Food Insecurity and Sexual Risk in an HIV Endemic Community in Uganda

Food insecurity has been linked to high-risk sexual behavior in sub-Saharan Africa, but there are limited data on these links among people living with HIV/AIDS, and on the mechanisms for how food insecurity predisposes individuals to risky sexual practices. We undertook a series of in-depth open-ended interviews with 41 individuals living with HIV/AIDS to understand the impact of food insecurity on sexual-risk behaviors. Participants were recruited from the Immune Suppression Clinic at the Mbarara University of Science and Technology in Mbarara, Uganda. Interviews were recorded, transcribed verbatim, translated, and coded following the strategy of grounded theory. Four major themes emerged from the interview data: the relationship between food insecurity and transactional sex for women; the impact of a husband\u27s death from HIV on worsening food insecurity among women and children; the impact of food insecurity on control over condom use, and the relationship between food insecurity and staying in violent/abusive relationships. Food insecurity led to increased sexual vulnerability among women. Women were often compelled to engage in transactional sex or remain in violent or abusive relationships due to their reliance on men in their communities to provide food for themselves and their children. There is an urgent need to prioritize food security programs for women living with HIV/AIDS and address broader gender-based inequities that are propelling women to engage in risky sexual behaviors based on hunger. Such interventions will play an important role in improving the health and well-being of people living with HIV/AIDS, and preventing HIV transmission

Food Insecurity and Sexual Risk in an HIV Endemic Community in Uganda

Food insecurity has been linked to high-risk sexual behavior in sub-Saharan Africa, but there are limited data on these links among people living with HIV/AIDS, and on the mechanisms for how food insecurity predisposes individuals to risky sexual practices. We undertook a series of in-depth open-ended interviews with 41 individuals living with HIV/AIDS to understand the impact of food insecurity on sexual-risk behaviors. Participants were recruited from the Immune Suppression Clinic at the Mbarara University of Science and Technology in Mbarara, Uganda. Interviews were recorded, transcribed verbatim, translated, and coded following the strategy of grounded theory. Four major themes emerged from the interview data: the relationship between food insecurity and transactional sex for women; the impact of a husband’s death from HIV on worsening food insecurity among women and children; the impact of food insecurity on control over condom use, and the relationship between food insecurity and staying in violent/abusive relationships. Food insecurity led to increased sexual vulnerability among women. Women were often compelled to engage in transactional sex or remain in violent or abusive relationships due to their reliance on men in their communities to provide food for themselves and their children. There is an urgent need to prioritize food security programs for women living with HIV/AIDS and address broader gender-based inequities that are propelling women to engage in risky sexual behaviors based on hunger. Such interventions will play an important role in improving the health and well-being of people living with HIV/AIDS, and preventing HIV transmission

Reinterpretation of LHC Results for New Physics: Status and recommendations after Run 2

We report on the status of efforts to improve the reinterpretation of searches and measurements at the LHC in terms of models for new physics, in the context of the LHC Reinterpretation Forum. We detail current experimental offerings in direct searches for new particles, measurements, technical implementations and Open Data, and provide a set of recommendations for further improving the presentation of LHC results in order to better enable reinterpretation in the future. We also provide a brief description of existing software reinterpretation frameworks and recent global analyses of new physics that make use of the current data

Genome-wide association study identifies 32 novel breast cancer susceptibility loci from overall and subtype-specific analyses.

Breast cancer susceptibility variants frequently show heterogeneity in associations by tumor subtype1-3. To identify novel loci, we performed a genome-wide association study including 133,384 breast cancer cases and 113,789 controls, plus 18,908 BRCA1 mutation carriers (9,414 with breast cancer) of European ancestry, using both standard and novel methodologies that account for underlying tumor heterogeneity by estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 status and tumor grade. We identified 32 novel susceptibility loci (P < 5.0 × 10-8), 15 of which showed evidence for associations with at least one tumor feature (false discovery rate < 0.05). Five loci showed associations (P < 0.05) in opposite directions between luminal and non-luminal subtypes. In silico analyses showed that these five loci contained cell-specific enhancers that differed between normal luminal and basal mammary cells. The genetic correlations between five intrinsic-like subtypes ranged from 0.35 to 0.80. The proportion of genome-wide chip heritability explained by all known susceptibility loci was 54.2% for luminal A-like disease and 37.6% for triple-negative disease. The odds ratios of polygenic risk scores, which included 330 variants, for the highest 1% of quantiles compared with middle quantiles were 5.63 and 3.02 for luminal A-like and triple-negative disease, respectively. These findings provide an improved understanding of genetic predisposition to breast cancer subtypes and will inform the development of subtype-specific polygenic risk scores

The FANCM:p.Arg658* truncating variant is associated with risk of triple-negative breast cancer.

Breast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic variants in DNA repair genes BRCA1, BRCA2, PALB2, ATM, and CHEK2 are associated with breast cancer risk. FANCM, which encodes for a DNA translocase, has been proposed as a breast cancer predisposition gene, with greater effects for the ER-negative and triple-negative breast cancer (TNBC) subtypes. We tested the three recurrent protein-truncating variants FANCM:p.Arg658*, p.Gln1701*, and p.Arg1931* for association with breast cancer risk in 67,112 cases, 53,766 controls, and 26,662 carriers of pathogenic variants of BRCA1 or BRCA2. These three variants were also studied functionally by measuring survival and chromosome fragility in FANCM -/- patient-derived immortalized fibroblasts treated with diepoxybutane or olaparib. We observed that FANCM:p.Arg658* was associated with increased risk of ER-negative disease and TNBC (OR = 2.44, P = 0.034 and OR = 3.79; P = 0.009, respectively). In a country-restricted analysis, we confirmed the associations detected for FANCM:p.Arg658* and found that also FANCM:p.Arg1931* was associated with ER-negative breast cancer risk (OR = 1.96; P = 0.006). The functional results indicated that all three variants were deleterious affecting cell survival and chromosome stability with FANCM:p.Arg658* causing more severe phenotypes. In conclusion, we confirmed that the two rare FANCM deleterious variants p.Arg658* and p.Arg1931* are risk factors for ER-negative and TNBC subtypes. Overall our data suggest that the effect of truncating variants on breast cancer risk may depend on their position in the gene. Cell sensitivity to olaparib exposure, identifies a possible therapeutic option to treat FANCM-associated tumors

The FANCM:p.Arg658* truncating variant is associated with risk of triple-negative breast cancer

Abstract: Breast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic variants in DNA repair genes BRCA1, BRCA2, PALB2, ATM, and CHEK2 are associated with breast cancer risk. FANCM, which encodes for a DNA translocase, has been proposed as a breast cancer predisposition gene, with greater effects for the ER-negative and triple-negative breast cancer (TNBC) subtypes. We tested the three recurrent protein-truncating variants FANCM:p.Arg658*, p.Gln1701*, and p.Arg1931* for association with breast cancer risk in 67,112 cases, 53,766 controls, and 26,662 carriers of pathogenic variants of BRCA1 or BRCA2. These three variants were also studied functionally by measuring survival and chromosome fragility in FANCM−/− patient-derived immortalized fibroblasts treated with diepoxybutane or olaparib. We observed that FANCM:p.Arg658* was associated with increased risk of ER-negative disease and TNBC (OR = 2.44, P = 0.034 and OR = 3.79; P = 0.009, respectively). In a country-restricted analysis, we confirmed the associations detected for FANCM:p.Arg658* and found that also FANCM:p.Arg1931* was associated with ER-negative breast cancer risk (OR = 1.96; P = 0.006). The functional results indicated that all three variants were deleterious affecting cell survival and chromosome stability with FANCM:p.Arg658* causing more severe phenotypes. In conclusion, we confirmed that the two rare FANCM deleterious variants p.Arg658* and p.Arg1931* are risk factors for ER-negative and TNBC subtypes. Overall our data suggest that the effect of truncating variants on breast cancer risk may depend on their position in the gene. Cell sensitivity to olaparib exposure, identifies a possible therapeutic option to treat FANCM-associated tumors

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Genome-wide association study of germline variants and breast cancer-specific mortality

BACKGROUND: We examined the associations between germline variants and breast cancer mortality using a large meta-analysis of women of European ancestry. METHODS: Meta-analyses included summary estimates based on Cox models of twelve datasets using ~10