Anti-tumour necrosis factor discontinuation in inflammatory bowel disease patients in remission: study protocol of a prospective, multicentre, randomized clinical trial

Background: Patients with inflammatory bowel disease who achieve remission with anti-tumour necrosis factor (anti-TNF) drugs may have treatment withdrawn due to safety concerns and cost considerations, but there is a lack of prospective, controlled data investigating this strategy. The primary study aim is to compare the rates of clinical remission at 1?year in patients who discontinue anti-TNF treatment versus those who continue treatment. Methods: This is an ongoing, prospective, double-blind, multicentre, randomized, placebo-controlled study in patients with Crohn?s disease or ulcerative colitis who have achieved clinical remission for ?6?months with an anti-TNF treatment and an immunosuppressant. Patients are being randomized 1:1 to discontinue anti-TNF therapy or continue therapy. Randomization stratifies patients by the type of inflammatory bowel disease and drug (infliximab versus adalimumab) at study inclusion. The primary endpoint of the study is sustained clinical remission at 1?year. Other endpoints include endoscopic and radiological activity, patient-reported outcomes (quality of life, work productivity), safety and predictive factors for relapse. The required sample size is 194 patients. In addition to the main analysis (discontinuation versus continuation), subanalyses will include stratification by type of inflammatory bowel disease, phenotype and previous treatment. Biological samples will be obtained to identify factors predictive of relapse after treatment withdrawal. Results: Enrolment began in 2016, and the study is expected to end in 2020. Conclusions: This study will contribute prospective, controlled data on outcomes and predictors of relapse in patients with inflammatory bowel disease after withdrawal of anti-TNF agents following achievement of clinical remission. Clinical trial reference number: EudraCT 2015-001410-1

All-sky search for short gravitational-wave bursts in the third Advanced LIGO and Advanced Virgo run

This paper presents the results of a search for generic short-duration gravitational-wave transients in data from the third observing run of Advanced LIGO and Advanced Virgo. Transients with durations of milliseconds to a few seconds in the 24–4096 Hz frequency band are targeted by the search, with no assumptions made regarding the incoming signal direction, polarization, or morphology. Gravitational waves from compact binary coalescences that have been identified by other targeted analyses are detected, but no statistically significant evidence for other gravitational wave bursts is found. Sensitivities to a variety of signals are presented. These include updated upper limits on the source rate density as a function of the characteristic frequency of the signal, which are roughly an order of magnitude better than previous upper limits. This search is sensitive to sources radiating as little as ∼10^−10 M⊙ c^2 in gravitational waves at ∼70 Hz from a distance of 10 kpc, with 50% detection efficiency at a false alarm rate of one per century. The sensitivity of this search to two plausible astrophysical sources is estimated: neutron star f modes, which may be excited by pulsar glitches, as well as selected core-collapse supernova models

Search for continuous gravitational waves from 20 accreting millisecond x-ray pulsars in O3 LIGO data

Results are presented of searches for continuous gravitational waves from 20 accreting millisecond x-ray pulsars with accurately measured spin frequencies and orbital parameters, using data from the third observing run of the Advanced LIGO and Advanced Virgo detectors. The search algorithm uses a hidden Markov model, where the transition probabilities allow the frequency to wander according to an unbiased random walk, while the J-statistic maximum-likelihood matched filter tracks the binary orbital phase. Three narrow subbands are searched for each target, centered on harmonics of the measured spin frequency. The search yields 16 candidates, consistent with a false alarm probability of 30% per subband and target searched. These candidates, along with one candidate from an additional target-of-opportunity search done for SAX J1808.4−3658, which was in outburst during one month of the observing run, cannot be confidently associated with a known noise source. Additional follow-up does not provide convincing evidence that any are a true astrophysical signal. When all candidates are assumed nonastrophysical, upper limits are set on the maximum wave strain detectable at 95% confidence, h_0^95%. The strictest constraint is h_0^95% = 4.7×10^−26 from IGR J17062−6143. Constraints on the detectable wave strain from each target lead to constraints on neutron star ellipticity and r-mode amplitude, the strictest of which are ε^95% = 3.1 × 10^−7 and α^95% = 1.8 × 10^−5 respectively. This analysis is the most comprehensive and sensitive search of continuous gravitational waves from accreting millisecond x-ray pulsars to date

Search for Subsolar-Mass Binaries in the First Half of Advanced LIGO???s and Advanced Virgo???s Third Observing Run

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⊙ < m PBH < 1.0 M⊙ is f PBH ≡ Ω PBH/Ω DM ≲ 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 M min = 1 M⊙, where f DBH ≡ Ω DBH/Ω DM ≲ 0.003%. These are the first constraints placed on dissipative dark models by subsolar-mass analyses