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The longstanding association between addiction, crime, and mortality has become increasingly severe in Canada, affecting larger numbers of individuals and communities. Diverse and irreconcilable courses of action have been proposed involving the decriminalization of drug possession, expanded resources to promote recovery from addiction, or both. The current review used the PICOTS method to identify peer-reviewed publications that reported outcomes of reducing the criminal consequences of drug possession and the specific relationship between law reform and the well-being of people who are at greatest risk for poisoning. We separately included notable reports and grey literature discussing outcomes associated with the Portuguese National Drug Strategy. Over 2,500 articles were retrieved from three databases, with six meeting all inclusion/exclusion criteria. An additional five manuscripts were retrieved specific to Portugal. The evidence reviewed indicates that drug decriminalization alone is associated with potential harms to drug users and their communities, and that potential benefits may be realized when law reform is closely coordinated with the provision of evidence-based resources that promote recovery from addiction. The evidence summarized in this review supports careful consideration of the factors necessary to promote social reintegration among people who are at highest risk for drug-related harms, including repeated criminal offending and death. [ABSTRACT FROM AUTHOR]

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. Author summary: Echinococcus multilocularis is a tiny tapeworm whose adults live in the intestines of wild and domestic canids and shed their eggs with the host feces. If accidentally ingested by people, eggs can cause human alveolar echinococcosis (AE), a highly lethal parasitic disease. Despite Em being common in North America, only two locally acquired AE human cases were reported in North America until 2013. However, in the last 6 years, 14 new cases have been detected in Alberta, Canada, and recent findings showed that the European strain of this parasite is now common in wildlife in this province, which could potentially increase the risk of infection in humans and domestic animals. In this study, we genetically characterized Em in coyotes and red foxes to assess the extent of the European-type strain distribution in three Canadian provinces. We used deep amplicon sequencing, an innovative approach that allows us to detect co-infections and the presence of less prevalent genetic variants by sampling a larger proportion of the parasite subpopulation per host. Our study showed an overwhelming prevalence of the European strain over the native North American strain in both hosts, and a limited geographical distribution of some European genetic variants, likely due to multiple introduction events of this invasive strain. [ABSTRACT FROM AUTHOR]

• Sequence polymorphism can counfound RNAseq analysis in genetically diverse organisms due to read mapping biases. • Optimising read mapping and excluding highly polymorphic genes reduces differential gene expression analysis biases. • Genetically divergent strains of Haemonchus contortus have very high levels of inter-strain transcriptional diversity. • Analyses of inter-strain differential expression must consider sequence polymorphism and overall transcriptional diversity. Differential expression analysis between parasitic nematode strains is commonly used to implicate candidate genes in anthelmintic resistance or other biological functions. We have tested the hypothesis that the high genetic diversity of an organism such as Haemonchus contortus could complicate such analyses. First, we investigated the extent to which sequence polymorphism affects the reliability of differential expression analysis between the genetically divergent H. contortus strains MHco3(ISE), MHco4(WRS) and MHco10(CAVR). Using triplicates of 20 adult female worms from each population isolated under parallel experimental conditions, we found that high rates of sequence polymorphism in RNAseq reads were associated with lower efficiency read mapping to gene models under default TopHat2 parameters, leading to biased estimates of inter-strain differential expression. We then showed it is possible to largely compensate for this bias by optimising the read mapping single nucleotide polymorphism (SNP) allowance and filtering out genes with particularly high single nucleotide polymorphism rates. Once the sequence polymorphism biases were removed, we then assessed the genuine transcriptional diversity between the strains, finding ≥824 differentially expressed genes across all three pairwise strain comparisons. This high level of inter-strain transcriptional diversity not only suggests substantive inter-strain phenotypic variation but also highlights the difficulty in reliably associating differential expression of specific genes with phenotypic differences. To provide a practical example, we analysed two gene families of potential relevance to ivermectin drug resistance; the ABC transporters and the ligand-gated ion channels (LGICs). Over half of genes identified as differentially expressed using default TopHat2 parameters were shown to be an artifact of sequence polymorphism differences. This work illustrates the need to account for sequence polymorphism in differential expression analysis. It also demonstrates that a large number of genuine transcriptional differences can occur between H. contortus strains and these must be considered before associating the differential expression of specific genes with phenotypic differences between strains. [ABSTRACT FROM AUTHOR]

The current study investigated whether a previously reported beneficial effect of methadone maintenance therapy (MMT) on antiretroviral adherence is also present in relation to antipsychotic treatment for schizophrenia. Administrative data were linked over a 17-year period for 1996 people who were dually diagnosed with schizophrenia and opioid dependence and, as an indicator of further marginalization, experienced at least one episode of correctional supervision in British Columbia. Adherence was estimated using the medication possession ratio (MPR ≥ 0.80), calculated in each 120-day period beginning with the first date of concurrent use of MMT and antipsychotic medication. Generalized Estimating Equations were used to estimate the association between independent and dependent variables. The probability of antipsychotic adherence doubled in periods that were preceded by a period of MMT adherence (AOR: P: 2.07; 95% CI: 1.90-2.26). Subgroup and sensitivity analyses yielded results similar to those derived through the primary analysis, examining: conviction history; length of follow-up; initiation of MMT prior to antipsychotic induction; excluding participants who died during the study period; and restricted to participants who received methadone exclusively as part of a MMT program. Despite a strong temporal association between MMT and antipsychotic adherence, overall MPRs for both prescriptions remained <0.50 throughout the study period. Antipsychotic adherence was more than twice as likely following periods of adherence to MMT among dually-diagnosed patients. Research is needed to identify the conditions responsible for MMT adherence, and to further clarify the relationship between opioid agonist treatment and antipsychotic pharmacotherapy in this vulnerable and under-studied population. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to investigate the level of adherence to antipsychotic prescription medication in a well-defined homeless cohort over a 15-year period. We hypothesized that adherence would be well below the recommended threshold for clinical effectiveness (80 %), and that it would be strongly associated with modifiable risk factors in the social environment in which homeless people live.Method: Linked baseline data (including comprehensive population-level administrative prescription records) were examined in a subpopulation of participants from two pragmatic-randomized trials that investigated Housing First for homeless and mentally ill adults. Adherence to antipsychotic medication was operationalized using the medication possession ratio. Multivariable logistic regression was used to estimate effect sizes between socio-demographic, homelessness-related and illness factors, and medication possession ratio.Results: Among the 290 participants who met inclusion criteria for the current analysis, adherence to antipsychotic prescription was significantly associated with: history of psychiatric hospitalization; receipt of primary medical services; long-acting injectable antipsychotic formulations; and duration of homelessness. Mean medication possession ratio in the pre-randomization period was 0.41. Socio-demographic characteristics previously correlated with antipsychotic non-adherence were not significantly related to medication possession ratio.Conclusions: This is the first study to quantify the very low level of adherence to antipsychotic medication among homeless people over an extended observation period of 15 years. Each of the four factors found to be significantly associated with adherence presents opportunities for intervention. Strategies to end homelessness for this population may represent the greatest opportunity to improve adherence to antipsychotic medication. [ABSTRACT FROM AUTHOR]

Purpose: To determine the radiographic landmarks of the anterolateral ligament (ALL) on the femur and tibia to assist in intraoperative graft placement during ALL reconstruction.Methods: The footprints of the ALL, fibular collateral ligament (FCL), popliteus insertion, lateral gastrocnemius insertion, and Gerdy's tubercle were isolated and centrally marked with tantalum beads in thirteen fresh-frozen cadaveric knees. Measurements were taken from the true lateral fluoroscopic images. On the femur, the mean distances from the ALL origin to the FCL origin and from the ALL origin to the popliteus insertion were measured. On the tibia, the mean distances from the ALL insertion to Gerdy's tubercle and from the ALL insertion to the lateral tibial plateau were measured. Furthermore, radiographic descriptions of the ALL origin and insertion were developed.Results: The ALL origin on the femur averaged 3.3 ± 1.5 mm anterior-distal to the FCL origin in one anatomical variant and 5.4 ± 1.4 mm posterior-proximal to the FCL origin in a second variant. The ALL origin was 9.9 ± 2.7 mm from the popliteus insertion. The ALL origin is described as overlying the posterior femoral cortical line, between Blumensaat's line and a line from the posterior condylar articular edge parallel to Blumensaat's line. The ALL insertion on the tibia averaged 24.7 ± 4.5 mm posterior to Gerdy's tubercle and 11.5 ± 2.9 mm distal to the lateral tibial plateau. The tibial ALL insertion is described between the posterior tibial cortical line and a parallel line drawn down from the apex of the tibial spine, and overlying a line drawn perpendicular to the posterior tibial cortical line starting from the apex of the posterior tibial condyles.Conclusions: Using direct lateral fluoroscopy, radiographic landmarks of the ALL origin and insertion have been described. [ABSTRACT FROM AUTHOR]

Haemonchus contortus is the leading parasitic nematode species used to study anthelmintic drug resistance. A variety of candidate loci have been implicated as being associated with ivermectin resistance in this parasite but definitive evidence of their importance is still lacking. We have previously performed two independent serial backcross experiments to introgress ivermectin resistance loci from two H. contortus ivermectin-resistant strains – MHco4(WRS) and MHco10(CAVR) – into the genetic background of the ivermectin-susceptible genome reference strain MHco3(ISE). We have interrogated a number of candidate ivermectin resistance loci in the resulting backcross populations and assessed the evidence for their genetic linkage to an ivermectin resistance locus. These include the microsatellite marker Hcms8a20 and six candidate genes Hco-glc-5 , Hco-avr-14 , Hco-lgc-37 (previously designated Hco-hg-1 ), Hco-pgp-9 (previously designated Hco-pgp-1) , Hco-pgp-2 and Hco-dyf-7 . We have sampled the haplotype diversity of amplicon markers within, or adjacent to, each of these loci in the parental strains and fourth generation backcross populations to assess the evidence for haplotype introgression from the resistant parental strain into the genomic background of the susceptible parental strain in each backcross. The microsatellite Hcms8a20 locus showed strong evidence of such introgression in both independent backcrosses, suggesting it is linked to an important ivermectin resistance mutation in both the MHco4(WRS) and MHco10(CAVR) strains. In contrast, Hco-glc-5 , Hco-avr-14 , Hco-pgp-9 and Hco-dyf-7 showed no evidence of introgression in either backcross. Hco-lgc-37 and Hco-pgp-2 showed only weak evidence of introgression in the MHco3/4 backcross but not in the MHco3/10 backcross. Overall, these results suggest that microsatellite marker Hcms8a20, but not the other candidate genes tested, is linked to a major ivermectin resistance locus in the MHco4(WRS) and MHco10(CAVR) strains. This work also emphasises the need for genome-wide approaches to identify mutations responsible for the ivermectin resistance in this parasite. [ABSTRACT FROM AUTHOR]

Background: A subgroup of individuals becomes entrenched in a “revolving door” involving corrections, health, and social welfare services. Little research has investigated the numbers of people that are in frequent contact with multiple public agencies, the costs associated with these encounters, or the characteristics of the people concerned. The present study used linked administrative data to examine offenders who were also very frequent users of health and social services. We investigated the magnitude and distribution of costs attributable to different categories of service for those in the top 10 % of sentences to either community or custodial settings. We hypothesized that the members of these subgroups would be significantly more likely to have substance use and other mental disorders than other members of the offender population. Methods: Data were linked across agencies responsible for services to the entire population of British Columbia spanning justice, health, and income assistance. Individuals were eligible for inclusion in the study if they were sentenced at least once in the Vancouver Provincial Court between 2003 and 2012. We examined the subset of participants who fell within the top 10 % of sentences and at least two of the following service categories: community physician services; hospital days; pharmaceutical costs; or income assistance between 2007 and 2012. We examined two groups of offenders separately (those in the top ten percent sentenced to community supervision or to custody) due to differences in time at risk and availability to receive community-based services. Results: From more than 14,000 offenders sentenced in Vancouver's Downtown Eastside, very High Frequency service users associated with community (n = 216) and custody (n = 107) sentences incurred average attributable public service costs of $168,000 and $247,000 respectively over a 5-year period of observation. Health-related costs for both groups were over $80,000 per person, primarily associated with hospital admissions. Across both groups, 99 % had been diagnosed with at least one mental disorder and over 80 % had co-occurring substance use and another mental disorder. Conclusions: A subset of offenders with concurrent psychiatric disorders receives extremely high levels of service from health, social welfare, and justice sectors in close temporal succession. Members of this subpopulation require targeted supports in order to produce positive outcomes and prevent the perpetuation of a costly and ineffective revolving door. [ABSTRACT FROM AUTHOR]

Background: The majority of Drug Treatment Court (DTC) research has examined the impact of DTCs on criminal recidivism. Comparatively little research has addressed the association between DTC participation and engagement with community-based health and social services. The present study investigated changes in participant involvement with outpatient healthcare and income assistance within a DTC cohort. We hypothesized that involvement with community-based (outpatient) health and social services would increase post-DTC participation, and that service levels would be higher among program graduates and offenders with histories of co-occurring mental and substance use disorders.Methods: Participants were 631 offenders at the DTC in Vancouver, Canada (DTCV). Administrative data representing hospital, outpatient medical care, and income assistance were examined one-year pre/post program to assess differences over time. Generalized estimating equations were used to investigate the association between changes in service use and program involvement. We also examined the relationship between level of service use and offender characteristics.Results: Members of the cohort were disproportionately Aboriginal (33 %), had been sentenced 2.7 times in the 2 years preceding their index offence, and 50 % had been diagnosed with a non substance-related mental disorder in the five years preceding the index offence. The mean number of outpatient services post DTCV was 51, and the mean amount of social assistance paid was $5,897. Outpatient service use increased following exposure to DTCV (Adjusted Rate Ratio (ARR) = 1.45) and was significantly higher among women (ARR = 1.47), program graduation (ARR = 1.23), and those previously diagnosed with concurrent substance use and mental disorders (ARR = 4.92). Overall, hospital admissions did not increase post-program, although rates were significantly higher among women (ARR = 1.76) and those with concurrent disorders (ARR = 2.71). Income assistance increased significantly post program (ARR = 1.16), and was significantly higher among women (ARR = 1.03), and those diagnosed with substance use disorders (ARR = 1.42) and concurrent disorders (ARR = 1.72).Conclusions: These findings suggest that the DTCV was a catalyst for increased participant engagement with community health and social supports, and that rates of service use were consistently higher among women and individuals with concurrent disorders. Research is needed to investigate the potential link between health and social support and reductions in recidivism associated with DTCs. [ABSTRACT FROM AUTHOR]

Drug Treatment Courts (DTCs) integrate therapeutic interventions for substance using offenders with the administration of justice. Available evidence indicates that DTCs are effective at reducing recidivism, but it is not yet established whether they are equally effective for all subgroups of offenders. The current study investigates the comparative effectiveness of a Canadian DTC among subgroups defined by ethnicity, gender, prior offending, and the presence of a co-occurring mental disorder. Results indicate greater reductions in recidivism among female and Aboriginal participants, and no differences in recidivism associated with the presence or absence of co-occurring mental disorders or the number of prior convictions. Longer duration of involvement with the DTC program was positively associated with reduced recidivism. The effectiveness of DTCs with distinct subpopulations may be related to their composition and inclusion of expertise relevant to the needs of diverse participants. [ABSTRACT FROM PUBLISHER]

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 [ABSTRACT FROM AUTHOR]

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]

The acetylated and amidated hexapeptide FRWWHR (combi-2), previously identified by combinatorial chemistry methods, shows strong antimicrobial activity. The binding of the peptide to 1-palmitoyl-2-oleoyl-sn-glycero-3-[(phospho-rac-(1-glycerol)] (POPG) and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) vesicles was studied using fluorescence spectroscopy and isothermal titration calorimetry (ITC). Differential scanning calorimetry (DSC) with dipalmitoylphosphatidylcholine (DPPC) and dipalmitoylphosphatidylglycerol (DPPG) multilamellar vesicles was performed to determine changes in the lipid phase behaviour upon binding the peptide. Two-dimensional proton nuclear magnetic resonance (NMR) spectroscopy, to solve the bound peptide structure, was performed in the presence of dodecylphosphatidylcholine (DPC) and sodium dodecyl sulphate (SDS) micelles. The fluorescence, ITC and DSC studies indicate that the peptide interacts preferentially with lipid vesicles containing negatively charged head groups. Conformational information determined using NMR indicate that the combi-2 peptide adopts a coiled amphipathic conformation when bound to SDS and DPC micelles. Leakage assays indicate that the peptide is not very efficient at causing leakage from calcein-filled large unilamellar vesicles comprised of POPG/POPC (1 : 1). The rapid passage of either the fluorescent-tagged peptides combi-2 or the previously studied peptide Ac-RRWWRF-NH2 (combi-1) intoEscherichia coliandStaphylococcus aureussuggests that instead of membrane disruption, the main bactericidal site of action of these peptides might be located inside bacteria. [ABSTRACT FROM AUTHOR]

Background: Opioid overdose deaths have become a public health crisis in North America, and those who are homeless are particularly vulnerable. Methadone maintenance treatment (MMT) may prevent overdose and death among homeless people with opioid dependence, but suboptimal medication adherence is a common limitation. Previous research found that Housing First (HF) increases antipsychotic medication adherence among formerly homeless people. However, no experimental trials have examined whether HF has a significant impact on MMT adherence. We examined the intervention effect of HF on MMT adherence in a randomized sample of homeless adults experiencing mental illness and opioid dependence in Vancouver, Canada.Methods: Comprehensive administrative and self-reported data from homeless adults living with serious mental illness recruited to the Vancouver At Home study were analyzed. Only methadone recipients were included (n = 97). The medication possession ratio (MPR) was utilized as the measure of adherence, and relevant data were obtained from provincial administrative pharmacy records. Study arms were HF and treatment as usual (TAU). Student t-tests were used to test for differences in MMT MPR between HF and TAU.Results: No significant differences were observed in MMT MPR between participants in HF and TAU (0.52 vs. 0.57, p = 0.559) in the post-randomization period.Conclusion: HF was not associated with significantly different MMT MPR compared to TAU. Additional interventions are indicated as HF alone was insufficient to facilitate improved MMT adherence among formerly homeless adults experiencing concurrent opioid dependence and serious mental illness. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective: This study examines key themes from narrative interviews conducted with 43 homeless adults with mental disorders 18 months after random assignment to Housing First with intensive supports or to treatment as usual (no housing or supports through the study). Method: Coding and thematic analysis of semistructured interviews was based on 2 research questions from participants' perspectives: (a) What changes were perceived over time? (b) What factors facilitated or hindered change? Results: The majority of participants assigned to Housing First reported positive change across multiple domains as a result of stable housing; whereas the majority of treatment as usual participants reported negative or neutral change. Key themes included feelings of security and pride; adjusting to living alone; housing as a learning process; and developing meaningful activity. The sense of security associated with stable housing was the most influential factor that supported change. Factors that helped or hindered change clustered into 4 key themes: the type and quality of services; the cumulative effects of trauma; social ties; and concurrent substance use. Conclusions and Implications for Practice: Our findings provide important context to the emerging body of quantitative research on Housing First and recovery from homelessness. Participants' experiences of recovery, particularly as it relates to housing and supports, shifts in identity, and meaningful activity must be acknowledged and incorporated into the design and evaluation of public services, and policy and service reforms. [ABSTRACT FROM AUTHOR]

The article reports the framework of long noncoding Ribonucleic acid RNA for a neuronal granule. It provides information on the functions of a condensate independently of its constituent proteins to maintain nervous system maturity. It shows how Drosophila long noncoding RNA, mimi, is required to scaffold large neuronal granules in the adult nervous system.

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<0.001), primarily comprised of significant reductions in property offences (p<0.001). Conclusions: Our findings indicate that CMT achieved significantly greater reductions in recidivism than traditional court among offenders with complex needs and high numbers of previous offences. Limitations of this research include a non-experimental design and one year follow up. Strengths include a robust matching process and extensive client level data spanning multiple sectors. Further research is needed to replicate the observed outcomes, to investigate the extension of community courts to settings with divergent offender needs and local resources, and to estimate potential cost avoidance attributable to this intervention. [ABSTRACT FROM AUTHOR]

Background: Anterior cruciate ligament (ACL) reconstruction (ACLR) has higher failure rates in young active patients returning to sports as compared with older, less active individuals. Augmentation of ACLR with an anterolateral procedure has been shown to reduce failure rates; however, indications for this procedure have yet to be clearly defined. Purpose/Hypothesis: The purpose of this study was to identify predictors of ACL graft failure in high-risk patients and determine key indications for when hamstring ACLR should be augmented by a lateral extra-articular tenodesis (LET). We hypothesized that different preoperative characteristics and surgical variables may be associated with graft failure characterized by asymmetric pivot shift and graft rupture. Study Design: Case-control study; Level of evidence, 3. Methods: Data were obtained from the Stability 1 Study, a multicenter randomized controlled trial of young active patients undergoing autologous hamstring ACLR with or without a LET. We performed 2 multivariable logistic regression analyses, with asymmetric pivot shift and graft rupture as the dependent variables. The following were included as predictors: LET, age, sex, graft diameter, tear chronicity, preoperative high-grade knee laxity, preoperative hyperextension on the contralateral side, medial meniscal repair/excision, lateral meniscal repair/excision, posterior tibial slope angle, and return-to-sports exposure time and level. Results: Of the 618 patients in the Stability 1 Study, 568 with a mean age of 18.8 years (292 female; 51.4%) were included in this analysis. Asymmetric pivot shift occurred in 152 (26.8%) and graft rupture in 43 (7.6%). The addition of a LET (odds ratio [OR], 0.56; 95% CI, 0.37-0.83) and increased graft diameter (OR, 0.62; 95% CI, 0.44-0.87) were significantly associated with lower odds of asymmetric pivot shift. The addition of a LET (OR, 0.40; 95% CI, 0.18-0.91) and older age (OR, 0.83; 95% CI, 0.72-0.96) significantly reduced the odds of graft rupture, while greater tibial slope (OR, 1.15; 95% CI, 1.01-1.32), preoperative high-grade knee laxity (OR, 3.27; 95% CI, 1.45-7.41), and greater exposure time to sport (ie, earlier return to sport) (OR, 1.18; 95% CI, 1.08-1.29) were significantly associated with greater odds of rupture. Conclusion: The addition of a LET and larger graft diameter were significantly associated with reduced odds of asymmetric pivot shift. Adding a LET was protective of graft rupture, while younger age, greater posterior tibial slope, high-grade knee laxity, and earlier return to sport were associated with increased odds of graft rupture. Orthopaedic surgeons should consider supplementing hamstring autograft ACLR with a LET in young active patients with morphological characteristics that make them at high risk of reinjury. [ABSTRACT FROM AUTHOR]

Background: Persistent anterolateral rotatory laxity after anterior cruciate ligament (ACL) reconstruction (ACLR) has been correlated with poor clinical outcomes and graft failure. Hypothesis: We hypothesized that a single-bundle, hamstring ACLR in combination with a lateral extra-articular tenodesis (LET) would reduce the risk of ACLR failure in young, active individuals. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: This is a multicenter, prospective, randomized clinical trial comparing a single-bundle, hamstring tendon ACLR with or without LET performed using a strip of iliotibial band. Patients 25 years or younger with an ACL-deficient knee were included and also had to meet at least 2 of the following 3 criteria: (1) grade 2 pivot shift or greater, (2) a desire to return to high-risk/pivoting sports, (3) and generalized ligamentous laxity (GLL). The primary outcome was ACLR clinical failure, a composite measure of rotatory laxity or a graft rupture. Secondary outcome measures included the P4 pain scale, Marx Activity Rating Scale, Knee injury Osteoarthritis and Outcome Score (KOOS), International Knee Documentation Committee score, and ACL Quality of Life Questionnaire. Patients were reviewed at 3, 6, 12, and 24 months postoperatively. Results: A total of 618 patients (297 males; 48%) with a mean age of 18.9 years (range, 14-25 years) were randomized. A total of 436 (87.9%) patients presented preoperatively with high-grade rotatory laxity (grade 2 pivot shift or greater), and 215 (42.1%) were diagnosed as having GLL. There were 18 patients lost to follow-up and 11 who withdrew (~5%). In the ACLR group, 120/298 (40%) patients sustained the primary outcome of clinical failure, compared with 72/291 (25%) in the ACLR+LET group (relative risk reduction [RRR], 0.38; 95% CI, 0.21-0.52; P <.0001). A total of 45 patients experienced graft rupture, 34/298 (11%) in the ACLR group compared with 11/291 (4%) in the ACL+LET group (RRR, 0.67; 95% CI, 0.36-0.83; P <.001). The number needed to treat with LET to prevent 1 patient from graft rupture was 14.3 over the first 2 postoperative years. At 3 months, patients in the ACLR group had less pain as measured by the P4 (P =.003) and KOOS (P =.007), with KOOS pain persisting in favor of the ACLR group to 6 months (P =.02). No clinically important differences in patient-reported outcome measures were found between groups at other time points. The level of sports activity was similar between groups at 2 years after surgery, as measured by the Marx Activity Rating Scale (P =.11). Conclusion: The addition of LET to a single-bundle hamstring tendon autograft ACLR in young patients at high risk of failure results in a statistically significant, clinically relevant reduction in graft rupture and persistent rotatory laxity at 2 years after surgery. Registration: NCT02018354 (ClinicalTrials.gov identifier) [ABSTRACT FROM AUTHOR]

Objective: 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). Methods: 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. Results: 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<0.001) and 74.5% in SHF (95% CI = 69.2, 79.7, p<0.001). Secondary outcomes favoured CHF but not SHF compared to TAU. Conclusion: HF in scattered and congregate formats is capable of achieving housing stability among people experiencing major mental illness and chronic homelessness. Only CHF was associated with improvement on select secondary outcomes. Registration: Current Controlled Trials: . [ABSTRACT FROM AUTHOR]

Background: Self-reported service use is an integral feature of interventional research with people who are homeless and mentally ill. The objective of this study was to investigate the accuracy of self-reported involvement with major categories of publicly funded services (health, justice, social welfare) within this sub-population. Methods: Measures were administered pre-randomization in two randomized controlled trials, using timeline follow back with calendar aids for Health, Social, and Justice Service Use, compared to linked administrative data. Variables examined were: psychiatric admissions (both extended stays of more than 6 months and two or more stays within 5 years); emergency department visits, general hospitalization and jail in the past 6 months; and income assistance in the past 1 month. Participants (n = 433) met criteria for homelessness and a least one mental illness. Results: Prevalence adjusted and bias adjusted kappa (PABAK) values ranged between moderate and almost perfect for extended psychiatric hospital separations (PABAK: 0.77; 95 % confidence interval (CI) = 0.71, 0.83), multiple psychiatric hospitalizations (PABAK = 0.50, 95 % CI = 0.41, 0.59), emergency department visits (PABAK: 0.77; 95 % CI = 0.71, 0.83), jail (PABAK: 0.74; 95 % CI = 0.68, 0.81), and income assistance (PABAK: 0.82; 95 % CI = 0.76, 0.87). Significant differences in under versus over reporting were alsofound. Conclusions: People who are homeless and mentally ill reliably reported their overall use of health, justice, and income assistance services. Evidence of under-reporting and over-reporting of certain variables has implications for specific research questions. ISRCTN registry: 57595077 (Vancouver at Home Study: Housing First plus Assertive Community Treatment versus congregate housing plus supports versus treatment as usual); and 66721740 (Vancouver at Home study: Housing First plus Intensive Case management versus treatment as usual). [ABSTRACT FROM AUTHOR]

Background: Anatomic anterolateral ligament (ALL) reconstruction has been proposed to assist anterior cruciate ligament (ACL) reconstruction in controlling anterolateral rotational laxity of the knee. However, the biomechanical effects have not been reported. Purpose: (1) To investigate the effect of ALL transection on rotational knee kinematics and (2) to determine the effect on knee biomechanics of ALL reconstruction procedures compared with lateral extra-articular tenodesis (LET). Study Design: Controlled laboratory study. Methods: A total of 12 cadaveric knee specimens were tested in the following sequence: (1) ACLintact, (2) anteromedial bundle of ACL sectioned (ACLamb), (3) complete ACL sectioned (ACLfull), (4) ALL sectioned (ALLsec), (5) anatomic ALL reconstruction (ALLanat), and (6) LET. Biomechanical anterior drawer and Lachman tests were performed in which a 90-N load was applied to the posterior tibia, and anterior translation was measured. A combined load to simulate the early phase of the pivot-shift test was executed in which a 5-N·m internal rotation moment was applied to a fully extended knee; anterior translation and internal rotation were measured. Results: Anterior translation increased across conditions for the biomechanical tests. Internal rotation during the simulated early-phase pivot-shift test was significantly different between ACLfull and ALLsec. Anatomic ALL reconstruction did not significantly reduce internal rotation or anterior translation during the simulated early-phase pivot-shift test. After LET, a significant decrease in anterior translation was found. There was no evidence of overconstraint of the knee with either anatomic ALL reconstruction or LET. Conclusion: The ALL demonstrated a role in controlling anterolateral laxity. LET had a composite effect in governing both anterior and rotational laxity. Anatomic ALL reconstruction did not reduce anterolateral rotational laxity. Clinical Relevance: Profiling the biomechanical characteristics of anterolateral reconstruction is integral to understanding the implications and potential benefit of such an additional procedure to ACL reconstruction. [ABSTRACT FROM AUTHOR]

Haemonchus contortus , a highly pathogenic and economically important parasitic nematode of sheep, is particularly adept at developing resistance to the anthelmintic drugs used in its treatment and control. The basis of anthelmintic resistance is poorly understood for many commonly used drugs with most research being focused on mechanisms involving drug targets or drug efflux. Altered or increased drug metabolism is a possible mechanism that has yet to receive much attention despite the clear role of xenobiotic metabolism in pesticide resistance in insects. The cytochrome P450s (CYPs) are a large family of drug-metabolising enzymes present in almost all living organisms, but for many years thought to be absent from parasitic nematodes. In this paper, we describe the CYP sequences encoded in the H. contortus genome and compare their expression in different parasite life-stages, sexes and tissues. We developed a novel real-time PCR approach based on partially assembled CYP sequences “tags” and confirmed findings in the subsequent draft genome with RNA-seq. Constitutive expression was highest in larval stages for the majority of CYPs, although higher expression was detected in the adult male or female for a small subset of genes. Many CYPs were expressed in the worm intestine. A number of H. contortus genes share high identity with Caenorhabditis elegans CYPs and the similarity in their expression profiles supports their classification as putative orthologues. Notably, H. contortus appears to lack the dramatic CYP subfamily expansions seen in C. elegans and other species, which are typical of CYPs with exogenous roles. However, a small group of H. contortus genes cluster with the C. elegans CYP34 and CYP35 subfamilies and may represent candidate xenobiotic metabolising genes in the parasite. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background Individuals with mental illnesses are overrepresented among the homeless. Housing First (HF) has been shown to promote positive outcomes in this population. However, key questions remain unresolved, including: how to match support services to client needs, the benefits of housing in scattered sites versus single congregate building, and the effectiveness of HF with individuals actively using substances. The present study aimed to recruit two samples of homeless mentally ill participants who differed in the complexity of their needs. Study details, including recruitment, randomization, and follow-up, are presented. Methods Eligibility was based on homeless status and current mental disorder. Participants were classified as either moderate needs (MN) or high needs (HN). Those with MN were randomized to HF with Intensive Case Management (HF-ICM) or usual care. Those with HN were randomized to HF with Assertive Community Treatment (HF-ACT), congregate housing with support, or usual care. Participants were interviewed every 3 months for 2 years. Separate consent was sought to access administrative data. Results Participants met eligibility for either MN (n = 200) or HN (n = 297) and were randomized accordingly. Both samples were primarily male and white. Compared to participants designated MN, HN participants had higher rates of hospitalization for psychiatric reasons prior to randomization, were younger at the time of recruitment, younger when first homeless, more likely to meet criteria for substance dependence, and less likely to have completed high school. Across all study arms, between 92% and 100% of participants were followed over 24 months post-randomization. Minimal significant differences were found between study arms following randomization. 438 participants (88%) provided consent to access administrative data. Conclusion The study successfully recruited participants meeting criteria for homelessness and current mental disorder. Both MN and HN groups had high rates of substance dependence, suicidality, and physical illness. Randomization resulted in no meaningful detectable differences between study arms. [ABSTRACT FROM AUTHOR]

To better elucidate the role of macrophages in bone morphogenetic protein (BMP)-induced bone repair, this study evaluated the effects of macrophages on the migration, metabolic activity and BMP-2-induced osteogenic differentiation of human mesenchymal stem cells (hMSCs). Human monocytes were induced into a macrophage phenotype, and the conditioned media (CM) from undifferentiated monocytes and differentiated macrophages were collected for treatment of hMSCs. Expression levels of osteoblastic marker genes, alkaline phosphatase (ALP) activity and mineral deposition were assessed. The migration of hMSCs was significantly decreased after treatment with the macrophage CM (but not monocyte CM), in a dose-dependent manner. Significant inhibition of hMSC metabolism was observed on days 3 and 7 after treatment with the macrophage CM. The osteoblastic marker genes analyzed (ALP, bone sialoprotein, osteocalcin and runt-related transcription factor-2) after exposure of hMSCs to BMP-2 were all significantly downregulated in cells treated with the macrophage CM. The hMSCs treated with macrophage CM showed significantly decreased enzymatic activity of ALP and calcium content compared with those treated with monocyte CM or basal medium. High levels of interleukin-1β and tumor necrosis factor-α found in macrophage CM may mediate these observed effects on hMSCs. We conclude that macrophage CM suppressed the BMP-2-induced osteogenic differentiation of hMSCs, suggesting that macrophages might contribute to decreased osteogenic effects of BMPs in a clinical setting. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The relationship between the size of the light harvesting antenna to photosystem II (LHCII) and quenching of non‐photochemical and dark level fluorescence was studied in wild‐type rye (Secale cereale L. cv. Musketeer) and barley (Hordeum vulgare L. cv. Gunilla) as well as in the barley chlorophyll b‐less chlorina F2 mutant (H. vulgare L. cv. Dornaria, chlorina‐F2). Exposure for 10 min to an irradiance of 500 μmol m−2 s−1 resulted in a strong (0.71–0.73) non‐photochemical (qs) quenching of the fluorescence yield in wild‐type (WT) material, while the barley chlorina F2‐mutant was quenched to 75% of this level. Relaxation of qs in darkness revealed a fast initial decay, related to relaxation of the high‐energy‐state dependent (qE) part of qs. Etiolated seedlings of rye and barley exposed to intermittent light (IML) for 36 cycles of 2 min light and 118 min darkness had suppressed Chl b and LHCII‐production in both WT rye and barley, while the barley chlorina F2‐mutant became totally devoid of all LHCII‐polypeptides. It was found that the levels of qs and qs were similar in control grown barley chlorina F2 and IML‐grown WT rye and barley, but qs was reduced by 30 to 35% and qs by 50 to 65%, respectively, as compared to control‐grown. WT plants. No significant qs could be detected in IML‐grown barley chlorina F2. It is clear, from these changes in in vivo fluorescence quenching in rye and barley that a significant level of qs is detectable even in the absence of LHCII. Only when the proximal antennae are totally absent, does qE completely disappear. We conclude that the presence of LHCII is not an absolute requirement for qE‐quenching and suggest that distal as well as proximal antenna may contribute to qE in vivo. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Individuals with mental illnesses are overrepresented among the homeless. Housing First (HF) has been shown to promote positive outcomes in this population. However, key questions remain unresolved, including: how to match support services to client needs, the benefits of housing in scattered sites versus single congregate building, and the effectiveness of HF with individuals actively using substances. The present study aimed to recruit two samples of homeless mentally ill participants who differed in the complexity of their needs. Study details, including recruitment, randomization, and follow-up, are presented.Methods: Eligibility was based on homeless status and current mental disorder. Participants were classified as either moderate needs (MN) or high needs (HN). Those with MN were randomized to HF with Intensive Case Management (HF-ICM) or usual care. Those with HN were randomized to HF with Assertive Community Treatment (HF-ACT), congregate housing with support, or usual care. Participants were interviewed every 3 months for 2 years. Separate consent was sought to access administrative data.Results: Participants met eligibility for either MN (n = 200) or HN (n = 297) and were randomized accordingly. Both samples were primarily male and white. Compared to participants designated MN, HN participants had higher rates of hospitalization for psychiatric reasons prior to randomization, were younger at the time of recruitment, younger when first homeless, more likely to meet criteria for substance dependence, and less likely to have completed high school. Across all study arms, between 92% and 100% of participants were followed over 24 months post-randomization. Minimal significant differences were found between study arms following randomization. 438 participants (88%) provided consent to access administrative data.Conclusion: The study successfully recruited participants meeting criteria for homelessness and current mental disorder. Both MN and HN groups had high rates of substance dependence, suicidality, and physical illness. Randomization resulted in no meaningful detectable differences between study arms.Trial Registration: Current Controlled Trials: ISRCTN57595077 (Vancouver at Home study: Housing First plus Assertive Community Treatment versus congregate housing plus supports versus treatment as usual) and ISRCTN66721740 (Vancouver At Home study: Housing First plus Intensive Case Management versus treatment as usual). [ABSTRACT FROM AUTHOR]