University of London

About: University of London is a education organization based out in London, United Kingdom. It is known for research contribution in the topics: Population & Public health. The organization has 44838 authors who have published 88086 publications receiving 4002499 citations. The organization is also known as: London University & Lond..

Pan-cancer analysis of whole genomes

Abstract: Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1,2,3. 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 promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5,6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8,9; and evaluates a range of more-specialized features of cancer genomes8,10,11,12,13,14,15,16,17,18.

Meta-analyses involving cross-over trials: methodological issues

Abstract: Background Meta-analysis of randomized controlled trials (RCTs) is usually based on trials where patients are randomized individually into two different, parallel, treatment groups. This paper concentrates on RCTs of a different design—two-period, twotreatment cross-over trials. Methods The characteristics of these trials are outlined, with detailed examples of methods for analysis for both continuous and binary data. These case studies are then extended into the context of a meta-analysis. The Cochrane Library was surveyed to assess current practice for synthesis. Results Methods are described for continuous and binary data for use both when the necessary paired data are given and also when they need to be calculated or imputed, and some suggestions are provided to help people wishing to synthesize data from cross-over trials into meta-analyses. The survey suggested that about 8% of the trials in the Cochrane library were cross-over trials and 18% of the reviews referred to such trials, although there was no consistent approach to their inclusion into the reviews. Conclusions Methods do exist for including valuable information from two-period, twotreatment cross-over trials into quantitative reviews. However, poor reporting of cross-over trials will often impede attempts to perform a meta-analysis using the available methods.

ABC of breast diseases. Breast cancer--epidemiology, risk factors and genetics.

Abstract: With 1 million new cases in the world each year, breast cancer is the commonest malignancy in women and comprises 18% of all female cancers In the United Kingdom, where the age standardised incidence and mortality is the highest in the world, the incidence among women aged 50 approaches two per 1000 women per year, and the disease is the single commonest cause of death among women aged 40-50, accounting for about a fifth of all deaths in this age group There are more than 14 000 deaths each year, and the incidence is increasing particularly among women aged 50-64, probably because of breast screening in this age group #### Worldwide incidence of cancers in women (1980) View this table: Worldwide incidence of cancers in women (1980) Of every 1000 women aged 50, two will recently have had breast cancer diagnosed and about 15 will have had a diagnosis made before the age of 50, giving a prevalence of breast cancer of nearly 2% ### Age The incidence of breast cancer increases with age, doubling about every 10 years until the menopause, when the rate of increase slows dramatically Compared with lung cancer, the incidence of breast cancer is higher at younger ages In some countries there is a flattening of the age-incidence curve after the menopause Percentage of all deaths in women attributable to breast cancer Standardised mortality for breast cancer in different countries ### Geographical variation Age adjusted incidence and mortality for breast cancer varies by up to a factor of five between countries The difference between Far Eastern and Western countries is diminishing but is still about fivefold Studies of migrants from Japan to Hawaii show that the rates of breast cancer in migrants assume the rate in the host country within one or two generations, indicating that environmental factors are of greater importance than genetic factors Age specific incidence and mortality for …

Consensus development methods, and their use in clinical guideline development.

Abstract: Record Status This is a bibliographic record of a published health technology assessment from a member of INAHTA. No evaluation of the quality of this assessment has been made for the HTA database. Citation Murphy M K, Black N A, Lamping D L, McKee C M, Sanderson C F B, Askham J, Marteau T. Consensus development methods, and their use in clinical guideline development: a review. Health Technology Assessment 1998; 2(3): 1-88 Authors' objectives To identify the factors that affect the decisions that emerge from consensus development methods. To assess the implications of the findings for the development of clinical guidelines. To recommend further methodological research for improving the use of consensus development methods as a basis for guideline production.

Patient safety, satisfaction, and quality of hospital care: cross sectional surveys of nurses and patients in 12 countries in Europe and the United States.

Abstract: Objective To determine whether hospitals with a good organisation of care (such as improved nurse staffing and work environments) can affect patient care and nurse workforce stability in European countries. Design Cross sectional surveys of patients and nurses. Setting Nurses were surveyed in general acute care hospitals (488 in 12 European countries; 617 in the United States); patients were surveyed in 210 European hospitals and 430 US hospitals. Participants 33 659 nurses and 11 318 patients in Europe; 27 509 nurses and more than 120 000 patients in the US. Main outcome measures Nurse outcomes (hospital staffing, work environments, burnout, dissatisfaction, intention to leave job in the next year, patient safety, quality of care), patient outcomes (satisfaction overall and with nursing care, willingness to recommend hospitals). Results The percentage of nurses reporting poor or fair quality of patient care varied substantially by country (from 11% (Ireland) to 47% (Greece)), as did rates for nurses who gave their hospital a poor or failing safety grade (4% (Switzerland) to 18% (Poland)). We found high rates of nurse burnout (10% (Netherlands) to 78% (Greece)), job dissatisfaction (11% (Netherlands) to 56% (Greece)), and intention to leave (14% (US) to 49% (Finland, Greece)). Patients’ high ratings of their hospitals also varied considerably (35% (Spain) to 61% (Finland, Ireland)), as did rates of patients willing to recommend their hospital (53% (Greece) to 78% (Switzerland)). Improved work environments and reduced ratios of patients to nurses were associated with increased care quality and patient satisfaction. In European hospitals, after adjusting for hospital and nurse characteristics, nurses with better work environments were half as likely to report poor or fair care quality (adjusted odds ratio 0.56, 95% confidence interval 0.51 to 0.61) and give their hospitals poor or failing grades on patient safety (0.50, 0.44 to 0.56). Each additional patient per nurse increased the odds of nurses reporting poor or fair quality care (1.11, 1.07 to 1.15) and poor or failing safety grades (1.10, 1.05 to 1.16). Patients in hospitals with better work environments were more likely to rate their hospital highly (1.16, 1.03 to 1.32) and recommend their hospitals (1.20, 1.05 to 1.37), whereas those with higher ratios of patients to nurses were less likely to rate them highly (0.94, 0.91 to 0.97) or recommend them (0.95, 0.91 to 0.98). Results were similar in the US. Nurses and patients agreed on which hospitals provided good care and could be recommended. Conclusions Deficits in hospital care quality were common in all countries. Improvement of hospital work environments might be a relatively low cost strategy to improve safety and quality in hospital care and to increase patient satisfaction.