Post-Exercise Assessment of Cardiac Repolarization Alternans in Patients With Coronary Artery Disease Using the Modified Moving Average Method

ObjectivesWe sought to evaluate the utility of T-wave alternans (TWA) assessment in the immediate post-exercise period to identify and validate cutpoints for the modified moving average (MMA) assessment method.BackgroundThe presence of TWA is associated with an increased risk of cardiovascular death (CVD). The immediate post-exercise period, where increased physiologic stress and minimal surface artifact coexist, appears ideal to implement the MMA method.MethodsA test (n = 322) and validation cohort (n = 681) provided 1,003 patients with coronary artery disease (CAD). We assessed TWA immediately after exercise. The outcomes, CVD and mortality, were adjudicated independent of the TWA results.ResultsDuring 48 months of follow-up 85 deaths, 54 categorized as CVD (64%), were observed. A linear relationship between the magnitude of TWA and the risk of CVD was identified. As a continuous measure TWA voltage was equivalent to ejection fraction in predicting the risk of CVD. To facilitate clinical application, a sensitive, modest predictive accuracy (20 μV) and a specific, greater predictive accuracy MMA cutpoint (60 μV) were identified and validated. Each cutpoint was associated with a 2.5-fold greater risk of CVD, independent of other important variables, including ejection fraction.ConclusionsPost-exercise assessment of TWA using the MMA method is a strong, independent predictor of risk in patients with CAD. The 20-μV cutpoint (87% sensitivity) appears to be most suitable in higher-risk patients, whereas the 60-μV cutpoint (95% specificity) appears more appropriate when TWA is used as a single screening test in those at lower risk. (Assessment of Noninvasive Methods to Identify Patients at Risk of Serious Arrhythmias After a Heart Attack; NCT00399503

Salivary antibodies induced by the seven-valent PncOMPC conjugate vaccine in the Finnish Otitis Media Vaccine Trial

BACKGROUND: Mucosal antibodies have been suggested to have a role in defence against pneumococcal infections. We investigated here the ability of a seven-valent pneumococcal conjugate vaccine, PncOMPC, to induce mucosal immune response. METHODS: Healthy Finnish children (n = 111), a subcohort of the Finnish Otitis Media Vaccine Trial, were recruited and 56 of them were immunised with the PncOMPC at the age of 2, 4, and 6 months. At 12 months of age, 49 of them received the PncOMPC and 7 were vaccinated with the pneumococcal polysaccharide vaccine (PncPS) as a booster. The control group of 55 children received a hepatitis B vaccine at the same ages. Salivary anti-Pnc IgG, IgA, IgA1, and IgA2 antibodies to serotypes 6B, 14, 19F, and 23F were measured in both groups at the age of 7 and 13 months. RESULTS: Salivary anti-Pnc IgG and IgA were detected more often in the PncOMPC than in the control group. However, the difference between groups was significant only for 19F and 23F IgA concentrations at the age of 7 months. At the age of 13 months, antibody concentrations did not differ between PncOMPC and control groups. The rises in IgA concentrations between 7 and 13 months of age were mainly of subclass IgA1. Further, there is a clear trend that PncPS booster induces higher salivary anti-Pnc PS antibody concentrations than the PncOMPC. CONCLUSION: We found that PncOMPC can induce a mucosal IgA response. However, the actual impact of mucosal antibodies in protection against pneumococcal infections is not clear

Metsätalouden pohjavesivaikutukset : MEPO-hankkeen loppuraportti 2021

Metsätalouden pohjavesivaikutukset (MEPO) hankkeen tavoite oli antaa tutkimustietoon perustuvia suosituksia pohjavesialueiden metsänhoitotoimenpiteisiin. Luokiteltuja pohjavesialueita on Suomen pinta-alasta 4 % ja metsätalous on alueiden merkittävin maankäyttömuoto. Metsätalouden toimia, joilla voi olla vaikutusta pohjaveteen, ovat hakkuut, maanmuokkaus, ojaston kunnossapito, kasvinsuojeluaineet, metsälannoitus sekä kulotus. Omana erityispiirteenään tarkasteltiin myös happamia sulfaattimaita. Tutkimustieto koottiin kirjallisuudesta sekä pohjavesiseurannoista. Pohjavesialueiden turvemaiden määrää, ojitusta, luontoarvoja ja metsänkäyttöä arvioitiin paikkatietomenetelmin. Lisäksi viimeisteltiin metsätalouden ojien kunnostuksen vaikutusten arviointiin kehitetty KUNNOS-työkalu. Hakkuut voivat nostaa pohjavedenpintaa ja lisätä purkautumista reuna-alueilla ja lähteissä. Hakkuutähteistä vapautuvat ravinteet kohottavat tyypillisesti pohjaveden NO3-N-pitoisuutta. Myös pohjaveden lämpötilan on joissakin tutkimuksissa havaittu kohoavan. Muiden toimenpiteiden vaikutusten osalta Suomesta ei ole tutkimus- ja seurantatietoja ja arvioissa on tukeuduttu kansainvälisiin tutkimustietoihin. Tärkeä jatkotoimenpide on seurannan kehittäminen. Hanke toteutettiin v. 2020–2021 yhteistyössä Suomen ympäristökeskuksen, Luonnonvarakeskuksen, Tapio Oy:n ja Oulun yliopiston tutkijoiden kanssa. Tärkeässä roolissa työkalujen kehittämisessä olivat WaterHope ja Gain Oy.Tämä julkaisu on toteutettu osana valtioneuvoston selvitys- ja tutkimussuunnitelman toimeenpanoa. (tietokayttoon.fi) Julkaisun sisällöstä vastaavat tiedon tuottajat, eikä tekstisisältö välttämättä edusta valtioneuvoston näkemystä

The social lab as a method for experimental engagement in participatory research

How does the Social Lab methodology support participatory research? This paper provides an evidence-based analysis of experiences of 19 implemented Social Labs applying experiential learning cycles on the question of how to induce Responsible Research and Innovation in the Horizon2020 research funding scheme of the European Commission and beyond. It looks at the potentials of Social Labs to allow participation in research and innovation addressing societal challenges and contrasts empirical results with the theoretical conceptualisation of a scientific Social Lab methodology. It discusses drivers and barriers of engagement, and provides evidence for the impacts of experimental engagement on participation in the context of the labs, substantiated by concrete examples from some of these labs

Hundreds of variants clustered in genomic loci and biological pathways affect human height

Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P < 0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.

Evaluative conversations: Translating between diverse stakeholders in regional RRI projects

Since the summer of 2020, researchers from ten projects pertaining to the Horizon2020 Science with and for Society (SwafS) call have been meeting virtually as the SwafS14 Monitoring and Evaluation ecosystem. Topics of discussion were the trials and tribulations of their regional Responsible Research and Innovation (RRI) projects as well as their strategies for monitoring and evaluation. In this paper we make a first attempt at presenting these issues as problems of translation between different kinds of stakeholders. After an exploration of the diversity of stakeholders and the process of translation in regional RRI, we suggest evaluative conversations as a way of improving regional RRI. We intend to develop this idea in the future and that these conversations will facilitate more responsible and engaged monitoring and evaluation and contribute to better R&I policies

The Finnish Cardiovascular Study (FINCAVAS): characterising patients with high risk of cardiovascular morbidity and mortality

BACKGROUND: The purpose of the Finnish Cardiovascular Study (FINCAVAS) is to construct a risk profile – using genetic, haemodynamic and electrocardiographic (ECG) markers – of individuals at high risk of cardiovascular diseases, events and deaths. METHODS AND DESIGN: All patients scheduled for an exercise stress test at Tampere University Hospital and willing to participate have been and will be recruited between October 2001 and December 2007. The final number of participants is estimated to reach 5,000. Technically successful data on exercise tests using a bicycle ergometer have been collected of 2,212 patients (1,400 men and 812 women) by the end of 2004. In addition to repeated measurement of heart rate and blood pressure, digital high-resolution ECG at 500 Hz is recorded continuously during the entire exercise test, including the resting and recovery phases. About 20% of the patients are examined with coronary angiography. Genetic variations known or suspected to alter cardiovascular function or pathophysiology are analysed to elucidate the effects and interactions of these candidate genes, exercise and commonly used cardiovascular medications. DISCUSSION: FINCAVAS compiles an extensive set of data on patient history, genetic variation, cardiovascular parameters, ECG markers as well as follow-up data on clinical events, hospitalisations and deaths. The data enables the development of new diagnostic and prognostic tools as well as assessments of the importance of existing markers

Plasma ceramides predict cardiovascular death in patients with stable coronary artery disease and acute coronary syndromes beyond LDL-cholesterol

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CNV-association meta-analysis in 191,161 European adults reveals new loci associated with anthropometric traits

Funding Information: This research has been conducted using the UK Biobank Resource. This research has been conducted using the Danish National Biobank resource. The authors are grateful to the Raine Study participants and their families, and to the Raine Study research staff for cohort co-ordination and data collection. QIMR is grateful to the twins and their families for their generous participation in these studies. We would like to thank staff at the Queensland Institute of Medical Research: Anjali Henders, Dixie Statham, Lisa Bowdler, Ann Eldridge, and Marlene Grace for sample collection, processing and genotyping, Scott Gordon, Brian McEvoy, Belinda Cornes and Beben Benyamin for data QC and preparation, and David Smyth and Harry Beeby for IT support. HBCS Acknowledgements: We thank all study participants as well as everybody involved in the Helsinki Birth Cohort Study. Helsinki Birth Cohort Study has been supported by grants from the Academy of Finland, the Finnish Diabetes Research Society, Folkhälsan Research Foundation, Novo Nordisk Foundation, Finska Läkaresällskapet, Juho Vainio Foundation, Signe and Ane Gyllenberg Foundation, University of Helsinki, Ministry of Education, Ahokas Foundation, Emil Aaltonen Foundation. Finrisk study is grateful for the THL DNA laboratory for its skillful work to produce the DNA samples used in this study and thanks the Sanger Institute and FIMM genotyping facilities for genotyping the samples. We thank the MOLGENIS team and Genomics Coordination Center of the University Medical Center Groningen for software development and data management, in particular Marieke Bijlsma and Edith Adriaanse. This work was supported by the Leenards Foundation (to Z.K.), the Swiss National Science Foundation (31003A_169929 to Z.K., Sinergia grant CRSII33-133044 to AR), Simons Foundation (SFARI274424 to AR) and SystemsX.ch (51RTP0_151019 to Z.K.). A.R.W., H.Y. and T.M.F. are supported by the European Research Council grant: 323195:SZ-245. M.A.T., M.N.W. and An.M. are supported by the Wellcome Trust Institutional Strategic Support Award (WT097835MF). For full funding information of all participating cohorts see Supplementary Note 2. Publisher Copyright: © 2017 The Author(s).There are few examples of robust associations between rare copy number variants (CNVs) and complex continuous human traits. Here we present a large-scale CNV association meta-analysis on anthropometric traits in up to 191,161 adult samples from 26 cohorts. The study reveals five CNV associations at 1q21.1, 3q29, 7q11.23, 11p14.2, and 18q21.32 and confirms two known loci at 16p11.2 and 22q11.21, implicating at least one anthropometric trait. The discovered CNVs are recurrent and rare (0.01-0.2%), with large effects on height (> 2.4 cm), weight ( 5 kg), and body mass index (BMI) (> 3.5 kg/m(2)). Burden analysis shows a 0.41 cm decrease in height, a 0.003 increase in waist-to-hip ratio and increase in BMI by 0.14 kg/m2 for each Mb of total deletion burden (P = 2.5 x 10(-10), 6.0 x 10(-5), and 2.9 x 10(-3)). Our study provides evidence that the same genes (e.g., MC4R, FIBIN, and FMO5) harbor both common and rare variants affecting body size and that anthropometric traits share genetic loci with developmental and psychiatric disorders.Peer reviewe