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El-Khoueiry, A.B.,Sangro, B.,Yau, T.,Crocenzi, T.S.,Kudo, M.,Hsu, C.,Kim, T.Y.,Choo, S.P.,Trojan, J.,Welling, T.H.,Meyer, T.,Kang, Y.K.,Yeo, W.,Chopra, A.,Anderson, J.,dela Cruz, C.,Lang, L.,Neely, J. J. Onwhyn ; Elsevier Science Ltd 2017 The Lancet Vol.389 No.10088
Background: For patients with advanced hepatocellular carcinoma, sorafenib is the only approved drug worldwide, and outcomes remain poor. We aimed to assess the safety and efficacy of nivolumab, a programmed cell death protein-1 (PD-1) immune checkpoint inhibitor, in patients with advanced hepatocellular carcinoma with or without chronic viral hepatitis. Methods: We did a phase ½, open-label, non-comparative, dose escalation and expansion trial (CheckMate 040) of nivolumab in adults (≥18 years) with histologically confirmed advanced hepatocellular carcinoma with or without hepatitis C or B (HCV or HBV) infection. Previous sorafenib treatment was allowed. A dose-escalation phase was conducted at seven hospitals or academic centres in four countries or territories (USA, Spain, Hong Kong, and Singapore) and a dose-expansion phase was conducted at an additional 39 sites in 11 countries (Canada, UK, Germany, Italy, Japan, South Korea, Taiwan). At screening, eligible patients had Child-Pugh scores of 7 or less (Child-Pugh A or B7) for the dose-escalation phase and 6 or less (Child-Pugh A) for the dose-expansion phase, and an Eastern Cooperative Oncology Group performance status of 1 or less. Patients with HBV infection had to be receiving effective antiviral therapy (viral load <100 IU/mL); antiviral therapy was not required for patients with HCV infection. We excluded patients previously treated with an agent targeting T-cell costimulation or checkpoint pathways. Patients received intravenous nivolumab 0.1-10 mg/kg every 2 weeks in the dose-escalation phase (3+3 design). Nivolumab 3 mg/kg was given every 2 weeks in the dose-expansion phase to patients in four cohorts: sorafenib untreated or intolerant without viral hepatitis, sorafenib progressor without viral hepatitis, HCV infected, and HBV infected. Primary endpoints were safety and tolerability for the escalation phase and objective response rate (Response Evaluation Criteria In Solid Tumors version 1.1) for the expansion phase. This study is registered with ClinicalTrials.gov, number NCT01658878. Findings: Between Nov 26, 2012, and Aug 8, 2016, 262 eligible patients were treated (48 patients in the dose-escalation phase and 214 in the dose-expansion phase). 202 (77%) of 262 patients have completed treatment and follow-up is ongoing. During dose escalation, nivolumab showed a manageable safety profile, including acceptable tolerability. In this phase, 46 (96%) of 48 patients discontinued treatment, 42 (88%) due to disease progression. Incidence of treatment-related adverse events did not seem to be associated with dose and no maximum tolerated dose was reached. 12 (25%) of 48 patients had grade ¾ treatment-related adverse events. Three (6%) patients had treatment-related serious adverse events (pemphigoid, adrenal insufficiency, liver disorder). 30 (63%) of 48 patients in the dose-escalation phase died (not determined to be related to nivolumab therapy). Nivolumab 3 mg/kg was chosen for dose expansion. The objective response rate was 20% (95% CI 15-26) in patients treated with nivolumab 3 mg/kg in the dose-expansion phase and 15% (95% CI 6-28) in the dose-escalation phase. Interpretation: Nivolumab had a manageable safety profile and no new signals were observed in patients with advanced hepatocellular carcinoma. Durable objective responses show the potential of nivolumab for treatment of advanced hepatocellular carcinoma. Funding: Bristol-Myers Squibb.
Abu-Zayyad, T.,Aida, R.,Allen, M.,Anderson, R.,Azuma, R.,Barcikowski, E.,Belz, J.W.,Bergman, D.R.,Blake, S.A.,Cady, R.,Cheon, B.G.,Chiba, J.,Chikawa, M.,Cho, E.J.,Cho, W.R.,Fujii, H.,Fujii, T.,Fukuda, North-Holland ; Elsevier Science Ltd 2013 Astroparticle physics Vol.48 No.-
We present a measurement of the energy spectrum of ultra-high-energy cosmic rays performed by the Telescope Array experiment using monocular observations from its two new FADC-based fluorescence detectors. After a short description of the experiment, we describe the data analysis and event reconstruction procedures. Since the aperture of the experiment must be calculated by Monte Carlo simulation, we describe this calculation and the comparisons of simulated and real data used to verify the validity of the aperture calculation. Finally, we present the energy spectrum calculated from the merged monocular data sets of the two FADC-based detectors, and also the combination of this merged spectrum with an independent, previously published monocular spectrum measurement performed by Telescope Array's third fluorescence detector [T. Abu-Zayyad et al., The energy spectrum of Telescope Array's middle drum detector and the direct comparison to the high resolution fly's eye experiment, Astroparticle Physics 39 (2012) 109-119, http://dx.doi.org/10.1016/j.astropartphys.2012.05.012, Available from: <arXiv:1202.5141>]. This combined spectrum corroborates the recently published Telescope Array surface detector spectrum [T. Abu-Zayyad, et al., The cosmic-ray energy spectrum observed with the surface detector of the Telescope Array experiment, ApJ 768 (2013) L1, http://dx.doi.org/10.1088/2041-8205/768/1/L1, Available from: <arXiv:1205.5067>] with independent systematic uncertainties.
Aartsen, M. G.,Ackermann, M.,Adams, J.,Aguilar, J. A.,Ahlers, M.,Ahrens, M.,Al Samarai, I.,Altmann, D.,Andeen, K.,Anderson, T.,Ansseau, I.,Anton, G.,Argü,elles, C.,Auffenberg, J.,Axani, S.,Bagherp Springer-Verlag 2017 European Physical Journal C Vol.77 No.9
<P>We present a search for a neutrino signal from dark matter self-annihilations in the Milky Way using the Ice-Cube Neutrino Observatory (IceCube). In 1005 days of data we found no significant excess of neutrinos over the background of neutrinos produced in atmospheric air showers from cosmic ray interactions. We derive upper limits on the velocity averaged product of the darkmatter self-annihilation cross section and the relative velocity of the dark matter particles <sigma Av >. Upper limits are set for darkmatter particle candidate masses ranging from 10GeV up to 1TeV while considering annihilation through multiple channels. This work sets the most stringent limit on a neutrino signal from dark matter with mass between 10 and 100GeV, with a limit of 1.18 . 10-23 cm(3)s(-1) for 100GeV dark matter particles self-annihilating via iota(+)iota(-) t-to neutrinos (assuming the Navarro-Frenk-White dark matter halo profile).</P>
Park, J.M.,Amare, Y.,Anderson, T.,Angelaszek, D.,Anthony, N.,Arnold, H.,Choi, G.H.,Copley, M.,Coutu, S.,Derome, L.,Ebongue, C.,Eraud, L.,Faddis, I.,Han, J.H.,Howley, I.J.,Huh, H.G.,Hwang, Y.S.,Hyun, H Elsevier 2018 ADVANCES IN SPACE RESEARCH Vol.62 No.10
<P><B>Abstract</B></P> <P>The Cosmic Ray Energetics and Mass experiment at the International Space Station (ISS-CREAM) is developed for studying the origin, acceleration and propagation mechanism of high energy cosmic rays. The Top and Bottom Counting Detectors (TCD/BCD), sub-detectors of the ISS-CREAM instrument, are developed for electron/ γ -ray physics. The TCD/BCD help distinguish electrons from protons by comparing the hit and shower width distributions for electrons and protons. The e/p separation capability of the TCD/BCD is studied by using the GEANT3 simulation package, and optimal parameters for the e/p separation are obtained.</P>
Lee, J.,Amare, Y.,Anderson, T.,Angelaszek, D.,Anthony, N.,Cheryian, K.,Choi, G.H.,Copley, M.,Coutu, S.,Derome, L.,Eraud, L.,Hagenau, L.,Han, J.H.,Hong, G.,Huh, H.G.,Hwang, Y.S.,Hyun, H.J.,Im, S.,Jeon, Elsevier 2019 Astroparticle physics Vol.112 No.-
<P><B>Abstract</B></P> <P>The Cosmic Ray Energetics And Mass experiment for the International Space Station (ISS-CREAM) is a space-borne mission designed for the precision measurement of the energy and elemental composition of cosmic rays. The Silicon Charge Detector (SCD), placed at the top of the ISS-CREAM payload, consists of 4 layers. Each layer has 2688 silicon pixels and associated electronics arranged in such a fashion that its active detection area of 78.2 × 73.6 cm<SUP>2</SUP> is free of dead area. The foremost goal of the SCD is to efficiently and precisely measure the charge of cosmic rays passing through it. The 4-layer configuration was chosen to achieve the best precision in measuring the charge of cosmic rays within the constraints on the mass, volume and power allotted to it. The amount of material used for its support structure was minimized as well to reduce the chance of interactions of the cosmic ray within the structure. Given the placement of the SCD, its 4-layer configuration and the minimal amount of material in the cosmic-ray trajectory, the SCD is designed to measure the charge of cosmic rays ranging from protons to iron nuclei with excellent detection efficiency and charge resolution. We present the design and fabrication of the SCD as well as its performance during space environment tests which it underwent successfully. We also present its performance in charge measurement using heavy ions in a beam test at CERN, the European Organization for Nuclear Research.</P>
Far-infrared observations of a massive cluster forming in the Monoceros R2 filament hub
Rayner, T. S. M.,Griffin, M. J.,Schneider, N.,Motte, F.,Kö,nyves, V.,André,, P.,Di Francesco, J.,Didelon, P.,Pattle, K.,Ward-Thompson, D.,Anderson, L. D.,Benedettini, M.,Bernard, J.-P.,Bonte Springer-Verlag 2017 Astronomy and astrophysics Vol.607 No.-
Abu-Zayyad, T.,Aida, R.,Allen, M.,Anderson, R.,Azuma, R.,Barcikowski, E.,Belz, J.W.,Bergman, D.R.,Blake, S.A.,Cady, R.,Cheon, B.G.,Chiba, J.,Chikawa, M.,Cho, E.J.,Cho, W.R.,Fujii, H.,Fujii, T.,Fukuda, North-Holland ; Elsevier Science Ltd 2012 Astroparticle physics Vol.39 No.-
The Telescope Array's Middle Drum fluorescence detector was instrumented with telescopes refurbished from the High Resolution Fly's Eye's HiRes-1 site. The data observed by Middle Drum in monocular mode was analyzed via the HiRes-1 profile-constrained geometry reconstruction technique and utilized the same calibration techniques enabling a direct comparison of the energy spectra and energy scales between the two experiments. The spectrum measured using the Middle Drum telescopes is based on a three-year exposure collected between December 16, 2007 and December 16, 2010. The calculated difference between the spectrum of the Middle Drum observations and the published spectrum obtained by the data collected by the HiRes-1 site allows the HiRes-1 energy scale to be transferred to Middle Drum. The HiRes energy scale is applied to the entire Telescope Array by making a comparison between Middle Drum monocular events and hybrid events that triggered both Middle Drum and the Telescope Array's scintillator ground array.
SEARCH FOR ANISOTROPY OF ULTRAHIGH ENERGY COSMIC RAYS WITH THE TELESCOPE ARRAY EXPERIMENT
Abu-Zayyad, T.,Aida, R.,Allen, M.,Anderson, R.,Azuma, R.,Barcikowski, E.,Belz, J. W.,Bergman, D. R.,Blake, S. A.,Cady, R.,Cheon, B. G.,Chiba, J.,Chikawa, M.,Cho, E. J.,Cho, W. R.,Fujii, H.,Fujii, T.,F IOP Publishing 2012 The Astrophysical journal Vol.757 No.1
<P>We study the anisotropy of Ultra-High Energy Cosmic Ray (UHECR) events collected by the Telescope Array (TA) detector in the first 40 months of operation. Following earlier studies, we examine event sets with energy thresholds of 10 EeV, 40 EeV, and 57 EeV. We find that the distributions of the events in right ascension and declination are compatible with an isotropic distribution in all three sets. We then compare with previously reported clustering of the UHECR events at small angular scales. No significant clustering is found in the TA data. We then check the events with E > 57 EeV for correlations with nearby active galactic nuclei. No significant correlation is found. Finally, we examine all three sets for correlations with the large-scale structure (LSS) of the universe. We find that the two higher-energy sets are compatible with both an isotropic distribution and the hypothesis that UHECR sources follow the matter distribution of the universe (the LSS hypothesis), while the event set with E > 10 EeV is compatible with isotropy and is not compatible with the LSS hypothesis at 95% CL unless large deflection angles are also assumed. We show that accounting for UHECR deflections in a realistic model of the Galactic magnetic field can make this set compatible with the LSS hypothesis.</P>
THE COSMIC-RAY ENERGY SPECTRUM OBSERVED WITH THE SURFACE DETECTOR OF THE TELESCOPE ARRAY EXPERIMENT
Abu-Zayyad, T.,Aida, R.,Allen, M.,Anderson, R.,Azuma, R.,Barcikowski, E.,Belz, J. W.,Bergman, D. R.,Blake, S. A.,Cady, R.,Cheon, B. G.,Chiba, J.,Chikawa, M.,Cho, E. J.,Cho, W. R.,Fujii, H.,Fujii, T.,F IOP Publishing 2013 ASTROPHYSICAL JOURNAL LETTERS - Vol.768 No.1