ISOWN: accurate somatic mutation identification in the absence of normal tissue controls.

BackgroundA key step in cancer genome analysis is the identification of somatic mutations in the tumor. This is typically done by comparing the genome of the tumor to the reference genome sequence derived from a normal tissue taken from the same donor. However, there are a variety of common scenarios in which matched normal tissue is not available for comparison.ResultsIn this work, we describe an algorithm to distinguish somatic single nucleotide variants (SNVs) in next-generation sequencing data from germline polymorphisms in the absence of normal samples using a machine learning approach. Our algorithm was evaluated using a family of supervised learning classifications across six different cancer types and ~1600 samples, including cell lines, fresh frozen tissues, and formalin-fixed paraffin-embedded tissues; we tested our algorithm with both deep targeted and whole-exome sequencing data. Our algorithm correctly classified between 95 and 98% of somatic mutations with F1-measure ranges from 75.9 to 98.6% depending on the tumor type. We have released the algorithm as a software package called ISOWN (Identification of SOmatic mutations Without matching Normal tissues).ConclusionsIn this work, we describe the development, implementation, and validation of ISOWN, an accurate algorithm for predicting somatic mutations in cancer tissues in the absence of matching normal tissues. ISOWN is available as Open Source under Apache License 2.0 from https://github.com/ikalatskaya/ISOWN

Improving Proficiency in Central Venous Catheter Insertion: Standardized Simulation Based Training for Internal Medicine House Staff

Objectives: The objectives of this study are to assess residents\u27 pre-workshop ability and comfort with CVC placement, undergo a standardized online didactic and hands-on clinical training simulation workshop, and subsequently undergo a proficiency test using simulation models to assess competency. The goal of a standardized training module is to create a universal approach to CVC placement in our institution and improve comfort and technical ability of house staff. We hypothesize that this will reduce complications and improve patient care and safety.https://jdc.jefferson.edu/patientsafetyposters/1063/thumbnail.jp

The Association Between Opioid-Related Industry Payments and Opioid Prescribing at the Individual and Ecological Level in Pennsylvania

Objective: to understand how industry payments related to opioid products are associated with opioid prescribing in Pennsylvania. Methods: we merged the Open Payments data, Medicare Part D public use file, and Dartmouth Hospital Atlas of Health Care Hospital Service Areas from 2015 to analyze relationships between opioid related payments and opioid prescribing. We used a binomial regression model to investigate individual-level trends and a log-linear model to investigate Hospital Service Area-level trends. We mapped the distribution of opioid-related payments in Pennsylvania using GIS software. Results: One additional payment to a physician was associated with 4.2% higher opioid-prescribing rate (OR = 1.0418, 95% CI 1.0416-1.0420, Chi-Square(1) = 122678, p Conclusions: We found a positive association between opioid-related payments to physicians and opioid prescribing. Policy makers and administrators should consider revising rules related to pharmaceutical company marketing tactics and promote judicious opioid prescribing

A four gene signature of chromosome instability (CIN4) predicts for benefit from taxanes in the NCIC-CTG MA21 clinical trial.

Recent evidence demonstrated CIN4 as a predictive marker of anthracycline benefit in early breast cancer. An analysis of the NCIC CTG MA.21 clinical trial was performed to test the role of existing CIN gene expression signatures as prognostic and predictive markers in the context of taxane based chemotherapy.RNA was extracted from patients in cyclophosphamide, epirubicin and flurouracil (CEF) and epirubicin, cyclophosphamide and paclitaxel (EC/T) arms of the NCIC CTG MA.21 trial and analysed using NanoString technology.After multivariate analysis both high CIN25 and CIN70 score was significantly associated with an increased in RFS (HR 1.76, 95%CI 1.07-2.86, p=0.0018 and HR 1.59, 95%CI 1.12-2.25, p=0.0096 respectively). Patients whose tumours had low CIN4 gene expression scores were associated with an increase in RFS (HR: 0.64, 95% CI 0.39-1.03, p=0.06) when treated with EC/T compared to patients treated with CEF.In conclusion we have demonstrated CIN25 and CIN70 as prognostic markers in breast cancer and that CIN4 is a potential predictive maker of benefit from taxane treatment

CP violation Beyond the MSSM: Baryogenesis and Electric Dipole Moments

We study electroweak baryogenesis and electric dipole moments in the presence of the two leading-order, non-renormalizable operators in the Higgs sector of the MSSM. Significant qualitative and quantitative differences from MSSM baryogenesis arise due to the presence of new CP-violating phases and to the relaxation of constraints on the supersymmetric spectrum (in particular, both stops can be light). We find: (1) spontaneous baryogenesis, driven by a change in the phase of the Higgs vevs across the bubble wall, becomes possible; (2) the top and stop CP-violating sources can become effective; (3) baryogenesis is viable in larger parts of parameter space, alleviating the well-known fine-tuning associated with MSSM baryogenesis. Nevertheless, electric dipole moments should be measured if experimental sensitivities are improved by about one order of magnitude.Comment: 33 pages, 6 figure

Optimization of admixture and three-layer particleboard made from oil palm empty fruit bunch and rubberwood clones

Empty fruit bunch (EFB) is a biomass that is widely available and has the potential to be used as industrial raw material especially in wood-based industries. This study focuses on producing a particleboard by incorporating EFB with two different rubberwood clones: Prang Besar (PB) 260 and RRIM 2002, respectively. PB 260 is a commercially planted clone and wood from matured (>25 year-old) trees are used by wood-based panel manufacturers. RRIM 2002 is a new clone planted at the Malaysian Rubber Board (MRB) research trial plots and consists of only 4-year-old trees. Two types of particleboards (admixture and three-layer) with different ratios were produced. The Japanese Industrial Standard (JIS-5908 2003 particleboard) was used to evaluate mechanical and dimensional stability properties of the particleboards. From the study, it was found that admixture particleboards showed superior properties compared to three-layer particleboards. Layering EFB and rubberwood significantly decreased board performance for all properties (except internal bonding). The optimum ratios of EFB and both rubberwood clones are found to be 1:1 (50% EFB: 50% rubberwood). Meanwhile, increasing the rubberwood clones ratio to 70% lowered board performance especially for EFB (30%):RRIM 2002 clone (70%) boards which showed the lowest values for all properties for both admixture and three-layer board

Slim Epistemology with a Thick Skin

The distinction between ‘thick’ and ‘thin’ value concepts, and its importance to ethical theory, has been an active topic in recent meta-ethics. This paper defends three claims regarding the parallel issue about thick and thin epistemic concepts. (1) Analogy with ethics offers no straightforward way to establish a good, clear distinction between thick and thin epistemic concepts. (2) Assuming there is such a distinction, there are no semantic grounds for assigning thick epistemic concepts priority over the thin. (3) Nor does the structure of substantive epistemological theory establish that thick epistemic concepts enjoy systematic theoretical priority over the thin. In sum, a good case has yet to be made for any radical theoretical turn to thicker epistemology

UK science press officers, professional vision and the generation of expectations

Science press officers can play an integral role in helping promote expectations and hype about biomedical research. Using this as a starting point, this article draws on interviews with 10 UK-based science press officers, which explored how they view their role as science reporters and as generators of expectations. Using Goodwin’s notion of ‘professional vision’, we argue that science press officers have a specific professional vision that shapes how they produce biomedical press releases, engage in promotion of biomedical research and make sense of hype. We discuss how these insights can contribute to the sociology of expectations, as well as inform responsible science communication.This project was funded by the Wellcome Trust (Wellcome Trust Biomedical Strategic Award 086034)