Precision and accuracy of single-molecule FRET measurements - a multi-laboratory benchmark study

Single-molecule Förster resonance energy transfer (smFRET) is increasingly being used to determine distances, structures, and dynamics of biomolecules in vitro and in vivo. However, generalized protocols and FRET standards to ensure the reproducibility and accuracy of measurements of FRET efficiencies are currently lacking. Here we report the results of a comparative blind study in which 20 labs determined the FRET efficiencies (E) of several dye-labeled DNA duplexes. Using a unified, straightforward method, we obtained FRET efficiencies with s.d. between ±0.02 and ±0.05. We suggest experimental and computational procedures for converting FRET efficiencies into accurate distances, and discuss potential uncertainties in the experiment and the modeling. Our quantitative assessment of the reproducibility of intensity-based smFRET measurements and a unified correction procedure represents an important step toward the validation of distance networks, with the ultimate aim of achieving reliable structural models of biomolecular systems by smFRET-based hybrid methods

Scholarly publishing depends on peer reviewers

The peer-review crisis is posing a risk to the scholarly peer-reviewed journal system. Journals have to ask many potential peer reviewers to obtain a minimum acceptable number of peers accepting reviewing a manuscript. Several solutions have been suggested to overcome this shortage. From reimbursing for the job, to eliminating pre-publication reviews, one cannot predict which is more dangerous for the future of scholarly publishing. And, why not acknowledging their contribution to the final version of the article published? PubMed created two categories of contributors: authors [AU] and collaborators [IR]. Why not a third category for the peer-reviewer?Scopu

Automatic detection of T wave alternans using tensor decompositions in multilead ECG signals

OBJECTIVE: T wave alternans (TWA) is a promising non-invasive risk stratification tool for sudden cardiac death which can be detected from surface ECG. This paper proposes a novel method to automatically detect TWA based on tensor decomposition methods. APPROACH: Two different tensor decomposition approaches are examined and compared, namely canonical polyadic decomposition and the more generalized variation PARAFAC2 which allows the T waves to shift in time. RESULTS AND SIGNIFICANCE: Results on different artificial and clinical signals show that the presented methods are a robust and reliable way for TWA detection, and show the potential benefit of tensors in ECG signal processing.status: publishe

A machine learning approach to detection and quantificiation of QRS fragmentation

OBJECTIVE: Fragmented QRS (fQRS) is an accessible biomarker and indication of myocardial scarring that can be detected from the electrocardiogram (ECG). Nowadays, fQRS scoring is done on a visual basis, which is time consuming and leads to subjective results. This study proposes an automated method to detect and quantify fQRS in a continuous way using features extracted from variational mode decomposition (VMD) and phase-rectified signal averaging (PRSA). METHODS: In the proposed framework, QRS complexes in the ECG signals were first segmented using VMD. Then, ten VMD- and PRSA-based features were computed and fed into well-known classifiers such as support vector machine (SVM), K-nearest neighbors (KNN), Naive Bayesian (NB), and TreeBagger (TB) in order to compare their performance. The proposed method was evaluated with 12-lead ECG data of 616 patients from the University Hospitals Leuven. The presence of fQRS in each ECG lead was scored by five raters. Both detection and quantification of fQRS could be achieved in this way. RESULTS: The experimental results indicated that the proposed method achieved AUC values of 0.95, 0.94, 0.90, and 0.89 using SVM, KNN, NB, and TB classifiers, respectively, for detecting QRS fragmentation. Assessment of quantification performance was done by comparing the fQRS score with the total score, obtained by summing the scores from the individual raters. Results showed that the fQRS score clearly correlated with this estimate of fQRS certainty. CONCLUSION: The proposed method obtained good results in both fQRS detection and quantification, and is a novel way of assessing the certainty of QRS fragmentation in the ECG signal.status: publishe

Significance of prolonged QTc in acute exacerbations of COPD requiring hospitalization

Oliver Van Oekelen,1,* Kristina Vermeersch,1,2,* Stephanie Everaerts,1,2 Bert Vandenberk,3,4 Rik Willems,3,4 Wim Janssens1,2 1Department of Respiratory Diseases, University Hospitals Leuven, Leuven, Belgium; 2Department of Chronic Diseases, Metabolism and Ageing, Laboratory of Respiratory Diseases, KU Leuven, Leuven, Belgium; 3Department of Cardiology, University Hospitals Leuven, Leuven, Belgium; 4Department of Cardiovascular Sciences, KU Leuven, Leuven, Belgium *These authors contributed equally to this work Background: A prolonged QT interval is associated with increased risk of Torsade de Pointes and cardiovascular death. The prevalence and clinical relevance of QT prolongation in acute exacerbations of COPD (AECOPD), with high risk for cardiac morbidity and mortality, is currently unclear. Methods: A dual cross-sectional study strategy was therefore designed. A retrospective study evaluated 140 patients with an AECOPD requiring hospitalization, half of which had prolonged QTc on the admission ECG. Univariate and multivariate analyses were conducted to determine associated factors; Kaplan–Meier and Cox regression analyses to assess prognostic significance. A prospective study evaluated 180 pulmonary patients with acute respiratory problems requiring hospitalization, to determine whether a prolonged QTc at admission represents an AECOPD-specific finding and to investigate the change in QTc-duration during hospitalization. Results: Retrospectively, hypokalemia, cardiac troponin T and conductance abnormalities on ECG were significantly and independently associated with QTc prolongation. A prolonged QTc was associated with increased all-cause mortality (HR 2.698 (95% CI 1.032–7.055), p=0.043), however, this association was no longer significant when corrected for age, FEV1 and cardiac troponin T. Prospectively, QTc prolongation was observed in 1/3 of the patients diagnosed with either an AECOPD, lung cancer, pulmonary infection or miscellaneous acute pulmonary disease, and was not more prevalent in AECOPD. The QTc-duration decreased significantly during hospitalization in patients with and without COPD. Conclusion: A prolonged QTc is a marker of underlying cardiovascular disease during an AECOPD. It is not COPD-specific, but a common finding during the acute phase of a pulmonary disease requiring urgent hospital admission. Keywords: COPD, acute exacerbation, cardiovascular morbidity, prolonged QT interval, ECG, Bazet

Influence of food intake on the QT and QT/RR relation

BACKGROUND: There are conflicting data on the influence of meal intake on the QT interval. METHODS: Ten healthy subjects were studied before and after a standardized breakfast and lunch with a sequence of supine resting, standing and exercise. Data collection was performed using a 12-lead Holter with semi-automated analysis. QT correction was performed using Fridericia (QTcF) correction formula and a subject-specific method based on individual QT/RR-regression (QTcI). RESULTS: Meal intake induced significant changes in HR (p<0.001), but not in QTcF (p=0.512) or QTcI (p=0.739). Postural analysis showed only significant differences in supine position for HR (p=0.010), not when standing or during exercise. CONCLUSION: Food intake induced an increase in heart rate limited to supine position. Using QTcF and QTcI no QTc changes were found.publisher: Elsevier articletitle: Influence of food intake on the QT and QT/RR relation journaltitle: Journal of Electrocardiology articlelink: http://dx.doi.org/10.1016/j.jelectrocard.2016.06.009 content_type: article copyright: © 2016 Elsevier Inc. All rights reserved.status: publishe

T-Wave Alternans Is Linked to Microvascular Obstruction and to Recurrent Coronary Ischemia After Myocardial Infarction

The purpose of this study is to investigate the relationship between T-wave alternans (TWA), infarct size and microvascular obstruction (MVO) and recurrent cardiac morbidity after ST elevation myocardial infarction (STEMI). One hundred six patients underwent TWA testing 1-12 months and 57 patients underwent cardiac magnetic resonance imaging (MRI) in the first 2-4 days after STEMI. During follow-up (3.5 ± 0.5 years), death (n = 2), ventricular tachycardia (n = 3), supraventricular tachycardia (n = 4), heart failure (n = 3) and recurrent coronary ischemia (n = 25) were observed. After multivariate analysis, positive TWA (HR2.59, CI1.10-6.11, p0.024) and larger MVO (HR1.08, CI1.01-1.16, p0.034) were associated with recurrent angina or ACS. Presence of MVO was correlated with TWA (Spearman rho 0.404, p0.002) and the impairment of LVEF (-0.524, p < 0.001). Patients after STEMI remain at a high risk of symptoms of coronary ischemia. The presence of MVO and TWA 1-12 months after STEMI is related to each other and to recurrent angina or ACS