rRNA sequencing in molecular microbiological diagnosis of bacterial infections in the autopsy setting

Diagnosing the aetiology of infectious diseases at autopsy, such as pneumonia, meningitis, sepsis or SUDI, is complicated due to issues including post mortem contamination, difficulty culturing fastidious organisms and subjective interpretation of polymicrobial cultures. Death of organisms may also occur post mortem, especially if antibiotics were given to the patient, but residual DNA from non-viable organisms, amenable to molecular detection, may remain. The 16S rRNA gene is present in all bacteria with conserved and hyper-variable regions along its length, allowing amplification and sequencing of all bacterial 16S sequences present in a sample. 16S sequencing offers potential advantages over culture-based diagnostics and is increasingly used in clinical practice. It has been used to identify bacteria in formalin fixed paraffin embedded (FFPE) surgical pathology specimens but its use has not been reported in autopsy diagnosis. This talk will summarise a study aimed to assess the utility of 16S sequencing as an adjunctive microbiological test in the autopsy. Our preliminary work has used post mortem lung tissue samples from children dying with pneumonia as part of the Pneumonia Etiology Research for Child Health (PERCH) project. The technique has identified known pathogens in some cases and provided additional diagnostic information in others. The presentation will discuss the technical aspects of 16S sequencing from FFPE and autopsy material, and the issues surrounding its application to diagnosis in comparison with standard culture based diagnostics on surgical/autopsy material

Half-AUC for the evaluation of sensitive or specific classifiers

This paper describes a simple, non-parametric variant of area under the receiver operating characteristic (ROC) curve (AUC), which we call half-AUC (HAUC). By measuring AUC in two halves: first when the true positive rate (TPR) is greater than the true negative rate (TNR) and then when TPR is less than TNR, we obtain a measure of a classifier's overall sensitivity (HAUC(Se)) and specificity (HAUC(Sp)) respectively. We show that these HAUC measures can be interpreted as the probability of correct ranking under the constraint that one class must have a higher detection rate than the other. We then go on to describe application domains where this constraint is appropriate and hence where HAUC may be superior to AUC. We show examples where HAUC discriminates ROC curves both when one curve dominates another and when the curves cross, but have an equivalent AUC. (C) 2013 Elsevier B.V. All rights reserved

Popular attitudes to memory, the body, and social identity : the rise of external commemoration in Britain, Ireland, and New England

A comparative analysis of samples of external memorials from burial grounds in Britain, Ireland and New England reveals a widespread pattern of change in monument style and content, and exponential growth in the number of permanent memorials from the 18th century onwards. Although manifested in regionally distinctive styles on which most academic attention has so far been directed, the expansion reflects global changes in social relationships and concepts of memory and the body. An archaeological perspective reveals the importance of external memorials in articulating these changing attitudes in a world of increasing material consumption

Intoxicants and the invention of 'consumption'

In 1600 the word ‘consumption’ was a term of medical pathology describing the ‘wasting, petrification of things’. By 1700 it was also a term of economic discourse: ‘In commodities, the value rises as its quantity is less and vent greater, which depends upon it being preferred in its consumption’. The article traces the emergence of this key category of economic analysis to debates over the economy in the 1620s and subsequent disputes over the excise tax, showing how ‘consumption’ was an early term in the developing lexicon of political economy. In so doing the article demonstrates the important role of ‘intoxicants’ – i.e. addictive and intoxicating commodities like alcohols and tobaccos – in shaping these early meanings and uses of ‘consumption’. It outlines the discursive importance of intoxicants, both as the foci for discussions of ‘superfluous’ and ‘necessary’ consumption and the target of legislation on consumption. And it argues that while these discussions had an ideological dimension, or dimensions, they were also responses to material increases in the volume and diversity of intoxicants in early seventeenth-century England. By way of conclusion the article suggests the significance of the Low Countries as a point of reference for English writers, as well as a more capacious and semantically sensitive approach to changes in early-modern consumption practices

The potential of breath analysis to improve outcome for patients with lung cancer

Lung cancer remains the most common cause of cancer related death in both the UK and USA. Development of diagnostic approaches that have the ability to detect lung cancer early are a research priority with potential to improve survival. Analysis of exhaled breath metabolites, or volatile organic compounds (VOCs) is an area of considerable interest as it could fulfil such requirements. Numerous studies have shown that VOC profiles are different in the breath of patients with lung cancer compared to healthy individuals or those with non-malignant lung diseases. This review provides a scientific and clinical assessment of the potential value of a breath test in lung cancer. It discusses the current understanding of metabolic pathways that contribute to exhaled VOC production in lung cancer and reviews the research conducted to date. Finally, we highlight important areas for future research and discuss how a breath test could be incorporated into various clinical pathways

Modifiable causes of premature death in middle-age in Western Europe: results from the EPIC cohort study

BACKGROUND: Life expectancy is increasing in Europe, yet a substantial proportion of adults still die prematurely before the age of 70 years. We sought to estimate the joint and relative contributions of tobacco smoking, hypertension, obesity, physical inactivity, alcohol and poor diet towards risk of premature death. METHODS: We analysed data from 264,906 European adults from the EPIC prospective cohort study, aged between 40 and 70 years at the time of recruitment. Flexible parametric survival models were used to model risk of death conditional on risk factors, and survival functions and attributable fractions (AF) for deaths prior to age 70 years were calculated based on the fitted models. RESULTS: We identified 11,930 deaths which occurred before the age of 70. The AF for premature mortality for smoking was 31 % (95 % confidence interval (CI), 31–32 %) and 14 % (95 % CI, 12–16 %) for poor diet. Important contributions were also observed for overweight and obesity measured by waist-hip ratio (10 %; 95 % CI, 8–12 %) and high blood pressure (9 %; 95 % CI, 7–11 %). AFs for physical inactivity and excessive alcohol intake were 7 % and 4 %, respectively. Collectively, the AF for all six risk factors was 57 % (95 % CI, 55–59 %), being 35 % (95 % CI, 32–37 %) among never smokers and 74 % (95 % CI, 73–75 %) among current smokers. CONCLUSIONS: While smoking remains the predominant risk factor for premature death in Europe, poor diet, overweight and obesity, hypertension, physical inactivity, and excessive alcohol consumption also contribute substantially. Any attempt to minimise premature deaths will ultimately require all six factors to be addressed.This work was supported by the French Social Affairs & Health Ministry, Department of Health (Direction Générale de la Santé). The work undertaken by David C Muller for this project was performed during the tenure of an IARC-Australia fellowship supported by Cancer Council Australia. Elio Riboli was supported by the Imperial College Biomedical Research Centre funded by the National Institute of Health Research of UK. The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by Danish Cancer Society (Denmark); Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l’Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM) (France); Deutsche Krebshilfe, Deutsches Krebsforschungszentrum and Federal Ministry of Education and Research (Germany); the Hellenic Health Foundation (Greece); Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy and National Research Council (Italy); Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands); Nordic Centre of Excellence programme on Food, Nutrition and Health. (Norway); Health Research Fund (FIS), PI13/00061 to Granada, Regional Governments of Andalucía, Asturias, Basque Country, Murcia (no. 6236) and Navarra, ISCIII RETIC (RD06/0020) (Spain); Swedish Cancer Society, Swedish Scientific Council and County Councils of Skåne and Västerbotten (Sweden); Cancer Research UK (14136 to EPIC-Norfolk; C570/A16491 to EPIC-Oxford), Medical Research Council (1000143 to EPIC-Norfolk) (United Kingdom)

Randomized controlled trial of urokinase versus placebo for nondraining malignant pleural effusion

Rationale: Patients with malignant pleural effusion experience breathlessness, which is treated by drainage and pleurodesis. Incomplete drainage results in residual dyspnea and pleurodesis failure. Intrapleural fibrinolytics lyse septations within pleural fluid, improving drainage. Objectives: To assess the effects of intrapleural urokinase on dyspnea and pleurodesis success in patients with nondraining malignant effusion. Methods: We conducted a prospective, double-blind, randomized trial. Patients with nondraining effusion were randomly allocated in a 1:1 ratio to intrapleural urokinase (100,000 IU, three doses, 12-hourly) or matched placebo. Measurements and Main Results: Co–primary outcome measures were dyspnea (average daily 100-mm visual analog scale scores over 28 d) and time to pleurodesis failure to 12 months. Secondary outcomes were survival, hospital length of stay, and radiographic change. A total of 71 subjects were randomized (36 received urokinase, 35 placebo) from 12 U.K. centers. The baseline characteristics were similar between the groups. There was no difference in mean dyspnea between groups (mean difference, 3.8 mm; 95% confidence interval [CI], −12 to 4.4 mm; P = 0.36). Pleurodesis failure rates were similar (urokinase, 13 of 35 [37%]; placebo, 11 of 34 [32%]; adjusted hazard ratio, 1.2; P = 0.65). Urokinase was associated with decreased effusion size visualized by chest radiography (adjusted relative improvement, −19%; 95% CI, −28 to −11%; P < 0.001), reduced hospital stay (1.6 d; 95% CI, 1.0 to 2.6; P = 0.049), and improved survival (69 vs. 48 d; P = 0.026). Conclusions: Use of intrapleural urokinase does not reduce dyspnea or improve pleurodesis success compared with placebo and cannot be recommended as an adjunct to pleurodesis. Other palliative treatments should be used. Improvements in hospital stay, radiographic appearance, and survival associated with urokinase require further evaluation. Clinical trial registered with ISRCTN (12852177) and EudraCT (2008-000586-26)