"You cannot eat rights": a qualitative study of views by Zambian HIV-vulnerable women, youth and MSM on human rights as public health tools

Background Human rights approaches now dominate the HIV prevention landscape across sub-Saharan Africa, yet little is known about how they are viewed by the populations they are designed to serve. Health interventions are most effective when they resonate with the worldviews and interests of target groups. This study examined local Zambian understandings of human rights approaches to HIV-prevention among three highly HIV-vulnerable groups: women, youth, and men-who-have-sex-with-men (MSM). Methods Focus groups included 23 women, youth, and MSM who had participated in activities organized by local non-governmental organizations (NGOs) using rights-based approaches, and interviews included 10 Zambian employees of these NGOs. Topics included participants’ experiences and views of the utility of these activities. Thematic analysis mapped out diverse ways participants viewed the concept of human rights in relation to HIV-prevention. Results Whilst NGO workers noted the need for human rights programs to address the complex drivers of the HIV epidemic, they struggled to tailor them to the Zambian context due to donor stipulations. Women program beneficiaries noted that the concept of human rights helped challenge harmful sexual practices and domestic abuse, and youth described rights-based approaches as more participatory than previous HIV-prevention efforts. However, they criticized the approach for conflicting with traditional values such as respect for elders and ‘harmonious’ marital relationships. They also critiqued it for threatening the social structures and relationships that they relied on for material survival, and for failing to address issues like poverty and unemployment. In contrast, MSM embraced the rights approach, despite being critical of its overly confrontational implementation. Conclusions A rights-based approach seeks to tackle the symbolic drivers of HIV—its undeniable roots in cultural and religious systems of discrimination. Yet, it fails to resonate with youth and women’s own understandings of their needs and priorities due to its neglect of material drivers of HIV such as poverty and unemployment. MSM, who suffer extreme stigma and discrimination, have less to lose and much to gain from an approach that challenges inequitable social systems. Developing effective HIV-prevention strategies requires careful dialogue with vulnerable groups and greater flexibility for context-specific implementation rather than a one-size-fits-all conceptualization of human rights

Conceptualising schools as a source of social capital for HIV affected children in southern Africa

Many AIDS-affected African children lack forms of adult support and guidance traditionally provided by families. There is growing policy attention to the role schools might play in caring for children in extreme adversity in ways that go far beyond traditional education. We use the concept of the “HIV competent school,” which incorporates bonding, bridging and linking social capital, to frame a selective review of the literature on school responses to HIV/AIDS in southern African countries, and an in-depth case study of indigenous school responses in eastern Zimbabwe. We call for greater attention to the ethic of care emerging from the interaction between AIDS-affected children and relevant peers and adults in the school setting and the way in which this is limited or enabled in particular social settings

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Considering Context: Variation in Food Availability and Diet Quality Among Children in Nepal’s Three Agroecological Zones

Background: Poor quality diets put Nepali children at risk for undernutrition. Designing and implementing interventions to effectively improve child diet quality requires an understanding of how contextual factors influence household access to non-staple nutritious foods. The Policy and Science for Health, Agriculture, and Nutrition (PoSHAN) data collection system monitors agricultural production, household food security, dietary intake, and nutritional status at 21-sites across Nepal. It offered a unique opportunity to examine child diet quality and household food access across varying agroecological settings and seasons. Additionally, the large integrated nutrition program Suaahara (meaning ‘good nutrition’ in Nepali) provided a chance to observe a nutrition-sensitive agriculture program’s efforts to improve food access and diet quality in one of Nepal’s most extreme settings. Methods: Chapter four quantitatively examines seasonal differences in children’s consumption frequency of non-staple nutritious food consumption frequency. It uses data from the PoSHAN study’s sentinel surveillance sites. In these three sites, data were collected three times per year over the course of two years. Analyses were conducted separately by region, allowing for assessment of how seasonal variation differed geographically. Interactions between season and caste/ethnicity and wealth were also explored. Chapter five also uses PoSHAN sentinel site data. It first examines associations between household food production and purchasing and children’s consumption of nutritious foods. It then analyzes associations between season, region, caste/ethnicity, and wealth and household food production and purchasing. Chapter six qualitatively examines implementation of the Suaahara program’s agriculture component in far-Western Nepal. It identifies and describes contextual factors that influenced participants’ abilities to engage in and benefit from the program. Results: Children’s consumption frequency of non-staple nutritious foods varied significantly by season. The magnitude and timing of seasonal differences differed by region, and in some cases by wealth and caste/ethnicity. Both household production of and household expenditure on nutritious foods were associated with their consumption frequency among children. Region, season, land ownership, and wealth influenced the likelihood of households producing and purchasing nutritious foods. Within the qualitative findings, water, land, and time emerged as key determinants of women’s abilities to engage in and benefit from a nutrition-sensitive agriculture program. Access to these resources depended upon sociocultural and biophysical environmental factors, as well as historic land and labor policies. Program participants and staff used a variety of strategies to address resource access challenges. These included: use of micro-irrigation equipment, arranging land-sharing agreements, engaging families in program activities, and role-modeling more equitable gendered division of labor. However, the feasibility of these strategies was also limited by contextual constraints. Conclusions: Access to nutritious foods, and subsequently child diet quality, vary substantially across Nepal’s agroecological regions. Sources of variation lie in both the biophysical and sociocultural environment, and must be understood in the context of current and historic policies and institutions. Interventions that increase year-round household production and purchasing of nutritious foods hold substantial promise for improving child diet quality, but must be tailored at the regional and even community level. More broadly, enabling interventions to reach and benefit the most marginalized households, and addressing the root causes of poor diet quality, will require addressing complex structural barriers. Chief among these are improvements in irrigation infrastructure, enactment of land reform, and establishment of robust social protection mechanisms

Small-Scale Livestock Production in Nepal Is Directly Associated with Children’s Increased Intakes of Eggs and Dairy, But Not Meat

Animal source foods (ASF) provide nutrients essential to child growth and development yet remain infrequently consumed in rural Nepal. Agriculture and nutrition programs aim to increase ASF intake among children through small-scale animal husbandry projects. The relationship between livestock ownership and children&rsquo;s consumption of ASF, however, is not well established. This study examined associations between livestock ownership and the frequency with which Nepali children consume eggs, dairy, and meat. We analyzed longitudinal 7-day food frequency data from sentinel surveillance sites of the Policy and Science of Health, Agriculture and Nutrition (PoSHAN) study. Data consisted of surveys from 485 Nepali farming households conducted twice per year for two years (a total of 1449 surveys). We used negative binomial regression analysis to examine the association between the number of cattle, poultry, and meat animals (small livestock) owned and children&rsquo;s weekly dairy, egg, and meat intakes, respectively, adjusting for household expenditure on each food type, mother&rsquo;s education level, caste/ethnicity, agroecological region, season, and child age and sex. We calculated predicted marginal values based on model estimates. Children consumed dairy 1.4 (95% CI 1.1&ndash;2.0), 2.3 (1.7&ndash;3.0) and 3.0 (2.1&ndash;4.2) more times per week in households owning 1, 2&ndash;4 and &gt;4 cattle, respectively, compared to children in households without cattle. Children consumed eggs 2.8 (2.1&ndash;3.7) more times per week in households owning 1 or 2 chickens compared to children in households without chickens. Child intake of meat was higher only in households owning more than seven meat animals. Children&rsquo;s intakes of dairy, eggs, and meat rose with household expenditure on these foods. Small-scale animal production may be an effective strategy for increasing children&rsquo;s consumption of eggs and dairy, but not meat. Increasing household ability to access ASF via purchasing appears to be an important approach for raising children&rsquo;s intakes of all three food types