Acquired von Willebrand Syndrome in Patients With Ventricular Assist Device

During the last decade the use of ventricular assist devices (VADs) for patients with severe heart failure has increased tremendously. However, flow disturbances, mainly high shear induced by the device is associated with bleeding complications. Shear stress-induced changes in VWF conformation are associated with a loss of high molecular weight multimers (HMW) of VWF and an increased risk of bleeding. This phenomenon and its cause will be elaborated and reviewed in the following

The photospheres of the hottest fastest stars in the Galaxy

We perform nonlocal thermodynamic equilibrium (NLTE) model atmosphere analyses of the three hottest hypervelocity stars (space velocities between $\approx$ 1500-2800 km s$^{-1}$) known to date, which were recently discovered spectroscopically and identified as runaways from Type Ia supernovae. The hottest of the three (J0546$+$0836, effective temperature $T_\mathrm{eff}$ = 95,000 $\pm$ 15,000 K, surface gravity log g = $5.5 \pm 0.5$) has an oxygen-dominated atmosphere with a significant amount of carbon (C = $0.10 \pm 0.05$, O = $0.90 \pm 0.05$, mass fractions). Its mixed absorption+emission line spectrum exhibits photospheric absorption lines from O V and O VI as well as O III and O IV emission lines that are formed in a radiation-driven wind with a mass-loss rate of the order of $10^{-8}$ $M_\odot$ yr$^{-1}$. Spectroscopically, J0546$+$0836 is a [WC]-PG1159 transition-type pre-white dwarf. The second object (J0927$-$6335) is a PG1159-type white dwarf with a pure absorption-line spectrum dominated by C III/C IV and O III/O IV. We find $T_\mathrm{eff}$ = 60,000 $\pm$ 5000 K, log g = $7.0 \pm 0.5$, and a carbon- and oxygen-dominated atmosphere with C = $0.47 \pm 0.25$, O = $0.48 \pm 0.25$, and possibly a minute amount of helium (He = $0.05 \pm 0.05$). Comparison with post-AGB evolutionary tracks suggests a mass of $M\approx0.5$ $M_\odot$ for both objects, if such tracks can safely be applied to these stars. We find the third object (J1332$-$3541) to be a relatively massive ($M=0.89 M_\odot$) hydrogen-rich (DAO) white dwarf with $T_\mathrm{eff}$ = 65,657 $\pm$ 2390 K, log g = $8.38 \pm 0.08$, and abundances H = $0.65 \pm 0.04$ and He = $0.35 \pm 0.04$. We discuss our results in the context of the "dynamically driven double-degenerate double-detonation" (D$^6$) scenario proposed for the origin of these stars.Comment: Accepted for publication in A&

The photospheres of the hottest fastest stars in the Galaxy

We perform nonlocal thermodynamic equilibrium (NLTE) model atmosphere analyses of the three hottest hypervelocity stars (space velocities between ≈1500–2800 km s−1) known to date, which were recently discovered spectroscopically and identified as runaways from Type Ia supernovae. The hottest of the three (J0546+0836, effective temperature Teff = 95 000 ± 15 000 K, surface gravity lo

Relevance of platelet desialylation and thrombocytopenia in type 2B von Willebrand disease: preclinical and clinical evidence

Patients with type 2B von Willebrand disease (vWD) (caused by gain-of-function mutations in the gene coding for von Willebrand factor) display bleeding to a variable extent and, in some cases, thrombocytopenia. There are several underlying causes of thrombocytopenia in type 2B vWD. It was recently suggested that desialylation-mediated platelet clearance leads to thrombocytopenia in this disease. However, this hypothesis has not been tested in vivo. The relationship between platelet desialylation and the platelet count was probed in 36 patients with type 2B von Willebrand disease (p.R1306Q, p.R1341Q, and p.V1316M mutations) and in a mouse model carrying the severe p.V1316M mutation (the 2B mouse). We observed abnormally high elevated levels of platelet desialylation in both patients with the p.V1316M mutation and the 2B mice. In vitro, we demonstrated that 2B p.V1316M/von Willebrand factor induced more desialylation of normal platelets than wild-type von Willebrand factor did. Furthermore, we found that N-glycans were desialylated and we identified αIIb and β3 as desialylation targets. Treatment of 2B mice with sialidase inhibitors (which correct platelet desialylation) was not associated with the recovery of a normal platelet count. Lastly, we demonstrated that a critical platelet desialylation threshold (not achieved in either 2B patients or 2B mice) was required to induce thrombocytopenia in vivo. In conclusion, in type 2B vWD, platelet desialylation has a minor role and is not sufficient to mediate thrombocytopenia

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements

Measurement of the top quark forward-backward production asymmetry and the anomalous chromoelectric and chromomagnetic moments in pp collisions at √s = 13 TeV

Abstract The parton-level top quark (t) forward-backward asymmetry and the anomalous chromoelectric (d̂ t) and chromomagnetic (μ̂ t) moments have been measured using LHC pp collisions at a center-of-mass energy of 13 TeV, collected in the CMS detector in a data sample corresponding to an integrated luminosity of 35.9 fb−1. The linearized variable AFB(1) is used to approximate the asymmetry. Candidate t t ¯ events decaying to a muon or electron and jets in final states with low and high Lorentz boosts are selected and reconstructed using a fit of the kinematic distributions of the decay products to those expected for t t ¯ final states. The values found for the parameters are AFB(1)=0.048−0.087+0.095(stat)−0.029+0.020(syst),μ̂t=−0.024−0.009+0.013(stat)−0.011+0.016(syst), and a limit is placed on the magnitude of | d̂ t| < 0.03 at 95% confidence level. [Figure not available: see fulltext.

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