vs 53.7%; adjusted OR (aOR), 1.67; 95% CI, 1.53 to 1.82; p

Abstract Background Osteoarthritis (OA) is a chronic debilitating disease impacting a significant percentage of the global population. While there are numerous surgical and non-invasive interventions that can postpone joint replacement, there are no current treatments which can reverse the joint damage occurring during the pathogenesis of the disease. While many groups are investigating the use of stem cell therapies in the treatment of OA, we still don’t have a clear understanding of the role of these cells in the body, including heterogeneity of tissue resident adult mesenchymal progenitor cells (MPCs). Methods In the current study, we examined MPCs from the synovium and individuals with or without a traumatic knee joint injury and explored the chondrogenic differentiation capacity of these MPCs in vitro and in vivo. Results We found that there is heterogeneity of MPCs with the adult synovium and distinct sub-populations of MPCs and the abundancy of these sub-populations change with joint injury. Furthermore, only some of these sub-populations have the ability to effect cartilage repair in vivo. Using an unbiased proteomics approach, we were able to identify cell surface markers that identify this pro-chondrogenic MPC population in normal and injured joints, specifically CD82LowCD59+ synovial MPCs have robust cartilage regenerative properties in vivo. Conclusions The results of this study clearly show that cells within the adult human joint can impact cartilage repair and that these sub-populations exist within joints that have undergone a traumatic joint injury. Therefore, these populations can be exploited for the treatment of cartilage injuries and OA in future clinical trials.

Altered expression and function of the extracellular matrix protein PRG4 have been associated with osteoarthritis. Here, the authors show that mast cell tryptase β cleaves PRG4, resulting in a reduction of lubrication and activation of inflammation in this context.

Objectives One-fifth of total knee arthroplasty (TKA) recipients experience a suboptimal outcome. Incorporation of patients’ preferences in TKA assessment may improve outcomes. We determined the discriminant ability of preoperative measures of TKA need, readiness/willingness and expectations for a good TKA outcome.Methods In patients with knee osteoarthritis (OA) undergoing primary TKA, we preoperatively assessed TKA need (Western Ontario-McMaster Universities OA Index (WOMAC) Pain Score and Knee injury and Osteoarthritis Outcome Score (KOOS) function, arthritis coping), health status, readiness (Patient Acceptable Symptom State, depressive symptoms), willingness (definitely yes—yes/no) and expectations (outcomes deemed ‘very important’). A good outcome was defined as symptom improvement (met Outcome Measures in Rheumatology and Osteoarthritis Research Society International (OMERACT–OARSI) responder criteria) and satisfaction with results 1 year post TKA. Using logistic regression, we assessed independent outcome predictors, model discrimination (area under the receiver operating characteristic curve, AUC) and the predicted probability of a good outcome for different need, readiness/willingness and expectations scenarios.Results Of 1,053 TKA recipients (mean age 66.9 years (SD 8.8); 58.6% women), 78.1% achieved a good outcome. With TKA need alone (WOMAC pain subscale, KOOS physical function short-form), model discrimination was good (AUC 0.67, 95% CI 0.63 to 0.71). Inclusion of readiness/willingness, depressive symptoms and expectations regarding kneeling, stair climbing, well-being and performing recreational activities improved discrimination (p=0.01; optimism corrected AUC 0.70, 0.66–0.74). The predicted probability of a good outcome ranged from 44.4% (33.9–55.5) to 92.4% (88.4–95.1) depending on level of TKA need, readiness/willingness, depressive symptoms and surgical expectations.Conclusions Although external validation is required, our findings suggest that incorporation of patients’ TKA readiness, willingness and expectations in TKA decision-making may improve the proportion of recipients that experience a good outcome.

Abstract An estimated 30% of the North American piping plover (Charadrius melodus) breeding population occurs in Canada, where it is Endangered. Predator exclosures are a common management tool across the species' range to increase nest success. Using data from 1998 to 2010 on 820 nests, collected as part of an ongoing management program in Alberta, we compare daily nest survival (DNS), numbers of chicks hatched and fledglings produced, and cost/chick among three treatments (large, medium, small exclosures) and natural nests. During the early period (1998–2001), when all three types of exclosures were applied, there were no significant differences in DNS between exclosed nests and natural nests. During the late period (2002–2010), when only small exclosures were applied, nests with small exclosures had a significantly higher DNS rate (x¯ = 0.994, n = 594) compared with natural nests (x¯ = 0.984, n = 88). Nests with small exclosures also hatched more chicks (x¯ = 3.21, n = 598) and produced more fledglings (x¯ = 1.17, n = 337) than natural nests (x¯ = 1.73 chicks, n = 31; x¯ = 0.59 fledglings, n = 21) during the late period. However, considering only successful nests, the differences were not significant for either period, indicating no added benefit of exclosures beyond protecting the nest. The cost/chick rate was lowest using small exclosures (cylindrical, 40 by 60 cm), and this portable design is well‐suited for widespread application in the field. We demonstrate increased DNS for nests with small exclosures and a mean fledging rate close to the goal of 1.25 chicks/nest/year, although this did not increase Alberta's piping plover population beyond the timeframe of systematic exclosure application. Long‐term, cost‐efficient management tools that increase nest success and fledging rates should continue.

Abstract Background Infections with helminths cause an enormous disease burden in billions of animals and plants worldwide. Large scale use of anthelmintics has driven the evolution of resistance in a number of species that infect livestock and companion animals, and there are growing concerns regarding the reduced efficacy in some human-infective helminths. Understanding the mechanisms by which resistance evolves is the focus of increasing interest; robust genetic analysis of helminths is challenging, and although many candidate genes have been proposed, the genetic basis of resistance remains poorly resolved. Results Here, we present a genome-wide analysis of two genetic crosses between ivermectin resistant and sensitive isolates of the parasitic nematode Haemonchus contortus, an economically important gastrointestinal parasite of small ruminants and a model for anthelmintic research. Whole genome sequencing of parental populations, and key stages throughout the crosses, identified extensive genomic diversity that differentiates populations, but after backcrossing and selection, a single genomic quantitative trait locus (QTL) localised on chromosome V was revealed to be associated with ivermectin resistance. This QTL was common between the two geographically and genetically divergent resistant populations and did not include any leading candidate genes, suggestive of a previously uncharacterised mechanism and/or driver of resistance. Despite limited resolution due to low recombination in this region, population genetic analyses and novel evolutionary models supported strong selection at this QTL, driven by at least partial dominance of the resistant allele, and that large resistance-associated haplotype blocks were enriched in response to selection. Conclusions We have described the genetic architecture and mode of ivermectin selection, revealing a major genomic locus associated with ivermectin resistance, the most conclusive evidence to date in any parasitic nematode. This study highlights a novel genome-wide approach to the analysis of a genetic cross in non-model organisms with extreme genetic diversity, and the importance of a high-quality reference genome in interpreting the signals of selection so identified.

Echinococcus multilocularis (Em) is a zoonotic parasite considered a global emergent pathogen. Recent findings indicate that the parasite is expanding its range in North America and that European-type haplotypes are circulating in western Canada. However, genetic analyses are usually conducted only on a few parasites out of thousands of individuals within each definitive host, likely underestimating the prevalence of less common haplotypes. Moreover, mixed infections with several mtDNA haplotypes in the same host have been reported, but their relative abundance within the host was never estimated. We aimed to 1) estimate the frequency of co-infections of different Em haplotypes in coyotes (Canis latrans) and red foxes (Vulpes vulpes) from western Canada and their relative abundance within the definitive hosts, 2) detect less prevalent haplotypes by sampling a larger proportion of the parasite subpopulation per host, and 3) investigate differences in the distribution of Em haplotypes in these main definitive hosts; foxes and coyotes. We extracted DNA from ~10% of the worm subpopulation per host (20 foxes and 47 coyotes) and used deep amplicon sequencing (NGS technology) on four loci, targeting the most polymorphic regions from the mitochondrial genes cox1 (814 bp), nad1 (344 bp), and cob (387 bp). We detected the presence of mixed infections with multiple Em haplotypes and with different Echinococcus species including Em and E. granulosus s.l. genotypes G8/G10, low intraspecific diversity of Em, and a higher abundance of the European-type haplotypes in both hosts. Our results suggest a population expansion of the European over the North American strain in Alberta and a limited distribution of some European-type haplotypes. Our findings indicate that deep amplicon sequencing represents a valuable tool to characterize Em in multiple hosts, to assess the current distribution and possible origins of the European strain in North America. The potential use of next-generation sequencing technologies is particularly important to understand the patterns of geographic expansion of this parasite.

Background: Methadone maintenance treatment (MMT) has important protective effects related to reduced illicit opioid use, infectious disease transmission, and overdose mortality. Adherence to MMT has not been examined among homeless people. We measured MMT adherence and reported relevant characteristics among homeless adults experiencing mental illness in Vancouver, British Columbia, Canada. Material and methods: Homeless adults living with mental illness who had received MMT prior to the baseline interview of the Vancouver At Home study (n=78) were included in analyses. The medication possession ratio (MPR) was used to estimate MMT adherence from retrospective administrative pharmacy and public health insurance data collected across 15years. Independent sample t tests and one-way ANOVA were used to test for significant differences in MMT MPR by participant characteristics. Results: Mean MMT MPR was 0.47. A large proportion of participants reported blood-borne infectious disease, three or more chronic physical health conditions, and substance use. Being single and never married was associated with significantly lower MMT MPR (0.40 vs. 0.55, p=0.036), while living with schizophrenia, bipolar disorder, or a mood disorder with psychotic features was associated with significantly higher MMT MPR (0.54 vs. 0.37, p=0.022). Daily drug use (excluding alcohol) was associated with significantly lower MMT MPR (0.39 vs. 0.54, p=0.051). Conclusions: The level of adherence to MMT was very low among homeless adults experiencing mental illness. Efforts are needed to improve adherence to MMT as a means of reducing illicit substance use, preventing overdose deaths, and attenuating infectious disease transmission. Keywords: Adherence, Medication possession ratio, Methadone, Opioid dependence, Homeless, Mental illness

Co-occurring health and public safety concerns involving mental illness, substance use, and homelessness are increasingly prevalent challenges for policymakers in cities worldwide. The Hub model is a roundtable process where the combined resources of diverse agencies are used to mitigate urgent risk of crime, victimization, illness and death, by establishing immediate connections with appropriate services and supports. Initiated in Scotland, the model has been replicated in more than 60 communities across Canada since 2012. In November 2105, the Surrey Mobilization and Resiliency Table (SMART) became the first Hub in British Columbia. Little peer-reviewed research has examined the impact of Hub inter-ventions from a client perspective. We conducted semi-structured interviews with 16 SMART clients and analyzed their responses thematically. We also examined demographic- and intervention-related characteristics reported in the SMART database. Participants described positive experiences with SMART service providers, and commented that the intervention was effective at meeting relatively circumscribed needs. However, most clients reported complex and mutually exacer-bating health and social conditions, and expressed the need for ongoing structured support (e.g., Assertive Community Treatment (ACT)). Our results emphasize the beneficial role played by SMART’s coordinated, real-time approach. They also indicate demand for social policies that include substantial and enduring forms of support to prevent crises and promote community safety.

Resistance to anthelmintic drugs is a major problem in the global fight against parasitic nematodes infecting humans and animals. While previous studies have identified mutations in drug target genes in resistant parasites, changes in the expression levels of both targets and transporters have also been reported. The mechanisms underlying these changes in gene expression are unresolved. Here, we take a novel approach to this problem by investigating the role of small regulatory RNAs in drug resistant strains of the important parasite Haemonchus contortus. microRNAs (miRNAs) are small (22 nt) non-coding RNAs that regulate gene expression by binding predominantly to the 3′ UTR of mRNAs. Changes in miRNA expression have been implicated in drug resistance in a variety of tumor cells. In this study, we focused on two geographically distinct ivermectin resistant strains of H. contortus and two lines generated by multiple rounds of backcrossing between susceptible and resistant parents, with ivermectin selection. All four resistant strains showed significantly increased expression of a single miRNA, hco-miR-9551, compared to the susceptible strain. This same miRNA is also upregulated in a multi-drug-resistant strain of the related nematode Teladorsagia circumcincta. hco-miR-9551 is enriched in female worms, is likely to be located on the X chromosome and is restricted to clade V parasitic nematodes. Genes containing predicted binding sites for hco-miR-9551 were identified computationally and refined based on differential expression in a transcriptomic dataset prepared from the same drug resistant and susceptible strains. This analysis identified three putative target mRNAs, one of which, a CHAC domain containing protein, is located in a region of the H. contortus genome introgressed from the resistant parent. hco-miR-9551 was shown to interact with the 3′ UTR of this gene by dual luciferase assay. This study is the first to suggest a role for miRNAs and the genes they regulate in drug resistant parasitic nematodes. miR-9551 also has potential as a biomarker of resistance in different nematode species.

No previous experimental trials have investigated Housing First (HF) in both scattered site (SHF) and congregate (CHF) formats. We hypothesized that CHF and SHF would be associated with a greater percentage of time stably housed as well as superior health and psychosocial outcomes over 24 months compared to treatment as usual (TAU).Inclusion criteria were homelessness, mental illness, and high need for support. Participants were randomised to SHF, CHF, or TAU. SHF consisted of market rental apartments with support provided by Assertive Community Treatment (ACT). CHF consisted of a single building with supports equivalent to ACT. TAU included existing services and supports.Of 800 people screened, 297 were randomly assigned to CHF (107), SHF (90), or TAU (100). The percentage of time in stable housing over 24 months was 26.3% in TAU (reference; 95% confidence interval (CI) = 20.5, 32.0), compared to 74.3% in CHF (95% CI = 69.3, 79.3, p

Abstract Background Varestrongylus alces, a lungworm in Eurasian moose from Europe has been considered a junior synonym of Varestrongylus capreoli, in European roe deer, due to a poorly detailed morphological description and the absence of a type-series. Methods Specimens used in the redescription were collected from lesions in the lungs of Eurasian moose, from Vestby, Norway. Specimens were described based on comparative morphology and integrated approaches. Molecular identification was based on PCR, cloning and sequencing of the ITS-2 region of the nuclear ribosomal DNA. Phylogenetic analysis compared V. alces ITS-2 sequences to these of other Varestrongylus species and other protostrongylids. Results Varestrongylus alces is resurrected for protostrongylid nematodes of Eurasian moose from Europe. Varestrongylus alces causes firm nodular lesions that are clearly differentiated from the adjacent lung tissue. Histologically, lesions are restricted to the parenchyma with adult, egg and larval parasites surrounded by multinucleated giant cells, macrophages, eosinophilic granulocytes, lymphocytes. The species is valid and distinct from others referred to Varestrongylus, and should be separated from V. capreoli. Morphologically, V. alces can be distinguished from other species by characters in the males that include a distally bifurcated gubernaculum, arched denticulate crura, spicules that are equal in length and relatively short, and a dorsal ray that is elongate and bifurcated. Females have a well-developed provagina, and are very similar to those of V. capreoli. Morphometrics of first-stage larvae largely overlap with those of other Varestrongylus. Sequences of the ITS-2 region strongly support mutual independence of V. alces, V. cf. capreoli, and the yet undescribed species of Varestrongylus from North American ungulates. These three taxa form a well-supported crown-clade as the putative sister of V. alpenae. The association of V. alces and Alces or its ancestors is discussed in light of host and parasite phylogeny and host historical biogeography. Conclusions Varestrongylus alces is a valid species, and should be considered distinct from V. capreoli. Phylogenetic relationships among Varestrongylus spp. from Eurasia and North America are complex and consistent with faunal assembly involving recurrent events of geographic expansion, host switching and subsequent speciation.

An estimated 30% of the North American piping plover (Charadrius melodus) breeding population occurs in Canada, where it is Endangered. Predator exclosures are a common management tool across the species' range to increase nest success. Using data from 1998 to 2010 on 820 nests, collected as part of an ongoing management program in Alberta, we compare daily nest survival (DNS), numbers of chicks hatched and fledglings produced, and cost/chick among three treatments (large, medium, small exclosures) and natural nests. During the early period (1998–2001), when all three types of exclosures were applied, there were no significant differences in DNS between exclosed nests and natural nests. During the late period (2002–2010), when only small exclosures were applied, nests with small exclosures had a significantly higher DNS rate (x¯ = 0.994, n = 594) compared with natural nests (x¯ = 0.984, n = 88). Nests with small exclosures also hatched more chicks (x¯ = 3.21, n = 598) and produced more fledglings (x¯ = 1.17, n = 337) than natural nests (x¯ = 1.73 chicks, n = 31; x¯ = 0.59 fledglings, n = 21) during the late period. However, considering only successful nests, the differences were not significant for either period, indicating no added benefit of exclosures beyond protecting the nest. The cost/chick rate was lowest using small exclosures (cylindrical, 40 by 60 cm), and this portable design is well‐suited for widespread application in the field. We demonstrate increased DNS for nests with small exclosures and a mean fledging rate close to the goal of 1.25 chicks/nest/year, although this did not increase Alberta's piping plover population beyond the timeframe of systematic exclosure application. Long‐term, cost‐efficient management tools that increase nest success and fledging rates should continue. [ABSTRACT FROM AUTHOR]

BACKGROUND: Problem solving courts (PSC) have been implemented internationally, with a common objective to prevent reoffending by addressing criminogenic needs and strengthening social determinants of health. There has been no empirical research on the effectiveness of community courts, which are a form of PSC designed to harness community resources and inter-disciplinary expertise to reduce recidivism in a geographic catchment area. METHOD: We used the propensity score matching method to examine the effectiveness of Vancouver's Downtown Community Court (DCC). We focused on the subset of DCC participants who were identified as having the highest criminogenic risk and were assigned to a case management team (CMT). A comparison group was derived using one-to-one matching on a large array variables including static and dynamic criminogenic factors, geography, and time. Reductions in offences (one year pre minus one year post) were compared between CMT and comparison groups. RESULTS: Compared to other DCC offenders, those triaged to CMT (9.5% of the DCC population) had significantly higher levels of healthcare, social service use, and justice system involvement over the ten years prior to the index offence. Compared to matched offenders who received traditional court outcomes, those assigned to CMT (n=249) exhibited significantly greater reductions in overall offending (p

BACKGROUND: Homelessness and mental illness have a strong association with public disorder and criminality. Experimental evidence indicates that Housing First (HF) increases housing stability and perceived choice among those experiencing chronic homelessness and mental disorders. HF is also associated with lower residential costs than common alternative approaches. Few studies have examined the effect of HF on criminal behavior. METHODS: Individuals meeting criteria for homelessness and a current mental disorder were randomized to one of three conditions treatment as usual (reference); scattered site HF; and congregate HF. Administrative data concerning justice system events were linked in order to study prior histories of offending and to test the relationship between housing status and offending following randomization for up to two years. RESULTS: The majority of the sample (67%) was involved with the justice system, with a mean of 8.07 convictions per person in the ten years prior to recruitment. The most common category of crime was "property offences" (mean=4.09). Following randomization, the scattered site HF condition was associated with significantly lower numbers of sentences than treatment as usual (Adjusted IRR=0.29; 95% CI 0.12-0.72). Congregate HF was associated with a marginally significant reduction in sentences compared to treatment as usual (Adjusted IRR=0.55; 95% CI: 0.26-1.14). CONCLUSIONS: This study is the first randomized controlled trial to demonstrate benefits of HF among a homeless sample with mental illness in the domain of public safety and crime. Our sample was frequently involved with the justice system, with great personal and societal costs. Further implementation of HF is strongly indicated, particularly in the scattered site format. Research examining interdependencies between housing, health, and the justice system is indicated. TRIAL REGISTRATION: ISRCTN57595077.