Space weather challenges of the polar cap ionosphere

This paper presents research on polar cap ionosphere space weather phenomena conducted during the European Cooperation in Science and Technology (COST) action ES0803 from 2008 to 2012. The main part of the work has been directed toward the study of plasma instabilities and scintillations in association with cusp flow channels and polar cap electron density structures/patches, which is considered as critical knowledge in order to develop forecast models for scintillations in the polar cap. We have approached this problem by multi-instrument techniques that comprise the EISCAT Svalbard Radar, SuperDARN radars, in-situ rocket, and GPS scintillation measurements. The Discussion section aims to unify the bits and pieces of highly specialized information from several papers into a generalized picture. The cusp ionosphere appears as a hot region in GPS scintillation climatology maps. Our results are consistent with the existing view that scintillations in the cusp and the polar cap ionosphere are mainly due to multi-scale structures generated by instability processes associated with the cross-polar transport of polar cap patches. We have demonstrated that the SuperDARN convection model can be used to track these patches backward and forward in time. Hence, once a patch has been detected in the cusp inflow region, SuperDARN can be used to forecast its destination in the future. However, the high-density gradient of polar cap patches is not the only prerequisite for high-latitude scintillations. Unprecedented highresolution rocket measurements reveal that the cusp ionosphere is associated with filamentary precipitation giving rise to kilometer scale gradients onto which the gradient drift instability can operate very efficiently. Cusp ionosphere scintillations also occur during IMF BZ north conditions, which further substantiates that particle precipitation can play a key role to initialize plasma structuring. Furthermore, the cusp is associated with flow channels and strong flow shears, and we have demonstrated that the Kelvin- Helmholtz instability process may be efficiently driven by reversed flow events

Readout of GEM Detectors Using the Medipix2 CMOS Pixel Chip

We have operated a Medipix2 CMOS readout chip, with amplifying, shaping and charge discriminating front-end electronics integrated on the pixel-level, as a highly segmented direct charge collecting anode in a three-stage gas electron multiplier (Triple-GEM) to detect the ionization from $^{55}$Fe X-rays and electrons from $^{106}$Ru. The device allows to perform moderate energy spectroscopy measurements (20 % FWHM at 5.9 keV $X$-rays) using only digital readout and two discriminator thresholds. Being a truly 2D-detector, it allows to observe individual clusters of minimum ionizing charged particles in $Ar/CO_2$ (70:30) and $He/CO_2$ (70:30) mixtures and to achieve excellent spatial resolution for position reconstruction of primary clusters down to $\sim 50 \mu m$, based on the binary centroid determination method.Comment: 18 pages, 14 pictures. submitted to Nuclear Instruments and Methods in Physics Research

THGEM-based detectors for sampling elements in DHCAL: laboratory and beam evaluation

We report on the results of an extensive R&D program aimed at the evaluation of Thick-Gas Electron Multipliers (THGEM) as potential active elements for Digital Hadron Calorimetry (DHCAL). Results are presented on efficiency, pad multiplicity and discharge probability of a 10x10 cm2 prototype detector with 1 cm2 readout pads. The detector is comprised of single- or double-THGEM multipliers coupled to the pad electrode either directly or via a resistive anode. Investigations employing standard discrete electronics and the KPiX readout system have been carried out both under laboratory conditions and with muons and pions at the CERN RD51 test beam. For detectors having a charge-induction gap, it has been shown that even a ~6 mm thick single-THGEM detector reached detection efficiencies above 95%, with pad-hit multiplicity of 1.1-1.2 per event; discharge probabilities were of the order of 1e-6 - 1e-5 sparks/trigger, depending on the detector structure and gain. Preliminary beam tests with a WELL hole-structure, closed by a resistive anode, yielded discharge probabilities of <2e-6 for an efficiency of ~95%. Methods are presented to reduce charge-spread and pad multiplicity with resistive anodes. The new method showed good prospects for further evaluation of very thin THGEM-based detectors as potential active elements for DHCAL, with competitive performances, simplicity and robustness. Further developments are in course.Comment: 15 pages, 11 figures, MPGD2011 conference proceedin

Theoretical and Numerical Analysis of an Optimal Execution Problem with Uncertain Market Impact

This paper is a continuation of Ishitani and Kato (2015), in which we derived a continuous-time value function corresponding to an optimal execution problem with uncertain market impact as the limit of a discrete-time value function. Here, we investigate some properties of the derived value function. In particular, we show that the function is continuous and has the semigroup property, which is strongly related to the Hamilton-Jacobi-Bellman quasi-variational inequality. Moreover, we show that noise in market impact causes risk-neutral assessment to underestimate the impact cost. We also study typical examples under a log-linear/quadratic market impact function with Gamma-distributed noise.Comment: 24 pages, 14 figures. Continuation of the paper arXiv:1301.648

Apixaban Concentrations with Lower than Recommended Dosing in Older Adults with Atrial Fibrillation

OBJECTIVES: Lower than recommended doses of direct-acting oral anticoagulants are often prescribed to older adults with nonvalvular atrial fibrillation (NVAF). Our goal was to determine the consequences of lower than recommended dosing on plasma apixaban concentrations during the clinical care of older adults with NVAF. DESIGN: Convenience sample of patients receiving anticoagulation during 2017. SETTING: Academic medical center. PARTICIPANTS: Stable adults older than 65 years with NVAF receiving apixaban on a chronic basis. MEASUREMENTS: Patient age, weight, creatinine, co-medications, and apixaban concentrations. RESULTS: A total of 110 older adults with NVAF (mean age = 80.4 y; range = 66-100 y with 45% women) were studied. Overall, 48 patients received recommended dosing of 5 mg twice/day, and 42 received lower than recommended dosing. One patient in each category had concentrations below the expected 5% to 95% range at time of peak concentrations. Differences in proportion of apixaban concentrations within or outside expected ranges were not significant between patients receiving lower than recommended doses and those dosed as recommended at 5 mg twice/day (P =.35). However, in patients dosed as recommended with 5 mg twice/day, four had concentrations above the 5% to 95% range for peak levels expected at 3 to 4 hours after dosing; in two, this occurred around the midpoint of the dosing interval. Twenty patients received 2.5 mg twice/day as recommended. One-third had apixaban concentrations higher than expected peak concentrations compared with the clinical trials, and more than two-thirds had levels above the reported median for peak concentrations. CONCLUSIONS: Apixaban concentrations in older adults with NVAF seen clinically were higher than expected based on clinical trial data. The findings raise questions about the optimal dosing of apixaban in older adults with NVAF encountered outside of clinical trials and suggest a role for the monitoring of apixaban concentrations during care of patients that differ from those in randomized trials or when considering dosing outside of published guidelines. J Am Geriatr Soc 67:1902–1906, 2019

Drug interactions and pharmacogenetic factors contribute to variation in apixaban concentration in atrial fibrillation patients in routine care

Factor Xa-inhibitor apixaban is an oral anticoagulant prescribed in atrial fibrillation (AF) for stroke prevention. Its pharmacokinetic profile is known to be affected by cytochrome P450 (CYP)3A metabolism, while it is also a substrate of the efflux transporters ATP-binding cassette (ABC)B1 (P-glycoprotein) and ABCG2 (breast cancer resistance protein, BCRP). In this study, we assessed the impact of interacting medication and pharmacogenetic variation to better explain apixaban concentration differences among 358 Caucasian AF patients. Genotyping (ABCG2, ABCB1, CYP3A4*22, CYP3A5*3) was performed by TaqMan assays, and apixaban quantified by mass spectrometry. The typical patient was on average 77.2 years old, 85.5 kg, and had a serum creatinine of 103.1 µmol/L. Concomitant amiodarone, an antiarrhythmic agent and moderate CYP3A/ABCB1 inhibitor, the impaired-function variant ABCG2 c.421C \u3e A, and sex predicted higher apixaban concentrations when controlling for age, weight and serum creatinine (multivariate regression; R2 = 0.34). Our findings suggest that amiodarone and ABCG2 genotype contribute to interpatient apixaban variability beyond known clinical factors

Arbitrage and deflators in illiquid markets

This paper presents a stochastic model for discrete-time trading in financial markets where trading costs are given by convex cost functions and portfolios are constrained by convex sets. The model does not assume the existence of a cash account/numeraire. In addition to classical frictionless markets and markets with transaction costs or bid-ask spreads, our framework covers markets with nonlinear illiquidity effects for large instantaneous trades. In the presence of nonlinearities, the classical notion of arbitrage turns out to have two equally meaningful generalizations, a marginal and a scalable one. We study their relations to state price deflators by analyzing two auxiliary market models describing the local and global behavior of the cost functions and constraints

Comment on "On the subtleties of searching for dark matter with liquid xenon detectors"

In a recent manuscript (arXiv:1208.5046) Peter Sorensen claims that XENON100's upper limits on spin-independent WIMP-nucleon cross sections for WIMP masses below 10 GeV "may be understated by one order of magnitude or more". Having performed a similar, though more detailed analysis prior to the submission of our new result (arXiv:1207.5988), we do not confirm these findings. We point out the rationale for not considering the described effect in our final analysis and list several potential problems with his study.Comment: 3 pages, no figure

An overview of the design, construction and performance of large area triple-GEM prototypes for future upgrades of the CMS forward muon system

GEM detectors are used in high energy physics experiments given their good spatial resolution, high rate capability and radiation hardness. An international collaboration is investigating the possibility of covering the 1.6 < vertical bar eta vertical bar < 2.4 region of the CMS muon endcaps with large-area triple-GEM detectors. The CMS high-eta area is actually not fully instrumented, only Cathode Strip Chamber (CSC) are installed. The vacant area presents an opportunity for a detector technology able to to cope with the harsh radiation environment; these micropattern gas detectors are an appealing option to simultaneously enhance muon tracking and triggering capabilities in a future upgrade of the CMS detector. A general overview of this feasibility study is presented. Design and construction of small (10cm x 10cm) and full-size trapezoidal (1m x 0.5m) triple-GEM prototypes is described. Results from measurements with x-rays and from test beam campaigns at the CERN SPS is shown for the small and large prototypes. Preliminary simulation studies on the expected muon reconstruction and trigger performances of this proposed upgraded muon system are reported