Prediction of sinus rhythm maintenance following DC-cardioversion of persistent atrial fibrillation – the role of atrial cycle length

BACKGROUND: Atrial electrical remodeling has been shown to influence the outcome the outcome following cardioversion of atrial fibrillation (AF) in experimental studies. The aim of the present study was to find out whether a non-invasively measured atrial fibrillatory cycle length, alone or in combination with other non-invasive parameters, could predict sinus rhythm maintenance after cardioversion of AF. METHODS: Dominant atrial cycle length (DACL), a previously validated non-invasive index of atrial refractoriness, was measured from lead V1 and a unipolar oesophageal lead prior to cardioversion in 37 patients with persistent AF undergoing their first cardioversion. RESULTS: 32 patients were successfully cardioverted to sinus rhythm. The mean DACL in the 22 patients who suffered recurrence of AF within 6 weeks was 152 ± 15 ms (V1) and 147 ± 14 ms (oesophagus) compared to 155 ± 17 ms (V1) and 151 ± 18 ms (oesophagus) in those maintaining sinus rhythm (NS). Left atrial diameter was 48 ± 4 mm and 44 ± 7 mm respectively (NS). The optimal parameter predicting maintenance of sinus rhythm after 6 weeks appeared to be the ratio of the lowest dominant atrial cycle length (oesophageal lead or V1) to left atrial diameter. This ratio was significantly higher in patients remaining in sinus rhythm (3.4 ± 0.6 vs. 3.1 ± 0.4 ms/mm respectively, p = 0.04). CONCLUSION: In this study neither an index of atrial refractory period nor left atrial diameter alone were predictors of AF recurrence within the 6 weeks of follow-up. The ratio of the two (combining electrophysiological and anatomical measurements) only slightly improve the identification of patients at high risk of recurrence of persistent AF. Consequently, other ways to asses electrical remodeling and / or other variables besides electrical remodeling are involved in determining the outcome following cardioversion

Genetic fine mapping and genomic annotation defines causal mechanisms at type 2 diabetes susceptibility loci.

We performed fine mapping of 39 established type 2 diabetes (T2D) loci in 27,206 cases and 57,574 controls of European ancestry. We identified 49 distinct association signals at these loci, including five mapping in or near KCNQ1. 'Credible sets' of the variants most likely to drive each distinct signal mapped predominantly to noncoding sequence, implying that association with T2D is mediated through gene regulation. Credible set variants were enriched for overlap with FOXA2 chromatin immunoprecipitation binding sites in human islet and liver cells, including at MTNR1B, where fine mapping implicated rs10830963 as driving T2D association. We confirmed that the T2D risk allele for this SNP increases FOXA2-bound enhancer activity in islet- and liver-derived cells. We observed allele-specific differences in NEUROD1 binding in islet-derived cells, consistent with evidence that the T2D risk allele increases islet MTNR1B expression. Our study demonstrates how integration of genetic and genomic information can define molecular mechanisms through which variants underlying association signals exert their effects on disease

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

Large-scale association analysis provides insights into the genetic architecture and pathophysiology of type 2 diabetes

To extend understanding of the genetic architecture and molecular basis of type 2 diabetes (T2D), we conducted a meta-analysis of genetic variants on the Metabochip involving 34,840 cases and 114,981 controls, overwhelmingly of European descent. We identified ten previously unreported T2D susceptibility loci, including two demonstrating sex-differentiated association. Genome-wide analyses of these data are consistent with a long tail of further common variant loci explaining much of the variation in susceptibility to T2D. Exploration of the enlarged set of susceptibility loci implicates several processes, including CREBBP-related transcription, adipocytokine signalling and cell cycle regulation, in diabetes pathogenesis

Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure &lt; 100 mmHg (n = 1127), estimated glomerular filtration rate &lt; 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

More than a follower : How PR-agencies describe meaningful relations on social media

Purpose: The purpose of this thesis is to bring a better understanding for how employees of PR- agencies describe a meaningful relation on social media. The thesis furthermore aim to bring further understanding about how employees of PR-agencies describe their strategies for meaningful relations on their agencies’ channels on social media. Theoretical framework: The chapter includes framework of PR and Relations, relations on social media and finally strategy to target audience. Method: A qualitative research method with a semi-structured approach has been implemented. Empirical framework: The empirical material is based on five semi structured interviews with employees of PR-agencies. The respondents obtain significant expertise of the topic, that makes their answers relevant to the purpose of the study. Conclusion: Our conclusion is that agencies pick their social media channels based on user base above all. Another factor is whether their target group uses the platform or not, but since the platforms chosen by the agencies were often market leading the answer is yes. An interesting finding was that informants spoke of channel adjustment rather than audience targeting. To build a meaningful relation with the audience the social media content were often based on personal and expertise aspects. The target groups were often described based on their job role, and not other social or personal factors. The informants’ descriptions of what a meaningful relation included varied a lot. Common patterns were that it included two way communication, that both parts would get something out of it and that the followers would feel comfortable commenting and sharing posts. Last but not least there was a goal that a meaningful relation would lead to some sort of business. Social media activity could lead to business if the relation was meaningful in the long run

Experimental analysis of stresses in curved sandwich structures

Some studies indicate that the cross-section of large wind turbine blades subjected to wind and gravity loads will ovalise due to the Brazier effects [1,2]. This feature could however not be verified by numerical experiments of a FE model of a fictive 61.5 m blade, based on the NREL 5MW reference turbine [3], subjected to simplified load cases. Accurate prediction of failure modes of sandwich structures based on finite element calculations are highly important if accurate predictions of such features in large wind turbine blades are to be investigated.In this study, an experimental setup designed to cause deflection and stress patterns in the core similar to what might be achieved by the Brazier effect in a wind turbine blade subjected to severe wind loads has been carried out. The test set up will highlight stress in the through-thickness direction, causing classical shell theory to be circumspect as a modelling tool. By designing specimens with different foam core material properties, stiffness and strength, different failure modes were observed in the test. Through the use of combinations of solid and shell elements and geometrically nonlinear analyses, the experimental effects were shown to be predictable by an otherwise linear FE model

Experimental analysis of stresses in sandwich structures due to the brazier effect

\ua9 2015 International Committee on Composite Materials. All rights reserved. Some studies indicate that the cross-section of large wind turbine blades subjected to wind and gravity loads will ovalise due to the Brazier effects [1,2]. This feature could however not be verified by numerical experiments of a FE model of a fictive 61.5 m blade, based on the NREL 5MW reference turbine [3], subjected to simplified load cases. Accurate prediction of failure modes of sandwich structures based on finite element calculations are highly important if accurate predictions of such features in large wind turbine blades are to be investigated. In this study, an experimental setup designed to cause deflection and stress patterns in the core similar to what might be achieved by the Brazier effect in a wind turbine blade subjected to severe wind loads has been carried out. The test set up will highlight stress in the through-thickness direction, causing classical shell theory to be circumspect as a modelling tool. By designing specimens with different foam core material properties, stiffness and strength, different failure modes were observed in the test. Through the use of combinations of solid and shell elements and geometrically nonlinear analyses, the experimental effects were shown to be predictable by an otherwise linear FE model