The NANOGrav 11-Year Data Set: Limits on Gravitational Waves from Individual Supermassive Black Hole Binaries

Observations indicate that nearly all galaxies contain supermassive black holes (SMBHs) at their centers. When galaxies merge, their component black holes form SMBH binaries (SMBHBs), which emit low-frequency gravitational waves (GWs) that can be detected by pulsar timing arrays (PTAs). We have searched the recently-released North American Nanohertz Observatory for Gravitational Waves (NANOGrav) 11-year data set for GWs from individual SMBHBs in circular orbits. As we did not find strong evidence for GWs in our data, we placed 95\% upper limits on the strength of GWs from such sources as a function of GW frequency and sky location. We placed a sky-averaged upper limit on the GW strain of $h_0 < 7.3(3) \times 10^{-15}$ at $f_\mathrm{gw}= 8$ nHz. We also developed a technique to determine the significance of a particular signal in each pulsar using ``dropout' parameters as a way of identifying spurious signals in measurements from individual pulsars. We used our upper limits on the GW strain to place lower limits on the distances to individual SMBHBs. At the most-sensitive sky location, we ruled out SMBHBs emitting GWs with $f_\mathrm{gw}= 8$ nHz within 120 Mpc for $\mathcal{M} = 10^9 \, M_\odot$, and within 5.5 Gpc for $\mathcal{M} = 10^{10} \, M_\odot$. We also determined that there are no SMBHBs with $\mathcal{M} > 1.6 \times 10^9 \, M_\odot$ emitting GWs in the Virgo Cluster. Finally, we estimated the number of potentially detectable sources given our current strain upper limits based on galaxies in Two Micron All-Sky Survey (2MASS) and merger rates from the Illustris cosmological simulation project. Only 34 out of 75,000 realizations of the local Universe contained a detectable source, from which we concluded it was unsurprising that we did not detect any individual sources given our current sensitivity to GWs.Comment: 10 pages, 11 figures. Accepted by Astrophysical Journal. Please send any comments/questions to S. J. Vigeland ([email protected]

Scintillator counters with WLS fiber/MPPC readout for the side muon range detector (SMRD)of the T2K experiment

The T2K neutrino experiment at J-PARC uses a set of near detectors to measure the properties of an unoscillated neutrino beam and neutrino interaction cross-sections. One of the sub-detectors of the near-detector complex, the side muon range detector (SMRD), is described in the paper. The detector is designed to help measure the neutrino energy spectrum, to identify background and to calibrate the other detectors. The active elements of the SMRD consist of 0.7 cm thick extruded scintillator slabs inserted into air gaps of the UA1 magnet yokes. The readout of each scintillator slab is provided through a single WLS fiber embedded into a serpentine shaped groove. Two Hamamatsu multi-pixel avalanche photodiodes (MPPC's) are coupled to both ends of the WLS fiber. This design allows us to achieve a high MIP detection efficiency of greater than 99%. A light yield of 25-50 p.e./MIP, a time resolution of about 1 ns and a spatial resolution along the slab better than 10 cm were obtained for the SMRD counters.Comment: 7 pages, 4 figures; talk at TIPP09, March 12-17, Tsukuba, Japan; to be published in the conference proceeding

The T2K Side Muon Range Detector

The T2K experiment is a long baseline neutrino oscillation experiment aiming to observe the appearance of {\nu} e in a {\nu}{\mu} beam. The {\nu}{\mu} beam is produced at the Japan Proton Accelerator Research Complex (J-PARC), observed with the 295 km distant Super- Kamiokande Detector and monitored by a suite of near detectors at 280m from the proton target. The near detectors include a magnetized off-axis detector (ND280) which measures the un-oscillated neutrino flux and neutrino cross sections. The present paper describes the outermost component of ND280 which is a side muon range detector (SMRD) composed of scintillation counters with embedded wavelength shifting fibers and Multi-Pixel Photon Counter read-out. The components, performance and response of the SMRD are presented.Comment: 13 pages, 19 figures v2: fixed several typos; fixed reference

Scintillator counters with WLS fiber/MPPC readout for the side muon range detector (SMRD) of the T2K experiment

The T2K neutrino experiment at J-PARC uses a set of near detectors to measure the properties of an unoscillated neutrino beam and neutrino interaction cross-sections. One of the sub-detectors of the near-detector complex, the side muon range detector (SMRD), is described in the paper. The detector is designed to help measure the neutrino energy spectrum, to identify background and to calibrate the other detectors. The active elements of the SMRD consist of 0.7 cm thick extruded scintillator slabs inserted into air gaps of the UA1 magnet yokes. The readout of each scintillator slab is provided through a single WLS fiber embedded into a serpentine-shaped groove. Two Hamamatsu multipixel avalanche photodiodes (MPPC\u27s) are coupled to both ends of the WLS fiber. This design allows us to achieve a high MIP detection efficiency of greater than 99%. A light yield of 2550 p.e./MIP, a time resolution of about 1 ns and a spatial resolution along the slab better than 10 cm were obtained for the SMRD counters. © 2010 Elsevier B.V. All rights reserved

Fixed-dose combination bictegravir, emtricitabine, and tenofovir alafenamide versus dolutegravir-containing regimens for initial treatment of HIV-1 infection: week 144 results from two randomised, double-blind, multicentre, phase 3, non-inferiority trials

Background: In the primary week-48 analyses of two phase 3 studies, coformulated bictegravir, emtricitabine, and tenofovir alafenamide was non-inferior to a dolutegravir-containing regimen in treatment-naive people with HIV. We report week-144 efficacy and safety results from these studies. Methods: We did two double-blind, active-controlled studies (now in open-label extension phase). Study 1 randomly assigned (1:1) HLA-B*5701-negative adults without hepatitis B virus co-infection to receive coformulated bictegravir 50 mg, emtricitabine 200 mg, and tenofovir alafenamide 25 mg, or coformulated dolutegravir 50 mg, abacavir 600 mg, and lamivudine 300 mg once daily. Study 2 randomly assigned (1:1) adults to bictegravir, emtricitabine, and tenofovir alafenamide, or dolutegravir 50 mg given with coformulated emtricitabine 200 mg and tenofovir alafenamide 25 mg. We previously reported non-inferiority at the primary endpoint. Here, we report the week-144 secondary outcome of proportion of participants with plasma HIV-1 RNA less than 50 copies per mL at week 144, by US Food and Drug Administration Snapshot algorithm, analysed in the same manner. These studies were registered with ClinicalTrials.gov, NCT02607930 and NCT02607956. Findings: 629 participants were randomly assigned and treated in study 1 (314 to bictegravir, emtricitabine, and tenofovir alafenamide, and 315 to dolutegravir, abacavir, and lamivudine) and 645 in study 2 (327 to bictegravir, emtricitabine, and tenofovir alafenamide, 325 to dolutegravir, emtricitabine, tenofovir alafenamide). At week 144, bictegravir, emtricitabine, and tenofovir alafenamide was non-inferior to both dolutegravir-containing regimens for efficacy. In study 1, 256 (82%) of 314 participants had plasma HIV-1 RNA less than 50 copies per mL in the bictegravir, emtricitabine, and tenofovir alafenamide group and 265 (84%) of 315 in the dolutegravir, abacavir, and lamivudine group (difference −2·6%, 95% CI −8·5 to 3·4). In study 2, 262 (82%) of 320 participants had plasma HIV-1 RNA less than 50 copies per mL in the bictegravir, emtricitabine, and tenofovir alafenamide group and 273 (84%) of 325 in the dolutegravir, emtricitabine, and tenofovir alafenamide group (difference −1·9%, −7·8 to 3·9). In both studies, no participant had treatment-emergent resistance to study drugs up to week 144. All treatment regimens were well tolerated with additional exposure. Adverse events that led to study drug discontinuation were reported for no participants in the bictegravir, emtricitabine, and tenofovir alafenamide group versus five (2%) of 315 in the dolutegravir, abacavir, and lamivudine group (study 1), and six (2%) of 320 in the bictegravir, emtricitabine, and tenofovir alafenamide versus six (2%) of 325 in the dolutegravir, emtricitabine, and tenofovir alafenamide group (study 2). In study 1, statistically significant differences were observed in median changes from baseline in fasting total cholesterol (14 mg/dL vs 10 mg/dL; p=0·034), direct LDL (21 mg/dL vs 14 mg/dL; p=0·004), and total cholesterol to HDL ratio (−0·1 vs −0·3; p=0·007) at week 144; no differences were observed between groups in study 2. Weight gain was seen across all treatment groups in both studies, with no differences in median changes from baseline in weight at week 144 for either study. Interpretation: These long-term data support the use of bictegravir, emtricitabine, and tenofovir alafenamide as a safe, well tolerated, and durable treatment for people with HIV, with no emergent resistance. Funding: Gilead Sciences. © 2020 Elsevier Lt

Structural and Functional Loss in Restored Wetland Ecosystems

In restored wetland ecosystems with apparently natural hydrology and biological structure, biogeochemical function may remain degraded, even a century after restoration efforts

The SMRD subdetector at the T2K near detector station

The T2K long-baseline neutrino oscillation experiment is running in Japan. The primary goals of the T2K are measurement of the mixing angle 13, and precise measurements of the mixing angle 23 and of the mass difference m2 23. The installation of the near detector complex was completed and first data were already registered. This article presents operation of the Side Muon Range Detector, a component of the Off-Axis near detector. Detector concept and implementation are presented, followed by a description of cosmic muon track reconstruction algorithm and finally current status

Long-Acting Cabotegravir and Rilpivirine after Oral Induction for HIV-1 Infection.

BACKGROUND: Long-acting injectable regimens may simplify therapy for patients with human immunodeficiency virus type 1 (HIV-1) infection. METHODS: We conducted a phase 3, randomized, open-label trial in which adults with HIV-1 infection who had not previously received antiretroviral therapy were given 20 weeks of daily oral induction therapy with dolutegravir-abacavir-lamivudine. Participants who had an HIV-1 RNA level of less than 50 copies per milliliter after 16 weeks were randomly assigned (1:1) to continue the current oral therapy or switch to oral cabotegravir plus rilpivirine for 1 month followed by monthly injections of long-acting cabotegravir plus rilpivirine. The primary end point was the percentage of participants who had an HIV-1 RNA level of 50 copies per milliliter or higher at week 48 (Food and Drug Administration snapshot algorithm). RESULTS: At week 48, an HIV-1 RNA level of 50 copies per milliliter or higher was found in 6 of 283 participants (2.1%) who received long-acting therapy and in 7 of 283 (2.5%) who received oral therapy (adjusted difference, -0.4 percentage points; 95% confidence interval [CI], -2.8 to 2.1), a result that met the criterion for noninferiority for the primary end point (margin, 6 percentage points). An HIV-1 RNA level of less than 50 copies per milliliter at week 48 was found in 93.6% who received long-acting therapy and in 93.3% who received oral therapy (adjusted difference, 0.4 percentage points; 95% CI, -3.7 to 4.5), a result that met the criterion for noninferiority for this end point (margin, -10 percentage points). Of the participants who received long-acting therapy, 86% reported injection-site reactions (median duration, 3 days; mild or moderate severity, 99% of cases); 4 participants withdrew from the trial for injection-related reasons. Grade 3 or higher adverse events and events that met liver-related stopping criteria occurred in 11% and 2%, respectively, who received long-acting therapy and in 4% and 1% who received oral therapy. Treatment satisfaction increased after participants switched to long-acting therapy; 91% preferred long-acting therapy at week 48. CONCLUSIONS: Therapy with long-acting cabotegravir plus rilpivirine was noninferior to oral therapy with dolutegravir-abacavir-lamivudine with regard to maintaining HIV-1 suppression. Injection-site reactions were common. (Funded by ViiV Healthcare and Janssen; FLAIR ClinicalTrials.gov number, NCT02938520.)