239 research outputs found

    Safety and pharmacokinetics of anti-TFPI antibody (concizumab) in healthy volunteers and patients with hemophilia: a randomized first human dose trial

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    BACKGROUND: Prophylaxis with either intravenous (i.v.) factor VIII (FVIII) or FIX is the gold standard of care for patients with severe hemophilia. A monoclonal antibody (concizumab) targeting tissue factor pathway inhibitor (TFPI) that can be administered subcutaneously (s.c.) has the potential to alter current concepts of prophylaxis in hemophilia. OBJECTIVES: To evaluate the safety and describe the pharmacokinetics and pharmacodynamics of single-dose concizumab in healthy volunteers and patients with hemophilia A or B. METHODS: In this first human dose, phase 1, multicenter, randomized, double-blind, placebo-controlled trial escalating single i.v. (0.5-9000 μg kg(-1) ) or s.c. (50-3000 μg kg(-1) ) doses of concizumab were administered to healthy volunteers (n = 28) and hemophilia patients (n = 24). RESULTS: Concizumab had a favorable safety profile after single i.v. or s.c. administration. There were no serious adverse events and no anti-concizumab antibodies. No clinically relevant changes in platelets, prothrombin time, activated partial thromboplastin time, fibrinogen, or antithrombin were found. A dose-dependent procoagulant effect of concizumab was seen as increased levels of D-dimers and prothrombin fragment 1 + 2. Nonlinear pharmacokinetics of concizumab was observed due to target-mediated clearance. A maximum mean AUC0-∞ of 33 960 h μg mL(-1) and a maximum mean concentration of 247 μg mL(-1) was measured at the highest dose. CONCLUSIONS: Concizumab showed a favorable safety profile after i.v. or s.c. administration and nonlinear pharmacokinetics was observed due to target-mediated clearance. A concentration-dependent procoagulant effect of concizumab was observed, supporting further study into the potential use of s.c. concizumab for hemophilia treatment

    Open Data from the Third Observing Run of LIGO, Virgo, KAGRA, and GEO

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    The global network of gravitational-wave observatories now includes five detectors, namely LIGO Hanford, LIGO Livingston, Virgo, KAGRA, and GEO 600. These detectors collected data during their third observing run, O3, composed of three phases: O3a starting in 2019 April and lasting six months, O3b starting in 2019 November and lasting five months, and O3GK starting in 2020 April and lasting two weeks. In this paper we describe these data and various other science products that can be freely accessed through the Gravitational Wave Open Science Center at https://gwosc.org. The main data set, consisting of the gravitational-wave strain time series that contains the astrophysical signals, is released together with supporting data useful for their analysis and documentation, tutorials, as well as analysis software packages

    A Joint Fermi-GBM and Swift-BAT Analysis of Gravitational-wave Candidates from the Third Gravitational-wave Observing Run

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    We present Fermi Gamma-ray Burst Monitor (Fermi-GBM) and Swift Burst Alert Telescope (Swift-BAT) searches for gamma-ray/X-ray counterparts to gravitational-wave (GW) candidate events identified during the third observing run of the Advanced LIGO and Advanced Virgo detectors. Using Fermi-GBM onboard triggers and subthreshold gamma-ray burst (GRB) candidates found in the Fermi-GBM ground analyses, the Targeted Search and the Untargeted Search, we investigate whether there are any coincident GRBs associated with the GWs. We also search the Swift-BAT rate data around the GW times to determine whether a GRB counterpart is present. No counterparts are found. Using both the Fermi-GBM Targeted Search and the Swift- BAT search, we calculate flux upper limits and present joint upper limits on the gamma-ray luminosity of each GW. Given these limits, we constrain theoretical models for the emission of gamma rays from binary black hole mergers

    Search for Eccentric Black Hole Coalescences during the Third Observing Run of LIGO and Virgo

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    Despite the growing number of confident binary black hole coalescences observed through gravitational waves so far, the astrophysical origin of these binaries remains uncertain. Orbital eccentricity is one of the clearest tracers of binary formation channels. Identifying binary eccentricity, however, remains challenging due to the limited availability of gravitational waveforms that include effects of eccentricity. Here, we present observational results for a waveform-independent search sensitive to eccentric black hole coalescences, covering the third observing run (O3) of the LIGO and Virgo detectors. We identified no new high-significance candidates beyond those that were already identified with searches focusing on quasi-circular binaries. We determine the sensitivity of our search to high-mass (total mass M>70M>70 MM_\odot) binaries covering eccentricities up to 0.3 at 15 Hz orbital frequency, and use this to compare model predictions to search results. Assuming all detections are indeed quasi-circular, for our fiducial population model, we place an upper limit for the merger rate density of high-mass binaries with eccentricities 0<e0.30 < e \leq 0.3 at 0.330.33 Gpc3^{-3} yr1^{-1} at 90\% confidence level.Comment: 24 pages, 5 figure

    Open data from the third observing run of LIGO, Virgo, KAGRA and GEO

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    The global network of gravitational-wave observatories now includes five detectors, namely LIGO Hanford, LIGO Livingston, Virgo, KAGRA, and GEO 600. These detectors collected data during their third observing run, O3, composed of three phases: O3a starting in April of 2019 and lasting six months, O3b starting in November of 2019 and lasting five months, and O3GK starting in April of 2020 and lasting 2 weeks. In this paper we describe these data and various other science products that can be freely accessed through the Gravitational Wave Open Science Center at https://gwosc.org. The main dataset, consisting of the gravitational-wave strain time series that contains the astrophysical signals, is released together with supporting data useful for their analysis and documentation, tutorials, as well as analysis software packages.Comment: 27 pages, 3 figure

    Search for continuous gravitational wave emission from the Milky Way center in O3 LIGO--Virgo data

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    We present a directed search for continuous gravitational wave (CW) signals emitted by spinning neutron stars located in the inner parsecs of the Galactic Center (GC). Compelling evidence for the presence of a numerous population of neutron stars has been reported in the literature, turning this region into a very interesting place to look for CWs. In this search, data from the full O3 LIGO--Virgo run in the detector frequency band [10,2000] Hz[10,2000]\rm~Hz have been used. No significant detection was found and 95%\% confidence level upper limits on the signal strain amplitude were computed, over the full search band, with the deepest limit of about 7.6×10267.6\times 10^{-26} at 142 Hz\simeq 142\rm~Hz. These results are significantly more constraining than those reported in previous searches. We use these limits to put constraints on the fiducial neutron star ellipticity and r-mode amplitude. These limits can be also translated into constraints in the black hole mass -- boson mass plane for a hypothetical population of boson clouds around spinning black holes located in the GC.Comment: 25 pages, 5 figure

    Search for gravitational waves from Scorpius X-1 with a hidden Markov model in O3 LIGO data

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    Search for subsolar-mass binaries in the first half of Advanced LIGO's and Advanced Virgo's third observing run

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    We report on a search for compact binary coalescences where at least one binary component has a mass between 0.2 M⊙ and 1.0 M⊙ in Advanced LIGO and Advanced Virgo data collected between 1 April 2019 1500 UTC and 1 October 2019 1500 UTC. We extend our previous analyses in two main ways: we include data from the Virgo detector and we allow for more unequal mass systems, with mass ratio q ≥ 0.1. We do not report any gravitational-wave candidates. The most significant trigger has a false alarm rate of 0.14 yr-1. This implies an upper limit on the merger rate of subsolar binaries in the range [220-24200] Gpc-3 yr-1, depending on the chirp mass of the binary. We use this upper limit to derive astrophysical constraints on two phenomenological models that could produce subsolar-mass compact objects. One is an isotropic distribution of equal-mass primordial black holes. Using this model, we find that the fraction of dark matter in primordial black holes in the mass range 0.2 M &lt; mPBH &lt; 1.0 M⊙ is fPBH ≡ ΩPBH/ΩDM ≤ 6%. This improves existing constraints on primordial black hole abundance by a factor of ∼3. The other is a dissipative dark matter model, in which fermionic dark matter can collapse and form black holes. The upper limit on the fraction of dark matter black holes depends on the minimum mass of the black holes that can be formed: the most constraining result is obtained at Mmin = 1 M⊙, where fDBH ≡ ΩDBH/ΩDM ≤ 0.003%. These are the first constraints placed on dissipative dark models by subsolar-mass analyses.<br/

    All-sky search for continuous gravitational waves from isolated neutron stars using Advanced LIGO and Advanced Virgo O3 data

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    We present results of an all-sky search for continuous gravitational waves which can be produced by spinning neutron stars with an asymmetry around their rotation axis, using data from the third observing run of the Advanced LIGO and Advanced Virgo detectors. Four different analysis methods are used to search in a gravitational-wave frequency band from 10 to 2048 Hz and a first frequency derivative from 108-10^{-8} to 10910^{-9} Hz/s. No statistically-significant periodic gravitational-wave signal is observed by any of the four searches. As a result, upper limits on the gravitational-wave strain amplitude h0h_0 are calculated. The best upper limits are obtained in the frequency range of 100 to 200 Hz and they are 1.1×1025{\sim}1.1\times10^{-25} at 95\% confidence-level. The minimum upper limit of 1.10×10251.10\times10^{-25} is achieved at a frequency 111.5 Hz. We also place constraints on the rates and abundances of nearby planetary- and asteroid-mass primordial black holes that could give rise to continuous gravitational-wave signals

    Search for subsolar-mass black hole binaries in the second part of Advanced LIGO’s and Advanced Virgo’s third observing run

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    We describe a search for gravitational waves from compact binaries with at least one component with mass 0.2–1.0 M and mass ratio q ≥ 0.1 in Advanced Laser Interferometer Gravitational-Wave Observatory (LIGO) and Advanced Virgo data collected between 2019 November 1, 15:00 UTC and 2020 March 27, 17:00 UTC. No signals were detected. The most significant candidate has a false alarm rate of 0.2 yr−1. We estimate the sensitivity of our search over the entirety of Advanced LIGO’s and Advanced Virgo’s third observing run, and present the most stringent limits to date on the merger rate of binary black holes with at least one subsolar-mass component. We use the upper limits to constrain two fiducial scenarios that could produce subsolar-mass black holes: primordial black holes (PBH) and a model of dissipative dark matter. The PBH model uses recent prescriptions for the merger rate of PBH binaries that include a rate suppression factor to effectively account for PBH early binary disruptions. If the PBHs are monochromatically distributed, we can exclude a dark matter fraction in PBHs fPBH 0.6 (at 90 per cent confidence) in the probed subsolar-mass range. However, if we allow for broad PBH mass distributions, we are unable to rule out fPBH = 1. For the dissipative model, where the dark matter has chemistry that allows a small fraction to cool and collapse into black holes, we find an upper bound fDBH &lt; 10−5 on the fraction of atomic dark matter collapsed into black holes
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