Health Sciences, Faculty of

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The ‘Stolen Generations' of Mothers and Daughters: Child Apprehension and Enhanced HIV Vulnerabilities for Sex Workers of Aboriginal Ancestry

Peer reviewed: 
Yes, item is peer reviewed.
Date created: 
2014-06-13
Abstract: 

Objectives

The number of children in care of the state continues to grow in BC, Canada with a historical legacy of child apprehension among criminalized and marginalized populations, particularly women of Aboriginal ancestry and sex workers. However, there is a paucity of research investigating child apprehension experiences among marginalized mothers. The objective of the current analysis is to examine the prevalence and correlates of child apprehensions among female sex workers in Vancouver, Canada.

Methods

Analyses were drawn from the AESHA (An Evaluation of Sex Workers Health Access, 2010-present), a prospective cohort of street and off-street SWs, through outreach and semi-annual visits to the research office. Bivariate and multivariate logistic regression were used to examine correlates of child apprehension.

Results

Of a total of 510 SWs, 350 women who had given birth to at least one child were included in the analyses (median age = 37 yrs: IQR: 31–44 yrs). The prevalence of child apprehension among mothers was 38.3%, with 37.4% reporting having been apprehended themselves by child welfare services. In multivariable analysis, servicing clients in outdoor public spaces (versus formal sex work establishments or informal indoor settings) (adjusted odds ratio, (aOR) = 2.73; 95%CI 1.27–5.90), history of injecting drugs (aOR = 2.53; 95%CI 1.42–4.49), Aboriginal ancestry (aOR = 1.66; 95%CI 1.01–2.74) were associated with increased odds of child apprehension.

Discussion/Conclusions

Child apprehension rates are high, particularly among the most marginalized sex workers, including sex workers who use drugs and sex workers of Aboriginal ancestry. Structural reforms to child protection are urgently needed, that support family-based care address the historical legacy of colonization affecting Aboriginal peoples.

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A TRIP230-Retinoblastoma Protein Complex Regulates Hypoxia-Inducible Factor-1α-Mediated Transcription and Cancer Cell Invasion

Peer reviewed: 
Yes, item is peer reviewed.
Date created: 
2014-06-11
Abstract: 

Localized hypoxia in solid tumors activates transcriptional programs that promote the metastatic transformation of cells. Like hypoxia-inducible hyper-vascularization, loss of the retinoblastoma protein (Rb) is a trait common to advanced stages of tumor progression in many metastatic cancers. However, no link between the role of Rb and hypoxia-driven metastatic processes has been established. We demonstrated that Rb is a key mediator of the hypoxic response mediated by HIF1α/β, the master regulator of the hypoxia response, and its essential co-activator, the thyroid hormone receptor/retinoblastoma-interacting protein (TRIP230). Furthermore, loss of Rb unmasks the full co-activation potential of TRIP230. Using small inhibitory RNA approaches in vivo, we established that Rb attenuates the normal physiological response to hypoxia by HIF1α. Notably, loss of Rb results in hypoxia-dependent biochemical changes that promote acquisition of an invasive phenotype in MCF7 breast cancer cells. In addition, Rb is present in HIF1α-ARNT/HIF1β transcriptional complexes associated with TRIP230 as determined by co-immuno-precipitation, GST-pull-down and ChIP assays. These results demonstrate that Rb is a negative modulator of hypoxia-regulated transcription by virtue of its direct effects on the HIF1 complex. This work represents the first link between the functional ablation of Rb in tumor cells and HIF1α-dependent transcriptional activation and invasion.

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Epigenetic Characterization of the Growth Hormone Gene Identifies SmcHD1 as a Regulator of Autosomal Gene Clusters

Peer reviewed: 
Yes, item is peer reviewed.
Date created: 
2014-05-12
Abstract: 

Regulatory elements for the mouse growth hormone (GH) gene are located distally in a putative locus control region (LCR) in addition to key elements in the promoter proximal region. The role of promoter DNA methylation for GH gene regulation is not well understood. Pit-1 is a POU transcription factor required for normal pituitary development and obligatory for GH gene expression. In mammals, Pit-1 mutations eliminate GH production resulting in a dwarf phenotype. In this study, dwarf mice illustrated that Pit-1 function was obligatory for GH promoter hypomethylation. By monitoring promoter methylation levels during developmental GH expression we found that the GH promoter became hypomethylated coincident with gene expression. We identified a promoter differentially methylated region (DMR) that was used to characterize a methylation-dependent DNA binding activity. Upon DNA affinity purification using the DMR and nuclear extracts, we identified structural maintenance of chromosomes hinge domain containing -1 (SmcHD1). To better understand the role of SmcHD1 in genome-wide gene expression, we performed microarray analysis and compared changes in gene expression upon reduced levels of SmcHD1 in human cells. Knock-down of SmcHD1 in human embryonic kidney (HEK293) cells revealed a disproportionate number of up-regulated genes were located on the X-chromosome, but also suggested regulation of genes on non-sex chromosomes. Among those, we identified several genes located in the protocadherin β cluster. In addition, we found that imprinted genes in the H19/Igf2 cluster associated with Beckwith-Wiedemann and Silver-Russell syndromes (BWS & SRS) were dysregulated. For the first time using human cells, we showed that SmcHD1 is an important regulator of imprinted and clustered genes.

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Genotypic and Functional Impact of HIV-1 Adaptation to Its Host Population during the North American Epidemic

Peer reviewed: 
Yes, item is peer reviewed.
Date created: 
2014-04-24
Abstract: 

HLA-restricted immune escape mutations that persist following HIV transmission could gradually spread through the viral population, thereby compromising host antiviral immunity as the epidemic progresses. To assess the extent and phenotypic impact of this phenomenon in an immunogenetically diverse population, we genotypically and functionally compared linked HLA and HIV (Gag/Nef) sequences from 358 historic (1979–1989) and 382 modern (2000–2011) specimens from four key cities in the North American epidemic (New York, Boston, San Francisco, Vancouver). Inferred HIV phylogenies were star-like, with approximately two-fold greater mean pairwise distances in modern versus historic sequences. The reconstructed epidemic ancestral (founder) HIV sequence was essentially identical to the North American subtype B consensus. Consistent with gradual diversification of a “consensus-like” founder virus, the median “background” frequencies of individual HLA-associated polymorphisms in HIV (in individuals lacking the restricting HLA[s]) were ~2-fold higher in modern versus historic HIV sequences, though these remained notably low overall (e.g. in Gag, medians were 3.7% in the 2000s versus 2.0% in the 1980s). HIV polymorphisms exhibiting the greatest relative spread were those restricted by protective HLAs. Despite these increases, when HIV sequences were analyzed as a whole, their total average burden of polymorphisms that were “pre-adapted” to the average host HLA profile was only ~2% greater in modern versus historic eras. Furthermore, HLA-associated polymorphisms identified in historic HIV sequences were consistent with those detectable today, with none identified that could explain the few HIV codons where the inferred epidemic ancestor differed from the modern consensus. Results are therefore consistent with slow HIV adaptation to HLA, but at a rate unlikely to yield imminent negative implications for cellular immunity, at least in North America. Intriguingly, temporal changes in protein activity of patient-derived Nef (though not Gag) sequences were observed, suggesting functional implications of population-level HIV evolution on certain viral proteins.

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Gender Inequities in Quality of Care among HIV-Positive Individuals Initiating Antiretroviral Treatment in British Columbia, Canada (2000–2010)

Peer reviewed: 
Yes, item is peer reviewed.
Date created: 
2014-03-18
Abstract: 

Objectives

We measured gender differences in “Quality of Care” (QOC) during the first year after initiation of antiretroviral therapy and investigated factors associated with poorer QOC among women.

Design

QOC was estimated using the Programmatic Compliance Score (PCS), a validated metric associated with all-cause mortality, among all patients (≥19 years) who initiated ART in British Columbia, Canada (2000–2010).

Methods

PCS includes six indicators of non-compliance with treatment initiation guidelines at baseline (not having drug resistance testing before treatment; starting on a non-recommended regimen; starting therapy at CD4<200 cells/mm3) and during first-year follow-up (receiving <3 CD4 tests; receiving <3 viral load tests; not achieving viral suppression within six months). Summary scores range from 0–6; higher scores indicate poorer QOC. Multivariable ordinal logistic regression was used to measure if female gender was an independent predictor of poorer QOC and factors associated with poorer QOC among women.

Results

QOC was determined for 3,642 patients (20% women). At baseline: 42% of women (34% men) did not have resistance testing before treatment; 17% of women (9% men) started on a non-recommended regimen (all p<0.001). At follow-up: 17% of women (11% men) received <3 CD4; 17% of women (11% men) received <3 VL; 50% of women (41% men) did not achieve viral suppression (all p<0.001). Overall, QOC was better among men (mean PSC = 1.54 (SD = 1.30)) compared with women (mean = 1.89 (SD = 1.37); p<0.001). In the multivariable model, female gender (AOR = 1.16 [95% CI: 0.99–1.35]; p = 0.062) remained associated with poorer QOC after covariate adjustment. Among women, those with injection drug use history, of Aboriginal ancestry, from Vancouver Island, and who initiated ART in earlier years were more likely to have poorer QOC.

Conclusions

Poorer QOC among women, especially from marginalized communities, demands that barriers undermining women's access to high-quality care be addressed to improve treatment and health for women with HIV.

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Examining the Impact of Case Management in Vancouver’s Downtown Community Court: A Quasi-Experimental Design

Peer reviewed: 
Yes, item is peer reviewed.
Date created: 
2014-03-05
Abstract: 

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.

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The Association between Acculturation and Dietary Patterns of South Asian Immigrants

Peer reviewed: 
Yes, item is peer reviewed.
Date created: 
2014-02-18
Abstract: 

Dietary acculturation, specifically the adoption of western dietary habits, may result in adverse health effects such as obesity and type 2 diabetes. Therefore, it is necessary to explore the role of acculturation in dietary patterns as well as awareness and knowledge of healthy nutrition among South Asian immigrants. This is an especially important population to target as South Asians have higher prevalence rates of type 2 diabetes and cardiovascular disease, which may be magnified with immigration. The current investigation is a sub-study of the Multi-Cultural Community Health Assessment Trial (M-CHAT). There were 207 participants of South Asian origin included in the initial study, 129 were born outside of Canada and had immigrated after the age of 18. The length of residence in Canada was used as a marker for acculturation. A questionnaire addressing perceived changes in dietary patterns, food preparation, and nutrition knowledge and awareness since immigration was used to assess dietary practices. The association between length of residence and variables related to perceived changes in dietary patterns was explored with Spearman correlation and significant associations were subsequently analyzed with ordinal logistic regression analysis adjusted for age, sex, education and body mass index. South Asian immigrants in Canada reported a variety of positive dietary practices, including an increased consumption of fruits and vegetables and an improvement in food preparation (including an increase in grilling and a decrease in deep frying when cooking). However, there was a reported increase in the consumption of convenience foods, sugar-sweetened beverages, red meat and in dining out. South Asian immigrants in Canada reported a variety of positive dietary practices including an improvement in food preparation. Future health promotion strategies should encourage cultural sensitivity in efforts to reduce the consumption of sugar-sweetened beverage, convenience foods and to encourage eating at home rather than dining out.

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Expansion of HAART Coverage Is Associated with Sustained Decreases in HIV/AIDS Morbidity, Mortality and HIV Transmission: The “HIV Treatment as Prevention” Experience in a Canadian Setting

Peer reviewed: 
Yes, item is peer reviewed.
Date created: 
2014-02-12
Abstract: 

Background

There has been renewed call for the global expansion of highly active antiretroviral therapy (HAART) under the framework of HIV treatment as prevention (TasP). However, population-level sustainability of this strategy has not been characterized.

Methods

We used population-level longitudinal data from province-wide registries including plasma viral load, CD4 count, drug resistance, HAART use, HIV diagnoses, AIDS incidence, and HIV-related mortality. We fitted two Poisson regression models over the study period, to relate estimated HIV incidence and the number of individuals on HAART and the percentage of virologically suppressed individuals.

Results

HAART coverage, median pre-HAART CD4 count, and HAART adherence increased over time and were associated with increasing virological suppression and decreasing drug resistance. AIDS incidence decreased from 6.9 to 1.4 per 100,000 population (80% decrease, p = 0.0330) and HIV-related mortality decreased from 6.5 to 1.3 per 100,000 population (80% decrease, p = 0.0115). New HIV diagnoses declined from 702 to 238 cases (66% decrease; p = 0.0004) with a consequent estimated decline in HIV incident cases from 632 to 368 cases per year (42% decrease; p = 0.0003). Finally, our models suggested that for each increase of 100 individuals on HAART, the estimated HIV incidence decreased 1.2% and for every 1% increase in the number of individuals suppressed on HAART, the estimated HIV incidence also decreased by 1%.

Conclusions

Our results show that HAART expansion between 1996 and 2012 in BC was associated with a sustained and profound population-level decrease in morbidity, mortality and HIV transmission. Our findings support the long-term effectiveness and sustainability of HIV treatment as prevention within an adequately resourced environment with no financial barriers to diagnosis, medical care or antiretroviral drugs. The 2013 Consolidated World Health Organization Antiretroviral Therapy Guidelines offer a unique opportunity to further evaluate TasP in other settings, particularly within generalized epidemics, and resource-limited setting, as advocated by UNAIDS.

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Perceptions of Individuals Living With Spinal Cord Injury toward Preference-Based Quality Of Life Instruments: A Qualitative Exploration

Peer reviewed: 
Yes, item is peer reviewed.
Date created: 
2014
Abstract: 

Background

Generic preference-based health-related quality of life instruments are widely used to measure health benefit within economic evaluation. The availability of multiple instruments raises questions about their relative merits and recent studies have highlighted the paucity of evidence regarding measurement properties in the context of spinal cord injury (SCI). This qualitative study explores the views of individuals living with SCI towards six established instruments with the objective of identifying ‘preferred’ outcome measures (from the perspective of the study participants).

Methods

Individuals living with SCI were invited to participate in one of three focus groups. Eligible participants were identified from Vancouver General Hospital’s Spine Program database; purposive sampling was used to ensure representation of different demographics and injury characteristics. Perceptions and opinions were solicited on the following questionnaires: 15D, Assessment of Quality of Life 8-dimension (AQoL-8D), EQ-5D-5L, Health Utilities Index (HUI), Quality of Well-Being Scale Self-Administered (QWB-SA), and the SF-36v2. Framework analysis was used to analyse the qualitative information gathered during discussion. Strengths and limitations of each questionnaire were thematically identified and managed using NVivo 9 software.

Results

Major emergent themes were (i) general perceptions, (ii) comprehensiveness, (iii) content, (iv) wording and (v) features. Two sub-themes pertinent to content were also identified; ‘questions’ and ‘options’. All focus group participants (n = 15) perceived the AQoL-8D to be the most relevant instrument to administer within the SCI population. This measure was considered to be comprehensive, with relevant content (i.e. wheelchair inclusive) and applicable items. Participants had mixed perceptions about the other questionnaires, albeit to varying degrees.

Conclusions

Despite a strong theoretical underpinning, the AQoL-8D (and other AQoL instruments) is infrequently used outside its country of origin (Australia). Empirical comparative analyses of the favoured instruments identified in this qualitative study are necessary within the context of spinal cord injury.

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Article
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Bicycling Crash Circumstances Vary By Route Type: A Cross-Sectional Analysis

Peer reviewed: 
Yes, item is peer reviewed.
Date created: 
2014
Abstract: 

Background

Widely varying crash circumstances have been reported for bicycling injuries, likely because of differing bicycling populations and environments. We used data from the Bicyclists’ Injuries and the Cycling Environment Study in Vancouver and Toronto, Canada, to describe the crash circumstances of people injured while cycling for utilitarian and leisure purposes. We examined the association of crash circumstances with route type.

Methods

Adult cyclists injured and treated in a hospital emergency department described their crash circumstances. These were classified into major categories (collision vs. fall, motor vehicle involved vs. not) and subcategories. The distribution of circumstances was tallied for each of 14 route types defined in an earlier analysis. Ratios of observed vs. expected were tallied for each circumstance and route type combination.

Results

Of 690 crashes, 683 could be characterized for this analysis. Most (74%) were collisions. Collisions included those with motor vehicles (34%), streetcar (tram) or train tracks (14%), other surface features (10%), infrastructure (10%), and pedestrians, cyclists, or animals (6%). The remainder of the crashes were falls (26%), many as a result of collision avoidance manoeuvres. Motor vehicles were involved directly or indirectly with 48% of crashes. Crash circumstances were distributed differently by route type, for example, collisions with motor vehicles, including “doorings”, were overrepresented on major streets with parked cars. Collisions involving streetcar tracks were overrepresented on major streets. Collisions involving infrastructure (curbs, posts, bollards, street furniture) were overrepresented on multiuse paths and bike paths.

Conclusions

These data supplement our previous analyses of relative risks by route type by indicating the types of crashes that occur on each route type. This information can guide municipal engineers and planners towards improvements that would make cycling safer.

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