The objective was to test the hypothesis that a described association between homozygosity for a 50bp deletion in the SOD1 promoter 1684bp upstream of the SOD1 ATG and an increased age of onset in SALS can be replicated in additional SALS and control sample sets from other populations. Our second objective was to examine whether this deletion attenuates expression of the SOD1 gene. Genomic DNA from more than 1200 SALS cases from Ireland, Scotland, Quebec and the USA was genotyped for the 50bp SOD1 promoter deletion. Reporter gene expression analysis, electrophoretic mobility shift assays and chromatin immunoprecipitation studies were utilized to examine the functional effects of the deletion. The genetic association for homozygosity for the promoter deletion with an increased age of symptom onset was confirmed overall in this further study (p=0.032), although it was only statistically significant in the Irish subset, and remained highly significant in the combined set of all cohorts (p=0.001). Functional studies demonstrated that this polymorphism reduces the activity of the SOD1 promoter by approximately 50%. In addition we revealed that the transcription factor SP1 binds within the 50bp deletion region in vitro and in vivo. Our findings suggest the hypothesis that this deletion reduces expression of the SOD1 gene and that levels of the SOD1 protein may modify the phenotype of SALS within selected populations.
Information about physician anaesthesiologist manpower in the countries of the European Union was collected from questionnaires sent to the delegates representing their respective countries on the European Board of Anaesthesiology. In the countries of the European Union and Switzerland and Norway 40,259 specialist anaesthesiologists are recorded. The number of anaesthesiologists in relation to population varies between as little as 4.4 and 4.6 (Ireland and UK) and as many as 15.6 (Italy), with a mean of 10.8/100,000 inhabitants. There are 11,610 physicians recorded in training in anaesthesiology. The ratio of trainees to specialists in the European Union countries was 28.8/100, varying from as low as 6.5 in France, to as high as 96.7 and 98/100 in Ireland and the UK respectively. These figures indicate a wide difference in the numbers of specialists and trainees between the European countries studied. However, the overall mean figure is close to that reported in the USA (9.2/100,000).
Amyotrophic lateral sclerosis shares characteristics with some cancers, such as onset being more common in later life, progression usually being rapid, the disease affecting a particular cell type, and showing complex inheritance. We used a model originally applied to cancer epidemiology to investigate the hypothesis that amyotrophic lateral sclerosis is a multistep process.
We generated incidence data by age and sex from amyotrophic lateral sclerosis population registers in Ireland (registration dates 1995-2012), the Netherlands (2006-12), Italy (1995-2004), Scotland (1989-98), and England (2002-09), and calculated age and sex-adjusted incidences for each register. We regressed the log of age-specific incidence against the log of age with least squares regression. We did the analyses within each register, and also did a combined analysis, adjusting for register.
We identified 6274 cases of amyotrophic lateral sclerosis from a catchment population of about 34 million people. We noted a linear relationship between log incidence and log age in all five registers: England r(2)=0·95, Ireland r(2)=0·99, Italy r(2)=0·95, the Netherlands r(2)=0·99, and Scotland r(2)=0·97; overall r(2)=0·99. All five registers gave similar estimates of the linear slope ranging from 4·5 to 5·1, with overlapping confidence intervals. The combination of all five registers gave an overall slope of 4·8 (95% CI 4·5-5·0), with similar estimates for men (4·6, 4·3-4·9) and women (5·0, 4·5-5·5).
A linear relationship between the log incidence and log age of onset of amyotrophic lateral sclerosis is consistent with a multistage model of disease. The slope estimate suggests that amyotrophic lateral sclerosis is a six-step process. Identification of these steps could lead to preventive and therapeutic avenues.
UK Medical Research Council; UK Economic and Social Research Council; Ireland Health Research Board; The Netherlands Organisation for Health Research and Development (ZonMw); the Ministry of Health and Ministry of Education, University, and Research in Italy; the Motor Neurone Disease Association of England, Wales, and Northern Ireland; and the European Commission (Seventh Framework Programme).
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Diabetes has reached pandemic proportions worldwide. To address and assist health care professionals in maintaining and updating their knowledge base on diabetes care, a multilateral project within the framework of the Lifelong Learning Programme and the Erasmus Curriculum Development - sub programme was initiated in 2008. Four European countries are involved in the project - Estonia, Finland, Ireland and Lithuania. Across all four countries the prevalence of diabetes is rising rapidly. The project's (DIPRA - Counselling for Practice - a pilot of improving counselling quality of diabetes) main product will be an on-line study module on patient education and counselling for health care professionals. The management of diabetes demands a broad range of skills which include, communication, leadership, counselling, teaching and research to name but a few. While it is acknowledged that nurses can incorporate these skills into practice and so benefit the care of the patient there is no uniformity across the four countries studied as to what constitutes a specialist diabetes nurse. The study module and all the materials (databank, on-line lectures, and interactive exercises) will be developed in English and translated into partners' national languages (Estonian, Finnish, Lithuanian) to maximize the accessibility of all professionals in partner countries.
OBJECTIVES: To describe the organizational characteristics of antenatal care and their relation to the utilization of health services and perinatal mortality in 13 European countries. METHODS: The main data source was a questionnaire on the organization and financing of antenatal care, filled out in 1995 by country representatives of a European Concerted Action. RESULTS: Thirteen systems for providing antenatal care were found. No clear grouping by organizational characteristics (uniformity, main care providers, integration, continuity of care, physical site, financing) emerged. Organizational characteristics and the utilization of antenatal services or perinatal mortality did not relate to each other. CONCLUSIONS: There is no single way to provide high-coverage services. Further studies are needed to relate organization characteristics to health impact, costs, and patient satisfaction.
The purpose of this study was to examine the association between lower socioeconomic status (SES), as ascertained by years of education, and outcomes in patients with acute ST-segment elevation myocardial infarction (STEMI).
Previous studies have shown an inverse relationship between SES and coronary heart disease and mortality. Whether a similar association between SES and mortality exists in STEMI patients is unknown.
We evaluated 11,326 patients with STEMI in the GUSTO-III (Global Use of Strategies to Open Occluded Coronary Arteries) trial study from countries that enrolled >500 patients. We evaluated clinical outcomes (adjusted using multivariate regression analysis) according to the number of years of education completed.
One-year mortality was inversely related to years of education and was 5-fold higher in patients with 16 years of education (17.5% vs. 3.5%, p
We formed the GEnetics of Nephropathy-an International Effort (GENIE) consortium to examine previously reported genetic associations with diabetic nephropathy (DN) in type 1 diabetes. GENIE consists of 6,366 similarly ascertained participants of European ancestry with type 1 diabetes, with and without DN, from the All Ireland-Warren 3-Genetics of Kidneys in Diabetes U.K. and Republic of Ireland (U.K.-R.O.I.) collection and the Finnish Diabetic Nephropathy Study (FinnDiane), combined with reanalyzed data from the Genetics of Kidneys in Diabetes U.S. Study (U.S. GoKinD). We found little evidence for the association of the EPO promoter polymorphism, rs161740, with the combined phenotype of proliferative retinopathy and end-stage renal disease in U.K.-R.O.I. (odds ratio [OR] 1.14, P = 0.19) or FinnDiane (OR 1.06, P = 0.60). However, a fixed-effects meta-analysis that included the previously reported cohorts retained a genome-wide significant association with that phenotype (OR 1.31, P = 2 × 10(-9)). An expanded investigation of the ELMO1 locus and genetic regions reported to be associated with DN in the U.S. GoKinD yielded only nominal statistical significance for these loci. Finally, top candidates identified in a recent meta-analysis failed to reach genome-wide significance. In conclusion, we were unable to replicate most of the previously reported genetic associations for DN, and significance for the EPO promoter association was attenuated.
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The benefits of prostate cancer screening on an individual level remain unevaluated.
Between 1993 and 1999, a total of 43,987 men, aged 55-74 years, were included in the intervention arm of the European Randomized Study of Screening for Prostate Cancer (ERSPC) section in the Netherlands, Sweden, and Finland. A total of 42,503 men, aged 55-74 years, were included in a clinical population in Northern Ireland. Serum prostate-specific antigen (PSA)
Diagnostic criteria for Cohen Syndrome are based largely on physical characteristics, and systematic information about behaviour and social functioning is limited. Typically, individuals with this condition are described as being very sociable and as showing low rates of pathology. However, recent studies have indicated that behavioural difficulties may occur more frequently than previously suggested and that autistic features may be relatively common. The present investigation of 45 individuals with Cohen Syndrome (age 4-48 years) found that, although 57% of the sample were reported as showing some behavioural disturbance, problems related mainly to anxiety and social interactions; marked anti-social behaviours were rare. Twenty-two individuals met criteria for autism on standardised diagnostic assessments, although the "autistic profile" was somewhat atypical. The implications of these findings for our understanding of Cohen Syndrome are discussed.