Sigma-term physics in the perturbative chiral quark model

We apply the perturbative chiral quark model (PCQM) at one loop to analyse meson-baryon sigma-terms. Analytic expressions for these quantities are obtained in terms of fundamental parameters of low-energy pion-nucleon physics (weak pion decay constant, axial nucleon coupling, strong pion-nucleon form factor) and of only one model parameter (radius of the nucleonic three-quark core). Our result for the piN sigma term of about 45 MeV is in good agreement with the value deduced by Gasser, Leutwyler and Sainio using dispersion-relation techniques and exploiting the chiral symmetry constraints.Comment: 19 pages, LaTeX-file, 2 Figure

Bomb-produced radiocarbon validation of growth-increment crossdating allows marine paleoclimate reconstruction

The bivalve Pacific geoduck (Panopea generosa) has been used in the eastern North Pacific Ocean to create proxies for environmental factors such as temperature and oceanographic conditions. This type of research depends upon accurate age determination of Pacific geoducks, which historically was based on shell growth-increment counts. A recent study comparing age estimates generated by the dendrochronology (tree-ring science) procedure of crossdating to those estimated from growth-increment counts found a significant difference between the methods for geoduck older than 30 years. Compared to the traditional age determination method of counting growth increments, the crossdating method estimates a greater longevity in this species, with some individuals living in excess of 150 years. In the present study, the accuracy of each method was independently assessed using bomb-produced radiocarbon (C-14) techniques. Specimens whose birth years were estimated to be within the era of the bomb-produced marine C-14 increase and where the differences between ages estimated by the two methods were greatest were selected for C-14 analysis. The difference between age estimates from traditional growth-increment counts and those from crossdating was evaluated using their respective C-14 chronologies in comparisons to a reference chronology as a standard. The comparisons relied on Bayesian nonlinear models using Markov Chain Monte Carlo simulation. This method of analysis showed that with a 50% probability geoducks were aged correctly when using the crossdating method, compared to the growth increment counts which had a 50% probability of underestimating the age by 4 years. Therefore, the crossdated age estimates were found to be more accurate than increment counts. Furthermore, these results provide new confidence in using Pacific geoduck biochronologies for paleoclimate and paleoenvironmental reconstruction. Published by Elsevier B.V.Keywords: Age determination, Pacific geoduck, Bomb-produced radiocarbon, Bayesian models, Shell growth-increment counts, Crossdating, Panopea generos

Causes, Timing, and Impact of Dual Antiplatelet Therapy Interruption for Surgery (From the PARIS Registry)

Temporary interruption of dual antiplatelet therapy (DAPT) is not infrequently required in patients undergoing percutaneous coronary intervention (PCI). We sought to describe the procedures and outcomes associated with DAPT interruption in patients treated with DAPT following successful PCI from the Patterns of non-adherence to anti-platelet regimens in stented patients registry (n = 5018). DAPT interruption was prespecified as physician recommended cessation forcohort, 490 patients (9.8%) experienced 594 DAPT interruptions over 2 years following PCI. Only 1 antiplatelet agent was interrupted in 57.2% cases and interruption was frequently recommended by noncardiologists (51.3%). Where type of surgery was reported, majority of DAPT interruptions occurred for minor surgery (68.4% vs 31.6%) and a similar cessation pattern of single versus dual antiplatelet cessation was observed regardless of minor or major surgery. Subsequent to DAPT interruption, 12 patients (2.4%) experienced 1 thrombotic event each, of which 5 (1.0%) occurred during the interruption period. All events occurred in patients who either stopped both agents (8 of 12) or clopidogrel-only (4 of 12), with no events occurring due to aspirin cessation alone. In conclusion, in the Patterns of Non-adherence to Anti-platelet Regiments in Stented Patients registry, 1 in 10 patients were recommended DAPT interruption for surgery within 2 years of PCI. Interruption was more common for a single agent rather than both antiplatelet agents regardless of severity of surgery, and was frequently recommended by noncardiologists. Only 1% of patients with DAPT interruption experienced a subsequent thrombotic event during the interruption period, which mainly occurred in patients stopping both antiplatelet agents

Identifying novel phenotypes of elevated left ventricular end diastolic pressure using hierarchical clustering of features derived from electromechanical waveform data

Introduction Elevated left ventricular end diastolic pressure (LVEDP) is a consequence of compromised left ventricular compliance and an important measure of myocardial dysfunction. An algorithm was developed to predict elevated LVEDP utilizing electro-mechanical (EM) waveform features. We examined the hierarchical clustering of selected features developed from these EM waveforms in order to identify important patient subgroups and assess their possible prognostic significance. Materials and methods Patients presenting with cardiovascular symptoms (N = 396) underwent EM data collection and direct LVEDP measurement by left heart catheterization. LVEDP was classified as non-elevated ( ≤ 12 mmHg) or elevated (≥25 mmHg). The 30 most contributive features to the algorithm output were extracted from EM data and input to an unsupervised hierarchical clustering algorithm. The resultant dendrogram was divided into five clusters, and patient metadata overlaid. Results The cluster with highest LVEDP (cluster 1) was most dissimilar from the lowest LVEDP cluster (cluster 5) in both clustering and with respect to clinical characteristics. In contrast to the cluster demonstrating the highest percentage of elevated LVEDP patients, the lowest was predominantly non-elevated LVEDP, younger, lower BMI, and males with a higher rate of significant coronary artery disease (CAD). The next adjacent cluster (cluster 2) to that of the highest LVEDP (cluster 1) had the second lowest LVEDP of all clusters. Cluster 2 differed from Cluster 1 primarily based on features extracted from the electrical data, and those that quantified predictability and variability of the signal. There was a low predictability and high variability in the highest LVEDP cluster 1, and the opposite in adjacent cluster 2. Conclusion This analysis identified subgroups of patients with varying degrees of LVEDP elevation based on waveform features. An approach to stratify movement between clusters and possible progression of myocardial dysfunction may include changes in features that differentiate clusters; specifically, reductions in electrical signal predictability and increases in variability. Identification of phenotypes of myocardial dysfunction evidenced by elevated LVEDP and knowledge of factors promoting transition to clusters with higher levels of left ventricular filling pressures could permit early risk stratification and improve patient selection for novel therapeutic interventions

Identification of 4 novel human ocular coloboma genes ANK3, BMPR1B, PDGFRA, and CDH4 through evolutionary conserved vertebrate gene analysis

Purpose: Ocular coloboma arises from genetic or environmental perturbations that inhibit optic fissure (OF) fusion during early eye development. Despite high genetic heterogeneity, 70% to 85% of patients remain molecularly undiagnosed. In this study, we have identified new potential causative genes using cross-species comparative meta-analysis. Methods: Evolutionarily conserved differentially expressed genes were identified through in silico analysis, with in situ hybridization, gene knockdown, and rescue performed to confirm spatiotemporal gene expression and phenotype. Interrogation of the 100,000 Genomes Project for putative pathogenic variants was performed. Results: Nine conserved differentially expressed genes between zebrafish and mouse were identified. Expression of zebrafish ank3a, bmpr1ba/b, cdh4, and pdgfaa was localized to the OF, periocular mesenchyme cells, or ciliary marginal zone, regions traversed by the OF. Knockdown of ank3, bmpr1b, and pdgfaa revealed a coloboma and/or microphthalmia phenotype. Novel pathogenic variants in ANK3, BMPR1B, PDGFRA, and CDH4 were identified in 8 unrelated coloboma families. We showed BMPR1B rescued the knockdown phenotype but variant messenger RNAs failed, providing evidence of pathogenicity. Conclusion: We show the utility of cross-species meta-analysis to identify several novel coloboma disease-causing genes. There is a potential to increase the diagnostic yield for new and unsolved patients while adding to our understanding of the genetic basis of OF morphogenesis