An innovative design of transcatheter implantable mitral valve prosthesis. Anatomy of the mitral valve in patients with functional mitral regurgitation and preliminary results of the implant in the animal model using quantitative 3D echocardiography and particle imaging velocimetry

Background: Transcatheter mitral valve replacement (TMVR) is a new therapeutic option for high surgical risk patients with mitral regurgitation (MR) and several prostheses are currently at different stages of development. Indeed, once prototypes of these prosthesis are designed, they need to undergo both bench testing and preclinical evaluation to test the performance and safety of the device and acquire useful information for guiding the secondary improvements. After this stage, if the prosthesis shows favourable results in terms of performance and safety, the manufacturer can apply for CE marking. In case of achievement of the CE mark, the clinical use can start in the European countries. The application of advanced echocardiography is useful not only in a preclinical experimental stage but results to be an irreplaceable tool in the proper selection of the treatment strategy with respect to the case-specific anatomic and functional mitral valve (MV) disease pattern and in the guidance of the correct bioprosthesis positioning and implantation during the procedure. Aims: To describe the feasibility and advantage of 3D and contrast echocardiography in a preclinical study and report the acute hemodynamic results after implantation of a novel transcatheter self- expandable D-shape mitral bioprosthesis characterized by asymmetric stent and advanced mono- leaflet structure. In addition, we aimed to assess the MV geometry in patients with functional MR (FMR) that would potentially benefit from TMVR, focusing on the comparison between mitral annulus (MA) geometry of patients with ischemic (IMR) and non-ischemic mitral regurgitation (nIMR). Methods: From May 2015 to August 2018, prosthesis prototypes were implanted under echocardiography guidance in 112 small-size healthy sheep using both trans-atrial (Ta) and trans- apical (TA) access. Multimodality imaging was used for animal selection and trans-pericardial echocardiography (TPE) was applied to obtain humanized image during intervention. Particle imaging velocimetry was used to assess intraventricular flow dynamics. We retrospectively selected 94 patients with severe FMR, both IMR and nIMR. 3D MA analysis was performed in early-diastole and mid-systoleby using a recent, commercially-available software package. Measure of interest were MA dimensions and geometry parameters, left atrial and left ventricular volumes. Results: 2D and 3D TPE was performed before and after implantation to measure MA dimensions (area: 6.4±0.8 cm2, perimeter: 9.4±0.8 cm) and assess prosthesis alignment and function. The vast majority of implantations showed none or just trivial intra- (n=104, 93%) and peri-prosthesis leak (n=86, 77%) with good valve function (mean gradient 4 ± 3 mmHg). At particle imaging velocimetry, left ventricular vortex properties did not change after implantation. In patients with severe FMR, 41 (43,6%) with IMR and 53 (56,4%) with nIMR, maximum MA 3D area (10.7±2.5 cm2 vs 11.6±2.7 cm2, p=0.124) and the best fit plane MA area (9.9±2.3 cm2 vs 10.7±2.5 cm2, p=0.135, respectively) were similar between IMR and nIMR. nIMR patients showed larger mid- systolic 3D area (9.8±2.3 cm2 vs 10.8±2.7 cm2, p=0.046) and perimeter (11.2±1.3 cm vs 11.8±1.5 cm, p=0.048), longer and larger leaflets, and wider aorto-mitral angle (135±10° vs 141±11°, p=0.011). Conversely, the area of MA at the best fit plane did not differ between IMR and nIMR patients (9±1.1 cm2 vs 9.9±1.5 cm2, p=0.063). Conclusions: In the healthy sheep model, initial preclinical experience with a novel mono-leaflet transcatheter self-expandable mitral prosthesis showed that the TA implantation of the valve was feasible, safe, and supported by good hemodynamic results. The application of advanced echocardiography on an animal model was feasible and helpful in guiding the continuous refinements needed to enhance the development of this new concept of bioprosthesis. Patients with ischemic and non-ischemic etiology of FMR have similar maximum dimension, yet systolic differences between the two groups should be considered to tailor prosthesis’s selection

Search for new particles in events with energetic jets and large missing transverse momentum in proton-proton collisions at root s=13 TeV

A search is presented for new particles produced at the LHC in proton-proton collisions at root s = 13 TeV, using events with energetic jets and large missing transverse momentum. The analysis is based on a data sample corresponding to an integrated luminosity of 101 fb(-1), collected in 2017-2018 with the CMS detector. Machine learning techniques are used to define separate categories for events with narrow jets from initial-state radiation and events with large-radius jets consistent with a hadronic decay of a W or Z boson. A statistical combination is made with an earlier search based on a data sample of 36 fb(-1), collected in 2016. No significant excess of events is observed with respect to the standard model background expectation determined from control samples in data. The results are interpreted in terms of limits on the branching fraction of an invisible decay of the Higgs boson, as well as constraints on simplified models of dark matter, on first-generation scalar leptoquarks decaying to quarks and neutrinos, and on models with large extra dimensions. Several of the new limits, specifically for spin-1 dark matter mediators, pseudoscalar mediators, colored mediators, and leptoquarks, are the most restrictive to date.Peer reviewe

Probing effective field theory operators in the associated production of top quarks with a Z boson in multilepton final states at root s=13 TeV

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MUSiC : a model-unspecific search for new physics in proton-proton collisions at root s=13TeV

Results of the Model Unspecific Search in CMS (MUSiC), using proton-proton collision data recorded at the LHC at a centre-of-mass energy of 13 TeV, corresponding to an integrated luminosity of 35.9 fb(-1), are presented. The MUSiC analysis searches for anomalies that could be signatures of physics beyond the standard model. The analysis is based on the comparison of observed data with the standard model prediction, as determined from simulation, in several hundred final states and multiple kinematic distributions. Events containing at least one electron or muon are classified based on their final state topology, and an automated search algorithm surveys the observed data for deviations from the prediction. The sensitivity of the search is validated using multiple methods. No significant deviations from the predictions have been observed. For a wide range of final state topologies, agreement is found between the data and the standard model simulation. This analysis complements dedicated search analyses by significantly expanding the range of final states covered using a model independent approach with the largest data set to date to probe phase space regions beyond the reach of previous general searches.Peer reviewe

Measurement of prompt open-charm production cross sections in proton-proton collisions at root s=13 TeV

The production cross sections for prompt open-charm mesons in proton-proton collisions at a center-of-mass energy of 13TeV are reported. The measurement is performed using a data sample collected by the CMS experiment corresponding to an integrated luminosity of 29 nb(-1). The differential production cross sections of the D*(+/-), D-+/-, and D-0 ((D) over bar (0)) mesons are presented in ranges of transverse momentum and pseudorapidity 4 < p(T) < 100 GeV and vertical bar eta vertical bar < 2.1, respectively. The results are compared to several theoretical calculations and to previous measurements.Peer reviewe

Combined searches for the production of supersymmetric top quark partners in proton-proton collisions at root s=13 TeV

A combination of searches for top squark pair production using proton-proton collision data at a center-of-mass energy of 13 TeV at the CERN LHC, corresponding to an integrated luminosity of 137 fb(-1) collected by the CMS experiment, is presented. Signatures with at least 2 jets and large missing transverse momentum are categorized into events with 0, 1, or 2 leptons. New results for regions of parameter space where the kinematical properties of top squark pair production and top quark pair production are very similar are presented. Depending on themodel, the combined result excludes a top squarkmass up to 1325 GeV for amassless neutralino, and a neutralinomass up to 700 GeV for a top squarkmass of 1150 GeV. Top squarks with masses from 145 to 295 GeV, for neutralino masses from 0 to 100 GeV, with a mass difference between the top squark and the neutralino in a window of 30 GeV around the mass of the top quark, are excluded for the first time with CMS data. The results of theses searches are also interpreted in an alternative signal model of dark matter production via a spin-0 mediator in association with a top quark pair. Upper limits are set on the cross section for mediator particle masses of up to 420 GeV

Measurement of B-c(2S)(+) and B-c*(2S)(+) cross section ratios in proton-proton collisions at root s=13 TeV

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Development and validation of HERWIG 7 tunes from CMS underlying-event measurements

This paper presents new sets of parameters (“tunes”) for the underlying-event model of the HERWIG7 event generator. These parameters control the description of multiple-parton interactions (MPI) and colour reconnection in HERWIG7, and are obtained from a fit to minimum-bias data collected by the CMS experiment at s=0.9, 7, and 13Te. The tunes are based on the NNPDF 3.1 next-to-next-to-leading-order parton distribution function (PDF) set for the parton shower, and either a leading-order or next-to-next-to-leading-order PDF set for the simulation of MPI and the beam remnants. Predictions utilizing the tunes are produced for event shape observables in electron-positron collisions, and for minimum-bias, inclusive jet, top quark pair, and Z and W boson events in proton-proton collisions, and are compared with data. Each of the new tunes describes the data at a reasonable level, and the tunes using a leading-order PDF for the simulation of MPI provide the best description of the dat

Measurement of the W gamma Production Cross Section in Proton-Proton Collisions at root s=13 TeV and Constraints on Effective Field Theory Coefficients

A fiducial cross section for W gamma production in proton-proton collisions is measured at a center-of-mass energy of 13 TeV in 137 fb(-1) of data collected using the CMS detector at the LHC. The W -> e nu and mu nu decay modes are used in a maximum-likelihood fit to the lepton-photon invariant mass distribution to extract the combined cross section. The measured cross section is compared with theoretical expectations at next-to-leading order in quantum chromodynamics. In addition, 95% confidence level intervals are reported for anomalous triple-gauge couplings within the framework of effective field theory.Peer reviewe