Simon Fraser University

VANCOUVER DRUG USERS STUDY: EVALUATING THE NATURAL HISTORY OF INJECTION DRUG USE

LOCALIZED ECONOMIC MODELING TO OPTIMIZE PUBLIC HEALTH STRATEGIES FOR HIV TREATMENT AND PREVENTION

SYNTHETIC BACTERIAL ANALOGS OF MAMMALIAN OLIGOMANNOSE FOR ELICITING NEUTRALIZING ANTIBODIES TO THE HIGH-MANNOSE PATCH ON HIV ENV

TOBACCO COMPANIES, PUBLIC POLICY AND GLOBAL HEALTH

VACCINES THAT REPLICATE THE NEUTRALIZATION-COMPETENT STRUCTURE OF THE GP41 MPER

DAT-EMULATING TARGET TRIALS WITH BIG DATA TO STRENGTHEN THE EVIDENCE BASE FOR THE CLINICAL MANAGEMENT OF OPIOID USE DISORDER - ABSTRACT DAT18-06 IN 2016, FOLLOWING A DRAMATIC INCREASE IN OPIOID-RELATED OVERDOSE DEATHS, THE PROVINCE OF BRITISH COLUMBIA (BC), CANADA DECLARED A PUBLIC HEALTH EMERGENCY. BC REPORTED 1,510 ILLICIT DRUG OVERDOSE DEATHS IN 2018, A RATE OF 31.0 PER 100,000, PLACING IT 10TH AMONG US STATES, EQUAL TO RHODE ISLAND (31.0), BEHIND WEST VIRGINIA (57.8), OHIO (46.3) AND PENNSYLVANIA (44.3) BUT AHEAD OF NEW JERSEY (30.0), MICHIGAN (27.8) AND FLORIDA (25.1). WHILE THE FOUR-FOLD INCREASE IN OVERDOSE DEATHS OBSERVED SINCE 2012 IS LARGELY ATTRIBUTABLE TO THE CONTAMINATION OF FENTANYL AND OTHER SYNTHETIC OPIOIDS IN THE ILLICIT DRUG SUPPLY, MANY DECEDENTS HAD SOUGHT TREATMENT IN THE PAST AND EXPERIENCED RELAPSES. OPIOID AGONIST TREATMENT (OAT) IS AMONG THE MOST EFFECTIVE TOOLS AVAILABLE TO COMBAT THE EPIDEMIC. HOWEVER, OAT UPTAKE AND RETENTION IS SUB-OPTIMAL IN BC AND INTERNATIONALLY, COMPROMISED LARGELY BY SOCIAL AND STRUCTURAL FACTORS BUT ALSO DEVIATIONS FROM EVIDENCE-BASED STANDARDS OF CARE AND FRAGMENTED CARE, PARTICULARLY FOR THOSE WITH CONCURRENT DISORDERS. FURTHERMORE, A NUMBER OF ASPECTS OF CANADIAN AND US CLINICAL GUIDELINES FOR THE MANAGEMENT OF OPIOID USE DISORDER (OUD) ARE BASED ON LIMITED AND LOW-QUALITY EVIDENCE. EVEN BASIC EVIDENCE ON THE COMPARATIVE EFFECTIVENESS OF AVAILABLE TREATMENT OPTIONS OVERALL AND FOR KEY POPULATIONS IN THE FENTANYL ERA IS LACKING. THIS PROPOSAL AIMS TO APPLY CUTTING-EDGE METHODS FOR CAUSAL INFERENCE IN EMULATING A SERIES OF ‘TARGET TRIALS’ IN THREE IMMEDIATE AIMS: (1) TO DETERMINE THE COMPARATIVE EFFECTIVENESS OF METHADONE VERSUS BUPRENORPHINE/NALOXONE FOR DIFFERENT PATIENT SUBGROUPS PRESENTING FOR OAT; (2) TO DETERMINE THE IMPACT OF URINE DRUG SCREENING – A UBIQUITOUS AND NON-EVIDENCE- BASED ELEMENT OF OUD CARE – ON OAT RETENTION AND MORTALITY; AND (3) TO DETERMINE THE COMPLEMENTARY EFFECTS OF OAT ON UPTAKE AND ADHERENCE TO DIRECTING-ACTING ANTIVIRALS FOR PEOPLE WITH OPIOID USE DISORDER (PWOUD) WITH CONCURRENT HEPATITIS C VIRUS. THE ‘TARGET TRIAL’ FRAMEWORK CHANNELS COUNTERFACTUAL THEORY IN PROVIDING A FLEXIBLE BASIS FOR COMPARING THE EFFECTS OF TREATMENT AND CLINICAL MANAGEMENT STRATEGIES ON EITHER AN INTENT-TO-TREAT OR PER-PROTOCOL BASIS. WE HAVE IDENTIFIED A NUMBER OF ADDITIONAL QUESTIONS RELATED TO THE CLINICAL MANAGEMENT OF PWOUD WHERE GUIDELINES ARE SUPPORTED BY WEAKER EMPIRICAL EVIDENCE AND WILL ENDEAVOR TO ANSWER AS MANY OF THESE QUESTIONS AS POSSIBLE, PRIORITIZING ANALYSIS USING A COMMON FRAMEWORK FOCUSED ON METHODOLOGICAL RIGOR AND

HAART OPTIMISM, DRUG USE AND RISKY SEXUAL BEHAVIOR AMONG MSM IN BRITISH COLUMBIA.

AN ETHNO-EPIDEMIOLOGICAL STUDY TO ADVANCE HIV PREVENTION AND TREATMENT FOR PWUD

DEVELOPMENT OF FERROELECTRIC MATERIALS WITH ENHANCED PIEZOELECTRIC AND OPTICAL PROPERTIES VIA DOMAIN ENGINEERING FOR ELECTROMECHANICAL TRANSDUCER APPL

HIGH-PERFORMANCE PIEZO- AND FERROELECTRIC MATERIALS FOR ELECTROMECHANICAL TRANSDUCER APPLICATIONS

DEVELOPMENT OF HIGH-PERFORMANCE PIEZO- AND FERROELECTRIC MATERIALS FOR ELECTROMECHANICAL TRANSDUCER APPLICATIONS

CONTROL OF ENERGY MINIMIZATION IN HUMAN LOCOMOTION.

FERTILITY DESIRE AND PREGNANCY IN A COHORT OF DISCORDANT UGANDAN COUPLES ON ART

GENETICS, DYNAMICS AND FITNESS OF THE HIV-1 LATENT RESERVOIR

DEVELOPMENT OF HIGH-PERFORMANCE PIEZO- AND FERRO-ELECTRIC MATERIALS FOR ELECTROMECHANICAL TRANSDUCTION APPLICATIONS

EXPLORING ANTIBODY RECOGNITION OF THE V3 REGION ON HIV-1 TO GUIDE VACCINE DESIGN

THE NON-FATAL OVERDOSE CRISIS: SEX AND GENDER DIFFERENCES IN HEALTHCARE UTILIZATION AND HEALTH OUTCOMES OF PEOPLE LIVING WITH AND WITHOUT HIV BETWEEN 2012 AND 2020 - PROJECT SUMMARY/ABSTRACT THE OVERDOSE (OD) CRISIS CONTINUES TO DEVASTATE COMMUNITIES ACROSS NORTH AMERICA. DESPITE 90% OF PARAMEDIC- ATTENDED ODS IN BRITISH COLUMBIA (BC), CANADA BEING NON-FATAL, MUCH OF THE RESEARCH HAS FOCUSED ON FATAL ODS. WHILE MEN ACCOUNT FOR OVER 70% OF FATAL ODS, THERE IS EVIDENCE OF A MORE BALANCED DISTRIBUTION OF MEN AND WOMEN EXPERIENCING NON-FATAL ODS (NFODS); FURTHER, WOMEN HAVE HIGHER MORTALITY RATES IN THE YEAR FOLLOWING AN NFOD. PEOPLE LIVING WITH HIV (PLHIV) ARE DISPROPORTIONATELY AFFECTED BY THE OD CRISIS AND ARE AT INCREASED RISK OF FATAL ODS, YET LITTLE IS KNOWN ABOUT THE LONGER-TERM IMPACTS OF NFODS ON PLHIV IN TERMS OF ADVERSE HEALTH OUTCOMES AND HEALTHCARE UTILIZATION (HCU). CONSIDERING THE INCREASINGLY HIGH RATES OF NFODS, GENDERED DIFFERENCES IN MORTALITY FOLLOWING AN NFOD, AND KNOWLEDGE GAPS CONCERNING HEALTH OUTCOMES FOLLOWING AN NFOD, THIS PROPOSAL SEEKS FUNDING TO INVESTIGATE THE ROLE OF SEX, GENDER, AND HIV STATUS IN DIFFERENTIAL NFOD OUTCOMES. BC’S UNIVERSAL HEALTHCARE SYSTEM AND DATA CENTRALIZATION ENABLED THE COMPARATIVE OUTCOMES AND SERVICE UTILIZATION TRENDS (COAST) STUDY, A POPULATION-BASED LONGITUDINAL COHORT COMPRISED OF LINKED ADMINISTRATIVE HEALTH DATASETS ON ALL KNOWN ADULT PLHIV AND A 10% RANDOM SAMPLE OF THE GENERAL POPULATION IN BC. USING COAST, WE AIM TO: (1) GENERATE ESTIMATES FOR THE INCIDENCE RATES OF FATAL AND NONFATAL ODS AMONG PEOPLE LIVING WITH AND WITHOUT HIV (2012-2020) IN BC; (2) ASSESS AND COMPARE CHANGES IN HEALTH CARE UTILIZATION, CHRONIC COMORBIDITY, AND MORTALITY AMONG PEOPLE LIVING WITH AND WITHOUT HIV WHO EXPERIENCED AN NFOD, MODIFIED BY SEX AND GENDER; AND (3) ASSESS AND COMPARE CHANGES IN HIV TREATMENT OUTCOMES IN PEOPLE LIVING WITH HIV WHO EXPERIENCED AN NFOD, MODIFIED BY SEX AND GENDER. THIS PROJECT WILL ALSO INVOLVE THE DEVELOPMENT OF A COMMUNITY ADVISORY BOARD (CAB) FOR PROPOSED AND FUTURE PROJECTS. THE CAB WILL PROVIDE GUIDANCE TO ENSURE RESEARCH SOUNDNESS AND RELEVANCE TO THE COMMUNITY THROUGHOUT THE RESEARCH AND KNOWLEDGE MOBILIZATION PROCESSES. OUR COLLABORATIVE RESEARCH WILL BE AN OPPORTUNITY TO EXPLORE OTHER RESEARCH POSSIBILITIES INITIATED BY THE CAB AS IMPORTANT FOR WOMEN AND GENDER MINORITIES LIVING WITH AND WITHOUT HIV WHO ARE AFFECTED BY THE OD CRISIS. IN RESPONSE TO THE NATIONAL INSTITUTE ON DRUG ABUSE NOTICE OF SPECIAL INTEREST NOT-DA- 21-021 TO ADVANCE RESEARCH SPECIFIC TO WOMEN AND OTHER UNDERREPRESENTED POPULATIONS INCLUDING GENDER MINORITIES, THIS PROPOSAL WILL INFORM FUTURE CAB-LED CYCLES OF INQUIRY AND ANALYSIS AMONGST OUR TEAM TO ANSWER RELEVANT RESEARCH QUESTIONS AND ADDRESS THE IDENTIFIED NEEDS OF CISGENDER WOMEN AND GENDER MINORITIES LIVING WITH AND WITHOUT HIV AFFECTED BY THE OD CRISIS.

RELEVANCE OF SERUM MANNOSIDASE RESISTANCE TO THE SPECIFICITY OF OLIGOMANNOSE-TARGETING ANTIBODIES - PROJECT SUMMARY THE GLYCANS THAT DECORATE THE HIV ENVELOPE GLYCOPROTEIN SPIKE (ENV) ARE CATEGORIZED NOMINALLY AS ‘SELF’ ANTIGENS GIVEN THAT THEY ARE IMPARTED BY THE MAMMALIAN CELL’S GLYCOSYLATION MACHINERY. HOWEVER, GLYCANS OF THE OLIGOMANNOSE-TYPE FOUND ON GP120 ARE MOSTLY CLUSTERED INTO A PATCH, CREATING A ‘NON-SELF’ ARCHITECTURE. THIS OLIGOMANNOSE PATCH IS VULNERABLE TO RECOGNITION BY ANTI-HIV BROADLY NEUTRALIZING ANTIBODIES (BNABS). GIVEN THE POTENCY AND BREADTH OF BNABS TO THE OLIGOMANNOSE PATCH, THERE IS GREAT INTEREST IN DEVELOPING IMMUNIZATION STRATEGIES TO ELICIT SIMILAR BNABS. THIS PROJECT AIMS TO FILL A GAP IN UNDERSTANDING BARRIERS TO THE ELICITATION OF OLIGOMANNOSE-SPECIFIC BNABS. WE AND OTHERS HAVE RECENTLY REPORTED ON A SOLUBLE MANNOSIDASE FOUND IN MAMMALIAN SERUM THAT TRIMS OLIGOMANNOSIDES ON GLYCOCONJUGATES DESIGNED TO ELICIT OLIGOMANNOSE-SPECIFIC ANTIBODIES UPON IMMUNIZATION. SUCH TRIMMING WOULD EXPLAIN WHY IMMUNIZING WITH OLIGOMANNOSIDIC GLYCOCONJUGATES TYPICALLY YIELDS ANTIBODIES THAT BIND WELL TO SUBSTRUCTURES OF OLIGOMANNOSE BUT THAT BIND WITH SUBSTANTIALLY LOWER AVIDITY TO FULL-SIZED OLIGOMANNOSE AS PRESENTED ON ENV; THE LATTER TYPIFIES THE BINDING MANNER OF BNABS THAT TARGET THE OLIGOMANNOSE PATCH. IN THIS APPLICATION, WE PROPOSE TO DETERMINE THE EXTENT TO WHICH SERUM MANNOSIDASE ACTIVITY IS RELEVANT TO THE QUALITY OF OLIGOMANNOSE-SPECIFIC ANTIBODY RESPONSES. SPECIFICALLY, WE INTEND TO CONSTRUCT A MANNOSIDASE-RESISTANT GLYCOSIDE, THUS REPRESENTING THE GREATEST POSSIBLE RESISTANCE TO MANNOSIDASE TRIMMING, AND DETERMINE THE SPECIFICITY OF THE ENSUING ANTIBODY RESPONSE COMPARED TO ITS MANNOSIDASE- SENSITIVE OPPOSITE. THE PROJECT WILL TAKE ADVANTAGE OF OUR PUBLISHED WORK OF A BACTERIALLY INSPIRED MIMIC OF OLIGOMANNOSE THAT, AS A NEOGLYCOCONJUGATE, ELICITS MODEST LEVELS OF HIV-NEUTRALIZING ANTIBODIES. WE WILL INVESTIGATE ANTIBODY RESPONSES AT THE POLYCLONAL SERUM LEVEL AS WELL AS THE MONOCLONAL LEVEL; THE LATTER SHOULD REVEAL SIMILARITIES, IF ANY, BETWEEN THE ELICITED ANTIBODIES AND EXISTING BNABS. IN SUM, WE EXPECT THE RESULTS OF THIS PROJECT TO SHED LIGHT ON BARRIERS TO EVOKING ANTIBODIES WITH CAPACITY TO BIND THE HIGHLY VULNERABLE OLIGOMANNOSE PATCH ON HIV ENV. ALTHOUGH THE DIFFICULTY IN ELICITING OLIGOMANNOSE-SPECIFIC BNABS IS OFTEN ASSUMED TO STEM FROM B CELL TOLERANCE, OUR PRELIMINARY STUDIES PROVIDE EVIDENCE FOR SERUM MANNOSIDASE POSING AT LEAST AN ADDITIONAL HINDRANCE.

DEVELOPMENT OF NOVEL HYBRID ORGANIC-INORGANIC HALIDE PEROVSKITE MATERIALS FOR PIEZOELECTRIC AND MULTIFUNCTIONAL DEVICES

ORIGIN OF ANTIBODIES WITH LONG CDR-H3 LOOPS IN HIV INFECTION & AUTOIMMUNE DISEASE

IDENTIFICATION CHARACTERIZATION AND VALIDATION OF GENETIC MUTATIONS INCURRED DURING IN VITRO ATTENUATION OF MAREK'S DISEASE VIRUS

DEVELOPMENT OF HIGH-PERFORMANCE PIEZO- AND FERROELECTRIC SINGLE CRYSTALS FOR ELECTROMECHANICAL TRANSDUCER APPLICATIONS

THE EFFECT OF NORMOXIC DIVES ON NARCOSIS AND HEART FUNCTION IN HUMAN AND CELLULAR MODELS

PRECLINICAL TESTING OF AN O-GLCNACASE INHIBITOR TO BLOCK NEURODEGENERATION FOR AD

GENETIC ANALYSIS OF IDIOPATHIC-TYPE CURVATURE IN MODEL TELEOSTS

SAWFISH CONSERVATION PLANNING IN EAST AFRICA

AN UNTARGETED NMR METABOLOMICS PLATFORM FOR FUNCTIONAL ANNOTATION OF NATURAL PRODUCT EXTRACTS.

SECURING A FUTURE FOR SAWFISHES: AN EXPERT WORKSHOP AND AWARENESS-RAISING ACTIVITIES

DEVELOPMENT OF PIEZOELECTRIC SINGLE CRYSTALS (PIEZOCRYSTALS) STANDARD

BEHAVIORAL ECOLOGY OF HOST SELECTION BY THE ASIAN LONGHORNED BEETLE: DEVELOPMENT OF A DETECTION METHODS

LAND-USE AND SEDIMENTATION PATTERNS IN SAINT LUCIA IN RELATION TO THEIR IMPACTS ON CORAL REEFS

WORKSHOP ON RELAXOR-BASED PIEZOELECTRIC SINGLE CRYSTALS

BEHAVIORAL ECOLOGY OF HOST SELECTION BY THE ASIAN LONGHORNED BEETLE: DEVELOPMENT OF A DETECTION METHODS

CSP - THE 6TH INTERNATIONAL WORKSHOP ON RELAXOR FERROELECTRICS (IWRF-2018)

CSP - THE 13TH INTERNATIONAL SYMPOSIUM ON FERROIC DOMAINS & MICRO- TO NANO-SCOPIC STRUCTURES (ISFD-13)

EFFECTS OF CLIMATE CHANGE ON MONTANE AMPHIBIANS

THE 20TH IMS NEW RESEARCHERS CONFERENCE

TO COVER TRAVEL COSTS FOR SEVERAL U.S. SPEAKERS TO PARTICIPATE IN CLEAN ENERGY CONFERENCE.

THE AWARD WILL BE USED TO COVER VENUE ROOM RENTAL AND PARTICIPATION OF UP TO EIGHT U.S. AUTHORS (HONORARIUM AND TRAVEL TO PARTICIPATE IN THE READING

IDENTIFICATION, CHARACTERIZATION, AND VALIDATION OF GENETIC MUTATIONS INCURRED DURING IN VITRO ATTENUATION OF MAREK#18;S DISEASE VIRUS

RELIABILITY OF MEASUREMENT TOOLS AND CHALLENGES TO ADHERENCE CLINICAL TRIALS AMON