1. |
- Kanai, M, et al.
(author)
-
- 2023
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swepub:Mat__t
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2. |
- Abe, K., et al.
(author)
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J-PARC Neutrino Beamline Upgrade Technical Design Report
- 2019
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Reports (peer-reviewed)abstract
- In this document, technical details of the upgrade plan of the J-PARC neutrino beamline for the extension of the T2K experiment are described. T2K has proposed to accumulate data corresponding to 2×1022 protons-on-target in the next decade, aiming at an initial observation of CP violation with 3σ or higher significance in the case of maximal CP violation. Methods to increase the neutrino beam intensity, which are necessary to achieve the proposed data increase, are described.
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3. |
- Abe, K., et al.
(author)
-
Neutron tagging following atmospheric neutrino events in a water Cherenkov detector
- 2022
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In: Journal of Instrumentation. - : Institute of Physics (IOP). - 1748-0221. ; 17:10
-
Journal article (peer-reviewed)abstract
- We present the development of neutron-tagging techniques in Super-Kamiokande IV using a neural network analysis. The detection efficiency of neutron capture on hydrogen is estimated to be 26%, with a mis-tag rate of 0.016 per neutrino event. The uncertainty of the tagging efficiency is estimated to be 9.0%. Measurement of the tagging efficiency with data from an Americium-Beryllium calibration agrees with this value within 10%. The tagging procedure was performed on 3,244.4 days of SK-IV atmospheric neutrino data, identifying 18,091 neutrons in 26,473 neutrino events. The fitted neutron capture lifetime was measured as 218 +/- 9 mu s.
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4. |
- Ambrosio, M, et al.
(author)
-
The MACRO detector at Gran Sasso
- 2002
-
In: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier. - 0168-9002 .- 1872-9576. ; 486:3, s. 663-707
-
Journal article (peer-reviewed)abstract
- MACRO was an experiment that ran in the Laboratori Nazionali del Gran Sasso from 1988 to 2000. Its principal goal was to observe magnetic monopoles or set significantly lower experimental flux limits than had been previously available in the velocity range from about beta = 10(-4) to unity. In addition it made a variety of other observations. Examples are: setting flux limits on other so far unobserved particles such as nuclearites and lightly ionizing particles, searching for WIMP annihilations in the Earth and the Sun and for neutrino bursts from stellar collapses in or near our Galaxy, and making measurements relevant to high energy muon and neutrino astronomy and of the flux of up-going muons as a function of nadir angle showing evidence for neutrino oscillations. The apparatus consisted of three principal types of detectors: liquid scintillator counters, limited streamer tubes, and nuclear track etch detectors. In addition, over part of its area it contained a transition radiation detector. The general design philosophy emphasized redundancy and complementarity. This paper describes the technical aspects of the complete MACRO detector, its operational performance, and the techniques used to calibrate it and verify its proper operation. It supplements a previously published paper which described the first portion of the detector that was built and operated. (C) 2002 Elsevier Science B.V. All rights reserved.
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5. |
- Aglietta, M, et al.
(author)
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The cosmic ray primary composition between 10(15) and 10(16) eV from Extensive Air Showers electromagnetic and TeV muon data
- 2004
-
In: Astroparticle physics. - : Elsevier. - 0927-6505 .- 1873-2852. ; 20:6, s. 641-652
-
Journal article (peer-reviewed)abstract
- The cosmic ray primary composition in the energy range between 10(15) and 10(16) eV, i.e., around the "knee" of the primary spectrum, has been studied through the combined measurements of the EAS-TOP air shower array (2005 m a. s.l., 10(5) m(2) collecting area) and the MACRO underground detector (963 m.a.s.l., 3100 m w.e. of minimum rock overburden, 920 m(2) effective area) at the National Gran Sasso Laboratories. The used observables are the air shower size (N-c) measured by EAS-TOP and the muon number (N-mu) recorded by MACRO. The two detectors are separated on average by 1200 m of rock, and located at a respective zenith angle of about 30degrees. The energy threshold at the surface for muons reaching the MACRO depth is approximately 1.3 TeV. Such muons are produced in the early stages of the shower development and in a kinematic region quite different from the one relevant for the usual N-mu - N-e studies. The measurement leads to a primary composition becoming heavier at the knee of the primary spectrum, the knee itself resulting from the steepening of the spectrum of a primary light component (p, He) of Deltay = 0.7 +/- 0.4 at E-0 similar to 4 x 10(15) eV. The result confirms the ones reported from the observation of the low energy muons at the surface (typically in the GeV energy range), showing that the conclusions do not depend on the production region kinematics. Thus, the hadronic interaction model used (CORSIKA/QGSJET) provides consistent composition results from data related to secondaries produced in a rapidity region exceeding the central one. Such an evolution of the composition in the knee region supports the "standard" galactic acceleration/propagation models that imply rigidity dependent breaks of the different components.. and therefore breaks occurring at lower energies in the spectra of the light nuclei. (C) 2003 Elsevier B.V. All rights reserved.
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6. |
- Aglietta, M, et al.
(author)
-
The cosmic ray proton, helium and CNO fluxes in the 100 TeV energy region from TeV muons and EAS atmospheric Cherenkov light observations of MACRO and EAS-TOP
- 2004
-
In: Astroparticle physics. - : Elsevier. - 0927-6505 .- 1873-2852. ; 21:3, s. 223-240
-
Journal article (peer-reviewed)abstract
- The primary cosmic ray (CR) proton, helium and CNO fluxes in the energy range 80-300 TeV are studied at the National Gran Sasso Laboratories by means of EAS-TOP (Campo Imperatore, 2005 m a.s.l.) and MACRO (deep underground, 3100 m w.e., the surface energy threshold for a muon reaching the detector being E-mu(th) approximate to 1.3 TeV). The measurement is based on: (a) the selection of primaries based on their energy/nucleon (i.e., with energy/nucleon sufficient to produce a muon with energy larger than 1.3 TeV) and the reconstruction of the shower geometry by means of the muons recorded by MACRO in the deep underground laboratories; (b) the detection of the associated atmospheric Cherenkov light (C.l.) signals by means of the C.l. detector of EAS-TOP. The C.l. density at core distance r > 100 m is directly related to the total primary energy E-0. Proton and helium ("p + He") and proton, helium and CNO ("p + He + CNO") primaries are thus selected at E-0 approximate to 80 TeV, and at E-0 similar or equal to 250 TeV, respectively. Their flux is measured: J(p+He)(80 TeV) = (1.8 +/- 0.4) x 10(-6) m(-1)-s(-1) sr(-1) TeV-1, and J(p+He+CNO)(250 TeV) = (1.1 +/- 0.3) x 10(-7) m(-2)-s(-1) sr(-1) TeV-1, their relative weights being J(p+He)(J(p+He+CNO)) over bar (250 TeV) = 0.78 +/- 0.17. By using the measurements of the proton spectrum obtained from the direct experiments and hadron flux data in the atmosphere, we obtain for the relative weights of the three components at 250 TeV: J(p) : J(He) : J(CNO) = (0.20 +/- 0.08) : (0.58 +/- 0.19) : (0.22 +/- 0.17). This corresponds to the dominance of helium over proton primaries at 100-1000 TeV, and a possible non-negligible contribution from CNO. The lateral distribution of Cherenkov light in Extensive Air Showers (EASs), which is related to the rate of energy deposit of the primary in the atmosphere, is measured for a selected proton and helium primary beam, and good agreement is found when compared with the one calculated with the CORSIKA/QGSJET simulation model. (C) 2004 Elsevier B.V. All rights reserved.
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7. |
- Ambrosio, M, et al.
(author)
-
Atmospheric neutrino oscillations from upward throughgoing muon multiple scattering in MACRO
- 2003
-
In: Physics Letters B. - 0370-2693 .- 1873-2445. ; 566:1-2, s. 35-44
-
Journal article (peer-reviewed)abstract
- The energy of atmospheric neutrinos detected by MACRO was estimated using multiple Coulomb scattering of upward throughgoing muons. This analysis allows a test of atmospheric neutrino oscillations, relying on the distortion of the muon energy distribution. These results have been combined with those coming from the upward throughgoing muon angular distribution only. Both analyses are independent of the neutrino flux normalization and provide strong evidence, above the for level, in favour of neutrino oscillations. (C) 2003 Published by Elsevier B.V.
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8. |
- Ambrosio, M, et al.
(author)
-
Moon and Sun shadowing effect in the MACRO detector
- 2003
-
In: Astroparticle physics. - : Elsevier. - 0927-6505 .- 1873-2852. ; 20:2, s. 145-156
-
Journal article (peer-reviewed)abstract
- Using data collected by the MACRO experiment from 1989 to the end of its operations in 2000, we have studied in the underground muon flux the shadowing. effects due to both the Moon and the Sun. We have observed the shadow cast by the Moon at its apparent position with a significance of 6.5sigma. The Moon shadowing effect has been used to verify the pointing capability of the detector and to determine the instrument resolution for the search of muon excesses from any direction of the celestial sphere. The dependence of the effect on the geomagnetic field is clearly shown by splitting the data sample in day and night observations. The Sun shadow, observed with a significance of 4.6sigma is displaced by about 0.6degrees from its apparent position. In this case however the explanation resides in the configuration of the Solar and Interplanetary Magnetic Fields, which affect the propagation of cosmic ray particles between the Sun, and the Earth. The displacement of the Sun shadow with respect to the real Sun position has been used to establish an upper limit on the antimatter flux in cosmic rays of about 48% at 68% c.l. and primary energies of about 20 TeV. (C) 2003 Elsevier B.V. All rights reserved.
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9. |
- Ambrosio, M, et al.
(author)
-
A combined analysis technique for the search for fast magnetic monopoles with the MACRO detector
- 2002
-
In: Astroparticle physics. - : Elsevier. - 0927-6505 .- 1873-2852. ; 18:1, s. 27-41
-
Journal article (peer-reviewed)abstract
- We describe a search method for fast moving (beta = v/c > 5 x 10(-3)) magnetic monopoles using simultaneously the scintillator, streamer tube and track-etch subdetectors of the MACRO apparatus. The first two subdetectors are used primarily for the identification of candidates while the track-etch one is used as the final tool for their rejection or confirmation. Using this technique, a first sample of more than two-years of data has been analyzed without any evidence of a magnetic monopole. We set a 90% CL upper limit to the local monopole flux of 1.5 x 10(-15) cm(-2) s(-1) sr(-1) in the velocity range 5 x 10(-3) less than or equal to beta less than or equal to 0.99 and for nucleon decay catalysis cross-section smaller than similar to1 mb (C) 2002 Elsevier Science B.V. All rights reserved.
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10. |
- Ambrosio, M, et al.
(author)
-
Final results of magnetic monopole searches with the MACRO experiment
- 2002
-
In: European Physical Journal C. - : Springer. - 1434-6044 .- 1434-6052. ; 25:4, s. 511-522
-
Journal article (peer-reviewed)abstract
- We present the final results obtained by the MACRO experiment in the search for GUT magnetic monopoles in the penetrating cosmic radiation, for the range 4 x 10(-5) < 3 < 1. Several searches with all the MACRO sub-detectors (i.e. scintillation counters, limited streamer tubes and nuclear track detectors) were performed, both in stand alone and combined ways. No candidates were detected and a 90% Confidence Level (C.L.) upper limit to the local magnetic monopole flux was set at the level of 1.4 x 10(-16) cm(-2) s(-1) sr(-1). This result is the first experimental limit obtained in direct searches which is well below the Parker bound in the whole 3 range in which GUT magnetic monopoles are,expected.
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11. |
- Ambrosio, M, et al.
(author)
-
Matter effects in upward-going muons and sterile neutrino oscillations
- 2001
-
In: Physics Letters B. - : Elsevier. - 0370-2693 .- 1873-2445. ; 517:1-2, s. 59-66
-
Journal article (peer-reviewed)abstract
- The angular distribution of upward-going muons produced by atmospheric neutrinos in the rock below the MACRO detector shows anomalies in good agreement with two flavor nu (mu) --> nu (tau) oscillations with maximum mixing and Deltam(2) around 0.0024 eV(2). Exploiting the dependence of magnitude of the matter effect on oscillation channel, and using a set of 809 upward-going muons observed in MACRO, we show that the two flavor nu (mu) --> nu (s) oscillation is disfavored with 99% C.L. with respect to nu (mu) --> nu (tau). (C) 2001 Elsevier Science B.V. All rights reserved.
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12. |
- Ambrosio, M, et al.
(author)
-
Measurements of atmospheric muon neutrino oscillations, global analysis of the data collected with MACRO detector
- 2004
-
In: European Physical Journal C. - : Springer. - 1434-6044 .- 1434-6052. ; 36:3, s. 323-339
-
Journal article (peer-reviewed)abstract
- The final analysis of atmospheric neutrino events collected with the MACRO detector is presented. Three different classes of events, generated by neutrinos in different energy ranges, are studied looking at rates, angular distributions and estimated energies. The results are consistent for all the subsamples and indicate a flux deficit that depends on energy and path - length of neutrinos. The no - oscillation hypothesis is excluded at similar to 5sigma, while the hypothesis of nu(mu) --> nu(tau) oscillation gives a satisfactory description of all data. The parameters with highest probability in a two flavor scenario are sin(2) 2theta(m) = 1 and Deltam(2) = 0.0023 eV(2). This result is independent of the absolute normalization of the atmospheric neutrino fluxes. The data can also be used to put experimental constrain on this normalization.
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13. |
- Ambrosio, M, et al.
(author)
-
Search for nucleon decays induced by GUT magnetic monopoles with the MACRO experiment
- 2002
-
In: European Physical Journal C. - : Springer. - 1434-6044 .- 1434-6052. ; 26:2, s. 163-172
-
Journal article (peer-reviewed)abstract
- The interaction of a Grand Unification Magnetic Monopole with a nucleon can lead to a barion-number violating process in which the nucleon decays into a lepton and one or more mesons (catalysis of nucleon decay). In this paper we report an experimental study of the effects of a catalysis process in the MACRO detector. Using a dedicated analysis we obtain new magnetic monopole (MM) flux upper limits at the level of similar to 3 (.) 10(-16) cm(-2) s(-1) sr(-1) for 1.1(.) 10(-4) less than or equal to \beta\ less than or equal to 5 (.) 10(-3), based on the search for catalysis events in the MACRO data. We also analyze the dependence of the MM flux limit on the catalysis cross section.
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14. |
- Dahmen, J., et al.
(author)
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Osteochondral Lesions of the Tibial Plafond and Ankle Instability With Ankle Cartilage Lesions: Proceedings of the International Consensus Meeting on Cartilage Repair of the Ankle
- 2022
-
In: Foot & Ankle International. - : SAGE Publications. - 1071-1007 .- 1944-7876. ; 43:3, s. 448-452
-
Journal article (peer-reviewed)abstract
- Background: An international consensus group of experts was convened to collaboratively advance toward consensus opinions based on the best available evidence on key topics within cartilage repair of the ankle. The purpose of this article is to present the consensus statements on osteochondral lesions of the tibial plafond (OLTP) and on ankle instability with ankle cartilage lesions developed at the 2019 International Consensus Meeting on Cartilage Repair of the Ankle. Methods: Forty-three experts in cartilage repair of the ankle were convened and participated in a process based on the Delphi method of achieving consensus. Questions and statements were drafted within 4 working groups focusing on specific topics within cartilage repair of the ankle, after which a comprehensive literature review was performed and the available evidence for each statement was graded. Discussion and debate occurred in cases where statements were not agreed on in unanimous fashion within the working groups. A final vote was then held. Results: A total of 11 statements on OLTP reached consensus. Four achieved unanimous support and 7 reached strong consensus (greater than 75% agreement). A total of 8 statements on ankle instability with ankle cartilage lesions reached consensus during the 2019 International Consensus Meeting on Cartilage Repair of the Ankle. One achieved unanimous support, and seven reached strong consensus (greater than 75% agreement). Conclusions: These consensus statements may assist clinicians in the management of these difficult clinical pathologies.
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15. |
- Togo, V, et al.
(author)
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Calibrations of CR39 and Makrofol nuclear track detectors and search for exotic particles
- 2003
-
In: Nuclear physics B, Proceedings supplements. - : Elsevier. - 0920-5632 .- 1873-3832. ; 125, s. 217-221
-
Journal article (peer-reviewed)abstract
- We present the final results of the search for exotic massive particles in the cosmic radiation performed with the MACRO underground experiment. Magnetic monopoles and nuclearites flux upper limits obtained with the CR39 nuclear track subdetector, the scintillation and streamer tube subdetectors are given. Searches at high altitude with the SLIM experiment are in progress.
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16. |
- Ambrosio, M, et al.
(author)
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Measurement of the residual energy of muons in the Gran Sasso underground laboratories
- 2003
-
In: Astroparticle physics. - : Elsevier. - 0927-6505 .- 1873-2852. ; 19:3, s. 313-328
-
Journal article (peer-reviewed)abstract
- The MACRO detector was located in the Hall B of the Gran Sasso underground laboratories under an average rock overburden of 3700 hg/cm(2). A transition radiation detector composed of three identical modules, covering a total horizontal area of 36 m(2), was installed inside the empty upper part of the detector in order to measure the residual energy of muons. This paper presents the measurement of the residual energy of single and double muons crossing the apparatus. Our data show that double muons are more energetic than single ones. This measurement is performed over a standard rock depth range from 3000 to 6500 hg/cm(2). (C) 2002 Elsevier Science B.V. All rights reserved.
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17. |
- Ambrosio, M, et al.
(author)
-
Muon energy estimate through multiple scattering with the MACRO detector
- 2002
-
In: Nuclear Instruments and Methods in Physics Research Section A. - 0168-9002 .- 1872-9576. ; 492:3, s. 376-386
-
Journal article (peer-reviewed)abstract
- Muon energy measurement represents an important issue for any experiment addressing neutrino-induced up-going muon studies. Since the neutrino oscillation probability depends on the neutrino energy, a measurement of the muon energy adds an important piece of information concerning the neutrino system. We show in this paper how the MACRO limited streamer tube system can be operated in drift mode by using the TDCs included in the QTPs, an electronics designed for magnetic monopole search. An improvement of the space resolution is obtained, through an analysis of the multiple scattering of muon tracks as they pass through our detector. This information can be used further to obtain an estimate of the energy of muons crossing the detector. Here we present the results of two dedicated tests, performed at CERN PS-T9 and SPS-X7 beam lines, to provide a full check of the electronics and to exploit the feasibility of such a multiple scattering analysis. We show that by using a neural network approach, we are able to reconstruct the muon energy for E-mu < 40 GeV. The test beam data provide an absolute energy calibration, which allows us to apply this method to MACRO data. (C) 2002 Elsevier Science B.V. All rights reserved.
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18. |
- Ambrosio, M, et al.
(author)
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Search for cosmic ray sources using muons detected by the MACRO experiment
- 2003
-
In: Astroparticle physics. - : Elsevier. - 0927-6505 .- 1873-2852. ; 18:6, s. 615-627
-
Journal article (peer-reviewed)abstract
- The MACRO underground detector at Gran Sasso Laboratory recorded 60 million secondary cosmic ray muons from February 1989 until December 2000. Different techniques were used to analyze this sample in search for density excesses from astrophysical point-like sources. No evidence for DC excesses for any source in an all-sky survey is reported. In addition, searches for muon excess correlated with the known binary periods of Cygnus X-3 and Hercules X-1, and searches for statistically significant bursting episodes from known gamma-ray sources are also proved negative. (C) 2002 Elsevier Science B.V. All rights reserved.
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19. |
- Ambrosio, M, et al.
(author)
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Search for diffuse neutrino flux from astrophysical sources with MACRO
- 2003
-
In: Astroparticle physics. - : Elsevier. - 0927-6505 .- 1873-2852. ; 19:1, s. 1-13
-
Journal article (peer-reviewed)abstract
- Many galactic and extragalactic astrophysical sources are currently considered promising candidates as high-energy neutrino emitters. Astrophysical neutrinos can be detected as upward-going muons produced in charged-current interactions with the medium surrounding the detector. The expected neutrino fluxes from various models start to dominate on the atmospheric neutrino background at neutrino energies above some tens of TeV. We present the results of a search for an excess of high-energy upward-going muons among the sample of data collected by MACRO during similar to5.8 years of effective running time. No significant evidence for this signal was found. As a consequence, an upper limit on the flux of upward-going muons from high-energy neutrinos was set at the level of 1.7 x 10(-14) cm(-2) s(-1) sr(-1). The corresponding upper limit for the diffuse neutrino flux was evaluated assuming a neutrino power law spectrum. Our result was compared with theoretical predictions and upper limits from other experiments. (C) 2002 Elsevier Science B.V. All rights reserved.
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20. |
- Ambrosio, M, et al.
(author)
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Search for the sidereal and solar diurnal modulations in the total MACRO muon data set
- 2003
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In: Physical Review D. Particles and fields. - : American Physical Society. - 0556-2821 .- 1089-4918. ; 67:4
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Journal article (peer-reviewed)abstract
- We have analyzed 44.3M single muons collected by MACRO from 1991 through 2000 in 2145 live days of operation. We have searched for the solar diurnal, apparent sidereal, and pseudosidereal modulation of the underground muon rate by computing hourly deviations of the muon rate from 6 month averages. We find evidence for statistically significant modulations with the solar diurnal and the sidereal periods. The amplitudes of these modulations are <0.1%, and are at the limit of the detector statistics. The pseudosidereal modulation is not statistically significant. The solar diurnal modulation is due to the daily atmospheric temperature variations at 20 km, the altitude of primary cosmic ray interactions with the atmosphere; MACRO is the deepest experiment to report this result. The sidereal modulation is in addition to the expected Compton-Getting modulation due to solar system motion relative to the local standard of rest; it represents motion of the solar system with respect to the galactic cosmic rays toward the galactic plane.
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21. |
- Addazi, A., et al.
(author)
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New high-sensitivity searches for neutrons converting into antineutrons and/or sterile neutrons at the HIBEAM/NNBAR experiment at the European Spallation Source
- 2021
-
In: Journal of Physics G. - : Institute of Physics Publishing (IOPP). - 0954-3899 .- 1361-6471. ; 48:7
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Journal article (peer-reviewed)abstract
- The violation of baryon number, , is an essential ingredient for the preferential creation of matter over antimatter needed to account for the observed baryon asymmetry in the Universe. However, such a process has yet to be experimentally observed. The HIBEAM/NNBAR program is a proposed two-stage experiment at the European Spallation Source to search for baryon number violation. The program will include high-sensitivity searches for processes that violate baryon number by one or two units: free neutron–antineutron oscillation () via mixing, neutron–antineutron oscillation via regeneration from a sterile neutron state (), and neutron disappearance (n → n'); the effective process of neutron regeneration () is also possible. The program can be used to discover and characterize mixing in the neutron, antineutron and sterile neutron sectors. The experiment addresses topical open questions such as the origins of baryogenesis and the nature of dark matter, and is sensitive to scales of new physics substantially in excess of those available at colliders. A goal of the program is to open a discovery window to neutron conversion probabilities (sensitivities) by up to three orders of magnitude compared with previous searches. The opportunity to make such a leap in sensitivity tests should not be squandered. The experiment pulls together a diverse international team of physicists from the particle (collider and low energy) and nuclear physics communities, while also including specialists in neutronics and magnetics.
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22. |
- Conley, R. B., et al.
(author)
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Secondary Fracture Prevention: Consensus Clinical Recommendations from a Multistakeholder Coalition
- 2020
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In: Journal of Bone and Mineral Research. - : Wiley. - 0884-0431 .- 1523-4681. ; 35:1, s. 36-52
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Journal article (peer-reviewed)abstract
- Osteoporosis-related fractures are undertreated, due in part to misinformation about recommended approaches to patient care and discrepancies among treatment guidelines. To help bridge this gap and improve patient outcomes, the American Society for Bone and Mineral Research assembled a multistakeholder coalition to develop clinical recommendations for the optimal prevention of secondary fracture among people aged 65 years and older with a hip or vertebral fracture. The coalition developed 13 recommendations (7 primary and 6 secondary) strongly supported by the empirical literature. The coalition recommends increased communication with patients regarding fracture risk, mortality and morbidity outcomes, and fracture risk reduction. Risk assessment (including fall history) should occur at regular intervals with referral to physical and/or occupational therapy as appropriate. Oral, intravenous, and subcutaneous pharmacotherapies are efficacious and can reduce risk of future fracture. Patients need education, however, about the benefits and risks of both treatment and not receiving treatment. Oral bisphosphonates alendronate and risedronate are first-line options and are generally well tolerated; otherwise, intravenous zoledronic acid and subcutaneous denosumab can be considered. Anabolic agents are expensive but may be beneficial for selected patients at high risk. Optimal duration of pharmacotherapy is unknown but because the risk for second fractures is highest in the early post-fracture period, prompt treatment is recommended. Adequate dietary or supplemental vitamin D and calcium intake should be assured. Individuals being treated for osteoporosis should be reevaluated for fracture risk routinely, including via patient education about osteoporosis and fractures and monitoring for adverse treatment effects. Patients should be strongly encouraged to avoid tobacco, consume alcohol in moderation at most, and engage in regular exercise and fall prevention strategies. Finally, referral to endocrinologists or other osteoporosis specialists may be warranted for individuals who experience repeated fracture or bone loss and those with complicating comorbidities (eg, hyperparathyroidism, chronic kidney disease). (c) 2019 American Society for Bone and Mineral Research.
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23. |
- Cordova, M., et al.
(author)
-
Atomic-level structure determination of amorphous molecular solids by NMR
- 2023
-
In: Nature Communications. - 2041-1723. ; 14:1
-
Journal article (peer-reviewed)abstract
- Structure determination of amorphous materials remains challenging, owing to the disorder inherent to these materials. Nuclear magnetic resonance (NMR) powder crystallography is a powerful method to determine the structure of molecular solids, but disorder leads to a high degree of overlap between measured signals, and prevents the unambiguous identification of a single modeled periodic structure as representative of the whole material. Here, we determine the atomic-level ensemble structure of the amorphous form of the drug AZD4625 by combining solid-state NMR experiments with molecular dynamics (MD) simulations and machine-learned chemical shifts. By considering the combined shifts of all 1H and 13C atomic sites in the molecule, we determine the structure of the amorphous form by identifying an ensemble of local molecular environments that are in agreement with experiment. We then extract and analyze preferred conformations and intermolecular interactions in the amorphous sample in terms of the stabilization of the amorphous form of the drug.
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24. |
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25. |
- Murawski, Christopher D., et al.
(author)
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Terminology for osteochondral lesions of the ankle: proceedings of the International Consensus Meeting on Cartilage Repair of the Ankle
- 2022
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In: JOURNAL OF ISAKOS JOINT DISORDERS & ORTHOPAEDIC SPORTS MEDICINE. - : Elsevier BV. - 2059-7754 .- 2059-7762. ; 7:2, s. 62-66
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Journal article (peer-reviewed)abstract
- Background: The evidence supporting best practice guidelines in the field of cartilage repair of the ankle is based on both low quality and low levels of evidence. Therefore, an international consensus group of experts was convened to collaboratively advance toward consensus opinions based on the best available evidence on key topics within cartilage repair of the ankle. The purpose of this article is to report the consensus statements on "terminology for osteochondral lesions of the ankle" developed at the 2019 International Consensus Meeting on Cartilage Repair of the Ankle. Methods: Forty-three international experts in cartilage repair of the ankle representing 20 countries were convened and participated in a process based on the Delphi method of achieving consensus. Questions and statements were drafted within four working groups focusing on specific topics within cartilage repair of the ankle, after which a comprehensive literature review was performed, and the available evidence for each state-ment was graded. Discussion and debate occurred in cases where statements were not agreed on in unanimous fashion within the working groups. A final vote was then held, and the strength of consensus was characterised as follows: consensus, 51%-74%; strong consensus, 75%-99%; unanimous, 100%. Results: A total of 11 statements on terminology and classification reached consensus during the 2019 Interna-tional Consensus Meeting on Cartilage Repair of the Ankle. Definitions are provided for osseous, chondral and osteochondral lesions, as well as bone marrow stimulation and injury chronicity, among others. An osteochondral lesion of the talus can be abbreviated as OLT. Conclusions: This international consensus derived from leaders in the field will assist clinicians with the appro-priate terminology for osteochondral lesions of the ankle.
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26. |
- Aboulatta, L, et al.
(author)
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Preterm birth and stillbirth rates associated with socioeconomic disparities during COVID-19 pandemic: a population-based cross-sectional study
- 2023
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In: BMJ paediatrics open. - : BMJ. - 2399-9772. ; 7:1
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Journal article (peer-reviewed)abstract
- Conflicting evidence exists on the impact of the COVID-19 pandemic restrictions on preterm birth (PTB) and stillbirth rates. We aimed to evaluate changes in PTB and stillbirth rates before and during the pandemic period and assess the potential effect modification of socioeconomic status (SES).MethodsUsing the linked administrative health databases from Manitoba, Canada, we conducted a cross-sectional study among all pregnant women, comparing 3.5 years pre-pandemic (1 October 2016 to 29 February 2020) to the first year of the pandemic (1 March 2020 to 31 March 2021). We used generalised linear models to assess the quarterly rates of PTB (<37 weeks) and stillbirths. We calculated the predicted trends based on pre-pandemic period data. Finally, we evaluated the PTB and stillbirth rates among lower and higher SES pregnant women (average annual household income) using subgroup analysis and interaction models.ResultsWe examined 70 931 pregnancies in Manitoba during the study period. The risk of PTB increased by 7.7% (95%CI 1.01 to 1.13) and stillbirths by 33% (95% CI 1.08 to 1.64) during the pandemic period. Following COVID-19 restrictions implemented in March 2020, there were increases in the quarterly rates of both PTB (immediate increase (β2)=1.37; p=0.0247) and stillbirths (immediate increase (β2)=0.12; p=0.4434). Among the lower income groups, the pandemic restrictions resulted in an immediate relative increase in PTB and stillbirth rates by 20.12% (immediate increase (β2)=3.17; p=0.0057) and 27.19% (immediate increase (β2)=0.48; p=0.0852). However, over the pandemic, the overall PTB rate significantly decreased as a rebound effect by 0.85% per quarter (p=0.0004), whereas the overall stillbirth rate did not decrease significantly (slope decrease (β3) =−0.01; p=0.8296) compared with the pre-pandemic period. The quarterly rates during the pandemic among the higher income group decreased by 0.39% (p=0.1296) for PTB and increased by 0.07% (p=0.1565) for stillbirth. We observed an effect modification by SES for PTB rates (p=0.047).ConclusionWhile the onset of COVID-19 pandemic restrictions was not associated with significant effects on stillbirth rates, we observed an immediate and rebound effect on PTB rates. The impact of COVID-19 on preterm birth was dependent on SES, with higher influence on families with lower SES. Further studies are needed to detect future trend changes during pandemic waves after 2021 and assess potential underlying mechanisms.
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- Cunningham, J.A., et al.
(author)
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Distinguishing geology from biology in the Ediacaran Doushantuo biota relaxes constraints on the timing of the origin of bilaterians.
- 2012
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In: Proceedings of the Royal Society. B. Biological Sciences. - : The Royal Society. - 0962-8452 .- 1471-2954. ; 279:1737, s. 2369-2376
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Journal article (peer-reviewed)abstract
- The Ediacaran Doushantuo biota has yielded fossils that include the oldest widely accepted record of the animal evolutionary lineage, as well as specimens with alleged bilaterian affinity. However, these systematic interpretations are contingent on the presence of key biological structures that have been reinterpreted by some workers as artefacts of diagenetic mineralization. On the basis of chemistry and crystallographic fabric, we characterize and discriminate phases of mineralization that reflect: (i) replication of original biological structure, and (ii) void-filling diagenetic mineralization. The results indicate that all fossils from the Doushantuo assemblage preserve a complex me´lange of mineral phases, even where subcellular anatomy appears to be preserved. The findings allow these phases to be distinguished in more controversial fossils, facilitating a critical re-evaluation of the Doushantuo fossil assemblage and its implications as an archive of Ediacaran animal diversity. We find that putative subcellular structures exhibit fabrics consistent with preservation of original morphology. Cells in later developmental stages are not in original configuration and are therefore uninformative concerning gastrulation. Key structures used to identify Doushantuo bilaterians can be dismissed as late diagenetic artefacts. Therefore, when diagenetic mineralization is considered, there is no convincing evidence for bilaterians in the Doushantuo assemblage.
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- Shambat, SM, et al.
(author)
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A point mutation in AgrC determines cytotoxic or colonizing properties associated with phenotypic variants of ST22 MRSA strains
- 2016
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In: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6, s. 31360-
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Journal article (peer-reviewed)abstract
- Methicillin-resistant Staphylococcus aureus (MRSA) is a major cause of skin and soft tissue infections. One of the highly successful and rapidly disseminating clones is MRSA ST22 commonly associated with skin tropism. Here we show that a naturally occurring single amino acid substitution (tyrosine to cysteine) at position 223 of AgrC determines starkly different ST22 S. aureus virulence phenotypes, e.g. cytotoxic or colonizing, as evident in both in vitro and in vivo skin infections. Y223C amino acid substitution destabilizes AgrC-AgrA interaction leading to a colonizing phenotype characterized by upregulation of bacterial surface proteins. The colonizing phenotype strains cause less severe skin tissue damage, show decreased susceptibility towards the antimicrobial LL-37 and induce autophagy. In contrast, cytotoxic strains with tyrosine at position 223 of AgrC cause infections characterized by inflammasome activation and severe skin tissue pathology. Taken together, the study demonstrates how a single amino acid substitution in the histidine kinase receptor AgrC of ST22 strains determines virulence properties and infection outcome.
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- Smith, Siobhan, et al.
(author)
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IL-16/miR-125a axis controls neutrophil recruitment in pristane-induced lung inflammation
- 2018
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In: JCI Insight. - : American Society for Clinical Investigation. - 2379-3708. ; 3:15
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Journal article (peer-reviewed)abstract
- Severe lung inflammation and alveolar hemorrhage can be life-threatening in systemic lupus erythematosus (SLE) patients if not treated early and aggressively. Neutrophil influx is the driver key of this pathology, but little is known regarding the molecular events regulating this recruitment. Here, we uncover a role for IL-16/mir-125a in this pathology and show not only that IL-16 is a target for miR-125a but that reduced miR-125a expression in SLE patients associates with lung involvement. Furthermore, in the pristane model of acute "SLE-like" lung inflammation and alveolar hemorrhage, we observed reduced pulmonary miR-125a and enhanced IL-16 expression. Neutrophil infiltration was markedly reduced in the peritoneal lavage of pristane-treated IL-16-deficient mice and elevated following i.n. delivery of IL-16. Moreover, a miR-125a mimic reduced pristane-induced IL-16 expression and neutrophil recruitment and rescued lung pathology. Mechanistically, IL-16 acts directly on the pulmonary epithelium and markedly enhances neutrophil chemoattractant expression both in vitro and in vivo, while the miR-125a mimic can prevent this. Our results reveal a role for miR-125a/IL-16 in regulating lung inflammation and suggest this axis may be a therapeutic target for management of acute lung injury in SLE.
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