No effects on myocardial ischaemia in patients with stable ischaemic heart disease after treatment with ramipril for 6 months

OBJECTIVE: To assess the effects of a 6-month angiotensin-converting enzyme (ACE) inhibitor intervention on myocardial ischaemia. METHOD: We randomized 389 patients with stable coronary artery disease to double-blind treatment with ramipril 5 mg/day (n = 133), ramipril 1.25 mg/day (n = 133), or placebo (n = 123). Forty-eight-hour ambulatory electrocardiography was performed at baseline, and after 1 and 6 months. RESULTS: Relevant baseline variables were similar in all groups. Changes over 6 months in duration of ≥ 1 mm ST-segment depression (STD), total ischaemic burden and maximum STD did not differ significantly between the treatment groups. There was no difference in the frequency of adverse events between the groups. CONCLUSION: ACE inhibitor treatment has little impact on incidence and severity of myocardial ischaemia in patients with stable ischaemic heart disease

A roadmap to improve the quality of atrial fibrillation management:proceedings from the fifth Atrial Fibrillation Network/European Heart Rhythm Association consensus conference

At least 30 million people worldwide carry a diagnosis of atrial fibrillation (AF), and many more suffer from undiagnosed, subclinical, or 'silent' AF. Atrial fibrillation-related cardiovascular mortality and morbidity, including cardiovascular deaths, heart failure, stroke, and hospitalizations, remain unacceptably high, even when evidence-based therapies such as anticoagulation and rate control are used. Furthermore, it is still necessary to define how best to prevent AF, largely due to a lack of clinical measures that would allow identification of treatable causes of AF in any given patient. Hence, there are important unmet clinical and research needs in the evaluation and management of AF patients. The ensuing needs and opportunities for improving the quality of AF care were discussed during the fifth Atrial Fibrillation Network/European Heart Rhythm Association consensus conference in Nice, France, on 22 and 23 January 2015. Here, we report the outcome of this conference, with a focus on (i) learning from our 'neighbours' to improve AF care, (ii) patient-centred approaches to AF management, (iii) structured care of AF patients, (iv) improving the quality of AF treatment, and (v) personalization of AF management. This report ends with a list of priorities for research in AF patients

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

Comprehensive analysis of chromothripsis in 2,658 human cancers using whole-genome sequencing

Chromothripsis is a mutational phenomenon characterized by massive, clustered genomic rearrangements that occurs in cancer and other diseases. Recent studies in selected cancer types have suggested that chromothripsis may be more common than initially inferred from low-resolution copy-number data. Here, as part of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA), we analyze patterns of chromothripsis across 2,658 tumors from 38 cancer types using whole-genome sequencing data. We find that chromothripsis events are pervasive across cancers, with a frequency of more than 50% in several cancer types. Whereas canonical chromothripsis profiles display oscillations between two copy-number states, a considerable fraction of events involve multiple chromosomes and additional structural alterations. In addition to non-homologous end joining, we detect signatures of replication-associated processes and templated insertions. Chromothripsis contributes to oncogene amplification and to inactivation of genes such as mismatch-repair-related genes. These findings show that chromothripsis is a major process that drives genome evolution in human cancer

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Kvalitetsupplevelse och Motivation vid konsumtion av en Functional Food

Abstract Denna uppsats behandlar frågeställningar kring konsumenters motivation och kvalitetsupplevelse i samband med köp och konsumtion av Functional Food. Vi har genomgående i uppsatsen haft ett konsument- och ett producentperspektiv för att kunna identifiera skillnader som kan föreligga mellan dessa två. På så sätt utröner vi om konsumentens kvalitetsupplevelse stämmer överens med de mervärden som producenten vill förmedla. Vi har även kartlagt vilka faktorer som motiverar konsumenter till köp av en Functional Food. Till vår hjälp i den empiriska del som grundar sig på kvalitativa djupintervjuer med ladderingteknik har vi haft tillgång till ProViva Active. Vi har genomfört vår studie på gym/idrottshallar i Malmö/Lund. Vår uppsats visar att motivation till köp av ProViva Active varierar bland annat beroende på vilken träningsnivå individen befinner sig på. En konsument som ligger på högre nivå ger upphov till ett stort behov av proteiner och motiveras därmed endast av produktens innehåll och effekt. En konsument som motionerar i generell bemärkelse motiveras snarare av smak, förpackning och marknadsföringsåtgärder. Producenten förmedlar gällande produktens egenskaper att återhämtningseffekten infinner sig. Denna effekt upplevs inte av konsumenten, utan det är andra faktorer som motiverar konsumenten till köp, vilka vi har nämnt ovan. I en hypotetisk situation där det finns en produkt som ger upphov till att konsumenten känner återhämtningseffekt vid konsumtion skulle denna efterfrågas

Fifteen-year risk of major coronary events predicted by Holter ST-monitoring in asymptomatic middle-aged men.

Background: Ambulatory electrocardiogram monitoring (Holter) with ST-analysis as a measure of myocardial ichemia has in populations with coronary heart disease been shown to predict major coronary events: death, myocardial infarction or coronary revascularization. There has, however, been conflicting evidence regarding the usefulness of this technique in identification of healthy subjects with increased risk for coronary heart disease. The aim of this study was to assess if Holter monitoring with ST-analysis could be used to predict future major coronary events in asymptomatic middle-aged men with a defined aggregation of traditional risk factors for coronary heart disease. Methods: One hundred and fifty-five asymptomatic participants from the city of Malmo, Sweden, with known levels of conventional cardiovascular risk factors underwent Holter monitoring for analysis of transient ST-segment depression at the age of 55 years. Fifteen years after the Holter monitoring, hospital records, diagnosis and death registries were revisited for major coronary events. Results: An ST-segment depression of 1 mm or greater (0.1 mV) was considered significant for myocardial ischemia and was found in 54 of the 155 men. There were no significant differences in risk factors in the two groups at baseline. The 15-year incidence of a first major coronary event was significantly higher in men with ST-segment depression (39%) than in men without ST-segment depression (20%) (P<0.015). A Holter electrocardiogram could predict future major coronary events with a positive and negative predictive value of 35 and 80%, respectively. Conclusions: Holter monitoring can be used as a complement to conventional risk factor evaluation in deciding whether or not to treat risk factors for CHD in asymptomatic subjects

The Dark Side of the Swoon: antihypertensive treatment in the elderly.

We would like to thank Prof. Dal Moro for his valuable contribution[1]. Indeed, many patients, especially those who are older and who suffer from several concomitant diseases, are at risk of being "overtreated with good intentions". The main problem is that the diagnosis of essential hypertension is at times assigned very liberally based on a single ambulatory measurement without taking into consideration the natural history and variation of systemic blood pressure[2]. The orthostatic intolerance is often asymptomatic and thus not being looked for. Consequently, the antihypertensive treatment may additionally reduce blood pressure on standing and lead to unexpected syncopal attacks. This article is protected by copyright. All rights reserved