AR-quiver approach to affine canonical basis elements

AbstractThis is the continuation of [Y. Li, Affine quivers of type A˜n and canonical bases, math.QA/0501175]. We describe the affine canonical basis elements in the case when the affine quiver has arbitrary orientation. This generalizes the description in [G. Lusztig, Affine quivers and canonical bases, Publ. Math. Inst. Hautes Études Sci. 76 (1992) 111–163]

Sequencing of the Hepatitis C Virus: A Systematic Review

Since the identification of hepatitis C virus (HCV), viral sequencing has been important in understanding HCV classification, epidemiology, evolution, transmission clustering, treatment response and natural history. The length and diversity of the HCV genome has resulted in analysis of certain regions of the virus, however there has been little standardisation of protocols. This systematic review was undertaken to map the location and frequency of sequencing on the HCV genome in peer reviewed publications, with the aim to produce a database of sequencing primers and amplicons to inform future research. Medline and Scopus databases were searched for English language publications based on keyword/MeSH terms related to sequence analysis (9 terms) or HCV (3 terms), plus "primer" as a general search term. Exclusion criteria included non-HCV research, review articles, duplicate records, and incomplete description of HCV sequencing methods. The PCR primer locations of accepted publications were noted, and purpose of sequencing was determined. A total of 450 studies were accepted from the 2099 identified, with 629 HCV sequencing amplicons identified and mapped on the HCV genome. The most commonly sequenced region was the HVR-1 region, often utilised for studies of natural history, clustering/transmission, evolution and treatment response. Studies related to genotyping/classification or epidemiology of HCV genotype generally targeted the 5'UTR, Core and NS5B regions, while treatment response/resistance was assessed mainly in the NS3-NS5B region with emphasis on the Interferon sensitivity determining region (ISDR) region of NS5A. While the sequencing of HCV is generally constricted to certain regions of the HCV genome there is little consistency in the positioning of sequencing primers, with the exception of a few highly referenced manuscripts. This study demonstrates the heterogeneity of HCV sequencing, providing a comprehensive database of previously published primer sets to be utilised in future sequencing studies

Molecular epidemiology of hepatitis C virus infection among people who inject drugs

Background: While the factors associated with acquisition of hepatitis C virus (HCV) among people who inject drugs (PWID) are well described, an enhanced understanding of HCV transmission is required. Aims: The broad aim of this research was to investigate the molecular epidemiology of HCV infection among PWID. Specific aims included the evaluation of HCV genome sequencing in the literature; evaluation of the degree of variability in the design of HCV sequencing reactions; to investigate phylogenetic clustering of HCV and associated factors among participants in a prospective cohort of PWID in Vancouver, Canada; and to investigate whether HCV infection among younger injectors occurs as a result of few or many transmission events from older injectors to younger injectors among PWID in Vancouver, Canada.Methods: In Chapter Two, data from a systematic review of HCV genome sequencing in the literature were analysed, including production of a comprehensive database containing primers from each accepted manuscript. In Chapter Three, data from the Vancouver Injection Drug User Study (VIDUS) were analysed, using maximum likelihood phylogenetic and logistic regression methods. In Chapter Four, data from the VIDUS and At-Risk Youth Study (ARYS) were analysed, using Bayesian phylogenetic inference, compartmentalisation (Association Index) and logistic regression methods. Key Finding: From the review of HCV sequencing, there was great heterogeneity in the positioning of population sequencing amplicons in studies performed to date. Phylogenetic clustering was common in the VIDUS cohort of PWID in Vancouver, and was independently associated with recent HCV seroconversion, HIV co-infection, younger age and recent syringe borrowing. The combined analysis of VIDUS and ARYS demonstrates that HCV transmission among PWID is complex and multifaceted, with transmission occurring both between and within older and younger PWID. Conclusion: Standardisation of HCV sequencing methodologies will strengthen future HCV virological research and improve collaboration across HCV research disciplines. In the era of highly effective direct acting antivirals, targeted intervention and public health strategies will rely on evidence-based assessment of HCV transmission and acquisition to maximise outcomes. Further research should focus on the integration of phylogenetic, clinical, epidemiological and network analyses to best inform treatment as prevention and intervention studies

Detection of serological markers of infection in cadaveric specimens

The use of serological screening assays is critical in ensuring the safety of transplantations for recipients in regards to transmission of infectious agents. As there are a greater number of patients awaiting transplantation than there are human tissue and cell based products available, an alternative to living donors is required. One potential source is the retrieval of materials from deceased donors. The quality of cadaveric specimens for infectious disease testing may differ from living donor, potentially affecting serological screening results. The present study aimed to identify changes in venous blood samples of cadaver donors that may influence the accuracy of testing by determining the overall rate of plasma dilution, through measurement of serum albumin, immunoglobulins G and M, and total proteins. While there was a significant difference in the mean and variance of total protein concentration in cadaveric and control donors and a significant difference in the variance of albumin concentration in the two populations, no significant difference was found in the mean concentrations of IgG, IgM or albumin between these groups. The relationship between biochemical marker concentrations and post-mortem interval was not significant for any markers. These results support previously published data that suggest negligible dilution of markers of infection occurs after death.Screening for serological markers of infection in the specimens collected using the Abbott Architect platform revealed a greater number of reactive results for human immunodeficiency virus (HIV Ag/Ab), hepatitis C virus (anti-HCV) and hepatitis B virus (anti-HBc) than the general Sydney community. Clinical and analytical sensitivity was found to be comparable for inoculated cadaveric and random living donors for the Abbott Architect HIV Ag/Ab, anti-HCV, anti-HBc II and HBsAg assays, demonstrating the suitability of cadaveric specimens in the detection of serological markers of infection.From this study it can be said that specimens collected from deceased donors are comparable to living donors in terms of plasma concentration of biochemical and serological markers, and that while false-reactive results may be more frequent than in living donors, inhibition of these assays does not occur

Prevalence and correlates of experiencing drug-related discrimination among people who use drugs presenting at emergency department at high risk of opioid overdose

Objectives: Our objective is to determine if specific sociodemographic characteristics were associated with perceived drug-related discrimination among people who use drugs (PWUD) presenting for care in the emergency department (ED). Methods: We conducted a secondary analysis of data from the Navigator trial, a randomized control trial of two behavioral interventions in the ED for people at risk of an opioid overdose. Participants included adult patients presenting to two Rhode Island EDs. Eligible participants included those high risk for an opioid overdose, resided or received most of their healthcare in Rhode Island, and were able to provide consent. The primary outcome of this analysis was self-reported feelings of drug-related discrimination by the medical community. The independent variables of interest included race/ethnicity, gender identity, and sexual orientation. Log-binomial multivariable regression models were constructed with all three independent variables of interest and a selection of sociodemographic covariates. Results: Of 620 eligible participants, 251 (40.5%) reported ever experiencing drug-related discrimination in their lifetime. In the adjusted model, participants who identified as women and participants who identified as LGBQIA+ were more likely to report experiencing drug-related discrimination from the medical community in EDs. Racial/ethnic minority groups were less likely than White (non-Hispanic) participants to report drug-related discrimination. Discussion: In this study population, White participants reported more drug-related discrimination than their minority counterparts, although female and LGBQIA+ patients reported more discrimination. Future studies should further assess the significance of these intersecting identities on self-reported discrimination. This knowledge could improve ED-based interventions, policies, and services for PWUD

Trends in methamphetamine and opioid use among clients of needle-syringe programs in Queensland, Australia: 2007-2015

Introduction and Aims: Needle-syringe programs (NSP) are an underutilized source of data on drug injection trends; these data are essential for informing public health interventions. We examine trends in NSP service occasions from 2007-2015. Design and Methods: Using standardised data from 26 NSP outlets through the Queensland NSP Minimum Data Set (QNSPMDS), trends in service occasions among clients intending to inject methamphetamine, heroin, opioid substitution therapy (OST) medications and other pharmaceutical opioids were assessed using multilevel mixed-effects negative binomial regression, adjusting for month, year, age and clustering by site. Results: Over 1.5 million service occasions were recorded in 2007-2015. Methamphetamine was the main \u27drug intended to inject\u27 (33.7%), however cf. 2007, the incidence rate ratio decreased to 0.64 (95% CI: 0.62, 0.66) in 2009, remaining low until 2015. Among clients reporting methamphetamine injection, there was a shift in the form from base to the higher-potency crystal methamphetamine since 2012. Heroin injection (22.5% service occasions) initially increased (cf. 2007), followed by a decline to 0.77 (95% CI: 0.75, 0.79) in 2015. Significant and sustained increases in OST and other pharmaceutical opioids injection were observed throughout the study period, accounting for 7.2% and 19.8% of total visits, respectively. Discussion and Conclusions: The QNSPMDS provides unique, routinely collected, jurisdiction-wide and standardised data on the demographics of people who inject drugs, types of drugs injected and regional variations; these data are essential in informing policy, planning and program implementation. There remains significant opportunity to enhance engagement and linkage to care alongside needle-syringe provision

Trends in methamphetamine and opioid use among clients of needle-syringe programs in Queensland, Australia: 2007-2015

Introduction and Aims: Needle-syringe programs (NSP) are an underutilized source of data on drug injection trends; these data are essential for informing public health interventions. We examine trends in NSP service occasions from 2007-2015. Design and Methods: Using standardised data from 26 NSP outlets through the Queensland NSP Minimum Data Set (QNSPMDS), trends in service occasions among clients intending to inject methamphetamine, heroin, opioid substitution therapy (OST) medications and other pharmaceutical opioids were assessed using multilevel mixed-effects negative binomial regression, adjusting for month, year, age and clustering by site. Results: Over 1.5 million service occasions were recorded in 2007-2015. Methamphetamine was the main \u27drug intended to inject\u27 (33.7%), however cf. 2007, the incidence rate ratio decreased to 0.64 (95% CI: 0.62, 0.66) in 2009, remaining low until 2015. Among clients reporting methamphetamine injection, there was a shift in the form from base to the higher-potency crystal methamphetamine since 2012. Heroin injection (22.5% service occasions) initially increased (cf. 2007), followed by a decline to 0.77 (95% CI: 0.75, 0.79) in 2015. Significant and sustained increases in OST and other pharmaceutical opioids injection were observed throughout the study period, accounting for 7.2% and 19.8% of total visits, respectively. Discussion and Conclusions: The QNSPMDS provides unique, routinely collected, jurisdiction-wide and standardised data on the demographics of people who inject drugs, types of drugs injected and regional variations; these data are essential in informing policy, planning and program implementation. There remains significant opportunity to enhance engagement and linkage to care alongside needle-syringe provision

Flow diagram describing the review process and study selection.

<p>Flow diagram describing the review process and study selection.</p

A randomized clinical trial of a theory-based fentanyl overdose education and fentanyl test strip distribution intervention to reduce rates of opioid overdose: study protocol for a randomized controlled trial

Background: Opioid overdose deaths involving synthetic opioids, particularly illicitly manufactured fentanyl, remain a substantial public health concern in North America. Responses to overdose events (e.g., administration of naloxone and rescue breathing) are effective at reducing mortality; however, more interventions are needed to prevent overdoses involving illicitly manufactured fentanyl. This study protocol aims to evaluate the effectiveness of a behavior change intervention that incorporates individual counseling, practical training in fentanyl test strip use, and distribution of fentanyl test strips for take-home use among people who use drugs. Methods: Residents of Rhode Island aged 18–65 years who report recent substance use (including prescription pills obtained from the street; heroin, powder cocaine, crack cocaine, methamphetamine; or any drug by injection) (n = 500) will be recruited through advertisements and targeted street-based outreach into a two-arm randomized clinical trial with 12 months of post-randomization follow-up. Eligible participants will be randomized (1:1) to receive either the RAPIDS intervention (i.e., fentanyl-specific overdose education, behavior change motivational interviewing (MI) sessions focused on using fentanyl test strips to reduce overdose risk, fentanyl test strip training, and distribution of fentanyl test strips for personal use) or standard overdose education as control. Participants will attend MI booster sessions (intervention) or attention-matched control sessions at 1, 2, and 3 months post-randomization. All participants will be offered naloxone at enrolment. The primary outcome is a composite measure of self-reported overdose in the previous month at 6- and/or 12-month follow-up visit. Secondary outcome measures include administratively linked data regarding fatal (post-mortem investigation) and non-fatal (hospitalization or emergency medical service utilization) overdoses. Discussion: If the RAPIDS intervention is found to be effective, its brief MI and fentanyl test strip training components could be easily incorporated into existing community-based overdose prevention programming to help reduce the rates of fentanyl-related opioid overdose. Trial registration ClinicalTrials.gov NCT04372238 . Registered on 01 May 2020Medicine, Faculty ofNon UBCPopulation and Public Health (SPPH), School ofReviewedFacult