Enhancement of Gap Junction Function During Acute Myocardial Infarction Modifies Healing and Reduces Late Ventricular Arrhythmia Susceptibility

Objectives: To investigate the effects of enhancing gap junction (GJ) coupling during acute myocardial infarction (MI) on the healed infarct scar morphology and late post-MI arrhythmia susceptibility. Background: Increased heterogeneity of myocardial scarring after MI is associated with greater arrhythmia susceptibility. We hypothesized that short-term enhancement of GJ coupling during acute MI can produce more homogeneous infarct scars, reducing late susceptibility to post-MI arrhythmias. Methods: Following arrhythmic characterisation of the rat 4-week post-MI model (n=24), a further 27 Sprague-Dawley rats were randomised to receive rotigaptide to enhance GJ coupling (n=13) or saline control (n=14) by osmotic minipump immediately prior to, and for the first 7 days following surgical MI. At 4 weeks post-MI, hearts were explanted for ex vivo programmed electrical stimulation (PES) and optical mapping. Heterogeneity of infarct border zone (IBZ) scarring was quantified by histomorphometry. Results: Despite no detectable difference in infarct size at 4 weeks post-MI, rotigaptide-treated hearts had reduced arrhythmia susceptibility during PES (Inducibility score: rotigaptide 2.40.8, control 5.00.6, p=0.02) and less heterogeneous IBZ scarring (standard deviation of IBZ Complexity Score: rotigaptide 1.10.1, control 1.40.1, p=0.04), associated with an improvement in IBZ conduction velocity (rotigaptide 43.13.4 cm/s, control 34.82.0 cm/s, p=0.04). Conclusions: Enhancement of GJ coupling for only 7 days at the time of acute MI produced more homogeneous IBZ scarring and reduced arrhythmia susceptibility at 4 weeks post-MI. Short-term GJ modulation at the time of MI may represent a novel treatment strategy to modify the healed infarct scar morphology and reduce late post-MI arrhythmic risk

Super-A-polynomial for knots and BPS states

We introduce and compute a 2-parameter family deformation of the A-polynomial that encodes the color dependence of the superpolynomial and that, in suitable limits, reduces to various deformations of the A-polynomial studied in the literature. These special limits include the t-deformation which leads to the "refined A-polynomial" introduced in the previous work of the authors and the Q-deformation which leads, by the conjecture of Aganagic and Vafa, to the augmentation polynomial of knot contact homology. We also introduce and compute the quantum version of the super-A-polynomial, an operator that encodes recursion relations for S^r-colored HOMFLY homology. Much like its predecessor, the super-A-polynomial admits a simple physical interpretation as the defining equation for the space of SUSY vacua (= critical points of the twisted superpotential) in a circle compactification of the effective 3d N=2 theory associated to a knot or, more generally, to a 3-manifold M. Equivalently, the algebraic curve defined by the zero locus of the super-A-polynomial can be thought of as the space of open string moduli in a brane system associated with M. As an inherent outcome of this work, we provide new interesting formulas for colored superpolynomials for the trefoil and the figure-eight knot.Comment: 47 pages, 8 figures; typos and references fixe

The association between a biomarker score for fruit and vegetable intake and incident type 2 diabetes: the EPIC-Norfolk study.

BACKGROUND/OBJECTIVES: Biomarkers for a mixed fruit and vegetable (FV) diet are needed to provide a better understanding of the association between FV intake and type 2 diabetes. We aimed to examine the prospective association between a composite score comprised of three biomarkers of FV intake in free-living populations and incident diabetes. SUBJECTS/METHODS: A total of 318 incident diabetes cases and 926 controls from the EPIC (European Prospective Investigation of Cancer)-Norfolk study aged 40-79 years at baseline (1993-1997), completed 7-day prospective food diary and had plasma vitamin C and carotenoid measures. A composite biomarker score (CB-score) comprising the sum of plasma vitamin C, beta-carotene and lutein was derived. Odds ratios (ORs) and 95% confidence intervals (CIs) for incident diabetes were estimated using multivariable logistic regression. RESULTS: A strong inverse association was found between the CB-score and incident diabetes. The ORs (95% CI) of diabetes comparing quartiles Q2, Q3 and Q4 of the CB-score with Q1 (reference category) were 0.70 (0.49, 1.00), 0.34 (0.23, 0.52) and 0.19 (0.12, 0.32), respectively, and 0.49 (0.40, 0.58) per s.d. change in CB-score in a model adjusted for demographic and lifestyle factors. The association was marginally attenuated after additionally adjusting for body mass index and waist circumference (0.60 (0.49 and 0.74) per s.d. change in CB-score). CONCLUSIONS: A combination of biomarkers representing the intake of a mixed FV diet was strongly inversely associated with incident diabetes. These findings provide further support for measuring dietary biomarkers in studies of diet-disease associations and highlight the importance of consuming FV for the prevention of diabetes.The EPIC Norfolk study is supported by programme grants from the Medical Research Council UK and Cancer Research UK. The sponsors did not participate in the design or conduct of this study; in the collection, management, analysis, or interpretation of data; in the writing of the manuscript; or in the preparation, review, approval, or decision to submit this manuscript for publication. We acknowledge support from the MRC Epidemiology Unit (MC_UU_12015/5).This is the author accepted manuscript. The final version is available from NPG via http://dx.doi.org/10.1038/ejcn.2014.24

Measurement of Fluctuation-induced Diamagnetism in BSCCO-2212 single crystals using Magneto-optics

Fluctuation induced diamagnetism in BSCCO single crystals with different doping levels (i.e., different oxygen stoichiometry) was measured using magneto-optics (MO) in a wide frequency range up to several MHz. A shift in Tc onset, measured by MO, of up to 6 K towards higher temperatures was observed at high frequencies in those samples which are far from the optimally doped condition. An explanation of the observed effect in terms of the phase fluctuations of the superconducting order parameter is proposed.Comment: 13 pages, 3 figure

Quantifying single nucleotide variant detection sensitivity in exome sequencing

BACKGROUND: The targeted capture and sequencing of genomic regions has rapidly demonstrated its utility in genetic studies. Inherent in this technology is considerable heterogeneity of target coverage and this is expected to systematically impact our sensitivity to detect genuine polymorphisms. To fully interpret the polymorphisms identified in a genetic study it is often essential to both detect polymorphisms and to understand where and with what probability real polymorphisms may have been missed. RESULTS: Using down-sampling of 30 deeply sequenced exomes and a set of gold-standard single nucleotide variant (SNV) genotype calls for each sample, we developed an empirical model relating the read depth at a polymorphic site to the probability of calling the correct genotype at that site. We find that measured sensitivity in SNV detection is substantially worse than that predicted from the naive expectation of sampling from a binomial. This calibrated model allows us to produce single nucleotide resolution SNV sensitivity estimates which can be merged to give summary sensitivity measures for any arbitrary partition of the target sequences (nucleotide, exon, gene, pathway, exome). These metrics are directly comparable between platforms and can be combined between samples to give “power estimates” for an entire study. We estimate a local read depth of 13X is required to detect the alleles and genotype of a heterozygous SNV 95% of the time, but only 3X for a homozygous SNV. At a mean on-target read depth of 20X, commonly used for rare disease exome sequencing studies, we predict 5–15% of heterozygous and 1–4% of homozygous SNVs in the targeted regions will be missed. CONCLUSIONS: Non-reference alleles in the heterozygote state have a high chance of being missed when commonly applied read coverage thresholds are used despite the widely held assumption that there is good polymorphism detection at these coverage levels. Such alleles are likely to be of functional importance in population based studies of rare diseases, somatic mutations in cancer and explaining the “missing heritability” of quantitative traits

Implementation evaluation of an Irish secondary-level whole school programme: a qualitative inquiry

Whole-of-school programmes (WSPs) are recommended to promote physical activity for adolescents. The Active School Flag (ASF) programme for secondary-level schools is one such WSP. Due to the difficulties of incorporating WSPs into the complex school system, there is a risk of poor implementation. The monitoring of unanticipated influences can help to understand key implementation processes prior to scale-up. The aims of this study were to identify perceived facilitators and barriers to implementing the ASF and recommend evidence-based implementation strategies. Focus groups and interviews (N = 50) were conducted in three schools with stakeholders involved in programme implementation, i.e. school management (n = 5), ASF coordinator (n = 4), student-leaders (aged 15–16 years) (n = 64) and staff committee (n = 25). Transcripts were analysed using codebook thematic analysis and were guided by the Consolidated Framework for Implementation Research. Implementation strategies were identified and were selected systematically to address contextual needs. Three themes surrounding the facilitators and barriers to implementation were generated: intervention design factors (e.g. capacity building and knowledge of implementers; and interest and buy-in for the programme), organizational factors (e.g. optimization of people and the busy school environment) and interpersonal factors (e.g. communication and collaboration). The examination of facilitators and barriers to implementation of the ASF has assisted with the identification of implementation strategies including (not limited to) a shared leadership programme for student leaders and a more flexible timeline for completion. These facilitative implementation strategies may assist in the effective implementation of the ASF

Influenza A H5N1 Detection

We developed a sensitive and rapid real-time reverse transcription-polymerase chain reaction (RT-PCR) assay to detect influenza A H5N1 virus in clinical samples. This assay was evaluated with samples from H5N1-infected patients and demonstrated greater sensitivity and faster turnaround time than nested RT-PCR

Photon Production from Nonequilibrium Disoriented Chiral Condensates in a Spherical Expansion

We study the production of photons through the non-equilibrium relaxation of a disoriented chiral condensate formed in the expanding hot central region in ultra-relativistic heavy-ion collisions. It is found that the expansion smoothes out the resonances in the process of parametric amplification such that the non-equilibrium photons are dominant to the thermal photons over the range 0.2-2 GeV. We propose that to search for non-equilibrium photons in the direct photon measurements of heavy-ion collisions can be a potential test of the formation of disoriented chiral condensates.Comment: 13 pages, 3 figure

Modeling Life as Cognitive Info-Computation

This article presents a naturalist approach to cognition understood as a network of info-computational, autopoietic processes in living systems. It provides a conceptual framework for the unified view of cognition as evolved from the simplest to the most complex organisms, based on new empirical and theoretical results. It addresses three fundamental questions: what cognition is, how cognition works and what cognition does at different levels of complexity of living organisms. By explicating the info-computational character of cognition, its evolution, agent-dependency and generative mechanisms we can better understand its life-sustaining and life-propagating role. The info-computational approach contributes to rethinking cognition as a process of natural computation in living beings that can be applied for cognitive computation in artificial systems.Comment: Manuscript submitted to Computability in Europe CiE 201

Relationships between emotional intelligence and sales performance in Kuwait

This study investigates the relationship between emotional intelligence (EI) and Total Sales Performance (TSP), and whether EI contributes to predicting the performance of sales professionals in Kuwait. The sample was 218 sales professionals working for 24 different car dealerships. An ability model of EI was measured using the Assessing Emotions Scale (AES) developed by Schutte et al. (1998) and its Arabic version. The trait model of EI was assessed using the Effective Intelligence Scale (EIS). The findings showed a negative but weak correlation between TSP and the AES and all its subscales. No correlation was found between TSP and the EIS. A weak positive correlation existed between Objective Sales Performance and each of total EIS, Accuracy, and Patience subscales