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

A longitudinal study of student and experienced nurses' self-concept.

Researchers continue to emphasise the importance of professional identity or nurses' self-concept in the retention debate, although limited research has been undertaken on this specific issue. The purpose of this study was to capitalise upon recent advances in self-concept theory and measurement to identify, compare, and contrast the development of self-concept for graduate and experienced nurses. The Self Description Questionnaire III was used to assess four areas of general self-concept and a newly developed Nurses Self-Concept Questionnaire was used to assess six domains of self-concept specific to nursing. Student nurses completed instrumentation during their final year of a University course (N=506) and 6 months after graduation (N=110). Experienced nurses completed instrumentation at the end of the year (N=528) and eight months later (N=332). The results revealed that graduate self-concept was lower than experienced nurse self-concept in most domains at initial measurement (Time 1). Whilst some graduate self-concept domains demonstrated a rise in mean scores at eight months (Time 2), scores remained significantly lower overall than those of experienced nurses. The domain of Nurse General Self-Concept had fallen significantly from the student to graduate experience. Little change in the self-concept domains occurred over time for the experienced nurse group. The results provide valuable empirical evidence elucidating the development of nurses' self-concept. Key implications include the need to monitor self-concept development in graduate nurses and develop strategies for self-concept enhancement particularly for new graduates' Nurse General Self-Concept

Causal modeling of self-concept, job satisfaction, and retention of nurses.

BACKGROUND: The critical shortage of nurses experienced throughout the western world has prompted researchers to examine one major component of this complex problem - the impact of nurses' professional identity and job satisfaction on retention. DESIGN: A descriptive correlational design with a longitudinal element was used to examine a causal model of nurses' self-concept, job satisfaction, and retention plans in 2002. METHOD: A random sample of 2000 registered nurses was selected from the state registering authority listing. A postal survey assessing multiple dimensions of nurses' self-concept (measured by the nurse self-concept questionnaire), job satisfaction (measured by the index of work satisfaction) was undertaken at Time 1 (n=528) and 8 months later at Time 2 (n=332) (including retention plans (measured by the Nurse Retention Index). Using confirmatory factor analysis, correlation matrices and path analysis, measurement and structural models were examined on matching pairs of data from T1 and T2 (total sample N=332). FINDINGS: Nurses' self-concept was found to have a stronger association with nurses' retention plans (B=.45) than job satisfaction (B=.28). Aspects of pay and task were not significantly related to retention plans, however, professional status (r=.51), and to a lesser extent, organizational policies (r=.27) were significant factors. Nurses' general self-concept was strongly related (r=.57) to retention plans. CONCLUSIONS: Strategies or interventions requiring implementation and evaluation include: counseling to improve nurse general self-concept, education programs and competencies in health communication between health professionals, reporting of nurse-initiated programs with substantial patient benefit, nurse-friendly organizational policies, common health team learning opportunities, and autonomous practice models

Diagnostic performance of a rapid magnetic resonance imaging method of measuring hepatic steatosis

Objectives: Hepatic steatosis is associated with an increased risk of developing serious liver disease and other clinical sequelae of the metabolic syndrome. However, visual estimates of steatosis from histological sections of biopsy samples are subjective and reliant on an invasive procedure with associated risks. The aim of this study was to test the ability of a rapid, routinely available, magnetic resonance imaging (MRI) method to diagnose clinically relevant grades of hepatic steatosis in a cohort of patients with diverse liver diseases. Materials and Methods: Fifty-nine patients with a range of liver diseases underwent liver biopsy and MRI. Hepatic steatosis was quantified firstly using an opposed-phase, in-phase gradient echo, single breath-hold MRI methodology and secondly, using liver biopsy with visual estimation by a histopathologist and by computer-assisted morphometric image analysis. The area under the receiver operating characteristic (ROC) curve was used to assess the diagnostic performance of the MRI method against the biopsy observations. Results: The MRI approach had high sensitivity and specificity at all hepatic steatosis thresholds. Areas under ROC curves were 0.962, 0.993, and 0.972 at thresholds of 5%, 33%, and 66% liver fat, respectively. MRI measurements were strongly associated with visual (r2 = 0.83) and computer-assisted morphometric (r2 = 0.84) estimates of hepatic steatosis from histological specimens. Conclusions: This MRI approach, using a conventional, rapid, gradient echo method, has high sensitivity and specificity for diagnosing liver fat at all grades of steatosis in a cohort with a range of liver diseases

Role of water in electron-initiated processes and radical chemistry: Issues and scientific advances

An understanding of electron-initiated processes in aqueous systems and the subsequent radical chemistry these processes induce is critical in diverse fields such as waste remediation and environmental cleanup, radiation processing, nuclear reactors, and medical diagnosis and therapy. This review outlines the opportunity in the scientific community to create a research thrust aimed at developing a fundamental understanding of electron-driven processes in aqueous systems. Successful research programs in radiation chemistry and condensed-phase chemical physics provide the foundation to build such an effort