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

Small hiatal hernia and postprandial reflux after vertical sleeve gastrectomy: A multiethnic Asian cohort.

BackgroundLaparoscopic vertical sleeve gastrectomy (LSG) is a popular bariatric procedure performed in Asia, as obesity continues to be on the rise in our population. A major problem faced is the development of de novo gastroesophageal reflux disease (GERD) after LSG, which can be chronic and debilitating. In this study, we aim to assess the relationship between the presence of small hiatal hernia (HH) and the development of postoperative GERD, as well as to explore the correlation between GERD symptoms after LSG and timing of meals. In doing so, we hope to gain a better understanding about the type of reflux that occurs after LSG and take a step closer towards effectively managing this difficult to treat condition.MethodsWe retrospectively reviewed data collected from patients who underwent LSG in our hospital from Dec 2008 to Dec 2016. All patients underwent preoperative upper GI endoscopy, during which the identification of hiatal hernia takes place. Patients' information and reflux symptoms are recorded using standardized questionnaires, which are administered preoperatively, and again during postoperative follow up visits.ResultsOf the 255 patients, 125 patients (74%) developed de novo GERD within 6 months post-sleeve gastrectomy. The rate of de novo GERD was 57.1% in the group with HH, and 76.4% in the group without HH. Adjusted analysis showed no significant association between HH and GERD (RR = 0.682; 95% CI 0.419 to 1.111; P = 0.125). 88% of the patients who developed postoperative GERD reported postprandial symptoms occurring only after meals, and the remaining 12% of patients reported no correlation between the timing of GERD symptoms and meals.ConclusionThere is no direct correlation between the presence of small hiatal hernia and GERD symptoms after LSG. Hence, the presence of a small sliding hiatal hernia should not be exclusion for sleeve gastrectomy. Electing not to perform concomitant hiatal hernia repair also does not appear to result in higher rates of postoperative or de novo GERD

Covert COVID-19 and false-positive dengue serology in Singapore

10.1016/S1473-3099(20)30158-4LANCET INFECTIOUS DISEASES205536-53

Expert knowledge-based co-development of scenarios for maritime spatial planning in the Northeast Atlantic

Scenarios constitute narratives or storylines that reasonably describe how the future is likely to unfold. The usefulness of scenarios in Maritime Spatial Planning (MSP) is now recognised within policy and research, with many institutions urging the development of likely trajectories in the future state of the marine environment and space. However, little progress exists in the actual development and application of actual scenario building approaches. This paper presents the methodology and results of such an approach developed within the framework of the “Geographical and Political Scenarios in Maritime Spatial Planning for the Azores and North Atlantic (GPS Azores)” project. A scenario-building approach for MSP in the area is developed and future scenarios’ storylines are formulated through the active engagement of regional experts. Outcomes from the analysis enable identifying the major risks and opportunities in the management and use of marine space and key maritime sectors, under different scenarios. Three storylines are developed representing distinct trajectories in the use and governance of marine space: (i) Nature at Work; (ii) Business-as-usual; and (iii) Blue Development. Final storylines are the outcome of intense experts’ engagement throughout the scenario-building exercise, stressing the usefulness of such participative approaches. Results can assist policymakers in the context of an adaptive and participatory MSP approach. The methodology can be tailored to other regions, while results can be revisited and adapted as new information and knowledge emerge.The study was conducted in the framework of the Geographical and Political Scenarios in Maritime Spatial Planning for the Azores and North Atlantic (GPS Azores) project (Ref: ACCORES-01-0145-FEDER-002 GPS Azores), financed by FEDER (85%) and with funds from the Azores 2020 Operational Programme (15%). The authors would like to thank Mike Phillips who provided input in an early version of the scenario-building exercise.info:eu-repo/semantics/publishedVersio

Post graduate remediation programs in medicine: a scoping review.

BackgroundRecognizing that physicians may struggle to achieve knowledge, skills, attitudes and or conduct at one or more stages during their training has highlighted the importance of the 'deliberate practice of improving performance through practising beyond one's comfort level under guidance'. However, variations in physician, program, contextual and healthcare and educational systems complicate efforts to create a consistent approach to remediation. Balancing the inevitable disparities in approaches and settings with the need for continuity and effective oversight of the remediation process, as well as the context and population specific nature of remediation, this review will scrutinise the remediation of physicians in training to better guide the design, structuring and oversight of new remediation programs.MethodsKrishna's Systematic Evidence Based Approach is adopted to guide this Systematic Scoping Review (SSR in SEBA) to enhance the transparency and reproducibility of this review. A structured search for articles on remediation programs for licenced physicians who have completed their pre-registration postings and who are in training positions published between 1st January 1990 and 31st December 2021 in PubMed, Scopus, ERIC, Google Scholar, PsycINFO, ASSIA, HMIC, DARE and Web of Science databases was carried out. The included articles were concurrently thematically and content analysed using SEBA's Split Approach. Similarities in the identified themes and categories were combined in the Jigsaw Perspective and compared with the tabulated summaries of included articles in the Funnelling Process to create the domains that will guide discussions.ResultsThe research team retrieved 5512 abstracts, reviewed 304 full-text articles and included 101 articles. The domains identified were characteristics, indications, frameworks, domains, enablers and barriers and unique features of remediation in licenced physicians in training programs.ConclusionBuilding upon our findings and guided by Hauer et al. approach to remediation and Taylor and Hamdy's Multi-theories Model, we proffer a theoretically grounded 7-stage evidence-based remediation framework to enhance understanding of remediation in licenced physicians in training programs. We believe this framework can guide program design and reframe remediation's role as an integral part of training programs and a source of support and professional, academic, research, interprofessional and personal development

Large-Scale Whole-Genome Sequencing of Three Diverse Asian Populations in Singapore

Because of Singapore's unique history of immigration, whole-genome sequence analysis of 4,810 Singaporeans provides a snapshot of the genetic diversity across East, Southeast, and South Asia.</p

Sex differences in oncogenic mutational processes

Funder: Canadian Network for Research and Innovation in Machining Technology, Natural Sciences and Engineering Research Council of Canada (NSERC Canadian Network for Research and Innovation in Machining Technology); doi: https://doi.org/10.13039/501100002790Funder: Genome Canada (Génome Canada); doi: https://doi.org/10.13039/100008762Funder: Canada Foundation for Innovation (Fondation canadienne pour l'innovation); doi: https://doi.org/10.13039/501100000196Funder: Terry Fox Research Institute (Institut de Recherche Terry Fox); doi: https://doi.org/10.13039/501100004376Abstract: Sex differences have been observed in multiple facets of cancer epidemiology, treatment and biology, and in most cancers outside the sex organs. Efforts to link these clinical differences to specific molecular features have focused on somatic mutations within the coding regions of the genome. Here we report a pan-cancer analysis of sex differences in whole genomes of 1983 tumours of 28 subtypes as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. We both confirm the results of exome studies, and also uncover previously undescribed sex differences. These include sex-biases in coding and non-coding cancer drivers, mutation prevalence and strikingly, in mutational signatures related to underlying mutational processes. These results underline the pervasiveness of molecular sex differences and strengthen the call for increased consideration of sex in molecular cancer research

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