Bounds and asymptotic expansions for the distribution of the maximum of a smooth stationary gaussian process

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Bounds and asymptotic expansions for the distribution of the Maximum of a smooth stationary Gaussian process

This paper uses the Rice method [18] to give bounds to the distribution of the maximum of a smooth stationary Gaussian process. We give simpler expressions of the first two terms of the Rice series [3,13] for the distribution of the maximum. Our main contribution is a simpler form of the second factorial moment of the number of upcrossings which is in some sense a generalization of Steinberg et al.'s formula ([7] p. 212). Then, we present a numerical application and asymptotic expansions that give a new interpretation of a result by Piterbarg [15]

Bounds and asymptotic expansions for the distribution of the maximum of a smooth stationary gaussian process

National audienc

Stereoselective block of hERG channel by (S)-methadone and QT interval prolongation in CYP2B6 slow metabolizer: evidence of a safer cardiac profile of (R)-methadone

Methadone is widely prescribed (about 215'000 opioid dependent patients and >275'000 patients treated for pain in the US, and about 150'000 subjects in methadone maintenance therapy in the EU). Methadone inhibits the cardiac potassium channel hERG and can cause a prolonged QT interval, with several described cases of torsades de pointes and sudden deaths. Methadone is chiral but its therapeutic (opioid) activity is mainly due to (R)-methadone. Using whole-cell patch-clamp experiments using cells expressing hERG, we showed, that (S)-methadone blocked the hERG current 3.5-fold more potently than (R)-methadone (IC50s at 37°C: 2 and 7µM; Eap et al., Clin Pharmacol Ther 81:719-28, 2007). In addition, as CYP2B6 slow metabolizer (SM) status results in a reduced ability to metabolize (S)-methadone (Crettol et al. Clin Pharmacol Ther, 78(6) :593-604, 2005), electrocardiograms, CYP2B6 genotypes, and (R)- and (S)-methadone plasma concentrations were obtained for 179 patients receiving (R,S)-methadone (Eap et al., Clin Pharmacol Ther 81:719-28, 2007). The mean heart-rate-corrected QT (QTc) was higher in CYP2B6 SMs (*6/*6 genotype; 43925ms; n=11) than in extensive metabolizers (non *6/*6; 42125ms; n=168; P=0.017). CYP2B6 SM status was associated with an increased risk of prolonged QTc (odds ratio=4.5, 95% confidence interval=1.2-17.7; P=0.03). This study reports a stereoselectivity in the hERG channel blockade and a potential safer cardiac profile of (R)-methadone. In addition, it reports the first genetic factor implicated in methadone metabolism that may increase the risk of cardiac arrhythmias and sudden death. The prescription of the pure enantiomer would therefore reduce the risk of cardiac toxicity and sudden death in the very large number of patients treated with methadone worldwide. Interestingly, our studies also suggests that stereoselectivity in the hERG current blockade should be more often considered in the field of drug-induced prolonged QT interval which, in addition to methadone, could lead to the finding of other, safer drugs

Open data from the first and second observing runs of Advanced LIGO and Advanced Virgo

Advanced LIGO and Advanced Virgo are monitoring the sky and collecting gravitational-wave strain data with sufficient sensitivity to detect signals routinely. In this paper we describe the data recorded by these instruments during their first and second observing runs. The main data products are gravitational-wave strain time series sampled at 16384 Hz. The datasets that include this strain measurement can be freely accessed through the Gravitational Wave Open Science Center at http://gw-openscience.org, together with data-quality information essential for the analysis of LIGO and Virgo data, documentation, tutorials, and supporting software

Search for intermediate-mass black hole binaries in the third observing run of Advanced LIGO and Advanced Virgo

International audienceIntermediate-mass black holes (IMBHs) span the approximate mass range 100−105 M⊙, between black holes (BHs) that formed by stellar collapse and the supermassive BHs at the centers of galaxies. Mergers of IMBH binaries are the most energetic gravitational-wave sources accessible by the terrestrial detector network. Searches of the first two observing runs of Advanced LIGO and Advanced Virgo did not yield any significant IMBH binary signals. In the third observing run (O3), the increased network sensitivity enabled the detection of GW190521, a signal consistent with a binary merger of mass ∼150 M⊙ providing direct evidence of IMBH formation. Here, we report on a dedicated search of O3 data for further IMBH binary mergers, combining both modeled (matched filter) and model-independent search methods. We find some marginal candidates, but none are sufficiently significant to indicate detection of further IMBH mergers. We quantify the sensitivity of the individual search methods and of the combined search using a suite of IMBH binary signals obtained via numerical relativity, including the effects of spins misaligned with the binary orbital axis, and present the resulting upper limits on astrophysical merger rates. Our most stringent limit is for equal mass and aligned spin BH binary of total mass 200 M⊙ and effective aligned spin 0.8 at 0.056 Gpc−3 yr−1 (90% confidence), a factor of 3.5 more constraining than previous LIGO-Virgo limits. We also update the estimated rate of mergers similar to GW190521 to 0.08 Gpc−3 yr−1.Key words: gravitational waves / stars: black holes / black hole physicsCorresponding author: W. Del Pozzo, e-mail: [email protected]† Deceased, August 2020