Abstract Background Vedolizumab, a gut-selective monoclonal antibody targeting α4β7-integrin, was recently licenced as a subcutaneous (SC) preparation after demonstrating efficacy compared to placebo at maintaining remission in IBD patients who had a clinical response to intravenous (IV) induction therapy. We aimed to assess real-world experience of switching patients to SC administration. Methods Patients across 10 UK centres who had completed induction with IV vedolizumab were offered SC therapy. Demographic data and baseline disease characteristics (disease type and behaviour, medication history) were collected, alongside biochemical markers (C-reactive protein, faecal calprotectin), disease activity scores (SCCAI, partial Mayo or modified Harvey Bradshaw Index) and quality of life scores (IBD-Control-8) at baseline (defined as the first dose of SC medication), 8 and 24. Data was also collected on drug persistence, hospital admissions, steroid use and reported adverse events. Results 351 patients were switched to SC dosing. All had data collected for weeks 0 and 8 and 164 had data at week 24. There were no statistically significant differences in biochemical markers, disease activity scores or quality of life at weeks 0, 8 or 24, nor were there statistically significant differences in rates of biochemical remission or clinical remission. Subcutaneous vedolizumab persistence at week 24 was 86% (141/164), with discontinuation due to disease activity (n=9), adverse events (n=11), non-compliance (n=2) and pregnancy (n=1). Of the 23 who discontinued SC, 12 switched back to IV (4 of whom at an escalated dose), 4 changed to another biologic and 7 stopped/paused biologic therapy. Within the 24-week study period, 7.9% (n=13) required steroids, 2.4% (n=4) had an IBD-related hospital admission and 8.5% (n=14) experienced an adverse reaction of which 7 were injection site-related. One patient experienced an anaphylactoid reaction upon restarting IV vedolizumab. There were no statistically significant associations between baseline characteristics (including clinical or biochemical markers, duration of vedolizumab use or prior ant-TNF exposure) and week 32 outcomes. Conclusion Switching from IV to SC vedolizumab appears to maintain rates of remission with no significant changes in biochemical markers, clinical scores or quality of life, with SC administration persistence of 86% at week 24. Further long-term data on safety is required.

We report on gravitational wave discoveries from compact binary coalescences detected by Advanced LIGO and Advanced Virgo in the first half of the third observing run (O3a) between 1 April 2019 15:00 UTC and 1 October 2019 15:00. By imposing a false-alarm-rate threshold of two per year in each of the four search pipelines that constitute our search, we present 39 candidate gravitational wave events. At this threshold, we expect a contamination fraction of less than 10%. Of these, 26 candidate events were reported previously in near real-time through GCN Notices and Circulars; 13 are reported here for the first time. The catalog contains events whose sources are black hole binary mergers up to a redshift of ~0.8, as well as events whose components could not be unambiguously identified as black holes or neutron stars. For the latter group, we are unable to determine the nature based on estimates of the component masses and spins from gravitational wave data alone. The range of candidate events which are unambiguously identified as binary black holes (both objects $\geq 3~M_\odot$) is increased compared to GWTC-1, with total masses from $\sim 14~M_\odot$ for GW190924_021846 to $\sim 150~M_\odot$ for GW190521. For the first time, this catalog includes binary systems with significantly asymmetric mass ratios, which had not been observed in data taken before April 2019. We also find that 11 of the 39 events detected since April 2019 have positive effective inspiral spins under our default prior (at 90% credibility), while none exhibit negative effective inspiral spin. Given the increased sensitivity of Advanced LIGO and Advanced Virgo, the detection of 39 candidate events in ~26 weeks of data (~1.5 per week) is consistent with GWTC-1.

The LIGO Scientific Collaboration and the Virgo Collaboration have cataloged eleven confidently detected gravitational-wave events during the first two observing runs of the advanced detector era. All eleven events were consistent with being from well-modeled mergers between compact stellar-mass objects: black holes or neutron stars. The data around the time of each of these events have been made publicly available through the gravitational-wave open science center. The entirety of the gravitational-wave strain data from the first and second observing runs have also now been made publicly available. There is considerable interest among the broad scientific community in understanding the data and methods used in the analyses. In this paper, we provide an overview of the detector noise properties and the data analysis techniques used to detect gravitational-wave signals and infer the source properties. We describe some of the checks that are performed to validate the analyses and results from the observations of gravitational-wave events. We also address concerns that have been raised about various properties of LIGO-Virgo detector noise and the correctness of our analyses as applied to the resulting data.

In 2017, moderate sedation (MS) was unbundled from procedural CPT codes and new MS codes were created. To assess the impact of unbundling, reimbursement for the new codes across major payors in an inpatient, academic radiology practice were evaluated to quantify the effects on revenue. Billing and reimbursement data for 23 months (available data from Fiscal Years (FY) 2018 and 2019, July 2017 – May 2019) of unbundled MS codes 99152 (initial 15 minutes of sedation administered by procedural operator) and 99153 (each subsequent 15 minutes) were analyzed for reimbursement rates and trends. Five index procedures were further identified and MS reimbursement for Medicare and the largest private payor were calculated. For the same five procedures performed in Fiscal Year 2016 (pre-unbundling), estimated MS reimbursement components were calculated. These values were then compared to the real, unbundled reimbursements for matched index procedures. Departmental reimbursement for unbundled moderate sedation in FY 2018 and 2019 totaled $669,701.34. When compared with the average reimbursement across all payors, Medicare reimbursed 22.8% and 0% per unit of 99152 and 99153, respectively, while the largest private payor, in line with the commercial payor average, averaged 235.3% and 218.1%. Across the five selected index procedures, Medicare reimbursement per case decreased by 1.3% after unbundling (range, 0.9-1.7) while private payor reimbursement increased by 11.9% (range, 5.8-16.4), resulting in a slight net increase in per case revenue. Revenue from moderate sedation accounted for 3.9% of procedural revenue (range, 1.2-5.6) from Medicare, and 5.5% of procedural revenue from the private payor (range, 1.0-7.9). After unbundling moderate sedation from procedural codes, average per case reimbursement from Medicare decreased, with losses fully mitigated by an overall positive but heterogeneous change in per case revenue from commercial payors. Departmental revenue from unbundling was significant, highlighting the need for consistent and accurate reporting of moderate sedation as Medicare reassesses MS valuation and adjusts reimbursement rates in the future.

We present a search for continuous gravitational waves from five radio pulsars, comprising three recycled pulsars (PSR J0437-4715, PSR J0711-6830, and PSR J0737-3039A) and two young pulsars: the Crab pulsar (J0534+2200) and the Vela pulsar (J0835-4510). We use data from the third observing run of Advanced LIGO and Virgo combined with data from their first and second observing runs. For the first time we are able to match (for PSR J0437-4715) or surpass (for PSR J0711-6830) the indirect limits on gravitational-wave emission from recycled pulsars inferred from their observed spin-downs, and constrain their equatorial ellipticities to be less than $10^{-8}$. For each of the five pulsars, we perform targeted searches that assume a tight coupling between the gravitational-wave and electromagnetic signal phase evolution. We also present constraints on PSR J0711-6830, the Crab pulsar and the Vela pulsar from a search that relaxes this assumption, allowing the gravitational-wave signal to vary from the electromagnetic expectation within a narrow band of frequencies and frequency derivatives.

We present the results from a search for gravitational-wave transients associated with core-collapse supernovae observed within a source distance of approximately 20 Mpc during the first and second observing runs of Advanced LIGO and Advanced Virgo. No significant gravitational-wave candidate was detected. We report the detection efficiencies as a function of the distance for waveforms derived from multidimensional numerical simulations and phenomenological extreme emission models. For neutrino-driven explosions the distance at which we reach 50% detection efficiency is approaching 5 kpc, and for magnetorotationally-driven explosions is up to 54 kpc. However, waveforms for extreme emission models are detectable up to 28 Mpc. For the first time, the gravitational-wave data enabled us to exclude part of the parameter spaces of two extreme emission models with confidence up to 83%, limited by coincident data coverage. Besides, using ad hoc harmonic signals windowed with Gaussian envelopes we constrained the gravitational-wave energy emitted during core-collapse at the levels of $4.27\times 10^{-4}\,M_\odot c^2$ and $1.28\times 10^{-1}\,M_\odot c^2$ for emissions at 235 Hz and 1304 Hz respectively. These constraints are two orders of magnitude more stringent than previously derived in the corresponding analysis using initial LIGO, initial Virgo and GEO 600 data.

We present results from offline searches of Fermi Gamma-ray Burst Monitor (GBM) data for gamma-ray transients coincident with the compact binary coalescences observed by the gravitational-wave (GW) detectors Advanced LIGO and Advanced Virgo during their first and second observing runs. In particular, we perform follow-up for both confirmed events and low significance candidates reported in the LIGO/Virgo catalog GWTC-1. We search for temporal coincidences between these GW signals and GBM-triggered gamma-ray bursts (GRBs). We also use the GBM Untargeted and Targeted subthreshold searches to find coincident gamma-rays below the onboard triggering threshold. This work implements a refined statistical approach by incorporating GW astrophysical source probabilities and GBM visibilities of LIGO/Virgo sky localizations to search for cumulative signatures of coincident subthreshold gamma-rays. All search methods recover the short gamma-ray burst GRB 170817A occurring ∼1.7 s after the binary neutron-star merger GW170817. We also present results from a new search seeking GBM counterparts to LIGO single-interferometer triggers. This search finds a candidate joint event, but given the nature of the GBM signal and localization, as well as the high joint false alarm rate of 1.1 × 10 −6 Hz, we do not consider it an astrophysical association. We find no additional coincidences.

To quantify the financial effect of delayed reporting of moderate sedation code changes implemented in 2017 in an academic interventional radiology practice and to identify barriers to delayed reporting. Billing and reimbursement data was collected for a 29-month period (Jan. 1, 2017 – May 31, 2019). Reporting of new moderate sedation codes 99152 (initial 15 minutes of sedation) and 99153 (each subsequent 15 minutes) was identified and compared to the number of procedures performed by interventional radiology annually over the study period. Code 99152 was used as a surrogate for the number of procedures coded appropriately, and payment data was used to estimate losses. A root cause analysis was then performed to further understand delayed reporting. Moderate sedation was reported with 2.3% of cases in 2017, 43.5% of cases in 2018 and 60.7% of cases in 2019. Appropriate coding was not achieved until June 2018, equating to a 17-month lag time in implementation. Lost revenue from inaccurate reporting of moderate sedation alone was estimated to be $20,972 ± $4068 per month. Primary barriers to an efficient transition were identified and include (1) the addition of new codes to the billing system, (2) educating coders on reporting the new coding set, (3) training nurses monitoring sedation to document sedation start and end times, (4) training technologists to record these times and provide them to operators, (5) training operators to dictate these times into reports, and (6) vetting by the institutional compliance office and adding a new moderate sedation statement to the procedural report templates. Delayed reporting of the new moderate sedation codes had a significant impact on reimbursement in an academic interventional radiology practice. Primary drivers of the delay were lags in education and coordination at multiple points in the reporting chain.Tabled 1Billing PeriodAverage Monthly Revenue ($)SD ($)January–June 2017586262July–December 2017640302January–June 201876026080July–December 201823,5013393January–May 201923,1282845 Open table in a new tab

The gravitational-wave signal GW190521 is consistent with a binary black hole merger source at redshift 0.8 with unusually high component masses, $85^{+21}_{-14}\,M_{\odot}$ and $66^{+17}_{-18}\,M_{\odot}$, compared to previously reported events, and shows mild evidence for spin-induced orbital precession. The primary falls in the mass gap predicted by (pulsational) pair-instability supernova theory, in the approximate range $65 - 120\,M_{\odot}$. The probability that at least one of the black holes in GW190521 is in that range is 99.0%. The final mass of the merger $(142^{+28}_{-16}\,M_{\odot})$ classifies it as an intermediate-mass black hole. Under the assumption of a quasi-circular binary black hole coalescence, we detail the physical properties of GW190521's source binary and its post-merger remnant, including component masses and spin vectors. Three different waveform models, as well as direct comparison to numerical solutions of general relativity, yield consistent estimates of these properties. Tests of strong-field general relativity targeting the merger-ringdown stages of coalescence indicate consistency of the observed signal with theoretical predictions. We estimate the merger rate of similar systems to be $0.13^{+0.30}_{-0.11}\,{\rm Gpc}^{-3}\,\rm{yr}^{-1}$. We discuss the astrophysical implications of GW190521 for stellar collapse, and for the possible formation of black holes in the pair-instability mass gap through various channels: via (multiple) stellar coalescence, or via hierarchical merger of lower-mass black holes in star clusters or in active galactic nuclei. We find it to be unlikely that GW190521 is a strongly lensed signal of a lower-mass black hole binary merger. We also discuss more exotic possible sources for GW190521, including a highly eccentric black hole binary, or a primordial black hole binary.

SA significantly underestimates frailty as compared to mFFI. Both frailty scores and MIF improved after LVAD, suggesting reversibility of the frailty syndrome. Understanding frailty will be key to improving outcomes in advanced HF.

We report the observation of a compact binary coalescence involving a 22.2-24.3 M-circle dot black hole and a compact object with a mass of 2.50-2.67 M-circle dot (all measurements quoted at the 90% credible level). The gravitational-wave signal, GW190814, was observed during LIGO's and Virgo's third observing run on 2019 August 14 at 21:10:39 UTC and has a signal-to-noise ratio of 25 in the three-detector network. The source was localized to 18.5 deg(2) at a distance of 241(-41)(+45) Mpc; no electromagnetic counterpart has been confirmed to date. The source has the most unequal mass ratio yet measured with gravitational waves, 0.112(-0.009)(+0.008), and its secondary component is either the lightest black hole or the heaviest neutron star ever discovered in a double compact-object system. The dimensionless spin of the primary black hole is tightly constrained to <= 0.07. Tests of general relativity reveal no measurable deviations from the theory, and its prediction of higher-multipole emission is confirmed at high confidence. We estimate a merger rate density of 1-23 Gpc(-3) yr(-1) for the new class of binary coalescence sources that GW190814 represents. Astrophysical models predict that binaries with mass ratios similar to this event can form through several channels, but are unlikely to have formed in globular clusters. However, the combination of mass ratio, component masses, and the inferred merger rate for this event challenges all current models of the formation and mass distribution of compact-object binaries.

Two analysis errors have been identified that affect the results for a handful of the high-value pulsars given in Table 1 of Abbott et al. (2019). One affects the Bayesian analysis for the five pulsars that glitched during the analysis period, and the other affects the 5n-vector analysis for J0711-6830. Updated results after correcting the errors are shown in Table 1, which now supersedes the results given for those pulsars in Table 1 of Abbott et al. (2019). Updated versions of figures can be seen in Figures 1-4. Bayesian analysis.-For the glitching pulsars, the signal phase evolution caused by the glitch was wrongly applied twice and was therefore not consistent with our expected model of the pulsar phase. This error did not affect the F/G-statistic or 5n-vector analysis. Analyses of the five pulsars PSR J0205+6449, PSR J0534+2200, PSR J0835-4510, PSR J1028-5819, and PSR J1718-3825 have been repeated after correcting for the error. There are small quantitative differences in the results, but the changes do not affect the main conclusions of the paper. The largest differences are for PSR J0835-4510 (the Vela pulsar), for which the updated upper limits from the Bayesian method are found to be between 1.1 and 2 times larger than those obtained when the error was present. This appears primarily to be due to the error leading to the decohering of a strong spectral line in the LIGO Livingston detector and thus lowering the amplitude limit. 5n-vector analysis.-An error was also identified in the settings of the 5n-vector analysis, which affected the upper limit computation at the rotation frequency for C21 95% of J0711-6830. Specifically, we found an incorrect choice for the range of amplitudes used to inject simulated signals in the O2 data. The updated upper limit is about 2.5 times worse than that obtained when the error was present. This error did not affect the Bayesian or F/G-statistic results. (Table Presented) (Figure Presented).

We report the observation of gravitational waves from a binary-black-hole coalescence during the first two weeks of LIGO's and Virgo's third observing run. The signal was recorded on April 12, 2019 at 05:30:44 UTC with a network signal-to-noise ratio of 19. The binary is different from observations during the first two observing runs most notably due to its asymmetric masses: a ~30 solar mass black hole merged with a ~8 solar mass black hole companion. The more massive black hole rotated with a dimensionless spin magnitude between 0.22 and 0.60 (90% probability). Asymmetric systems are predicted to emit gravitational waves with stronger contributions from higher multipoles, and indeed we find strong evidence for gravitational radiation beyond the leading quadrupolar order in the observed signal. A suite of tests performed on GW190412 indicates consistency with Einstein's general theory of relativity. While the mass ratio of this system differs from all previous detections, we show that it is consistent with the population model of stellar binary black holes inferred from the first two observing runs.

GW170817 is the very first observation of gravitational waves originating from the coalescence of two compact objects in the mass range of neutron stars, accompanied by electromagnetic counterparts, and offers an opportunity to directly probe the internal structure of neutron stars. We perform Bayesian model selection on a wide range of theoretical predictions for the neutron star equation of state. For the binary neutron star hypothesis, we find that we cannot rule out the majority of theoretical models considered. In addition, the gravitational-wave data alone does not rule out the possibility that one or both objects were low-mass black holes. We discuss the possible outcomes in the case of a binary neutron star merger, finding that all scenarios from prompt collapse to long-lived or even stable remnants are possible. For long-lived remnants, we place an upper limit of 1.9 kHz on the rotation rate. If a black hole was formed any time after merger and the coalescing stars were slowly rotating, then the maximum baryonic mass of non-rotating neutron stars is at most 3.05 $M_\odot$, and three equations of state considered here can be ruled out. We obtain a tighter limit of 2.67 $M_\odot$ for the case that the merger results in a hypermassive neutron star.

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The National Physical Laboratory (NPL) provides traceable high accuracy measurements for absorbed dose via primary standard graphite calorimeters. Patients undergoing radiotherapy for cancer treatments in the U.K. receive a dose that is traceable to these devices. In the case of hadron radiotherapy, reducing the uncertainty of these measurements requires the addition of spatial information to understand not only the integral dose delivered, but where the energy is deposited locally. The PRaVDA consortium developed strip detectors able to track individual protons at low rates for proton computed tomography. For calorimetry at clinical dose rates only real-time spot location is required, which could be projected to reconstruct a 2D visualisation from which the beam centre can be determined. This work reports on a proof-of-concept trial carried out using 6 MV X-rays using an Elekta Synergy linear accelerator. We show how the beam positions can be determined within +/- 0.5 mm of the expected radiation beam position, which is similar to the tolerances of the field defining multileaf collimator within the linear accelerator treatment head. The trial will be extended to perform measurements in a clinical proton beam alongside the NPL graphite proton calorimeter.

The recent discovery by Advanced LIGO and Advanced Virgo of a gravitational wave signal from a binary neutron star inspiral has enabled tests of general relativity (GR) with this new type of source. This source, for the first time, permits tests of strong-field dynamics of compact binaries in the presence of matter. In this Letter, we place constraints on the dipole radiation and possible deviations from GR in the post-Newtonian coefficients that govern the inspiral regime. Bounds on modified dispersion of gravitational waves are obtained; in combination with information from the observed electromagnetic counterpart we can also constrain effects due to large extra dimensions. Finally, the polarization content of the gravitational wave signal is studied. The results of all tests performed here show good agreement with GR.

The Dark matter Experiment using Argon Pulse-shape discrimination (DEAP) has been designed for a direct detection search for particle dark matter using a single-phase liquid argon target. The projected cross section sensitivity for DEAP-3600 to the spin-independent scattering of Weakly Interacting Massive Particles (WIMPs) on nucleons is 10(-46) cm(2) for a 100 GeV/c(2) WIMP mass with a fiducial exposure of 3 tonne-years. This paper describes the physical properties and construction of the DEAP-3600 detector. (C) 2018 Elsevier B.V. All rights reserved.

We present the results from three gravitational-wave searches for coalescing compact binaries with component masses above 1 M-circle dot during the first and second observing runs of the advanced gravitational-wave detector network. During the first observing run (O1), from September 12, 2015 to January 19, 2016, gravitational waves from three binary black hole mergers were detected. The second observing run (O2), which ran from November 30, 2016 to August 25, 2017, saw the first detection of gravitational waves from a binary neutron star inspiral, in addition to the observation of gravitational waves from a total of seven binary black hole mergers, four of which we report here for the first time: GW170729, GW170809, GW170818, and GW170823. For all significant gravitational-wave events, we provide estimates of the source properties. The detected binary black holes have total masses between 18.6(-0.7)(+3.2) M-circle dot and 84.4(-11.1)(+15.8) M-circle dot and range in distance between 320(-110)(+120) and 2840(-1360)(+1400) Mpc. No neutron star-black hole mergers were detected. In addition to highly significant gravitational-wave events, we also provide a list of marginal event candidates with an estimated false-alarm rate less than 1 per 30 days. From these results over the first two observing runs, which include approximately one gravitational-wave detection per 15 days of data searched, we infer merger rates at the 90% confidence intervals of 110 - 3840 Gpc(-3) y(-1) for binary neutron stars and 9.7 - 101 Gpc(-3) y(-1) for binary black holes assuming fixed population distributions and determine a neutron star-black hole merger rate 90% upper limit of 610 Gpc(-3) y(-1).