SwePub - search: WFRF:(MacFarlane Peter)

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1.	van de Vegte, Yordi, et al. (author) Genetic insights into resting heart rate and its role in cardiovascular disease 2023 In: Nature Communications. - : Springer Nature. - 2041-1723. ; 14:1 Journal article (peer-reviewed)abstract The genetics and clinical consequences of resting heart rate (RHR) remain incompletely understood. Here, the authors discover new genetic variants associated with RHR and find that higher genetically predicted RHR decreases risk of atrial fibrillation and ischemic stroke. Resting heart rate is associated with cardiovascular diseases and mortality in observational and Mendelian randomization studies. The aims of this study are to extend the number of resting heart rate associated genetic variants and to obtain further insights in resting heart rate biology and its clinical consequences. A genome-wide meta-analysis of 100 studies in up to 835,465 individuals reveals 493 independent genetic variants in 352 loci, including 68 genetic variants outside previously identified resting heart rate associated loci. We prioritize 670 genes and in silico annotations point to their enrichment in cardiomyocytes and provide insights in their ECG signature. Two-sample Mendelian randomization analyses indicate that higher genetically predicted resting heart rate increases risk of dilated cardiomyopathy, but decreases risk of developing atrial fibrillation, ischemic stroke, and cardio-embolic stroke. We do not find evidence for a linear or non-linear genetic association between resting heart rate and all-cause mortality in contrast to our previous Mendelian randomization study. Systematic alteration of key differences between the current and previous Mendelian randomization study indicates that the most likely cause of the discrepancy between these studies arises from false positive findings in previous one-sample MR analyses caused by weak-instrument bias at lower P-value thresholds. The results extend our understanding of resting heart rate biology and give additional insights in its role in cardiovascular disease development.
2.	Roselli, Carolina, et al. (author) Multi-ethnic genome-wide association study for atrial fibrillation 2018 In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 50:9, s. 1225-1233 Journal article (peer-reviewed)abstract Atrial fibrillation (AF) affects more than 33 million individuals worldwide(1) and has a complex heritability(2). We conducted the largest meta-analysis of genome-wide association studies (GWAS) for AF to date, consisting of more than half a million individuals, including 65,446 with AF. In total, we identified 97 loci significantly associated with AF, including 67 that were novel in a combined-ancestry analysis, and 3 that were novel in a European-specific analysis. We sought to identify AF-associated genes at the GWAS loci by performing RNA-sequencing and expression quantitative trait locus analyses in 101 left atrial samples, the most relevant tissue for AF. We also performed transcriptome-wide analyses that identified 57 AF-associated genes, 42 of which overlap with GWAS loci. The identified loci implicate genes enriched within cardiac developmental, electrophysiological, contractile and structural pathways. These results extend our understanding of the biological pathways underlying AF and may facilitate the development of therapeutics for AF.
3.	Furberg, Helena, et al. (author) Genome-wide meta-analyses identify multiple loci associated with smoking behavior 2010 In: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 42:5, s. 134-441 Journal article (peer-reviewed)abstract Consistent but indirect evidence has implicated genetic factors in smoking behavior1,2. We report meta-analyses of several smoking phenotypes within cohorts of the Tobacco and Genetics Consortium (n = 74,053). We also partnered with the European Network of Genetic and Genomic Epidemiology (ENGAGE) and Oxford-GlaxoSmithKline (Ox-GSK) consortia to follow up the 15 most significant regions (n > 140,000). We identified three loci associated with number of cigarettes smoked per day. The strongest association was a synonymous 15q25 SNP in the nicotinic receptor gene CHRNA3 (rs1051730[A], b = 1.03, standard error (s.e.) = 0.053, beta = 2.8 x 10(-73)). Two 10q25 SNPs (rs1329650[G], b = 0.367, s. e. = 0.059, beta = 5.7 x 10(-10); and rs1028936[A], b = 0.446, s. e. = 0.074, beta = 1.3 x 10(-9)) and one 9q13 SNP in EGLN2 (rs3733829[G], b = 0.333, s. e. = 0.058, P = 1.0 x 10(-8)) also exceeded genome-wide significance for cigarettes per day. For smoking initiation, eight SNPs exceeded genome-wide significance, with the strongest association at a nonsynonymous SNP in BDNF on chromosome 11 (rs6265[C], odds ratio (OR) = 1.06, 95% confidence interval (Cl) 1.04-1.08, P = 1.8 x 10(-8)). One SNP located near DBH on chromosome 9 (rs3025343[G], OR = 1.12, 95% Cl 1.08-1.18, P = 3.6 x 10(-8)) was significantly associated with smoking cessation.
4.	Ntalla, Ioanna, et al. (author) Multi-ancestry GWAS of the electrocardiographic PR interval identifies 202 loci underlying cardiac conduction 2020 In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1 Journal article (peer-reviewed)abstract The electrocardiographic PR interval reflects atrioventricular conduction, and is associated with conduction abnormalities, pacemaker implantation, atrial fibrillation (AF), and cardiovascular mortality. Here we report a multi-ancestry (N=293,051) genome-wide association meta-analysis for the PR interval, discovering 202 loci of which 141 have not previously been reported. Variants at identified loci increase the percentage of heritability explained, from 33.5% to 62.6%. We observe enrichment for cardiac muscle developmental/contractile and cytoskeletal genes, highlighting key regulation processes for atrioventricular conduction. Additionally, 8 loci not previously reported harbor genes underlying inherited arrhythmic syndromes and/or cardiomyopathies suggesting a role for these genes in cardiovascular pathology in the general population. We show that polygenic predisposition to PR interval duration is an endophenotype for cardiovascular disease, including distal conduction disease, AF, and atrioventricular pre-excitation. These findings advance our understanding of the polygenic basis of cardiac conduction, and the genetic relationship between PR interval duration and cardiovascular disease. On the electrocardiogram, the PR interval reflects conduction from the atria to ventricles and also serves as risk indicator of cardiovascular morbidity and mortality. Here, the authors perform genome-wide meta-analyses for PR interval in multiple ancestries and identify 141 previously unreported genetic loci.
5.	Lubitz, Steven A, et al. (author) Genetic Risk Prediction of Atrial Fibrillation 2017 In: Circulation. - 0009-7322. ; 135:14, s. 1311-1320 Journal article (peer-reviewed)abstract BACKGROUND—: Atrial fibrillation (AF) has a substantial genetic basis. Identification of individuals at greatest AF risk could minimize the incidence of cardioembolic stroke. METHODS—: To determine whether genetic data can stratify risk for development of AF, we examined associations between AF genetic risk scores and incident AF in five prospective studies comprising 18,919 individuals of European ancestry. We examined associations between AF genetic risk scores and ischemic stroke in a separate study of 509 ischemic stroke cases (202 cardioembolic [40%]) and 3,028 referents. Scores were based on 11 to 719 common variants (≥5%) associated with AF at P-values ranging from <1x10 to <1x10 in a prior independent genetic association study. RESULTS—: Incident AF occurred in 1,032 (5.5%) individuals. AF genetic risk scores were associated with new-onset AF after adjusting for clinical risk factors. The pooled hazard ratio for incident AF for the highest versus lowest quartile of genetic risk scores ranged from 1.28 (719 variants; 95%CI, 1.13-1.46; P=1.5x10) to 1.67 (25 variants; 95%CI, 1.47-1.90; P=9.3x10). Discrimination of combined clinical and genetic risk scores varied across studies and scores (maximum C statistic, 0.629-0.811; maximum ΔC statistic from clinical score alone, 0.009-0.017). AF genetic risk was associated with stroke in age- and sex-adjusted models. For example, individuals in the highest versus lowest quartile of a 127-variant score had a 2.49-fold increased odds of cardioembolic stroke (95%CI, 1.39-4.58; P=2.7x10). The effect persisted after excluding individuals (n=70) with known AF (odds ratio, 2.25; 95%CI, 1.20-4.40; P=0.01). CONCLUSIONS—: Comprehensive AF genetic risk scores were associated with incident AF beyond associations for clinical AF risk factors, though offered small improvements in discrimination. AF genetic risk was also associated with cardioembolic stroke in age- and sex-adjusted analyses. Efforts are warranted to determine whether AF genetic risk may improve identification of subclinical AF or help distinguish between stroke mechanisms.
6.	Mason, Jay W, et al. (author) Recommendations for the standardization and interpretation of the electrocardiogram: part II: Electrocardiography diagnostic statement list: a scientific statement from the American Heart Association Electrocardiography and Arrhythmias Committee, Council on Clinical Cardiology; the American College of Cardiology Foundation; and the Heart Rhythm Society: endorsed by the International Society for Computerized Electrocardiology 2007 In: Circulation. - 1524-4539. ; 115:10, s. 1325-1332 Journal article (peer-reviewed)abstract This statement provides a concise list of diagnostic terms for ECG interpretation that can be shared by students, teachers, and readers of electrocardiography. This effort was motivated by the existence of multiple automated diagnostic code sets containing imprecise and overlapping terms. An intended outcome of this statement list is greater uniformity of ECG diagnosis and a resultant improvement in patient care. The lexicon includes primary diagnostic statements, secondary diagnostic statements, modifiers, and statements for the comparison of ECGs. This diagnostic lexicon should be reviewed and updated periodically.
7.	Mason, Jay W, et al. (author) Recommendations for the standardization and interpretation of the electrocardiogram: part II: electrocardiography diagnostic statement list a scientific statement from the American Heart Association Electrocardiography and Arrhythmias Committee, Council on Clinical Cardiology; the American College of Cardiology Foundation; and the Heart Rhythm Society Endorsed by the International Society for Computerized Electrocardiology 2007 In: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097. ; 49:10, s. 1128-1128 Journal article (peer-reviewed)abstract This statement provides a concise list of diagnostic terms for ECG interpretation that can be shared by students, teachers, and readers of electrocardiography. This effort was motivated by the existence of multiple automated diagnostic code sets containing imprecise and overlapping terms. An intended outcome of this statement list is greater uniformity of ECG diagnosis and a resultant improvement in patient care. The lexicon includes primary diagnostic statements, secondary diagnostic statements, modifiers, and statements for the comparison of ECGs. This diagnostic lexicon should be reviewed and updated periodically.
8.	McKay, James D., et al. (author) A Genome-Wide Association Study of Upper Aerodigestive Tract Cancers Conducted within the INHANCE Consortium 2011 In: PLOS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 7:3 Journal article (peer-reviewed)abstract Genome-wide association studies (GWAS) have been successful in identifying common genetic variation involved in susceptibility to etiologically complex disease. We conducted a GWAS to identify common genetic variation involved in susceptibility to upper aero-digestive tract (UADT) cancers. Genome-wide genotyping was carried out using the Illumina HumanHap300 beadchips in 2,091 UADT cancer cases and 3,513 controls from two large European multi-centre UADT cancer studies, as well as 4,821 generic controls. The 19 top-ranked variants were investigated further in an additional 6,514 UADT cancer cases and 7,892 controls of European descent from an additional 13 UADT cancer studies participating in the INHANCE consortium. Five common variants presented evidence for significant association in the combined analysis (p <= 5 x 10(-7)). Two novel variants were identified, a 4q21 variant (rs1494961, p = 1 x 10(-8)) located near DNA repair related genes HEL308 and FAM175A (or Abraxas) and a 12q24 variant (rs4767364, p = 2 x 10(-8)) located in an extended linkage disequilibrium region that contains multiple genes including the aldehyde dehydrogenase 2 (ALDH2) gene. Three remaining variants are located in the ADH gene cluster and were identified previously in a candidate gene study involving some of these samples. The association between these three variants and UADT cancers was independently replicated in 5,092 UADT cancer cases and 6,794 controls non-overlapping samples presented here (rs1573496-ADH7, p = 5 x 10(-8); rs1229984-ADH1B, p = 7 x 10(-9); and rs698-ADH1C, p = 0.02). These results implicate two variants at 4q21 and 12q24 and further highlight three ADH variants in UADT cancer susceptibility.
9.	Sinner, Moritz F, et al. (author) Integrating Genetic, Transcriptional, and Functional Analyses to Identify Five Novel Genes for Atrial Fibrillation. 2014 In: Circulation. - 1524-4539. ; 130:5, s. 1225-1225 Journal article (peer-reviewed)abstract -Atrial fibrillation (AF) affects over 30 million individuals worldwide and is associated with an increased risk of stroke, heart failure, and death. AF is highly heritable, yet the genetic basis for the arrhythmia remains incompletely understood.
10.	van Setten, Jessica, et al. (author) PR interval genome-wide association meta-analysis identifies 50 loci associated with atrial and atrioventricular electrical activity 2018 In: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 9 Journal article (peer-reviewed)abstract Electrocardiographic PR interval measures atrio-ventricular depolarization and conduction, and abnormal PR interval is a risk factor for atrial fibrillation and heart block. Our genomewide association study of over 92,000 European-descent individuals identifies 44 PR interval loci (34 novel). Examination of these loci reveals known and previously not-yet-reported biological processes involved in cardiac atrial electrical activity. Genes in these loci are overrepresented in cardiac disease processes including heart block and atrial fibrillation. Variants in over half of the 44 loci were associated with atrial or blood transcript expression levels, or were in high linkage disequilibrium with missense variants. Six additional loci were identified either by meta-analysis of similar to 105,000 African and European-descent individuals and/or by pleiotropic analyses combining PR interval with heart rate, QRS interval, and atrial fibrillation. These findings implicate developmental pathways, and identify transcription factors, ionchannel genes, and cell-junction/cell-signaling proteins in atrio-ventricular conduction, identifying potential targets for drug development.
11.	Wagner, Galen, et al. (author) Consideration of pitfalls in and omissions from the current ECG standards for diagnosis of myocardial ischemia/infarction in patients who have acute coronary syndromes 2006 In: Cardiology Clinics. - : Elsevier BV. - 1558-2264 .- 0733-8651. ; 24:3, s. 331-331 Journal article (peer-reviewed)abstract The ECG is the key clinical test available for the emergency determination of which patients who presenting with acute coronary syndromes indeed have acute myocardial ischemia/infarction. Because typically the etiology is thrombosis, the correct clinical decision regarding reperfusion therapy is crucial. This review follows the efforts of an AHA working group to develop new standards for clinical application of electrocardiology. The pitfalls in the current diagnostic standards regarding ischemia/infarction that have been identified by sufficiently documented studies are corrected in their report. This article focuses on the pitfalls for which new standards will emerge in future years.
12.	Weng, Lu Chen, et al. (author) Genetic Interactions with Age, Sex, Body Mass Index, and Hypertension in Relation to Atrial Fibrillation : The AFGen Consortium 2017 In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7:1 Journal article (peer-reviewed)abstract It is unclear whether genetic markers interact with risk factors to influence atrial fibrillation (AF) risk. We performed genome-wide interaction analyses between genetic variants and age, sex, hypertension, and body mass index in the AFGen Consortium. Study-specific results were combined using meta-analysis (88,383 individuals of European descent, including 7,292 with AF). Variants with nominal interaction associations in the discovery analysis were tested for association in four independent studies (131,441 individuals, including 5,722 with AF). In the discovery analysis, the AF risk associated with the minor rs6817105 allele (at the PITX2 locus) was greater among subjects ≤ 65 years of age than among those > 65 years (interaction p-value = 4.0 × 10-5). The interaction p-value exceeded genome-wide significance in combined discovery and replication analyses (interaction p-value = 1.7 × 10-8). We observed one genome-wide significant interaction with body mass index and several suggestive interactions with age, sex, and body mass index in the discovery analysis. However, none was replicated in the independent sample. Our findings suggest that the pathogenesis of AF may differ according to age in individuals of European descent, but we did not observe evidence of statistically significant genetic interactions with sex, body mass index, or hypertension on AF risk.
13.	Young, William J., et al. (author) Genetic analyses of the electrocardiographic QT interval and its components identify additional loci and pathways 2022 In: Nature Communications. - : Springer Nature. - 2041-1723. ; 13 Journal article (peer-reviewed)abstract The QT interval is a heritable electrocardiographic measure associated with arrhythmia risk when prolonged. Here, the authors used a series of genetic analyses to identify genetic loci, pathways, therapeutic targets, and relationships with cardiovascular disease. The QT interval is an electrocardiographic measure representing the sum of ventricular depolarization and repolarization, estimated by QRS duration and JT interval, respectively. QT interval abnormalities are associated with potentially fatal ventricular arrhythmia. Using genome-wide multi-ancestry analyses (>250,000 individuals) we identify 177, 156 and 121 independent loci for QT, JT and QRS, respectively, including a male-specific X-chromosome locus. Using gene-based rare-variant methods, we identify associations with Mendelian disease genes. Enrichments are observed in established pathways for QT and JT, and previously unreported genes indicated in insulin-receptor signalling and cardiac energy metabolism. In contrast for QRS, connective tissue components and processes for cell growth and extracellular matrix interactions are significantly enriched. We demonstrate polygenic risk score associations with atrial fibrillation, conduction disease and sudden cardiac death. Prioritization of druggable genes highlight potential therapeutic targets for arrhythmia. Together, these results substantially advance our understanding of the genetic architecture of ventricular depolarization and repolarization.
14.	Zuntini, Alexandre R., et al. (author) Phylogenomics and the rise of the angiosperms 2024 In: NATURE. - 0028-0836 .- 1476-4687. ; 629, s. 843-850 Journal article (peer-reviewed)abstract Angiosperms are the cornerstone of most terrestrial ecosystems and human livelihoods(1,2). A robust understanding of angiosperm evolution is required to explain their rise to ecological dominance. So far, the angiosperm tree of life has been determined primarily by means of analyses of the plastid genome(3,4). Many studies have drawn on this foundational work, such as classification and first insights into angiosperm diversification since their Mesozoic origins(5-7). However, the limited and biased sampling of both taxa and genomes undermines confidence in the tree and its implications. Here, we build the tree of life for almost 8,000 (about 60%) angiosperm genera using a standardized set of 353 nuclear genes(8). This 15-fold increase in genus-level sampling relative to comparable nuclear studies(9) provides a critical test of earlier results and brings notable change to key groups, especially in rosids, while substantiating many previously predicted relationships. Scaling this tree to time using 200 fossils, we discovered that early angiosperm evolution was characterized by high gene tree conflict and explosive diversification, giving rise to more than 80% of extant angiosperm orders. Steady diversification ensued through the remaining Mesozoic Era until rates resurged in the Cenozoic Era, concurrent with decreasing global temperatures and tightly linked with gene tree conflict. Taken together, our extensive sampling combined with advanced phylogenomic methods shows the deep history and full complexity in the evolution of a megadiverse clade.
15.	Anantharaman, Devasena, et al. (author) Combined effects of smoking and HPV16 in oropharyngeal cancer 2016 In: International Journal of Epidemiology. - : Oxford University Press (OUP). - 0300-5771 .- 1464-3685. ; 45:3, s. 752-761 Journal article (peer-reviewed)abstract Background: Although smoking and HPV infection are recognized as important risk factors for oropharyngeal cancer, how their joint exposure impacts on oropharyngeal cancer risk is unclear. Specifically, whether smoking confers any additional risk to HPV-positive oropharyngeal cancer is not understood.Methods: Using HPV serology as a marker of HPV-related cancer, we examined the interaction between smoking and HPV16 in 459 oropharyngeal (and 1445 oral cavity and laryngeal) cancer patients and 3024 control participants from two large European multicentre studies. Odds ratios and credible intervals [CrI], adjusted for potential confounders, were estimated using Bayesian logistic regression.Results: Both smoking [odds ratio (OR [CrI]: 6.82 [4.52, 10.29]) and HPV seropositivity (OR [CrI]: 235.69 [99.95, 555.74]) were independently associated with oropharyngeal cancer. The joint association of smoking and HPV seropositivity was consistent with that expected on the additive scale (synergy index [CrI]: 1.32 [0.51, 3.45]), suggesting they act as independent risk factors for oropharyngeal cancer.Conclusions: Smoking was consistently associated with increase in oropharyngeal cancer risk in models stratified by HPV16 seropositivity. In addition, we report that the prevalence of oropharyngeal cancer increases with smoking for both HPV16-positive and HPV16-negative persons. The impact of smoking on HPV16-positive oropharyngeal cancer highlights the continued need for smoking cessation programmes for primary prevention of head and neck cancer.
16.	Bellamy, Chyrell D., et al. (author) An analysis of groups in consumer-centered programs 2006 In: American Journal of Psychiatric Rehabilitation. - : University of Nebraska Press. - 1548-7768 .- 1548-7776. ; 9:3, s. 219-240 Journal article (peer-reviewed)abstract This study used a mixed methods approach to describe and analyze data from groups observed in two types of mental health consumer-centered programs, namely consumer-run drop-in centers and clubhouses. An overview of consumer-centered programs is presented, followed by a report of the study which includes a description of the groups in the sample and data on the effects of group process and group leader characteristics on group functioning. Results indicate that, for the most part, the groups were task oriented (e.g., planning events or discussing issues about the center). Psychoeducation and recovery were also frequent topics in the group meetings. In terms of group participation, consumers took on various assignments, served as facilitators, assumed tasks and roles, shared experiences, and provided support to other group participants. A major finding is that group leaders displayed both good and poor leadership behaviors. The good leadership behaviors were often efforts to respond to problematic responses of members and poor leadership behaviors often elicited such responses. The qualitative analysis provided examples of how these behaviors affected the group sessions. This pilot study, by identifying some of the group conditions present in such groups, should lead to new studies that are based on specific hypotheses concerning the relationships that exist among group conditions, interventions to improve such conditions, and outcomes for participants.
17.	Bellamy, Chyrell D., et al. (author) Relevance of spirituality for people with mental illness attending consumer-centered services 2007 In: Psychiatric rehabilitation journal. - : American Psychological Association (APA). - 1095-158X .- 1559-3126. ; 30:4, s. 287-294 Journal article (peer-reviewed)abstract Spirituality has been cited in the literature as having a positive effect on mental health outcomes. This paper explores the relationship of spirituality to demographic, psychiatric illness history and psychological constructs for people with mental illness (N=1835) involved in consumer-centered services (CCS-Clubhouses and Consumer run drop-in centers). Descriptive statistics indicate that spirituality is important for at least two thirds of the members in the study. Members primarily indicated participation in public spiritual activities (i.e., church, bible study groups), followed by private activities (prayer, reading the bible, and meditation) (both of which were centered on belief in the transcendent). A logistic regression analysis was done to explore variables related to spirituality (i.e., demographics, psychiatric illness history, and psychological constructs). Results suggest that age, gender, having psychotic symptoms, having depressive symptoms, and having a higher global quality of life, hope and sense of community were all significant correlates of spirituality.
18.	Birnbaum, Yochai, et al. (author) Common pitfalls in the interpretation of electrocardiograms from patients with acute coronary syndromes with narrow QRS: a consensus report 2012 In: Journal of Electrocardiology. - : Elsevier BV. - 1532-8430 .- 0022-0736. ; 45:5, s. 463-475 Journal article (peer-reviewed)abstract Acute coronary syndromes (ACS) with narrow QRS are divided into 2 groups: ST-elevation ACS that requires emergency percutaneous coronary intervention, and non-ST elevation ACS. The classification of ACS into these 2 groups is not always straightforward. In this document, we discuss several electrocardiogram patterns of acute ischemia that are often misinterpreted. We suggest that any new recommendations or guidelines from the Scientific Societies should acknowledge these aspects of electrocardiogram interpretation by including appropriate diagnostic criteria that should prove helpful for the optimal management of patients with ACS. (C) 2012 Elsevier Inc. All rights reserved.
19.	Brandes, Axel, et al. (author) Consumer-Led Screening for Atrial Fibrillation : Frontier Review of the AF-SCREEN International Collaboration 2022 In: Circulation. - 0009-7322 .- 1524-4539. ; 146:19, s. 1461-1474 Research review (peer-reviewed)abstract The technological evolution and widespread availability of wearables and handheld ECG devices capable of screening for atrial fibrillation (AF), and their promotion directly to consumers, has focused attention of health care professionals and patient organizations on consumer-led AF screening. In this Frontiers review, members of the AF-SCREEN International Collaboration provide a critical appraisal of this rapidly evolving field to increase awareness of the complexities and uncertainties surrounding consumer-led AF screening. Although there are numerous commercially available devices directly marketed to consumers for AF monitoring and identification of unrecognized AF, health care professional-led randomized controlled studies using multiple ECG recordings or continuous ECG monitoring to detect AF have failed to demonstrate a significant reduction in stroke. Although it remains uncertain if consumer-led AF screening reduces stroke, it could increase early diagnosis of AF and facilitate an integrated approach, including appropriate anticoagulation, rate or rhythm management, and risk factor modification to reduce complications. Companies marketing AF screening devices should report the accuracy and performance of their products in high- and low-risk populations and avoid claims about clinical outcomes unless improvement is demonstrated in randomized clinical trials. Generally, the diagnostic yield of AF screening increases with the number, duration, and temporal dispersion of screening sessions, but the prognostic importance may be less than for AF detected by single-time point screening, which is largely permanent, persistent, or high-burden paroxysmal AF. Consumer-initiated ECG recordings suggesting possible AF always require confirmation by a health care professional experienced in ECG reading, whereas suspicion of AF on the basis of photoplethysmography must be confirmed with an ECG. Consumer-led AF screening is unlikely to be cost-effective for stroke prevention in the predominantly young, early adopters of this technology. Studies in older people at higher stroke risk are required to demonstrate both effectiveness and cost-effectiveness. The direct interaction between companies and consumers creates new regulatory gaps in relation to data privacy and the registration of consumer apps and devices. Although several barriers for optimal use of consumer-led screening exist, results of large, ongoing trials, powered to detect clinical outcomes, are required before health care professionals should support widespread adoption of consumer-led AF screening.
20.	De Groot, Natasja M.S., et al. (author) Critical appraisal of technologies to assess electrical activity during atrial fibrillation : a position paper from the European Heart Rhythm Association and European Society of Cardiology Working Group on eCardiology in collaboration with the Heart Rhythm Society, Asia Pacific Heart Rhythm Society, Latin American Heart Rhythm Society and Computing in Cardiology 2022 In: Europace. - : Oxford University Press (OUP). - 1099-5129. ; 24:2, s. 313-330 Research review (peer-reviewed)abstract We aim to provide a critical appraisal of basic concepts underlying signal recording and processing technologies applied for (i) atrial fibrillation (AF) mapping to unravel AF mechanisms and/or identifying target sites for AF therapy and (ii) AF detection, to optimize usage of technologies, stimulate research aimed at closing knowledge gaps, and developing ideal AF recording and processing technologies. Recording and processing techniques for assessment of electrical activity during AF essential for diagnosis and guiding ablative therapy including body surface electrocardiograms (ECG) and endo- or epicardial electrograms (EGM) are evaluated. Discussion of (i) differences in uni-, bi-, and multi-polar (omnipolar/Laplacian) recording modes, (ii) impact of recording technologies on EGM morphology, (iii) global or local mapping using various types of EGM involving signal processing techniques including isochronal-, voltage- fractionation-, dipole density-, and rotor mapping, enabling derivation of parameters like atrial rate, entropy, conduction velocity/direction, (iv) value of epicardial and optical mapping, (v) AF detection by cardiac implantable electronic devices containing various detection algorithms applicable to stored EGMs, (vi) contribution of machine learning (ML) to further improvement of signals processing technologies. Recording and processing of EGM (or ECG) are the cornerstones of (body surface) mapping of AF. Currently available AF recording and processing technologies are mainly restricted to specific applications or have technological limitations. Improvements in AF mapping by obtaining highest fidelity source signals (e.g. catheter-electrode combinations) for signal processing (e.g. filtering, digitization, and noise elimination) is of utmost importance. Novel acquisition instruments (multi-polar catheters combined with improved physical modelling and ML techniques) will enable enhanced and automated interpretation of EGM recordings in the near future.
21.	Dionne, Clermont E, et al. (author) A consensus approach toward the standardization of back pain definitions for use in prevalence studies. 2008 In: Spine. - : Lippincott Williams & Wilkins. - 1528-1159 .- 0362-2436. ; 33:1, s. 95-103 Journal article (peer-reviewed)abstract A modified Delphi study conducted with 28 experts in back pain research from 12 countries.
22.	Galluzzi, L, et al. (author) Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018 2018 In: Cell death and differentiation. - : Springer Science and Business Media LLC. - 1476-5403 .- 1350-9047. ; 25:3, s. 486-541 Journal article (peer-reviewed)
23.	Glynn, Liam, et al. (author) The Limerick Declaration on Rural Health Care 2022 2023 In: Rural and Remote Health. - 1445-6354. ; 23:1, s. 7905-7905 Journal article (peer-reviewed)abstract The 19th World Rural Health Conference, hosted in rural Ireland and the University of Limerick, with over 650 participants coming from 40 countries and an additional 1600 engaging online, has carefully considered how best rural communities can be empowered to improve their own health and the health of those around them. The conference also considered the role of national health systems and all stakeholders, in keeping with the commitments made through the Sustainable Development Goals and the enjoyment of the highest attainable standard of health as one of the fundamental rights of every human being. This conference declaration, the Limerick Declaration on Rural Healthcare, is designed to inform rural communities, academics and policymakers about how to achieve the goal of delivering high quality health care in rural and remote areas most effectively, with a particular focus on the Irish healthcare system. Congruent with current evidence and best international practice, the participants of the conference endorsed a series of recommendations for the creation of high quality, sustainable and cost-effective healthcare delivery for rural communities in Ireland and globally. The recommendations focused on four major themes: rural healthcare needs and delivery, rural workforce, advocacy and policy, and research for rural health care. Equal access to health care is a crucial marker of democracy. Hence, we call on all governments, policymakers, academic institutions and communities globally to commit to providing their rural dwellers with equitable access to health care that is properly resourced and fundamentally patient-centred in its design.
24.	Hayes, Conor F., et al. (author) A Brief Guide to Multi-Objective Reinforcement Learning and Planning 2023 In: Proceedings of the 22nd International Conference on Autonomous Agents and Multiagent Systems (AAMAS). - 9781450394321 ; , s. 1988-1990 Conference paper (peer-reviewed)abstract Real-world sequential decision-making tasks are usually complex, and require trade-offs between multiple–often conflicting–objectives. However, the majority of research in reinforcement learning (RL) and decision-theoretic planning assumes a single objective, or that multiple objectives can be handled via a predefined weighted sum over the objectives. Such approaches may oversimplify the underlying problem, and produce suboptimal results. This extended abstract outlines the limitations of using a semi-blind iterative process to solve multi-objective decision making problems. Our extended paper [4], serves as a guide for the application of explicitly multi-objective methods to difficult problems.
25.	Hayes, Conor F., et al. (author) A practical guide to multi-objective reinforcement learning and planning 2022 In: Autonomous Agents and Multi-Agent Systems. - New York, NY, United States : Springer. - 1387-2532 .- 1573-7454. ; 36:1 Journal article (peer-reviewed)abstract Real-world sequential decision-making tasks are generally complex, requiring trade-offs between multiple, often conflicting, objectives. Despite this, the majority of research in reinforcement learning and decision-theoretic planning either assumes only a single objective, or that multiple objectives can be adequately handled via a simple linear combination. Such approaches may oversimplify the underlying problem and hence produce suboptimal results. This paper serves as a guide to the application of multi-objective methods to difficult problems, and is aimed at researchers who are already familiar with single-objective reinforcement learning and planning methods who wish to adopt a multi-objective perspective on their research, as well as practitioners who encounter multi-objective decision problems in practice. It identifies the factors that may influence the nature of the desired solution, and illustrates by example how these influence the design of multi-objective decision-making systems for complex problems.
26.	Heenan, Peter B., et al. (author) Morphological and phylogenetic relationships of the threatened geophyte Wurmbea novae-zelandiae (Colchicaceae) from New Zealand, with notes on typification 2017 In: Phytotaxa. - : MAGNOLIA PRESS. - 1179-3155 .- 1179-3163. ; 307:2, s. 123-132 Journal article (peer-reviewed)abstract The new combination Wurmbea novae-zelandiae was recently made based on published phylogenetic studies, but little information was provided on its relationships based on morphology. This species was originally described as Anguillaria novae-zelandiae, for which a lectotype is designated. Morphological characters of W. novae-zelandiae are re-evaluated and shown to be characteristic of Wurmbea, thereby supporting the revised generic placement. However, W. novae-zelandiae differs from all other Wurmbea species in its diminutive stature, fewer tepals and stamens, and variable floral morphology, with 1-3 carpels, often leaf-like tepals, and aberrant tepal shape and number. DNA sequence data places W. novae-zelandiae as the sister species of W. uniflora, a species not included in earlier phylogenetic studies. These two species share mostly solitary flowers with white tepals, nectaries two per tepal and similar in form and position, small yellow anthers, and styles that are relatively short and recurve as flowering proceeds, with the inner style surface stigmatic for up to half of its length. A revised generic description of Wurmbea is provided to take account of the recently widened concept.
27.	Holter, Mark, et al. (author) Critical ingredients of consumer run services : Results of a national survey 2004 In: Community mental health journal. - 0010-3853 .- 1573-2789. ; 40:1, s. 47-63 Journal article (peer-reviewed)abstract Fidelity criteria are increasingly used in program monitoring and evaluation, but are difficult to derive for emerging models (i.e., those not based on theory or a research demonstration project). We describe steps used to develop and operationalize fidelity criteria for consumer-run (CR) mental health services: articulating and operationalizing criteria based on published literature, then revising and validating the criteria through expert judgments using a modified Delphi method. Respondents rated highest those structural and process components emphasizing the value of consumerism: consumer control, consumer choices and opportunities for decision-making, voluntary participation (and the absence of coercion), and respect for members by staff.
28.	Hung, Rayjean J, et al. (author) A susceptibility locus for lung cancer maps to nicotinic acetylcholine receptor subunit genes on 15q25 2008 In: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 452:7187, s. 633-637 Journal article (peer-reviewed)abstract Lung cancer is the most common cause of cancer death worldwide, with over one million cases annually. To identify genetic factors that modify disease risk, we conducted a genome-wide association study by analysing 317,139 single-nucleotide polymorphisms in 1,989 lung cancer cases and 2,625 controls from six central European countries. We identified a locus in chromosome region 15q25 that was strongly associated with lung cancer (P = 9 x 10(-10)). This locus was replicated in five separate lung cancer studies comprising an additional 2,513 lung cancer cases and 4,752 controls (P = 5 x 10(-20) overall), and it was found to account for 14% (attributable risk) of lung cancer cases. Statistically similar risks were observed irrespective of smoking status or propensity to smoke tobacco. The association region contains several genes, including three that encode nicotinic acetylcholine receptor subunits (CHRNA5, CHRNA3 and CHRNB4). Such subunits are expressed in neurons and other tissues, in particular alveolar epithelial cells, pulmonary neuroendocrine cells and lung cancer cell lines, and they bind to N'-nitrosonornicotine and potential lung carcinogens. A non-synonymous variant of CHRNA5 that induces an amino acid substitution (D398N) at a highly conserved site in the second intracellular loop of the protein is among the markers with the strongest disease associations. Our results provide compelling evidence of a locus at 15q25 predisposing to lung cancer, and reinforce interest in nicotinic acetylcholine receptors as potential disease candidates and chemopreventative targets.
29.	Kligfield, Paul, et al. (author) Recommendations for the standardization and interpretation of the electrocardiogram. Part I: The electrocardiogram and its technology. A scientific statement from the American Heart Association Electrocardiography and Arrhythmias Committee, Council on Clinical Cardiology; the American College of Cardiology Foundation; and the Heart Rhythm Society 2007 In: Heart Rhythm. - : Elsevier BV. - 1547-5271. ; 4:3, s. 394-412 Journal article (peer-reviewed)abstract This statement examines the relation of the resting ECG to its technology. Its purpose is to foster understanding of how the modern ECG is derived and displayed and to establish standards that will improve the accuracy and usefulness of the ECG in practice. Derivation of representative waveforms and measurements based on global intervals are described. Special emphasis is placed on digital signal acquisition and computer-based signal processing, which provide automated measurements that lead to computer-generated diagnostic statements. Lead placement, recording methods, and waveform presentation are reviewed. Throughout the statement, recommendations for ECG standards are placed in context of the clinical implications of evolving ECG technology.
30.	Kligfield, Paul, et al. (author) Recommendations for the standardization and interpretation of the electrocardiogram: part I: The electrocardiogram and its technology: a scientific statement from the American Heart Association Electrocardiography and Arrhythmias Committee, Council on Clinical Cardiology; the American College of Cardiology Foundation; and the Heart Rhythm Society: endorsed by the International Society for Computerized Electrocardiology 2007 In: Circulation. - 1524-4539. ; 115:10, s. 1306-1324 Journal article (peer-reviewed)abstract This statement examines the relation of the resting ECG to its technology. Its purpose is to foster understanding of how the modern ECG is derived and displayed and to establish standards that will improve the accuracy and usefulness of the ECG in practice. Derivation of representative waveforms and measurements based on global intervals are described. Special emphasis is placed on digital signal acquisition and computer-based signal processing, which provide automated measurements that lead to computer-generated diagnostic statements. Lead placement, recording methods, and waveform presentation are reviewed. Throughout the statement, recommendations for ECG standards are placed in context of the clinical implications of evolving ECG technology.
31.	Kligfield, Paul, et al. (author) Recommendations for the standardization and interpretation of the electrocardiogram: part I: the electrocardiogram and its technology a scientific statement from the American Heart Association Electrocardiography and Arrhythmias Committee, Council on Clinical Cardiology; the American College of Cardiology Foundation; and the Heart Rhythm Society endorsed by the International Society for Computerized Electrocardiology 2007 In: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097. ; 49:10, s. 1109-1127 Journal article (peer-reviewed)abstract This statement examines the relation of the resting ECG to its technology. Its purpose is to foster understanding of how the modern ECG is derived and displayed and to establish standards that will improve the accuracy and usefulness of the ECG in practice. Derivation of representative waveforms and measurements based on global intervals are described. Special emphasis is placed on digital signal acquisition and computer-based signal processing, which provide automated measurements that lead to computer-generated diagnostic statements. Lead placement, recording methods, and waveform presentation are reviewed. Throughout the statement, recommendations for ECG standards are placed in context of the clinical implications of evolving ECG technology.
32.	Lang Kuhs, Krystle A, et al. (author) Human Papillomavirus 16 E6 Antibodies in Individuals without Diagnosed Cancer : A Pooled Analysis 2015 In: Cancer Epidemiology, Biomarkers and Prevention. - : American Association for Cancer Research. - 1055-9965 .- 1538-7755. ; 24:4, s. 683-689 Journal article (peer-reviewed)abstract BACKGROUND: The increasing incidence of oropharyngeal cancer in many developed countries has been attributed to human papillomavirus type 16 (HPV16) infections. Recently, HPV16 E6 serology has been identified as a promising early marker for oropharyngeal cancer. Therefore, characterization of HPV16 E6 seropositivity among individuals without cancer is warranted.METHODS: A total of 4,666 controls were pooled from several studies of cancer and HPV seropositivity, all tested within the same laboratory. HPV16 E6 seropositive controls were classified as having (i) moderate [mean fluorescent intensity (MFI) ≥ 484 and <1,000] or (ii) high seroreactivity (MFI ≥ 1,000). Associations of moderate and high HPV16 E6 seroreactivity with (i) demographic risk factors; and seropositivity for (ii) other HPV16 proteins (E1, E2, E4, E7, and L1), and (iii) E6 proteins from non-HPV16 types (HPV6, 11, 18, 31, 33, 45, and 52) were evaluated.RESULTS: Thirty-two (0.7%) HPV16 E6 seropositive controls were identified; 17 (0.4%) with moderate and 15 (0.3%) with high seroreactivity. High HPV16 E6 seroreactivity was associated with former smoking [odds ratio (OR), 5.5; 95% confidence interval (CI), 1.2-51.8], and seropositivity against HPV16 L1 (OR, 4.8; 95% CI, 1.3-15.4); E2 (OR, 7.7; 95% CI, 1.4-29.1); multiple HPV16 proteins (OR, 25.3; 95% CI, 2.6-119.6 for three HPV16 proteins beside E6) and HPV33 E6 (OR, 17.7; 95% CI, 1.9-81.8). No associations were observed with moderate HPV16 E6 seroreactivity.CONCLUSIONS: High HPV16 E6 seroreactivity is rare among individuals without diagnosed cancer and was not explained by demographic factors.IMPACT: Some HPV16 E6 seropositive individuals without diagnosed HPV-driven cancer, especially those with seropositivity against other HPV16 proteins, may harbor a biologically relevant HPV16 infection.
33.	Mowbray, Carol T, et al. (author) Characteristics of users of consumer-run drop-in centers versus clubhouses 2009 In: Journal of Behavioral Health Services & Research. - : Springer Science and Business Media LLC. - 1094-3412 .- 1556-3308. ; 36:3, s. 361-371 Journal article (peer-reviewed)abstract Clubhouses and consumer-run drop-in centers (CRDIs) are two of the most widely implemented models of consumer-centered services for persons with serious mental illness. Differences in structure and goals suggest that they may be useful to different types of consumers. Information on what types of consumers use which programs would be useful in service planning. This study analyzes data from the authors' NIMH-funded research on 31 geographically matched pairs of clubhouses and CRDIs involving more than 1,800 consumers to address the following question: are there significant differences in the characteristics and outcomes of members of clubhouses versus CRDIs? Results from multilevel analyses indicated that clubhouse members were more likely to be female, to receive SSI/SSDI, to report having a diagnosis of schizophrenia, and to live in dependent care; and they reported both a greater number of lifetime hospitalizations and current receipt of higher intensity traditional MH services. Controlling for differences in demographic characteristics, psychiatric history, and mental health service receipt, clubhouse members also reported higher quality of life and were more likely to report being in recovery. CRDI consumers were more likely to have substance abuse histories. Possible reasons for the differences are discussed. The results suggest that CRDIs are a viable alternative to more traditional mental health services for individuals who might not otherwise receive mental health services.
34.	Paixão, Gabriela M. M., et al. (author) Electrocardiographic Predictors of Mortality: Data from a Primary Care Tele-Electrocardiography Cohort of Brazilian Patients 2021 In: Hearts. - : MDPI AG. - 2673-3846. ; 2:4, s. 449-458 Journal article (peer-reviewed)abstract Computerized electrocardiography (ECG) has been widely used and allows linkage to electronic medical records. The present study describes the development and clinical applications of an electronic cohort derived from a digital ECG database obtained by the Telehealth Network of Minas Gerais, Brazil, for the period 2010–2017, linked to the mortality data from the national information system, the Clinical Outcomes in Digital Electrocardiography (CODE) dataset. From 2,470,424 ECGs, 1,773,689 patients were identified. A total of 1,666,778 (94%) underwent a valid ECG recording for the period 2010 to 2017, with 1,558,421 patients over 16 years old; 40.2% were men, with a mean age of 51.7 [SD 17.6] years. During a mean follow-up of 3.7 years, the mortality rate was 3.3%. ECG abnormalities assessed were: atrial fibrillation (AF), right bundle branch block (RBBB), left bundle branch block (LBBB), atrioventricular block (AVB), and ventricular pre-excitation. Most ECG abnormalities (AF: Hazard ratio [HR] 2.10; 95% CI 2.03–2.17; RBBB: HR 1.32; 95%CI 1.27–1.36; LBBB: HR 1.69; 95% CI 1.62–1.76; first degree AVB: Relative survival [RS]: 0.76; 95% CI0.71–0.81; 2:1 AVB: RS 0.21 95% CI0.09–0.52; and RS 0.36; third degree AVB: 95% CI 0.26–0.49) were predictors of overall mortality, except for ventricular pre-excitation (HR 1.41; 95% CI 0.56–3.57) and Mobitz I AVB (RS 0.65; 95% CI 0.34–1.24). In conclusion, a large ECG database established by a telehealth network can be a useful tool for facilitating new advances in the fields of digital electrocardiography, clinical cardiology and cardiovascular epidemiology.
35.	Ribeiro, Antônio H., et al. (author) Automatic diagnosis of the 12-lead ECG using a deep neural network 2020 In: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 11:1 Journal article (peer-reviewed)abstract The role of automatic electrocardiogram (ECG) analysis in clinical practice is limited by the accuracy of existing models. Deep Neural Networks (DNNs) are models composed of stacked transformations that learn tasks by examples. This technology has recently achieved striking success in a variety of task and there are great expectations on how it might improve clinical practice. Here we present a DNN model trained in a dataset with more than 2 million labeled exams analyzed by the Telehealth Network of Minas Gerais and collected under the scope of the CODE (Clinical Outcomes in Digital Electrocardiology) study. The DNN outperform cardiology resident medical doctors in recognizing 6 types of abnormalities in 12-lead ECG recordings, with F1 scores above 80% and specificity over 99%. These results indicate ECG analysis based on DNNs, previously studied in a single-lead setup, generalizes well to 12-lead exams, taking the technology closer to the standard clinical practice. The role of automatic electrocardiogram (ECG) analysis in clinical practice is limited by the accuracy of existing models. In that context, the authors present a Deep Neural Network (DNN) that recognizes different abnormalities in ECG recordings which matches or outperform cardiology and emergency resident medical doctors.
36.	Urayama, Kevin Y., et al. (author) Genome-Wide Association Study of Classical Hodgkin Lymphoma and Epstein-Barr Virus Status-Defined Subgroups 2012 In: Journal of the National Cancer Institute. - Oxford : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 104:3, s. 240-253 Journal article (peer-reviewed)abstract Accumulating evidence suggests that risk factors for classical Hodgkin lymphoma (cHL) differ by tumor Epstein-Barr virus (EBV) status. This potential etiological heterogeneity is not recognized in current disease classification. We conducted a genome-wide association study of 1200 cHL patients and 6417 control subjects, with validation in an independent replication series, to identify common genetic variants associated with total cHL and subtypes defined by tumor EBV status. Multiple logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) assuming a log-additive genetic model for the variants. All statistical tests were two-sided. Two novel loci associated with total cHL irrespective of EBV status were identified in the major histocompatibility complex region; one resides adjacent to MICB (rs2248462: OR = 0.61, 95% CI = 0.53 to 0.69, P = 1.3 x 10(-13)) and the other at HLA-DRA (rs2395185: OR = 0.56, 95% CI = 0.50 to 0.62, P = 8.3 x 10(-25)) with both results confirmed in an independent replication series. Consistent with previous reports, associations were found between EBV-positive cHL and genetic variants within the class I region (rs2734986, HLA-A: OR = 2.45, 95% CI = 2.00 to 3.00, P = 1.2 x 10(-15); rs6904029, HCG9: OR = 0.46, 95% CI = 0.36 to 0.59, P = 5.5 x 10(-10)) and between EBV-negative cHL and rs6903608 within the class II region (rs6903608, HLA-DRA: OR = 2.08, 95% CI = 1.84 to 2.35, P = 6.1 x 10(-31)). The association between rs6903608 and EBV-negative cHL was confined to the nodular sclerosis histological subtype. Evidence for an association between EBV-negative cHL and rs20541 (5q31, IL13: OR = 1.53, 95% CI = 1.32 to 1.76, P = 5.4 x 10(-9)), a variant previously linked to psoriasis and asthma, was observed; however, the evidence for replication was less clear. Notably, one additional psoriasis-associated variant, rs27524 (5q15, ERAP1), showed evidence of an association with cHL in the genome-wide association study (OR = 1.21, 95% CI = 1.10 to 1.33, P = 1.5 x 10(-4)) and replication series (P = .03). Overall, these results provide strong evidence that EBV status is an etiologically important classification of cHL and also suggest that some components of the pathological process are common to both EBV-positive and EBV-negative patients.
37.	Vitale, I, et al. (author) Apoptotic cell death in disease-Current understanding of the NCCD 2023 2023 In: Cell death and differentiation. - 1476-5403. ; 30:5, s. 1097-1154 Journal article (peer-reviewed)
38.	Vitale, I, et al. (author) Apoptotic cell death in disease-Current understanding of the NCCD 2023 2023 In: Cell death and differentiation. - 1476-5403. ; 30:5, s. 1097-1154 Journal article (peer-reviewed)
39.	Zirlik, A, et al. (author) Mac-1 mediates CD40L-induced atherogenesis 2007 In: ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY. - 1079-5642. ; 27:6, s. E120-E120 Conference paper (other academic/artistic)

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