Vacuum/Compression Valving (VCV) Using Parrafin-Wax on a Centrifugal Microfluidic CD Platform

This paper introduces novel vacuum/compression valves (VCVs) utilizing paraffin wax. A VCV is implemented by sealing the venting channel/hole with wax plugs (for normally-closed valve), or to be sealed by wax (for normally-open valve), and is activated by localized heating on the CD surface. We demonstrate that the VCV provides the advantages of avoiding unnecessary heating of the sample/reagents in the diagnostic process, allowing for vacuum sealing of the CD, and clear separation of the paraffin wax from the sample/reagents in the microfluidic process. As a proof of concept, the microfluidic processes of liquid flow switching and liquid metering is demonstrated with the VCV. Results show that the VCV lowers the required spinning frequency to perform the microfluidic processes with high accuracy and ease of control.open5

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

Methodology to assess the effects of magnetohydrodynamic electromagnetic pulse (MHD-EMP) on power systems

This paper summarizes a method to evaluate the possible effects of magnetohydrodynamic-electromagnetic pulse (MHD-EMP) on power systems. This method is based on the approach adapted to study the impact of geomagnetic storms on power systems. The paper highlights the similarities and differences between the two phenomena. Also presented are areas of concern which are anticipated from MHD-EMP on the overall system operation. 12 refs., 1 fig

Non-contact heat management for nucleic acid hybridization in sample-to-answer centrifugal microfluidics

This report focuses on the application of a newly developed non-contact heat management system, based on infrared radiation, to achieve advanced nucleic acid (NA) hybridization on a centrifugal microfluidic platform. Our system was used to eliminate formamide, a common reagent used to enable hybridization at room temperatures. Formamide poses significant challenges in the development of molecular ??TAS platforms with respect to issues such as reagent storage and low analyte detection. Thermal energy can be used to replace formamide during NA hybridization, allowing for the processing of more targets and the elimination of a highly corrosive reagent. The developed heat management system was implemented to produce highly stringent conditions for formamide-free NA hybridization of genetic material from clinical samples containing parainfluenza viruses on a rotating microfluidic platform

Natural history and implantable cardioverter-defibrillator implantation after revascularization for stable coronary artery disease with depressed ejection fraction

Background Following revascularization, most payors require 3 months of medical therapy, followed by left ventricular ejection fraction (LVEF) reassessment, before implantable cardioverter-defibrillator (ICD) implantation possibly contributing to incomplete follow-up and suboptimal utilization of ICD therapy. The natural history of these patients, and their fate regarding ICD implantation, is unknown. Hypothesis We hypothesized that a waiting period after revascularization for stable CAD results in missed opportunities to provide care with regard to ICD implantation. Methods We followed patients with LVEF ≤ 35% and no ICD who underwent revascularization (coronary artery bypass grafting [CABG] or percutaneous coronary intervention [PCI]) for stable CAD. Follow-up used chart review and scripted telephone interviews. Results Among 3164 revascularized patients (2198 [69%] PCI, 966 [31%] CABG), only 62 (2%; 33 [53%] male, age 67 ± 12 y, LVEF 28% ± 6%) had stable CAD, depressed LVEF, and no ICD. Over 35 ± 19 months, 35 (56%) of these 62 patients were no longer candidates for ICD based on improved LVEF, 14 (23%) received an ICD, 5 (8%) declined ICD despite physician recommendation, 3 (5%) were not offered ICD despite continued eligibility, 2 (3%) died, 1 (2%) was not a candidate due to substance abuse, and 1 (2%) had ICD implantation temporarily deferred. Only 1 (2%) was lost to follow-up. Conclusions Following revascularization for stable CAD with depressed LVEF, ≥50% of patients' ventricular function improved enough to make ICD implantation unnecessary. A waiting period after revascularization prior to ICD implantation appears appropriate and does not significantly negatively impact follow-up or the rate of appropriate ICD implantation