Mechanisms and outcome of severe mitral regulation after inoue balloon valvuloplasty

AbstractObjectives. The purpose of this study was to assess the incidence, mechanism and outcome of severe mitral regurgitation after treatment of mitral stenosis with percutaneous mitral valvuloplasty using the Inoue balloon.Background. Severe mitral regurgitation occurs in up to 15% of percutaneous balloon valvuloplasty procedures for acquired mitral stenosis. The incidence and mechanism of production of mitral regurgitation with the recently introduced single-ballon lnone technique have not been characterized.Methods. We examined the incidence, mechanism, predictors and outcome of severe mitral regurgitation after Inoue balloon valvuloplasty in 280 patients in the North American multicenter registry. Twenty-one patients who developed either clinically significant or angiographically severe regurgitation were identified, and their echocardiograms were reviewed to determine the mechanism of regurgitation. These patients were then compared with the remaining patients without severe regurgitation to identify predictors of this outcome.Results. The incidence of severe regurgitation in this study was 7.5%, and the mean grade of angiographic regurgitation in these patients increased from 0.9 ± 1.0 to 2.8 ± 0.7 (p < 0.05). The most common cause of regurgitation (43%) was rupture of clhordae tendineae to the anterior or posterior mitral leaflet. Tearing of a leaflet (usually the posterior one) occurred in 30% of patients; and no recognizable structural abnormality, with wide splitting of the commissures and a central regurgitant jet, was present in five patients (26%). All patients with definite posterior leaflet tears had heavily calcified leaflet. Patients who developed severe regurgitation had fewer balloon inflations and a higher grade of preexisting mitral regurgitation but were otherwish similar to the remaining patients without severe regurgitation. During 6-month follow-up, 71% of the patients with severe regurgitation were treated surgically; the grade of regurgitation decreased in four patients (19%), and five (24%) not required mitral valve replacement during 18 ± 5 month of follow-up.Conclusions. Severe mitral regurgitation is a relatively infrequent complication of Inoue balloon valvutoplasty and results from disruption of the valve integrity, chordal rapture and leaflet tearing. Careful balloon positioning may help avoid chordal rapture, and heavily calcified posterior lesflets may be at greater risk of tearing. Most patients who develop severe regurgitation will require nonemergency mitral valve replacement

Projecting Climate Dependent Coastal Flood Risk With a Hybrid Statistical Dynamical Model

ABSTRACT: Numerical models for tides, storm surge, and wave runup have demonstrated ability to accurately define spatially varying flood surfaces. However these models are typically too computationally expensive to dynamically simulate the full parameter space of future oceanographic, atmospheric, and hydrologic conditions that will constructively compound in the nearshore to cause both extreme event and nuisance flooding during the 21st century. A surrogate modeling framework of waves, winds, and tides is developed in this study to efficiently predict spatially varying nearshore and estuarine water levels contingent on any combination of offshore forcing conditions. The surrogate models are coupled with a time-dependent stochastic climate emulator that provides efficient downscaling for hypothetical iterations of offshore conditions. Together, the hybrid statistical-dynamical framework can assess present day and future coastal flood risk, including the chronological characteristics of individual flood and wave-induced dune overtopping events and their changes into the future. The framework is demonstrated at Naval Base Coronado in San Diego, CA, utilizing the regional Coastal Storm Modeling System (CoSMoS; composed of Delft3D and XBeach) as the dynamic simulator and Gaussian process regression as the surrogate modeling tool. Validation of the framework uses both in-situ tide gauge observations within San Diego Bay, and a nearshore cross-shore array deployment of pressure sensors in the open beach surf zone. The framework reveals the relative influence of large-scale climate variability on future coastal flood resilience metrics relevant to the management of an open coast artificial berm, as well as the stochastic nature of future total water levels.This work was funded by the Strategic Environmental Research Development Program (DOD/SERDP RC-2644). Any use of trade, firm, or product names is for descriptive purposes only and does not imply endorsement by the U.S. Government. F. J. Mendez, A. Rueda, and L. Cagigal acknowledge the partial funding from the Spanish Ministry of Science and Innovation, project Beach4cast PID2019-107053RB-I00. The authors thank the Scripps Center for Coastal Studies for their efforts to deploy, recover, and process surf zone pressure sensor data used as validation in this study. The authors thank Melisa Menendez for sharing GOW2 hindcast data for Southern California. The authors thank the sea-level rise projection authors for developing and making the sea-level rise projections available, multiple funding agencies for supporting the development of the projections, and the NASA Sea-Level Change Team for developing and hosting the IPCC AR6 Sea-Level Projection Tool

Nucleus size and DNA accessibility are linked to the regulation of paraspeckle formation in cellular differentiation

Background Many long noncoding RNAs (lncRNAs) have been implicated in general and cell type-specific molecular regulation. Here, we asked what underlies the fundamental basis for the seemingly random appearance of nuclear lncRNA condensates in cells, and we sought compounds that can promote the disintegration of lncRNA condensates in vivo. Results As a basis for comparing lncRNAs and cellular properties among different cell types, we screened lncRNAs in human pluripotent stem cells (hPSCs) that were differentiated to an atlas of cell lineages. We found that paraspeckles, which form by aggregation of the lncRNA NEAT1, are scaled by the size of the nucleus, and that small DNA-binding molecules promote the disintegration of paraspeckles and other lncRNA condensates. Furthermore, we found that paraspeckles regulate the differentiation of hPSCs. Conclusions Positive correlation between the size of the nucleus and the number of paraspeckles exist in numerous types of human cells. The tethering and structure of paraspeckles, as well as other lncRNAs, to the genome can be disrupted by small molecules that intercalate in DNA. The structure-function relationship of lncRNAs that regulates stem cell differentiation is likely to be determined by the dynamics of nucleus size and binding site accessibility.FWN – Publicaties zonder aanstelling Universiteit Leide

Identification of regulatory variants associated with genetic susceptibility to meningococcal disease

Non-coding genetic variants play an important role in driving susceptibility to complex diseases but their characterization remains challenging. Here, we employed a novel approach to interrogate the genetic risk of such polymorphisms in a more systematic way by targeting specific regulatory regions relevant for the phenotype studied. We applied this method to meningococcal disease susceptibility, using the DNA binding pattern of RELA - a NF-kB subunit, master regulator of the response to infection - under bacterial stimuli in nasopharyngeal epithelial cells. We designed a custom panel to cover these RELA binding sites and used it for targeted sequencing in cases and controls. Variant calling and association analysis were performed followed by validation of candidate polymorphisms by genotyping in three independent cohorts. We identified two new polymorphisms, rs4823231 and rs11913168, showing signs of association with meningococcal disease susceptibility. In addition, using our genomic data as well as publicly available resources, we found evidences for these SNPs to have potential regulatory effects on ATXN10 and LIF genes respectively. The variants and related candidate genes are relevant for infectious diseases and may have important contribution for meningococcal disease pathology. Finally, we described a novel genetic association approach that could be applied to other phenotypes

Searches for lepton-flavour-violating decays of the Higgs boson in s=13\sqrt{s}=13 TeV pp\mathit{pp} collisions with the ATLAS detector

This Letter presents direct searches for lepton flavour violation in Higgs boson decays, H → eτ and H → μτ , performed with the ATLAS detector at the LHC. The searches are based on a data sample of proton–proton collisions at a centre-of-mass energy √s = 13 TeV, corresponding to an integrated luminosity of 36.1 fb−1. No significant excess is observed above the expected background from Standard Model processes. The observed (median expected) 95% confidence-level upper limits on the leptonflavour-violating branching ratios are 0.47% (0.34+0.13−0.10%) and 0.28% (0.37+0.14−0.10%) for H → eτ and H → μτ , respectively.publishedVersio

Search for flavour-changing neutral currents in processes with one top quark and a photon using 81 fb⁻¹ of pp collisions at \sqrts = 13 TeV with the ATLAS experiment

A search for flavour-changing neutral current (FCNC) events via the coupling of a top quark, a photon, and an up or charm quark is presented using 81 fb−1 of proton–proton collision data taken at a centre-of-mass energy of 13 TeV with the ATLAS detector at the LHC. Events with a photon, an electron or muon, a b-tagged jet, and missing transverse momentum are selected. A neural network based on kinematic variables differentiates between events from signal and background processes. The data are consistent with the background-only hypothesis, and limits are set on the strength of the tqγ coupling in an effective field theory. These are also interpreted as 95% CL upper limits on the cross section for FCNC tγ production via a left-handed (right-handed) tuγ coupling of 36 fb (78 fb) and on the branching ratio for t→γu of 2.8×10−5 (6.1×10−5). In addition, they are interpreted as 95% CL upper limits on the cross section for FCNC tγ production via a left-handed (right-handed) tcγ coupling of 40 fb (33 fb) and on the branching ratio for t→γc of 22×10−5 (18×10−5). © 2019 The Author(s

Beam-induced backgrounds measured in the ATLAS detector during local gas injection into the LHC beam vacuum

Inelastic beam-gas collisions at the Large Hadron Collider (LHC), within a few hundred metres of the ATLAS experiment, are known to give the dominant contribution to beam backgrounds. These are monitored by ATLAS with a dedicated Beam Conditions Monitor (BCM) and with the rate of fake jets in the calorimeters. These two methods are complementary since the BCM probes backgrounds just around the beam pipe while fake jets are observed at radii of up to several metres. In order to quantify the correlation between the residual gas density in the LHC beam vacuum and the experimental backgrounds recorded by ATLAS, several dedicated tests were performed during LHC Run 2. Local pressure bumps, with a gas density several orders of magnitude higher than during normal operation, were introduced at different locations. The changes of beam-related backgrounds, seen in ATLAS, are correlated with the local pressure variation. In addition the rates of beam-gas events are estimated from the pressure measurements and pressure bump profiles obtained from calculations. Using these rates, the efficiency of the ATLAS beam background monitors to detect beam-gas events is derived as a function of distance from the interaction point. These efficiencies and characteristic distributions of fake jets from the beam backgrounds are found to be in good agreement with results of beam-gas simulations performed with theFluka Monte Carlo programme