Myocardial Architecture and Patient Variability in Clinical Patterns of Atrial Fibrillation

Atrial fibrillation (AF) increases the risk of stroke by a factor of four to five and is the most common abnormal heart rhythm. The progression of AF with age, from short self-terminating episodes to persistence, varies between individuals and is poorly understood. An inability to understand and predict variation in AF progression has resulted in less patient-specific therapy. Likewise, it has been a challenge to relate the microstructural features of heart muscle tissue (myocardial architecture) with the emergent temporal clinical patterns of AF. We use a simple model of activation wavefront propagation on an anisotropic structure, mimicking heart muscle tissue, to show how variation in AF behaviour arises naturally from microstructural differences between individuals. We show that the stochastic nature of progressive transversal uncoupling of muscle strands (e.g., due to fibrosis or gap junctional remodelling), as occurs with age, results in variability in AF episode onset time, frequency, duration, burden and progression between individuals. This is consistent with clinical observations. The uncoupling of muscle strands can cause critical architectural patterns in the myocardium. These critical patterns anchor micro-re-entrant wavefronts and thereby trigger AF. It is the number of local critical patterns of uncoupling as opposed to global uncoupling that determines AF progression. This insight may eventually lead to patient specific therapy when it becomes possible to observe the cellular structure of a patient's heart.Comment: 5 pages, 4 figures. For supplementary materials please contact Kishan A. Manani at [email protected]

A Simple Model for Identifying Critical Structures in Atrial Fibrillation

Atrial fibrillation (AF) is the most common abnormal heart rhythm and the single biggest cause of stroke. Ablation, destroying regions of the atria, is applied largely empirically and can be curative but with a disappointing clinical success rate. We design a simple model of activation wavefront propagation on a structure mimicking the branching network architecture of heart muscle and show how AF emerges spontaneously as age-related parameters change. We identify regions responsible for the initiation and maintenance of AF, the ablation of which terminates AF. The simplicity of the model allows us to calculate analytically the risk of arrhythmia. This analytical result allows us to locate the transition in parameter space and highlights that the transition from regular to fibrillatory behaviour is a finite-size effect present in systems of any size. These clinically testable predictions might inform ablation therapies and arrhythmic risk assessment.Comment: 5 pages, 4 figures. For supplementary materials please contact Kishan A. Manani at [email protected]

Promotility Action of the Probiotic Bifidobacterium lactis HN019 Extract Compared with Prucalopride in Isolated Rat Large Intestine

Copyright © 2017 Dalziel, Anderson, Peters, Lynch, Spencer, Dekker and Roy. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.Attention is increasingly being focussed on probiotics as potential agents to restore or improve gastrointestinal (GI) transit. Determining mechanism of action would support robust health claims. The probiotic bacterium Bifidobacterium lactis HN019 reduces transit time, but its mechanisms of action and effects on motility patterns are poorly understood. The aim of this study was to investigate changes in GI motility induced by an extract of HN019 on distinct patterns of colonic motility in isolated rat large intestine, compared with a known promotility modulator, prucalopride. The large intestines from male Sprague Dawley rats (3–6 months) were perfused with Kreb's buffer at 37°C in an oxygenated tissue bath. Isometric force transducers recorded changes in circular muscle activity at four independent locations assessing contractile propagation between the proximal colon and the rectum. HN019 extract was perfused through the tissue bath and differences in tension and frequency quantified relative to pre-treatment controls. Prucalopride (1 μM) increased the frequency of propagating contractions (by 75 ± 26%) in the majority of preparations studied (10/12), concurrently decreasing the frequency of non-propagating contractions (by 50 ± 11%). HN019 extract had no effect on contractile activity during exposure (n = 8). However, following wash out, contraction amplitude of propagating contractions increased (by 55 ± 18%) in the distal colon, while the frequency of non-propagating proximal contractions decreased by 57 ± 7%. The prokinetic action of prucalopride increased the frequency of synchronous contractions along the length of colon, likely explaining increased colonic rate of transit in vivo. HN019 extract modified motility patterns in a different manner by promoting propagating contractile amplitude and inhibiting non-propagations, also demonstrating prokinetic activity consistent with the reduction of constipation by B. lactis HN019 in humans

Infrared and Raman screening of seized novel psychoactive substances:a large scale study of >200 samples

The potential of IR absorption and Raman spectroscopy for rapid identification of novel psychoactive sub- stances (NPS) has been tested using a set of 221 unsorted seized samples suspected of containing NPS. Both IR and Raman spectra showed large variation between the different sub-classifications of NPS and smaller, but still distinguishable, differences between closely related compounds within the same class. In initial tests, screening the samples using spectral searching against a limited reference library allowed only 41% of the samples to be fully identified. The limiting factor in the identification was the large number of active compounds in the seized samples for which no reference vibrational data were available in the libraries rather than poor spectral quality. Therefore, when 33 of these compounds were independently identified by NMR and mass spectrometry and their spectra used to extend the libraries, the percentage of samples identified by IR and Raman screening alone increased to 76%, with only 7% of samples having no identifiable constituents. This study, which is the largest of its type ever carried out, therefore demon- strates that this approach of detecting non-matching samples and then identifying them using standard analytical methods has considerable potential in NPS screening since it allows rapid identification of the constituents of the majority of street quality samples. Only one complete feedback cycle was carried out in this study but there is clearly the potential to carry out continuous identification/updating when this system is used in operational settings

Analysis workflow to assess de novo genetic variants from human whole-exome sequencing

Here, we present a protocol to analyz

Cross-linked structure of network evolution

We study the temporal co-variation of network co-evolution via the cross-link structure of networks, for which we take advantage of the formalism of hypergraphs to map cross-link structures back to network nodes. We investigate two sets of temporal network data in detail. In a network of coupled nonlinear oscillators, hyperedges that consist of network edges with temporally co-varying weights uncover the driving co-evolution patterns of edge weight dynamics both within and between oscillator communities. In the human brain, networks that represent temporal changes in brain activity during learning exhibit early co-evolution that then settles down with practice. Subsequent decreases in hyperedge size are consistent with emergence of an autonomous subgraph whose dynamics no longer depends on other parts of the network. Our results on real and synthetic networks give a poignant demonstration of the ability of cross-link structure to uncover unexpected co-evolution attributes in both real and synthetic dynamical systems. This, in turn, illustrates the utility of analyzing cross-links for investigating the structure of temporal networks