Product type and the risk of inhibitor development in nonsevere haemophilia A patients: a case‒control study

Inhibitor development is a major complication of treatment with factor VIII concentrates in nonsevere haemophilia A. It has been suggested that plasma-derived factor VIII (FVIII) concentrates elicit fewer inhibitors than recombinant FVIII concentrates, but studies in severe haemophilia A patients have shown conflicting results. We designed a case‒control study to investigate the clinical and genetic risk factors for inhibitor development in nonsevere haemophilia A patients. We investigated whether the type of FVIII concentrate was associated with inhibitor development in nonsevere haemophilia A patients. This nested case‒control study includes 75 inhibitor patients and 223 controls, from a source population of the INSIGHT study, including all nonsevere haemophilia A patients (FVIII:C 2–40%) that were treated with FVIII concentrates in 33 European and one Australian centre. Cases and controls were matched for date of birth and cumulative number of exposure days (CED) to FVIII concentrate. A conditional logistic regression model was used to calculate unadjusted and adjusted odds ratios. No increased risk for inhibitor development was found for any type of FVIII concentrate; either when comparing recombinant FVIII concentrates to plasma-derived FVIII concentrates (adjusted odds ratio 0·96, 95% confidence interval (CI) 0·36–2·52) or for specific types of FVIII concentrates

Potential-density pairs for axisymmetric galaxies: the influence of scalar fields

We present a formulation for potential-density pairs to describe axisymmetric galaxies in the Newtonian limit of scalar-tensor theories of gravity. The scalar field is described by a modified Helmholtz equation with a source that is coupled to the standard Poisson equation of Newtonian gravity. The net gravitational force is given by two contributions: the standard Newtonian potential plus a term stemming from massive scalar fields. General solutions have been found for axisymmetric systems and the multipole expansion of the Yukawa potential is given. In particular, we have computed potential-density pairs of galactic disks for an exponential profile and their rotation curves.Comment: 8 pages, no figures, corrected version to the one that will appear in Gen. Relativ. Gravit., where a small typo in eq. (13) is presen

The factor VIII treatment history of non-severe hemophilia A

Background: In patients with non-severe hemophilia A, we lack detailed knowledge on the timing of treatment with factor VIII (FVIII) concentrates. This knowledge could provide information about the expected treatment timing in patients with severe hemophilia A treated with non-replacement therapies. Objective: To assess the FVIII treatment history in patients with non-severe hemophilia A. Methods: Patients with non-severe hemophilia (baseline FVIII activity [FVIII:C] 2-40 IU/dL) were included from the INSIGHT study. The primary outcome was median age at first FVIII exposure (ED1). In a subgroup of patients for whom more detailed information was available, we analyzed the secondary outcomes: median age at first 20 EDs, annualized bleeding rate for all bleeds (ABR), joint bleeds (AJBR), and major spontaneous bleeds (ASmBR). Results: In the total cohort (n = 1013), median baseline FVIII activity was 8 IU/dL (interquartile range [IQR] 4-15) and the median age at ED1 was 3.7 years (IQR 1.4-7.7). Median age at ED1 rose from 2.5 years (IQR 1.2-5.7) in patients with FVIII:C 2-5 IU/dL to 9.7 years (IQR 4.8-16.0) in patients with FVIII:C 25-40 IU/dL. In the subgroup (n = 104), median age at ED1, ED5, ED10, and ED20 was 4.0 years (IQR 1.4-7.6), 5.6 years (IQR 2.9-9.3), 7.5 years (IQR 4.4-11.3), and 10.2 years (IQR 6.5-14.2), respectively. Median ABR, AJBR, and ASmBR were 1.1 (IQR 0.5-2.6), 0.3 (IQR 0.1-0.7), and 0 (IQR 0-0), respectively. Conclusion: This study demonstrates that in non-severe hemophilia A, the age at first FVIII exposure increases with baseline FVIII:C and that major spontaneous bleeds rarely occur

Treatment-related risk factors for inhibitor development in non-severe hemophilia A after 50 cumulative exposure days: a case-control study

Background Non-severe hemophilia A patients have a life-long inhibitor risk. Yet, no studies have analyzed risk factors for inhibitor development after 50 factor VIII (FVIII) exposure days (EDs). Objectives This case-control study investigated treatment-related risk factors for inhibitor development in non-severe hemophilia A and assessed whether these risk factors were different for early versus late inhibitor development. Patients/Methods Non-severe hemophilia A patients (FVIII:C 2%-40%) were selected from the INSIGHT study. Inhibitor-positive patients were defined as early (50EDs) cases and matched to 1-4 inhibitor-negative controls by year of birth, cumulative number of EDs, and center/country. We investigated treatment intensity during the last 10 EDs prior to inhibitor development. Intensive treatment was defined as: surgery, peak treatment (10 consecutive EDs), and high mean FVIII dose (>45 IU/kg/ED). Odds ratios (OR) were calculated by logistic regression. Results Of 2709 patients, we analyzed 63 early and 26 late cases and 195 and 71 respectively matched controls. Peak treatment was associated with early and late inhibitor risk (crude OR 1.8, 95% confidence interval [CI] 1.0-3.4; 4.0, 95%CI 1.1-14.3). This association was slightly less pronounced after adjustment for mean FVIII dose. High mean FVIII dose was also associated with early and late inhibitor risk (crude OR 2.8, 95%CI 1.5-5.1; 4.5, 95%CI 1.2-16.6). Surgery increased inhibitor risk for early cases. This was less pronounced for late cases. Conclusions Our findings suggest that intensive FVIII treatment remains a risk factor for inhibitor development in non-severe hemophilia A after more than 50 EDs. Therefore, persistent caution is required throughout the life-time treatment course.Clinical epidemiolog

Search for Gravitational Waves Associated with Gamma-Ray Bursts Detected by Fermi and Swift during the LIGO-Virgo Run O3b

We search for gravitational-wave signals associated with gamma-ray bursts (GRBs) detected by the Fermi and Swift satellites during the second half of the third observing run of Advanced LIGO and Advanced Virgo (2019 November 1 15:00 UTC-2020 March 27 17:00 UTC). We conduct two independent searches: A generic gravitational-wave transients search to analyze 86 GRBs and an analysis to target binary mergers with at least one neutron star as short GRB progenitors for 17 events. We find no significant evidence for gravitational-wave signals associated with any of these GRBs. A weighted binomial test of the combined results finds no evidence for subthreshold gravitational-wave signals associated with this GRB ensemble either. We use several source types and signal morphologies during the searches, resulting in lower bounds on the estimated distance to each GRB. Finally, we constrain the population of low-luminosity short GRBs using results from the first to the third observing runs of Advanced LIGO and Advanced Virgo. The resulting population is in accordance with the local binary neutron star merger rate. © 2022. The Author(s). Published by the American Astronomical Society

Narrowband Searches for Continuous and Long-duration Transient Gravitational Waves from Known Pulsars in the LIGO-Virgo Third Observing Run

Isolated neutron stars that are asymmetric with respect to their spin axis are possible sources of detectable continuous gravitational waves. This paper presents a fully coherent search for such signals from eighteen pulsars in data from LIGO and Virgo's third observing run (O3). For known pulsars, efficient and sensitive matched-filter searches can be carried out if one assumes the gravitational radiation is phase-locked to the electromagnetic emission. In the search presented here, we relax this assumption and allow both the frequency and the time derivative of the frequency of the gravitational waves to vary in a small range around those inferred from electromagnetic observations. We find no evidence for continuous gravitational waves, and set upper limits on the strain amplitude for each target. These limits are more constraining for seven of the targets than the spin-down limit defined by ascribing all rotational energy loss to gravitational radiation. In an additional search, we look in O3 data for long-duration (hours-months) transient gravitational waves in the aftermath of pulsar glitches for six targets with a total of nine glitches. We report two marginal outliers from this search, but find no clear evidence for such emission either. The resulting duration-dependent strain upper limits do not surpass indirect energy constraints for any of these targets. © 2022. The Author(s). Published by the American Astronomical Society

Search for gravitational-wave transients associated with magnetar bursts in advanced LIGO and advanced Virgo data from the third observing run

Gravitational waves are expected to be produced from neutron star oscillations associated with magnetar giant f lares and short bursts. We present the results of a search for short-duration (milliseconds to seconds) and longduration (∼100 s) transient gravitational waves from 13 magnetar short bursts observed during Advanced LIGO, Advanced Virgo, and KAGRA’s third observation run. These 13 bursts come from two magnetars, SGR1935 +2154 and SwiftJ1818.0−1607. We also include three other electromagnetic burst events detected by FermiGBM which were identified as likely coming from one or more magnetars, but they have no association with a known magnetar. No magnetar giant flares were detected during the analysis period. We find no evidence of gravitational waves associated with any of these 16 bursts. We place upper limits on the rms of the integrated incident gravitational-wave strain that reach 3.6 × 10−²³ Hz at 100 Hz for the short-duration search and 1.1 ×10−²² Hz at 450 Hz for the long-duration search. For a ringdown signal at 1590 Hz targeted by the short-duration search the limit is set to 2.3 × 10−²² Hz. Using the estimated distance to each magnetar, we derive upper limits upper limits on the emitted gravitational-wave energy of 1.5 × 1044 erg (1.0 × 1044 erg) for SGR 1935+2154 and 9.4 × 10^43 erg (1.3 × 1044 erg) for Swift J1818.0−1607, for the short-duration (long-duration) search. Assuming isotropic emission of electromagnetic radiation of the burst fluences, we constrain the ratio of gravitational-wave energy to electromagnetic energy for bursts from SGR 1935+2154 with the available fluence information. The lowest of these ratios is 4.5 × 103

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

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

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

Constraints on the cosmic expansion history from GWTC–3

We use 47 gravitational wave sources from the Third LIGO–Virgo–Kamioka Gravitational Wave Detector Gravitational Wave Transient Catalog (GWTC–3) to estimate the Hubble parameter H(z), including its current value, the Hubble constant H0. Each gravitational wave (GW) signal provides the luminosity distance to the source, and we estimate the corresponding redshift using two methods: the redshifted masses and a galaxy catalog. Using the binary black hole (BBH) redshifted masses, we simultaneously infer the source mass distribution and H(z). The source mass distribution displays a peak around 34 M⊙, followed by a drop-off. Assuming this mass scale does not evolve with the redshift results in a H(z) measurement, yielding ${H}_{0}={68}_{-8}^{+12}\,\mathrm{km}\ \,\ {{\rm{s}}}^{-1}\,{\mathrm{Mpc}}^{-1}$ (68% credible interval) when combined with the H0 measurement from GW170817 and its electromagnetic counterpart. This represents an improvement of 17% with respect to the H0 estimate from GWTC–1. The second method associates each GW event with its probable host galaxy in the catalog GLADE+, statistically marginalizing over the redshifts of each event's potential hosts. Assuming a fixed BBH population, we estimate a value of ${H}_{0}={68}_{-6}^{+8}\,\mathrm{km}\ \,\ {{\rm{s}}}^{-1}\,{\mathrm{Mpc}}^{-1}$ with the galaxy catalog method, an improvement of 42% with respect to our GWTC–1 result and 20% with respect to recent H0 studies using GWTC–2 events. However, we show that this result is strongly impacted by assumptions about the BBH source mass distribution; the only event which is not strongly impacted by such assumptions (and is thus informative about H0) is the well-localized event GW190814