Long term CMR follow up of patients with right ventricular abnormality and clinically suspected arrhythmogenic right ventricular cardiomyopathy (ARVC)

Background: The Task Force Criteria (TFC) for arrhythmogenic right ventricular cardiomyopathy (ARVC) was updated in 2010 to improve specificity. There was concern however that the revised cardiovascular magnetic resonance (CMR) criteria was too restrictive and not sensitive enough to detect early forms of the condition. We previously described patients with clinically suspected ARVC who satisfied criteria from non-imaging TFC categories and fulfilled parameters from the original but not the revised CMR criteria; as a result, these patients were not confirmed as definite ARVC but may represent an early phenotype. Methods: Patients scanned between 2008 and 2015 who had either right ventricular (RV) dilatation or regional dyskinesia satisfying at least minor imaging parameters from the original criteria and without contra-indication underwent serial CMR scanning using a 1.5 T scanner. The aims were to assess the risk of progressive RV abnormalities, evaluate the accuracy of the revised CMR criteria and the need for guideline directed CMR surveillance in at-risk individuals. Results: Overall, 48 patients were re-scanned; 24 had a first-degree relative diagnosed with ARVC using the revised TFC or a first-degree relative with premature sudden death from suspected ARVC and 24 patients had either left bundle branch morphology ventricular tachycardia or > 500 ventricular extra-systoles in 24-h. Mean follow up was 69+/- 25 months. The indexed RV end-diastolic, end-systolic volumes and ejection fraction were calculated for both scans. There was significant reduction in RV volumes and improvement in RV ejection fraction (EF) irrespective of changes to body surface area; - 11.7+/- 15.2 mls/m2, - 6.4+/- 10.5 mls/m2 and + 3.3 +/- 7.9% (p = 0.01, 0.01 and 0.04). Applying the RV parameters to the revised CMR criteria, two patients from the family history group (one with confirmed ARVC and one with a premature death) had progressive RV abnormalities satisfying major criteria. The remaining patients (n = 46) did not satisfy the criteria and either had normal RV parameters with regression of structural abnormalities (27,56.3%) or stable abnormalities (19,43.7%). Conclusion: The revised CMR criteria represents a robust tool in the evaluation of patients with clinical suspicion of ARVC, especially for those with ventricular arrhythmias without a family history for ARVC. For patients with RV abnormalities that do not fulfill the revised criteria but have a family history of ARVC or an ARVC associated gene mutation, a surveillance CMR scan should be considered as part of the clinical follow up protocol

Predicting adverse outcomes following catheter ablation treatment for atrial fibrillation

Objective: To develop prognostic survival models for predicting adverse outcomes after catheter ablation treatment for non-valvular atrial fibrillation (AF). Methods: We used a linked dataset including hospital administrative data, prescription medicine claims, emergency department presentations, and death registrations of patients in New South Wales, Australia. The cohort included patients who received catheter ablation for AF. Traditional and deep survival models were trained to predict major bleeding events and a composite of heart failure, stroke, cardiac arrest, and death. Results: Out of a total of 3285 patients in the cohort, 177 (5.3%) experienced the composite outcomeheart failure, stroke, cardiac arrest, deathand 167 (5.1%) experienced major bleeding events after catheter ablation treatment. Models predicting the composite outcome had high risk discrimination accuracy, with the best model having a concordance index > 0.79 at the evaluated time horizons. Models for predicting major bleeding events had poor risk discrimination performance, with all models having a concordance index < 0.66. The most impactful features for the models predicting higher risk were comorbidities indicative of poor health, older age, and therapies commonly used in sicker patients to treat heart failure and AF. Conclusions: Diagnosis and medication history did not contain sufficient information for precise risk prediction of experiencing major bleeding events. The models for predicting the composite outcome have the potential to enable clinicians to identify and manage high-risk patients following catheter ablation proactively. Future research is needed to validate the usefulness of these models in clinical practice.Comment: Under journal revie

Drawing from Grotowski and Beyond: Kuo Pao Kun’s Discourse on Audiences in Singapore in the 1980s

Much has been researched on Kuo Pao Kun’s multilingualism and multiculturalism. However, as one of one of the most important Asian dramatists, the analysis of Kuo’s discourse on audiences remains largely unexplored. There is a pressing need to understand the ways which theatre practitioners imagine audiences as it points to issues of subjectivity, audience participation and social engagement, especially in a neoliberal society like Singapore where people are often positioned as docile economic subjects. Among the many Asian and Western dramatists Kuo drew inspiration from, Jerzy Grotowski was pivotal. This essay seeks to address this gap by examining how the latter’s ideas was crucial to understanding how Kuo envisioned theatre and audiences alongside his artistic practice

Emergence of Oseltamivir-Resistant Pandemic (H1N1) 2009 Virus within 48 Hours

An oseltamivir-resistant influenza A pandemic (H1N1) 2009 virus evolved and emerged from zero to 52% of detectable virus within 48 hours of a patient’s exposure to oseltamivir. Phylogenetic analysis and data gathered by pyrosequencing and cloning directly on clinical samples suggest that the mutant emerged de novo

Lineage Divergence and Historical Gene Flow in the Chinese Horseshoe Bat (Rhinolophus sinicus)

PMCID: PMC3581519This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

A direct physical interaction between Nanog and Sox2 regulates embryonic stem cell self-renewal

Embryonic stem (ES) cell self-renewal efficiency is determined by the Nanog protein level. However, the protein partners of Nanog that function to direct self-renewal are unclear. Here, we identify a Nanog interactome of over 130 proteins including transcription factors, chromatin modifying complexes, phosphorylation and ubiquitination enzymes, basal transcriptional machinery members, and RNA processing factors. Sox2 was identified as a robust interacting partner of Nanog. The purified Nanog–Sox2 complex identified a DNA recognition sequence present in multiple overlapping Nanog/Sox2 ChIP-Seq data sets. The Nanog tryptophan repeat region is necessary and sufficient for interaction with Sox2, with tryptophan residues required. In Sox2, tyrosine to alanine mutations within a triple-repeat motif (S X T/S Y) abrogates the Nanog–Sox2 interaction, alters expression of genes associated with the Nanog-Sox2 cognate sequence, and reduces the ability of Sox2 to rescue ES cell differentiation induced by endogenous Sox2 deletion. Substitution of the tyrosines with phenylalanine rescues both the Sox2–Nanog interaction and efficient self-renewal. These results suggest that aromatic stacking of Nanog tryptophans and Sox2 tyrosines mediates an interaction central to ES cell self-renewal

Biofortified red mottled beans (Phaseolus vulgaris L.) in a maize and bean diet provide more bioavailable iron than standard red mottled beans: Studies in poultry (Gallus gallus) and an in vitro digestion/Caco-2 model

<p>Abstract</p> <p>Background</p> <p>Our objective was to compare the capacities of biofortified and standard colored beans to deliver iron (Fe) for hemoglobin synthesis. Two isolines of large-seeded, red mottled Andean beans (<it>Phaseolus vulgaris </it>L.), one standard ("Low Fe") and the other biofortified ("High Fe") in Fe (49 and 71 μg Fe/g, respectively) were used. This commercial class of red mottled beans is the preferred varietal type for most of the Caribbean and Eastern and Southern Africa where almost three quarters of a million hectares are grown. Therefore it is important to know the affect of biofortification of these beans on diets that simulate human feeding studies.</p> <p>Methods</p> <p>Maize-based diets containing the beans were formulated to meet the nutrient requirements for broiler except for Fe (Fe concentrations in the 2 diets were 42.9 ± 1.2 and 54.6 ± 0.9 mg/kg). One day old chicks (<it>Gallus gallus</it>) were allocated to the experimental diets (n = 12). For 4 wk, hemoglobin, feed-consumption and body-weights were measured.</p> <p>Results</p> <p>Hemoglobin maintenance efficiencies (HME) (means ± SEM) were different between groups on days 14 and 21 of the experiment (P < 0.05). Final total body hemoglobin Fe contents were different between the standard (12.58 ± 1.0 mg {0.228 ± 0.01 μmol}) and high Fe (15.04 ± 0.65 mg {0.273 ± 0.01 μmol}) bean groups (P < 0.05). At the end of the experiment, tissue samples were collected from the intestinal duodenum and liver for further analyses. Divalent-metal-transporter-1, duodenal-cytochrome-B, and ferroportin expressions were higher and liver ferritin was lower (P < 0.05) in the standard group vs. the biofortified group. <it>In-vitro </it>analysis showed lower iron bioavailability in cells exposed to standard ("Low Fe") bean based diet.</p> <p>Conclusions</p> <p>We conclude that the <it>in-vivo </it>results support the <it>in-vitro </it>observations; biofortified colored beans contain more bioavailable-iron than standard colored beans. In addition, biofortified beans seems to be a promising vehicle for increasing intakes of bioavailable Fe in human populations that consume these beans as a dietary staple. This justifies further work on the large-seeded Andean beans which are the staple of a large-region of Africa where iron-deficiency anemia is a primary cause of infant death and poor health status.</p

Performance of CMS muon reconstruction in pp collision events at sqrt(s) = 7 TeV

The performance of muon reconstruction, identification, and triggering in CMS has been studied using 40 inverse picobarns of data collected in pp collisions at sqrt(s) = 7 TeV at the LHC in 2010. A few benchmark sets of selection criteria covering a wide range of physics analysis needs have been examined. For all considered selections, the efficiency to reconstruct and identify a muon with a transverse momentum pT larger than a few GeV is above 95% over the whole region of pseudorapidity covered by the CMS muon system, abs(eta) < 2.4, while the probability to misidentify a hadron as a muon is well below 1%. The efficiency to trigger on single muons with pT above a few GeV is higher than 90% over the full eta range, and typically substantially better. The overall momentum scale is measured to a precision of 0.2% with muons from Z decays. The transverse momentum resolution varies from 1% to 6% depending on pseudorapidity for muons with pT below 100 GeV and, using cosmic rays, it is shown to be better than 10% in the central region up to pT = 1 TeV. Observed distributions of all quantities are well reproduced by the Monte Carlo simulation.Comment: Replaced with published version. Added journal reference and DO

Positive and Negative Regulation of Gli Activity by Kif7 in the Zebrafish Embryo

Loss of function mutations of Kif7, the vertebrate orthologue of the Drosophila Hh pathway component Costal2, cause defects in the limbs and neural tubes of mice, attributable to ectopic expression of Hh target genes. While this implies a functional conservation of Cos2 and Kif7 between flies and vertebrates, the association of Kif7 with the primary cilium, an organelle absent from most Drosophila cells, suggests their mechanisms of action may have diverged. Here, using mutant alleles induced by Zinc Finger Nuclease-mediated targeted mutagenesis, we show that in zebrafish, Kif7 acts principally to suppress the activity of the Gli1 transcription factor. Notably, we find that endogenous Kif7 protein accumulates not only in the primary cilium, as previously observed in mammalian cells, but also in cytoplasmic puncta that disperse in response to Hh pathway activation. Moreover, we show that Drosophila Costal2 can substitute for Kif7, suggesting a conserved mode of action of the two proteins. We show that Kif7 interacts with both Gli1 and Gli2a and suggest that it functions to sequester Gli proteins in the cytoplasm, in a manner analogous to the regulation of Ci by Cos2 in Drosophila. We also show that zebrafish Kif7 potentiates Gli2a activity by promoting its dissociation from the Suppressor of Fused (Sufu) protein and present evidence that it mediates a Smo dependent modification of the full length form of Gli2a. Surprisingly, the function of Kif7 in the zebrafish embryo appears restricted principally to mesodermal derivatives, its inactivation having little effect on neural tube patterning, even when Sufu protein levels are depleted. Remarkably, zebrafish lacking all Kif7 function are viable, in contrast to the peri-natal lethality of mouse kif7 mutants but similar to some Acrocallosal or Joubert syndrome patients who are homozygous for loss of function KIF7 alleles

Performance of CMS muon reconstruction in pp collision events at sqrt(s) = 7 TeV

The performance of muon reconstruction, identification, and triggering in CMS has been studied using 40 inverse picobarns of data collected in pp collisions at sqrt(s) = 7 TeV at the LHC in 2010. A few benchmark sets of selection criteria covering a wide range of physics analysis needs have been examined. For all considered selections, the efficiency to reconstruct and identify a muon with a transverse momentum pT larger than a few GeV is above 95% over the whole region of pseudorapidity covered by the CMS muon system, abs(eta) < 2.4, while the probability to misidentify a hadron as a muon is well below 1%. The efficiency to trigger on single muons with pT above a few GeV is higher than 90% over the full eta range, and typically substantially better. The overall momentum scale is measured to a precision of 0.2% with muons from Z decays. The transverse momentum resolution varies from 1% to 6% depending on pseudorapidity for muons with pT below 100 GeV and, using cosmic rays, it is shown to be better than 10% in the central region up to pT = 1 TeV. Observed distributions of all quantities are well reproduced by the Monte Carlo simulation.Comment: Replaced with published version. Added journal reference and DO