Hiring, Training, and Supporting Peer Research Associates: Operationalizing Community-Based Research Principles within Epidemiological Studies By, With, and For Women Living With HIV

Background A community-based research (CBR) approach is critical to redressing the exclusion of women—particularly, traditionally marginalized women including those who use substances—from HIV research participation and benefit. However, few studies have articulated their process of involving and engaging peers, particularly within large-scale cohort studies of women living with HIV where gender, cultural and linguistic diversity, HIV stigma, substance use experience, and power inequities must be navigated. Methods Through our work on the Canadian HIV Women’s Sexual and Reproductive Health Cohort Study (CHIWOS), Canada’s largest community-collaborative longitudinal cohort of women living with HIV (n = 1422), we developed a comprehensive, regionally tailored approach for hiring, training, and supporting women living with HIV as Peer Research Associates (PRAs). To reflect the diversity of women with HIV in Canada, we initially hired 37 PRAs from British Columbia, Ontario, and Quebec, prioritizing women historically under-represented in research, including women who use or have used illicit drugs, and women living with HIV of other social identities including Indigenous, racialized, LGBTQ2S, and sex work communities, noting important points of intersection between these groups. Results Building on PRAs’ lived experience, research capacity was supported through a comprehensive, multi-phase, and evidence-based experiential training curriculum, with mentorship and support opportunities provided at various stages of the study. Challenges included the following: being responsive to PRAs’ diversity; ensuring PRAs’ health, well-being, safety, and confidentiality; supporting PRAs to navigate shifting roles in their community; and ensuring sufficient time and resources for the translation of materials between English and French. Opportunities included the following: mutual capacity building of PRAs and researchers; community-informed approaches to study the processes and challenges; enhanced recruitment of harder-to-reach populations; and stronger community partnerships facilitating advocacy and action on findings. Conclusions Community-collaborative studies are key to increasing the relevance and impact potential of research. For women living with HIV to participate in and benefit from HIV research, studies must foster inclusive, flexible, safe, and reciprocal approaches to PRA engagement, employment, and training tailored to regional contexts and women’s lives. Recommendations for best practice are offered

Change in maternal body mass index is associated with offspring body mass index: a 21-year prospective study

High body-mass index (BMI; defined as 25 kg/m(2) or greater) is associated with increased risk of cancer. To inform public health policy and future research, we estimated the global burden of cancer attributable to high BMI in 2012

Generation of tumour-specific cytotoxic T-cell clones from histocompatibility leucocyte antigen-identical siblings of patients with melanoma

Lymphodepletion and infusion of autologous expanded tumour-infiltrating lymphocytes is effective therapy for patients with malignant melanoma. Antitumour responses are likely to be mediated by HLA class I- and II-restricted immune responses directed at tumour antigens. We assessed whether the peripheral blood of normal HLA-matched siblings of patients with melanoma could be used to generate lymphocytes with antimelanoma activity for adoptive immunotherapy after allogeneic blood or marrow transplantation. Melanoma cell lines were derived from two donors and were used to stimulate the mononuclear cells of three HLA-identical siblings. CD4+ clones dominated cultures. Of these, approximately half were directly cytotoxic towards recipient melanoma cells and secreted interferon-γ in response to tumour stimulation. More than half of the noncytotoxic clones also secreted interferon-γ after melanoma stimulation. No CD4+ clones responded to stimulation with recipient haemopoietic cells. The majority of CD8+ clones directly lysed recipient melanoma, but did not persist in long-term culture in vitro. No crossreactivity with recipient haemopoietic cells was observed. The antigenic target of one CD4+ clone was determined to be an HLA-DR11-restricted MAGE-3 epitope. Antigenic targets of the remaining clones were not elucidated, but appeared to be restricted through a non-HLA-DR class II molecule. We conclude that the blood of allogeneic HLA-matched sibling donors contains melanoma-reactive lymphocyte precursors directed at tumour-associated antigens. Adoptive immunotherapy with unselected or ex vivo-stimulated donor lymphocytes after allogeneic stem cell transplantation has a rational basis for the treatment of malignant melanoma

In vitro irradiation of basement membrane enhances the invasiveness of breast cancer cells

Following removal of the primary breast tumour by conservative surgery, patients may still have additional malignant foci scattered throughout the breast. Radiation treatments are not designed to eliminate all these residual cancer cells. Rather, the radiation dose is calculated to optimise long-term results with minimal complications. In a tumour, cancer cells are surrounded by a basement membrane, which plays an important role in the regulation of gene expression. Using an invasion chamber, we have shown that irradiation before cell plating of a reconstituted basement membrane (Matrigel; Becton Dickinson, Bedford, MA, USA) increased the invasiveness of the breast cancer cells MDA-MB-231. This radiation enhancement of invasion was associated with the upregulation of the pro-invasive gene matrix metalloproteinase (MMP)-2. The expression of membrane type 1 matrix metalloproteinase (MT1-MMP) and tissue inhibitor of metalloproteinase-2 (TIMP), which are required to activate the MMP-2, were also increased. Confirming the role of MMP-2 and MT1-MMP, radiation enhancement of cancer cell invasion was prevented by an MMP-2 inhibitor and an anti-MT1-MMP antibody. This study also demonstrated that radiation can potentially enhance the invasion ability by inducing the release of pro-invasive factors stored in the Matrigel. Conversely, no enhancement of invasiveness was observed with the low metastatic cell line MCF-7. This lack of invasiveness correlated with the absence of the MMP-2 activator MT1-MMP in the MCF-7 cells. Radiotherapy is an efficient modality to treat breast cancer which could be further improved by inhibiting the pro-invasive gene upregulated by radiation

Hiring, training, and supporting Peer Research Associates: Operationalizing community-based research principles within epidemiological studies by, with, and for women living with HIV

Background: A community-based research (CBR) approach is critical to redressing the exclusion of women—particularly, traditionally marginalized women including those who use substances—from HIV research participation and benefit. However, few studies have articulated their process of involving and engaging peers, particularly within large-scale cohort studies of women living with HIV where gender, cultural and linguistic diversity, HIV stigma, substance use experience, and power inequities must be navigated. Methods: Through our work on the Canadian HIV Women’s Sexual and Reproductive Health Cohort Study (CHIWOS), Canada’s largest community-collaborative longitudinal cohort of women living with HIV (n = 1422), we developed a comprehensive, regionally tailored approach for hiring, training, and supporting women living with HIV as Peer Research Associates (PRAs). To reflect the diversity of women with HIV in Canada, we initially hired 37 PRAs from British Columbia, Ontario, and Quebec, prioritizing women historically under-represented in research, including women who use or have used illicit drugs, and women living with HIV of other social identities including Indigenous, racialized, LGBTQ2S, and sex work communities, noting important points of intersection between these groups. Results: Building on PRAs’ lived experience, research capacity was supported through a comprehensive, multi-phase, and evidence-based experiential training curriculum, with mentorship and support opportunities provided at various stages of the study. Challenges included the following: being responsive to PRAs’ diversity; ensuring PRAs’ health, well-being, safety, and confidentiality; supporting PRAs to navigate shifting roles in their community; and ensuring sufficient time and resources for the translation of materials between English and French. Opportunities included the following: mutual capacity building of PRAs and researchers; community-informed approaches to study the processes and challenges; enhanced recruitment of harder-to-reach populations; and stronger community partnerships facilitating advocacy and action on findings. Conclusions: Community-collaborative studies are key to increasing the relevance and impact potential of research. For women living with HIV to participate in and benefit from HIV research, studies must foster inclusive, flexible, safe, and reciprocal approaches to PRA engagement, employment, and training tailored to regional contexts and women’s lives. Recommendations for best practice are offered.Other UBCNon UBCReviewedFacult