Estimation of Extreme Values by the Average Conditional Exceedance Rate Method

This paper details a method for extreme value prediction on the basis of a sampled time series. The method is specifically designed to account for statistical dependence between the sampled data points in a precise manner. In fact, if properly used, the new method will provide statistical estimates of the exact extreme value distribution provided by the data in most cases of practical interest. It avoids the problem of having to decluster the data to ensure independence, which is a requisite component in the application of, for example, the standard peaks-over-threshold method. The proposed method also targets the use of subasymptotic data to improve prediction accuracy. The method will be demonstrated by application to both synthetic and real data. From a practical point of view, it seems to perform better than the POT and block extremes methods, and, with an appropriate modification, it is directly applicable to nonstationary time series

Educational differences in cardiovascular mortality:The role of shared family factors and cardiovascular risk factors

Aims: To explore the confounding effects of early family factors shared by siblings and cardiovascular risk factors in midlife on the educational differences in mortality from cardiovascular disease (CVD). Methods: Data from national and regional health surveys in Norway (1974–2003) were linked with data from the Norwegian Family Based Life Course Study, the National Educational Registry and the Cause of Death Registry. The study population consisted of participants with at least one full sibling among the health survey participants ( n=271,310). Data were available on CVD risk factors, including weight, height, blood pressure, total cholesterol and smoking. Results: The hazards ratio (HR) of CVD mortality was 3.44 (95% confidence interval (CI) 2.98–3.96) in the lowest educational group relative to the highest. The HRs were little altered in the within-sibship analyses. Adjusted for risk factors, the HR for CVD mortality in the cohort analyses was 2.05 (CI 1.77–2.37) in the lowest educational group relative to the highest. The respective HR in the within-sibship analyses was 2.46 (CI 1.48–2.24). Conclusions: Using a sibling design, we did not find that the association between education and CVD mortality was confounded by early life factors shared by siblings, but it was explained to a large extent by CVD risk factors. These results suggest that reducing levels of CVD risk factors could have the greatest effect on mortality in less well-educated people. </jats:p

Early Life Socioeconomic Circumstance and Late Life Brain Hyperintensities : A Population Based Cohort Study

Funding: Image acquisition and image analysis for this study was funded by the Alzheimer's Research Trust (now Alzheimer's Research UK). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Acknowledgments The authors would like to thank the participants of the Aberdeen 1936 Birth Cohort (ABC36), without whom this research would not have been possible.Peer reviewedPublisher PD

Long-term particulate matter exposure and mortality: a review of European epidemiological studies

<p>Abstract</p> <p>Background</p> <p>Several studies considered the relation between long-term exposure to particulate matter (PM) and total mortality, as well as mortality from cardiovascular and respiratory diseases. Our aim was to provide a comprehensive review of European epidemiological studies on the issue.</p> <p>Methods</p> <p>We searched the Medline database for epidemiological studies on air pollution and health outcomes published between January 2002 and December 2007. We also examined the reference lists of individual papers and reviews. Two independent reviewers classified the studies according to type of air pollutant, duration of exposure and health outcome considered. Among European investigations that examined long-term PM exposure we found 4 cohort studies (considering total and cardiopulmonary mortality), 1 case-control study (considering mortality from myocardial infarction), and 4 ecologic studies (2 studies considering total and cardiopulmonary mortality and 2 studies focused on cardiovascular mortality).</p> <p>Results</p> <p>Measurement indicators of PM exposure used in European studies, including PM10, PM2.5, total suspended particulate and black smoke, were heterogeneous. This notwithstanding, in all analytic studies total mortality was directly associated with long-term exposure to PM. The excesses in mortality were mainly due to cardiovascular and respiratory causes. Three out of 4 ecologic studies found significant direct associations between PM indexes and mortality.</p> <p>Conclusion</p> <p>European studies on long-term exposure to PM indicate a direct association with mortality, particularly from cardiovascular and respiratory diseases.</p

Simplifying the clinical classification of polymerase gamma (POLG) disease based on age of onset; studies using a cohort of 155 cases

Background: Variants in POLG are one of the most common causes of inherited mitochondrial disease. Phenotypic classification of POLG disease has evolved haphazardly making it complicated and difficult to implement in everyday clinical practise. The aim of our study was to simplify the classification and facilitate better clinical recognition. / Methods: A multinational, retrospective study using data from 155 patients with POLG variants recruited from seven European countries. / Results: We describe the spectrum of clinical features associated with POLG variants in the largest known cohort of patients. While clinical features clearly form a continuum, stratifying patients simply according to age of onset—onset prior to age 12 years; onset between 12 and 40 years and onset after the age of 40 years, permitted us to identify clear phenotypic and prognostic differences. Prior to 12 years of age, liver involvement (87%), seizures (84%), and feeding difficulties (84%) were the major features. For those with onset between 12 and 40 years, ataxia (90%), peripheral neuropathy (84%), and seizures (71%) predominated, while for those with onset over 40 years, ptosis (95%), progressive external ophthalmoplegia (89%), and ataxia (58%) were the major clinical features. The earlier the onset the worse the prognosis. Patients with epilepsy and those with compound heterozygous variants carried significantly worse prognosis. / Conclusion: Based on our data, we propose a simplified POLG disease classification, which can be used to guide diagnostic investigations and predict disease course

The impact of gender, puberty, and pregnancy in patients with POLG disease

OBJECTIVE: To study the impact of gender, puberty, and pregnancy on the expression of POLG disease, one of the most common mitochondrial diseases known. METHODS: Clinical, laboratory, and genetic data were collected retrospectively from 155 patients with genetically confirmed POLG disease recruited from seven European countries. We used the available data to study the impact of gender, puberty, and pregnancy on disease onset and deterioration. RESULTS: We found that disease onset early in life was common in both sexes but there was also a second peak in females around the time of puberty. Further, pregnancy had a negative impact with 10 of 14 women (71%) experiencing disease onset or deterioration during pregnancy. INTERPRETATION: Gender clearly influences the expression of POLG disease. While onset very early in life was common in both males and females, puberty in females appeared associated both with disease onset and increased disease activity. Further, both disease onset and deterioration, including seizure aggravation and status epilepticus, appeared to be associated with pregnancy. Thus, whereas disease activity appears maximal early in life with no subsequent peaks in males, both menarche and pregnancy appear associated with disease onset or worsening in females. This suggests that hormonal changes may be a modulating factor

Comparison of the predictive performance of the BIG, TRISS, and PS09 score in an adult trauma population derived from multiple international trauma registries

The BIG score (Admission base deficit (B), International normalized ratio (I), and Glasgow Coma Scale (G)) has been shown to predict mortality on admission in pediatric trauma patients. The objective of this study was to assess its performance in predicting mortality in an adult trauma population, and to compare it with the existing Trauma and Injury Severity Score (TRISS) and probability of survival (PS09) score. A retrospective analysis using data collected between 2005 and 2010 from seven trauma centers and registries in Europe and the United States of America was performed. We compared the BIG score with TRISS and PS09 scores in a population of blunt and penetrating trauma patients. We then assessed the discrimination ability of all scores via receiver operating characteristic (ROC) curves and compared the expected mortality rate (precision) of all scores with the observed mortality rate. In total, 12,206 datasets were retrieved to validate the BIG score. The mean ISS was 15 ± 11, and the mean 30-day mortality rate was 4.8%. With an AUROC of 0.892 (95% confidence interval (CI): 0.879 to 0.906), the BIG score performed well in an adult population. TRISS had an area under ROC (AUROC) of 0.922 (0.913 to 0.932) and the PS09 score of 0.825 (0.915 to 0.934). On a penetrating-trauma population, the BIG score had an AUROC result of 0.920 (0.898 to 0.942) compared with the PS09 score (AUROC of 0.921; 0.902 to 0.939) and TRISS (0.929; 0.912 to 0.947). The BIG score is a good predictor of mortality in the adult trauma population. It performed well compared with TRISS and the PS09 score, although it has significantly less discriminative ability. In a penetrating-trauma population, the BIG score performed better than in a population with blunt trauma. The BIG score has the advantage of being available shortly after admission and may be used to predict clinical prognosis or as a research tool to risk stratify trauma patients into clinical trial

Hunting for health, well-being, and quality of life

Health, well-being, quality of life, and lifestyle are central concepts within health science, although generally accepted definitions are still lacking. Lifestyle can either be seen as an independent variable and the cause of unhealthy behaviour or as a dependent variable, which is affected by conditions in the society. In the first case, the attention is directed on each individual case: maintaining or improving health requires changes in lifestyle and living habits. In this perspective, diet and physical activity are important features for health promotion. In the second case the attention is rather directed on structural conditions in society, for example the food industry, the lunches for children at school, and the “fast food” industry should be influenced to protect human health. The structural perspective has, so far, received restricted impact when it concerns prevention and promotion of health. Processes of individualisation in the society have to an increasing extent viewed health as an affair for the individual. The benefits of physical activity, healthy food and beverage, social support, and joy are documented scientifically. In general, the trend towards increasing responsibility for one's lifestyle and health is positive, but might reinforce the inequality in health. With an even harder climate in society there might be a risk that individual health projects undermine the solidarity and the will to accept costs for medical treatment and care for people who risk their health through an unhealthy and risk-taking lifestyle. However, we argue that peoples’ well-being and quality of life presupposes a society that stands up for all people

Must we measure what we mean?

This paper excavates a debate concerning the claims of ordinary language philosophers that took place during the middle of the last century. The debate centers on the status of statements about “what we say”. On one side of the debate, critics of ordinary language philosophy argued that statements about “what we say” should be evaluated as empirical observations about how people do in fact speak, on a par with claims made in the language sciences. By that standard, ordinary language philosophers were not entitled to the claims that they made about what we would say about various topics. On the other side of the debate, defenders of the methods of ordinary language philosophy sought to explain how philosophers can be entitled to statements about what we would say without engaging in extensive observations of how people do in fact use language. In this paper I defend the idea that entitlement to claims about what we say can be had in a way that doesn’t require empirical observation, and I argue that ordinary language philosophers are (at least sometimes) engaged in a different project than linguists or empirically minded philosophers of language, which is subject to different conditions of success