Multiple breast cancer risk variants are associated with differential transcript isoform expression in tumors.

Genome-wide association studies have identified over 70 single-nucleotide polymorphisms (SNPs) associated with breast cancer. A subset of these SNPs are associated with quantitative expression of nearby genes, but the functional effects of the majority remain unknown. We hypothesized that some risk SNPs may regulate alternative splicing. Using RNA-sequencing data from breast tumors and germline genotypes from The Cancer Genome Atlas, we tested the association between each risk SNP genotype and exon-, exon-exon junction- or transcript-specific expression of nearby genes. Six SNPs were associated with differential transcript expression of seven nearby genes at FDR < 0.05 (BABAM1, DCLRE1B/PHTF1, PEX14, RAD51L1, SRGAP2D and STXBP4). We next developed a Bayesian approach to evaluate, for each SNP, the overlap between the signal of association with breast cancer and the signal of association with alternative splicing. At one locus (SRGAP2D), this method eliminated the possibility that the breast cancer risk and the alternate splicing event were due to the same causal SNP. Lastly, at two loci, we identified the likely causal SNP for the alternative splicing event, and at one, functionally validated the effect of that SNP on alternative splicing using a minigene reporter assay. Our results suggest that the regulation of differential transcript isoform expression is the functional mechanism of some breast cancer risk SNPs and that we can use these associations to identify causal SNPs, target genes and the specific transcripts that may mediate breast cancer risk

The effect of offering different numbers of colorectal cancer screening test options in a decision aid: a pilot randomized trial

BACKGROUND: Decision aids can improve decision making processes, but the amount and type of information that they should attempt to communicate is controversial. We sought to compare, in a pilot randomized trial, two colorectal cancer (CRC) screening decision aids that differed in the number of screening options presented. METHODS: Adults ages 48–75 not currently up to date with screening were recruited from the community and randomized to view one of two versions of our previously tested CRC screening decision aid. The first version included five screening options: fecal occult blood test (FOBT), sigmoidoscopy, a combination of FOBT and sigmoidoscopy, colonoscopy, and barium enema. The second discussed only the two most frequently selected screening options, FOBT and colonoscopy. Main outcomes were differences in screening interest and test preferences between groups after decision aid viewing. Patient test preference was elicited first without any associated out-of-pocket costs (OPC), and then with the following costs: FOBT-$10, sigmoidoscopy-$50, barium enema-$50, and colonoscopy-$200. RESULTS: 62 adults participated: 25 viewed the 5-option decision aid, and 37 viewed the 2-option version. Mean age was 54 (range 48–72), 58% were women, 71% were White, 24% African-American; 58% had completed at least a 4-year college degree. Comparing participants that viewed the 5-option version with participants who viewed the 2-option version, there were no differences in screening interest after viewing (1.8 vs. 1.9, t-test p = 0.76). Those viewing the 2-option version were somewhat more likely to choose colonoscopy than those viewing the 5-option version when no out of pocket costs were assumed (68% vs. 46%, p = 0.11), but not when such costs were imposed (41% vs. 42%, p = 1.00). CONCLUSION: The number of screening options available does not appear to have a large effect on interest in colorectal cancer screening. The effect of offering differing numbers of options may affect test choice when out-of-pocket costs are not considered

The 2023 Whippoorwill Award: The 2023 Whippoorwill Award: Complex Representations of Rural Identities and Places

Announcing the 2023 Whippoorwill Award winners

Rater training for standardised assessment of objective structured clinical examinations in rural Tanzania

In this study, six healthcare providers assessed and scored 42 training scenarios. Raters identified average test proficiency 50% of the time. Experts in the field of clinician-based training for frontline staff recommend that all examiners undergo rater training prior to becoming an Objective Structured Clinical Examination (OSCE) assessor. Helping Babies Breathe, Essential Care for Every Baby and Bleeding after Birth are standardised training programmes in maternal and child health care. Studies examining the reliability of assessments are rare. This study shows that rater training is critical to ensure that the potential of training programmes translates to improved outcomes for mothers and babies.Innovating for Maternal and Child Health in Africa (IMCHA) initiativeGlobal Affairs Canada (GAC)Canadian Institutes of Health Research (CIHR

Bibliography of Secondary Sources on the History of Dermatology II. Obituaries and Biographies in English Supplemented through 2015

Introduction A bibliographic record on the history of dermatology has been a project that started over 4 decades ago. It is a collection of all forms of history, ranging from dermatologic conditions, to famous dermatologists and physicians who have advanced the field of both dermatology and medicine, to the different countries that promoted the development of scientists, researchers and physicians alike. It was decided that the bibliographic record would encompass journals, books and a compilation of obituaries. A pertinent question is whether a manually created bibliographic project is still warranted in the 21st century. In short, yes. While Index Medicus has expanded the number of journals that are indexed, the number of dermatology publications currently included by Index Medicus exceeds 164; however, not all are in English or easily accessible. Although most of the papers of dermatologic interest are included in these journals, some contributions are also located in non-indexed publications. In addition, many documents of an historical interest or of a biographical nature are not necessarily selected for indexing in Index Medicus. The amalgamation of these historical publications from 2010-2015 will be divided into 3 separate contributions: journals, obituaries and books, with only those in English being recorded. Not only will this bibliographic record serve as a formal collection on the history of dermatology, it will also provide a reference to those wishing to enrich their knowledge on the expansion of the different fields of dermatology over time. It will also serve as a reminder of the achievements of our dermatology forefathers, from whom we have still so much to learn

Bibliography of Secondary Sources on the History of Dermatology

Introduction A bibliographic record on the history of dermatology has been a project that started over 4 decades ago. It is a collection of all forms of history, ranging from dermatologic conditions, to famous dermatologists and physicians who have advanced the field of both dermatology and medicine, to the different countries that promoted the development of scientists, researchers and physicians alike. It was decided that the bibliographic record would encompass journals, books and a compilation of obituaries. A pertinent question is whether a manually created bibliographic project is still warranted in the 21st century. In short, yes. While Index Medicus has expanded the number of journals that are indexed, the number of dermatology publications currently included by Index Medicus exceeds 164; however, not all are in English or easily accessible. Although most of the papers of dermatologic interest are included in these journals, some contributions are also located in non-indexed publications. In addition, many documents of an historical interest or of a biographical nature are not necessarily selected for indexing in Index Medicus. The amalgamation of these historical publications from 2010-2015 will be divided into 3 separate contributions: journals, obituaries and books, with only those in English being recorded. Not only will this bibliographic record serve as a formal collection on the history of dermatology, it will also provide a reference to those wishing to enrich their knowledge on the expansion of the different fields of dermatology over time. It will also serve as a reminder of the achievements of our dermatology forefathers, from whom we have still so much to learn

Adherence to Competing Strategies for Colorectal Cancer Screening Over 3 Years

We have shown that, in a randomized trial comparing adherence to different colorectal cancer (CRC) screening strategies, participants assigned to either fecal occult blood testing (FOBT) or given a choice between FOBT and colonoscopy had significantly higher adherence than those assigned to colonoscopy during the first year. However, how adherence to screening changes over time is unknown