1. |
- Murari, A., et al.
(author)
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A control oriented strategy of disruption prediction to avoid the configuration collapse of tokamak reactors
- 2024
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In: Nature Communications. - 2041-1723 .- 2041-1723. ; 15:1
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Journal article (peer-reviewed)abstract
- The objective of thermonuclear fusion consists of producing electricity from the coalescence of light nuclei in high temperature plasmas. The most promising route to fusion envisages the confinement of such plasmas with magnetic fields, whose most studied configuration is the tokamak. Disruptions are catastrophic collapses affecting all tokamak devices and one of the main potential showstoppers on the route to a commercial reactor. In this work we report how, deploying innovative analysis methods on thousands of JET experiments covering the isotopic compositions from hydrogen to full tritium and including the major D-T campaign, the nature of the various forms of collapse is investigated in all phases of the discharges. An original approach to proximity detection has been developed, which allows determining both the probability of and the time interval remaining before an incoming disruption, with adaptive, from scratch, real time compatible techniques. The results indicate that physics based prediction and control tools can be developed, to deploy realistic strategies of disruption avoidance and prevention, meeting the requirements of the next generation of devices.
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7. |
- Zillikens, M. C., et al.
(author)
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Large meta-analysis of genome-wide association studies identifies five loci for lean body mass
- 2017
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8:1
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Journal article (peer-reviewed)abstract
- Lean body mass, consisting mostly of skeletal muscle, is important for healthy aging. We performed a genome-wide association study for whole body (20 cohorts of European ancestry with n = 38,292) and appendicular (arms and legs) lean body mass (n = 28,330) measured using dual energy X-ray absorptiometry or bioelectrical impedance analysis, adjusted for sex, age, height, and fat mass. Twenty-one single-nucleotide polymorphisms were significantly associated with lean body mass either genome wide (p < 5 x 10(-8)) or suggestively genome wide (p < 2.3 x 10(-6)). Replication in 63,475 (47,227 of European ancestry) individuals from 33 cohorts for whole body lean body mass and in 45,090 (42,360 of European ancestry) subjects from 25 cohorts for appendicular lean body mass was successful for five single-nucleotide polymorphisms in/ near HSD17B11, VCAN, ADAMTSL3, IRS1, and FTO for total lean body mass and for three single-nucleotide polymorphisms in/ near VCAN, ADAMTSL3, and IRS1 for appendicular lean body mass. Our findings provide new insight into the genetics of lean body mass.
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8. |
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9. |
- Patrignani, C., et al.
(author)
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REVIEW OF PARTICLE PHYSICS : Particle Data Group
- 2016
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In: Chinese Physics C. - : IOP Publishing. - 1674-1137 .- 2058-6132. ; 40:10
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Journal article (peer-reviewed)abstract
- The Review summarizes much of particle physics and cosmology. Using data from previous editions, plus 3,062 new measurements from 721 papers, we list, evaluate, and average measured properties of gauge bosons and the recently discovered Higgs boson, leptons, quarks, mesons, and baryons. We summarize searches for hypothetical particles such as supersymmetric particles, heavy bosons, axions, dark photons, etc. All the particle properties and search limits are listed in Summary Tables. We also give numerous tables, figures, formulae, and reviews of topics such as Higgs Boson Physics, Supersymmetry, Grand Unified Theories, Neutrino Mixing, Dark Energy, Dark Matter, Cosmology, Particle Detectors, Colliders, Probability and Statistics. Among the 117 reviews are many that are new or heavily revised, including new reviews on Pentaquarks and Inflation. The complete Review is published online in a journal and on the website of the Particle Data Group (http://pdg.lbl.gov). The printed PDG Book contains the Summary Tables and all review articles but no longer includes the detailed tables from the Particle Listings. A Booklet with the Summary Tables and abbreviated versions of some of the review articles is also available.
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10. |
- Olive, K. A., et al.
(author)
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REVIEW OF PARTICLE PHYSICS Particle Data Group
- 2014
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In: Chinese Physics C. - : IOP Publishing. - 1674-1137 .- 2058-6132. ; 38:9
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Research review (peer-reviewed)abstract
- The Review summarizes much of particle physics and cosmology. Using data from previous editions, plus 3,283 new measurements from 899 Japers, we list, evaluate, and average measured properties of gauge bosons and the recently discovered Higgs boson, leptons, quarks, mesons, and baryons. We summarize searches for hypothetical particles such as heavy neutrinos, supersymmetric and technicolor particles, axions, dark photons, etc. All the particle properties and search limits are listed in Summary Tables. We also give numerous tables, figures, formulae, and reviews of topics such as Supersymmetry, Extra Dimensions, Particle Detectors, Probability, and Statistics. Among the 112 reviews are many that are new or heavily revised including those on: Dark Energy, Higgs Boson Physics, Electroweak Model, Neutrino Cross Section Measurements, Monte Carlo Neutrino Generators, Top Quark, Dark Matter, Dynamical Electroweak Symmetry Breaking, Accelerator Physics of Colliders, High-Energy Collider Parameters, Big Bang Nucleosynthesis, Astrophysical Constants and Cosmological Parameters.
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11. |
- Karasik, D., et al.
(author)
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Disentangling the genetics of lean mass
- 2019
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In: American Journal of Clinical Nutrition. - : Elsevier BV. - 0002-9165 .- 1938-3207. ; 109:2, s. 276-287
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Journal article (peer-reviewed)abstract
- Background: Lean body mass (LM) plays an important role in mobility and metabolic function. We previously identified five loci associated with LM adjusted for fat mass in kilograms. Such an adjustment may reduce the power to identify genetic signals having an association with both lean mass and fat mass. Objectives: To determine the impact of different fat mass adjustments on genetic architecture of LM and identify additional LM loci. Methods: We performed genome-wide association analyses for whole-body LM (20 cohorts of European ancestry with n = 38,292) measured using dual-energy X-ray absorptiometry) or bioelectrical impedance analysis, adjusted for sex, age, age(2), and height with or without fat mass adjustments (Model 1 no fat adjustment; Model 2 adjustment for fat mass as a percentage of body mass; Model 3 adjustment for fat mass in kilograms). Results: Seven single-nucleotide polymorphisms (SNPs) in separate loci, including one novel LM locus (TNRC6B), were successfully replicated in an additional 47,227 individuals from 29 cohorts. Based on the strengths of the associations in Model 1 vs Model 3, we divided the LM loci into those with an effect on both lean mass and fat mass in the same direction and refer to those as "sumo wrestler" loci (FTO and MC4R). In contrast, loci with an impact specifically on LMwere termed "body builder" loci (VCAN and ADAMTSL3). Using existing available genome-wide association study databases, LM increasing alleles of SNPs in sumo wrestler loci were associated with an adverse metabolic profile, whereas LM increasing alleles of SNPs in "body builder" loci were associated with metabolic protection. Conclusions: In conclusion, we identified one novel LM locus (TNRC6B). Our results suggest that a genetically determined increase in lean mass might exert either harmful or protective effects on metabolic traits, depending on its relation to fat mass.
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12. |
- Beringer, J., et al.
(author)
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REVIEW OF PARTICLE PHYSICS Particle Data Group
- 2012
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In: Physical Review D. - 1550-7998 .- 1550-2368. ; 86:1, s. 010001-
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Research review (peer-reviewed)abstract
- This biennial Review summarizes much of particle physics. Using data from previous editions, plus 2658 new measurements from 644 papers, we list, evaluate, and average measured properties of gauge bosons, leptons, quarks, mesons, and baryons. We summarize searches for hypothetical particles such as Higgs bosons, heavy neutrinos, and supersymmetric particles. All the particle properties and search limits are listed in Summary Tables. We also give numerous tables, figures, formulae, and reviews of topics such as the Standard Model, particle detectors, probability, and statistics. Among the 112 reviews are many that are new or heavily revised including those on Heavy-Quark and Soft-Collinear Effective Theory, Neutrino Cross Section Measurements, Monte Carlo Event Generators, Lattice QCD, Heavy Quarkonium Spectroscopy, Top Quark, Dark Matter, V-cb & V-ub, Quantum Chromodynamics, High-Energy Collider Parameters, Astrophysical Constants, Cosmological Parameters, and Dark Matter. A booklet is available containing the Summary Tables and abbreviated versions of some of the other sections of this full Review. All tables, listings, and reviews (and errata) are also available on the Particle Data Group website: http://pdg.lbl.gov.
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13. |
- Nakamura, K., et al.
(author)
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Review Of Particle Physics
- 2010
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In: Journal of Physics G: Nuclear and Particle Physics. - 0954-3899 .- 1361-6471. ; 37:7A, s. 1-1422
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Research review (peer-reviewed)abstract
- This biennial Review summarizes much of particle physics. Using data from previous editions, plus 2158 new measurements from 551 papers, we list, evaluate, and average measured properties of gauge bosons, leptons, quarks, mesons, and baryons. We also summarize searches for hypothetical particles such as Higgs bosons, heavy neutrinos, and supersymmetric particles. All the particle properties and search limits are listed in Summary Tables. We also give numerous tables, figures, formulae, and reviews of topics such as the Standard Model, particle detectors, probability, and statistics. Among the 108 reviews are many that are new or heavily revised including those on neutrino mass, mixing, and oscillations, QCD, top quark, CKM quark-mixing matrix, V-ud & V-us, V-cb & V-ub, fragmentation functions, particle detectors for accelerator and non-accelerator physics, magnetic monopoles, cosmological parameters, and big bang cosmology. A booklet is available containing the Summary Tables and abbreviated versions of some of the other sections of this full Review. All tables, listings, and reviews (and errata) are also available on the Particle Data Group website: http://pdg.1b1.gov.
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14. |
- Amsler, C., et al.
(author)
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Review of particle physics
- 2008
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In: Physics Letters. Section B: Nuclear, Elementary Particle and High-Energy Physics. - : Elsevier BV. - 0370-2693 .- 1873-2445. ; 667:1-5, s. 1-1
-
Research review (peer-reviewed)abstract
- This biennial Review summarizes much of particle physics. Using data from previous editions., plus 2778 new measurements from 645 papers, we list, evaluate, and average measured properties of gauge bosons, leptons, quarks, mesons, and baryons. We also summarize searches for hypothetical particles such as Higgs bosons, heavy neutrinos, and supersymmetric particles. All the particle properties and search limits are listed in Summary Tables. We also give numerous tables, figures, formulae, and reviews of topics such as the Standard Model, particle detectors., probability, and statistics. Among the 108 reviews are many that are new or heavily revised including those on CKM quark-mixing matrix, V-ud & V-us, V-cb & V-ub, top quark, muon anomalous magnetic moment, extra dimensions, particle detectors, cosmic background radiation, dark matter, cosmological parameters, and big bang cosmology.
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15. |
- de Graauw, Th., et al.
(author)
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The Herschel-Heterodyne Instrument for the Far-Infrared (HIFI)
- 2010
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 518, s. L6-
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Journal article (peer-reviewed)abstract
- Aims: This paper describes the Heterodyne Instrument for the Far-Infrared (HIFI) that was launched onboard ESA's Herschel Space Observatory in May 2009. Methods: The instrument is a set of 7 heterodyne receivers that are electronically tuneable, covering 480-1250 GHz with SIS mixers and the 1410-1910 GHz range with hot electron bolometer (HEB) mixers. The local oscillator (LO) subsystem comprises a Ka-band synthesizer followed by 14 chains of frequency multipliers and 2 chains for each frequency band. A pair of auto-correlators and a pair of acousto-optical spectrometers process the two IF signals from the dual-polarization, single-pixel front-ends to provide instantaneous frequency coverage of 2 × 4 GHz, with a set of resolutions (125 kHz to 1 MHz) that are better than 0.1 km s-1. Results: After a successful qualification and a pre-launch TB/TV test program, the flight instrument is now in-orbit and completed successfully the commissioning and performance verification phase. The in-orbit performance of the receivers matches the pre-launch sensitivities. We also report on the in-orbit performance of the receivers and some first results of HIFI's operations. Herschel is an ESA space observatory with science instruments provided by European-led Principal Investigator consortia and with important participation from NASA.
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16. |
- Yao, W-M, et al.
(author)
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Review of Particle Physics
- 2006
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In: Journal of Physics G: Nuclear and Particle Physics. - : IOP Publishing. - 0954-3899 .- 1361-6471. ; 33:1, s. 1-1
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Journal article (peer-reviewed)
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17. |
- Jiang, X., et al.
(author)
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Genome-wide association study in 79,366 European-ancestry individuals informs the genetic architecture of 25-hydroxyvitamin D levels
- 2018
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9:1
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Journal article (peer-reviewed)abstract
- Vitamin D is a steroid hormone precursor that is associated with a range of human traits and diseases. Previous GWAS of serum 25-hydroxyvitamin D concentrations have identified four genome-wide significant loci (GC, NADSYN1/DHCR7, CYP2R1, CYP24A1). In this study, we expand the previous SUNLIGHT Consortium GWAS discovery sample size from 16,125 to 79,366 (all European descent). This larger GWAS yields two additional loci harboring genome-wide significant variants (P = 4.7x10(-9) at rs8018720 in SEC23A, and P = 1.9x10(-14) at rs10745742 in AMDHD1). The overall estimate of heritability of 25-hydroxyvitamin D serum concentrations attributable to GWAS common SNPs is 7.5%, with statistically significant loci explaining 38% of this total. Further investigation identifies signal enrichment in immune and hematopoietic tissues, and clustering with autoimmune diseases in cell-type-specific analysis. Larger studies are required to identify additional common SNPs, and to explore the role of rare or structural variants and gene-gene interactions in the heritability of circulating 25-hydroxyvitamin D levels.
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18. |
- Cirasuolo, M., et al.
(author)
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MOONS: the Multi-Object Optical and Near-infrared Spectrograph for the VLT
- 2014
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In: Ground-based and Airborne Instrumentation for Astronomy V. - : SPIE. - 1996-756X .- 0277-786X. ; 9147, s. 91470-91470
-
Conference paper (peer-reviewed)abstract
- MOONS (the Multi-Object Optical and Near-infrared Spectrograph) has been selected by ESO as a third-generation instrument for the Very Large Telescope (VLT). The light grasp of the large collecting area offered by the VLT (8.2m diameter), combined with the large multiplex and wavelength coverage (optical to near-IR: 0.8 -1.8 mu m) of MOONS will provide the European astronomical community with a powerful, unique instrument able to pioneer a wide range of Galactic, extragalactic and cosmological studies, and it will provide crucial follow-up for major facilities such as Gaia, VISTA, Euclid and LSST. MOONS has the observational power needed to unveil galaxy formation and evolution over the entire history of the Universe, from stars in our Milky Way, through the redshift desert, and up to the epoch of very first galaxies and reionization of the Universe at redshifts of z > 8-9, just a few million years after the Big Bang. From five years of observations MOONS will provide high-quality spectra for > 3M stars in our Galaxy and the Local Group, and for 1-2M galaxies at z > 1 (for an SDSS-like survey), promising to revolutionize our understanding of the Universe. The baseline design consists of similar to 1000 fibres, deployable over a field-of-view of similar to 500 arcmin(2), the largest patrol field offered by the Nasmyth focus at the VLT. The total wavelength coverage is 0.8 -1.8 mu m with two spectral resolving powers: in the medium-resolution mode (R similar to 4,000-6,000) the entire wavelength range is observed simultaneously, while the high-resolution mode will cover three selected sub-regions simultaneously: one region with R similar to 8,000 near the Ca II triplet to measure stellar radial velocities, and two regions at R similar to 20,000 (one in each of the J- and H-bands), for precision measurements of chemical abundances.
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19. |
- Estrada, Karol, et al.
(author)
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Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture.
- 2012
-
In: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 44:5, s. 491-501
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Journal article (peer-reviewed)abstract
- Bone mineral density (BMD) is the most widely used predictor of fracture risk. We performed the largest meta-analysis to date on lumbar spine and femoral neck BMD, including 17 genome-wide association studies and 32,961 individuals of European and east Asian ancestry. We tested the top BMD-associated markers for replication in 50,933 independent subjects and for association with risk of low-trauma fracture in 31,016 individuals with a history of fracture (cases) and 102,444 controls. We identified 56 loci (32 new) associated with BMD at genome-wide significance (P < 5 × 10(-8)). Several of these factors cluster within the RANK-RANKL-OPG, mesenchymal stem cell differentiation, endochondral ossification and Wnt signaling pathways. However, we also discovered loci that were localized to genes not known to have a role in bone biology. Fourteen BMD-associated loci were also associated with fracture risk (P < 5 × 10(-4), Bonferroni corrected), of which six reached P < 5 × 10(-8), including at 18p11.21 (FAM210A), 7q21.3 (SLC25A13), 11q13.2 (LRP5), 4q22.1 (MEPE), 2p16.2 (SPTBN1) and 10q21.1 (DKK1). These findings shed light on the genetic architecture and pathophysiological mechanisms underlying BMD variation and fracture susceptibility.
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20. |
- Geach, J.E., et al.
(author)
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The SCUBA-2 Cosmology Legacy Survey: 850 μm maps, catalogues and number counts
- 2017
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In: Monthly Notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 465:2, s. 1789-1806
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Journal article (peer-reviewed)abstract
- We present a catalogue of similar to 3000 submillimetre sources detected (>= 3.5 sigma) at 850 mu m over similar to 5 deg(2) surveyed as part of the James Clerk Maxwell Telescope (JCMT) SCUBA-2 Cosmology Legacy Survey (S2CLS). This is the largest survey of its kind at 850 mu m, increasing the sample size of 850 mu m selected submillimetre galaxies by an order of magnitude. The wide 850 mu m survey component of S2CLS covers the extragalactic fields: UKIDSS-UDS, COSMOS, Akari-NEP, Extended Groth Strip, Lockman Hole North, SSA22 and GOODS-North. The average 1s depth of S2CLS is 1.2 mJy beam(-1), approaching the SCUBA-2 850 mu m confusion limit, which we determine to be sigma(c) approximate to 0.8 mJy beam(-1). We measure the 850 mu m number counts, reducing the Poisson errors on the differential counts to approximately 4 per cent at S-850 approximate to 3 mJy. With several independent fields, we investigate field-to-field variance, finding that the number counts on 0.5 degrees-1 degrees scales are generally within 50 per cent of the S2CLS mean for S-850 > 3 mJy, with scatter consistent with the Poisson and estimated cosmic variance uncertainties, although there is a marginal (2 sigma) density enhancement in GOODS-North. The observed counts are in reasonable agreement with recent phenomenological and semi-analytic models, although determining the shape of the faint-end slope (S-850 < 3 mJy) remains a key test. The large solid angle of S2CLS allows us to measure the bright-end counts: at S-850 > 10 mJy there are approximately 10 sources per square degree, and we detect the distinctive up-turn in the number counts indicative of the detection of local sources of 850 mu m emission
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21. |
- Hagiwara, K, et al.
(author)
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Review of particle physics
- 2002
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In: Physical Review D (Particles and Fields). - 0556-2821. ; 66:1
-
Research review (peer-reviewed)abstract
- This biennial Review summarizes much of Particle Physics Using data from previous editions, plus 2205 new measurements from 667 papers, we list, evaluate, and average measured properties of gauge bosons, leptons, quarks, mesons, and baryons We also summarize searches for hypothetical particles such as Higgs bosons, heavy neutrinos, and supersymmetric particles All the particle properties and search limits are listed in Summary Tables We also give numerous tables, figures, formulae, and reviews of topics such as the Standard Model, particle detectors, probability, and statistics This edition features expanded coverage of CP violation in B mesons and of neutrino oscillations For the first time we cover searches for evidence of extra dimensions (both in the particle listings and in a new review) Another new review is on Grand Unified Theories A booklet is available containing the Summary Tables and abbreviated versions of some of the other sections of this full Review All tables, listings, and reviews (and errata) are also available on the Particle Data Group website http //pdg 1b1 gov.
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23. |
- Geach, J.E., et al.
(author)
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The SCUBA-2 Cosmology Legacy Survey: blank-field number counts of 450-mu m-selected galaxies and their contribution to the cosmic infrared background
- 2013
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In: Monthly Notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 432:1, s. 53-61
-
Journal article (peer-reviewed)abstract
- The first deep blank-field 450 mu m map (1 sigma approximate to 1.3 mJy) from the Submillimetre Common-User Bolometer Array-2 SCUBA-2 Cosmology Legacy Survey (S2CLS), conducted with the James Clerk Maxwell Telescope (JCMT) is presented. Our map covers 140 arcmin(2) of the Cosmological Evolution Survey field, in the footprint of the Hubble Space Telescope (HST) Cosmic Assembly Near-Infrared Deep Extragalactic Legacy Survey. Using 60 submillimetre galaxies detected at >= 3.75s, we evaluate the number counts of 450-mu m-selected galaxies with flux densities S-450 > 5 mJy. The 8 arcsec JCMT beam and high sensitivity of SCUBA-2 now make it possible to directly resolve a larger fraction of the cosmic infrared background (CIB, peaking at. similar to 200 mu m) into the individual galaxies responsible for its emission than has previously been possible at this wavelength. At S450 > 5 mJy, we resolve (7.4 +/- 0.7) x 10(-2) MJy sr(-1) of the CIB at 450 mu m (equivalent to 16 +/- 7 per cent of the absolute brightness measured by the Cosmic Background Explorer at this wavelength) into point sources. A further similar to 40 per cent of the CIB can be recovered through a statistical stack of 24 mu m emitters in this field, indicating that the majority (approximate to 60 per cent) of the CIB at 450 mu m is emitted by galaxies with S450 > 2 mJy. The average redshift of 450 mu m emitters identified with an optical/near-infrared counterpart is estimated to be = 1.3, implying that the galaxies in the sample are in the ultraluminous class (LIR approximate to 1.1 x 1012 L approximate to). If the galaxies contributing to the statistical stack lie at similar redshifts, then the majority of the CIB at 450 mu m is emitted by galaxies in the luminous infrared galaxy (LIRG) class with LIR > 3.6 x 1011 L-circle dot.
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24. |
- Elks, Cathy E, et al.
(author)
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Thirty new loci for age at menarche identified by a meta-analysis of genome-wide association studies
- 2010
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:12, s. 1077-85
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Journal article (peer-reviewed)abstract
- To identify loci for age at menarche, we performed a meta-analysis of 32 genome-wide association studies in 87,802 women of European descent, with replication in up to 14,731 women. In addition to the known loci at LIN28B (P = 5.4 × 10⁻⁶⁰) and 9q31.2 (P = 2.2 × 10⁻³³), we identified 30 new menarche loci (all P < 5 × 10⁻⁸) and found suggestive evidence for a further 10 loci (P < 1.9 × 10⁻⁶). The new loci included four previously associated with body mass index (in or near FTO, SEC16B, TRA2B and TMEM18), three in or near other genes implicated in energy homeostasis (BSX, CRTC1 and MCHR2) and three in or near genes implicated in hormonal regulation (INHBA, PCSK2 and RXRG). Ingenuity and gene-set enrichment pathway analyses identified coenzyme A and fatty acid biosynthesis as biological processes related to menarche timing.
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25. |
- Robinson-Cohen, C., et al.
(author)
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Genetic Variants Associated with Circulating Fibroblast Growth Factor 23
- 2018
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In: Journal of the American Society of Nephrology. - : Ovid Technologies (Wolters Kluwer Health). - 1046-6673 .- 1533-3450. ; 29:10, s. 2583-2592
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Journal article (peer-reviewed)abstract
- Background Fibroblast growth factor 23 (FGF23), a bone-derived hormone that regulates phosphorus and vitamin D metabolism, contributes to the pathogenesis of mineral and bone disorders in CKD and is an emerging cardiovascular risk factor. Central elements of FGF23 regulation remain incompletely understood; genetic variation may help explain interindividual differences. Methods We performed a meta-analysis of genome-wide association studies of circulating FGF23 concentrations among 16,624 participants of European ancestry from seven cohort studies, excluding participants with eGFR<30 ml/min per 1.73 m(2) to focus on FGF23 under normal conditions. We evaluated the association of single-nucleotide polymorphisms (SNPs) with natural log-transformed FGF23 concentration, adjusted for age, sex, study site, and principal components of ancestry. A second model additionally adjusted for BMI and eGFR. Results We discovered 154 SNPs from five independent regions associated with FGF23 concentration. The SNP with the strongest association, rs17216707 (P=3.0x10(-24)), lies upstream of CYP24A1, which encodes the primary catabolic enzyme for 1,25-dihydroxyvitamin D and 25-hydroxyvitamin D. Each additional copy of the T allele at this locus is associated with 5% higher FGF23 concentration. Another locus strongly associated with variations in FGF23 concentration is rs11741640, within RGS14 and upstream of SLC34A1 (a gene involved in renal phosphate transport). Additional adjustment for BMI and eGFR did not materially alter the magnitude of these associations. Another top locus (within ABO, the ABO blood group transferase gene) was no longer statistically significant at the genome-wide level. Conclusions Common genetic variants located near genes involved in vitamin D metabolism and renal phosphate transport are associated with differences in circulating FGF23 concentrations.
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28. |
- Coppin, K. E. K., et al.
(author)
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The SCUBA-2 Cosmology Legacy Survey: the submillimetre properties of Lyman-break galaxies at z=3-5
- 2015
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In: Monthly Notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 446:2, s. 1293-1304
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Journal article (peer-reviewed)abstract
- We present detections at 850 mu m of the Lyman-break galaxy (LBG) population at z approximate to 3, 4, and 5 using data from the Submillimetre Common User Bolometer Array 2 Cosmology Legacy Survey in the United Kingdom Infrared Deep Sky Survey 'Ultra Deep Survey' field. We employ stacking to probe beneath the survey limit, measuring the average 850 mu m flux density of LBGs at z approximate to 3, 4, and 5 with typical ultraviolet luminosities of L-1700 approximate to 10(29) erg s(-1) Hz(-1). We measure 850 mu m flux densities of (0.25 +/- 0.03), (0.41 +/- 0.06), and (0.88 +/- 0.23) mJy, respectively, finding that they contribute at most 20 per cent to the cosmic far-infrared (IR) background at 850 mu m. Fitting an appropriate range of spectral energy distributions to the z similar to 3, 4, and 5 LBG stacked 24-850 mu m fluxes, we derive IR luminosities of L8-1000 (mu m) approximate to 3.2, 5.5, and 11.0 x 10(11) L-circle dot [and star formation rates (SFRs) of approximate to 50-200M(circle dot) yr(-1)], respectively. We find that the evolution in the IR luminosity density of LBGs is broadly consistent with model predictions for the expected contribution of luminous-to-ultraluminous IR galaxies at these epochs. We observe a positive correlation between stellar mass and IR luminosity and confirm that, for a fixed mass, the reddest LBGs (UV slope beta -> 0) are redder due to dust extinction, with SFR (IR)/SFR (UV) increasing by about an order of magnitude over -2
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29. |
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30. |
- Hart, R. G., et al.
(author)
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Rivaroxaban for Stroke Prevention after Embolic Stroke of Undetermined Source
- 2018
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In: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 378:23, s. 2191-2201
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Journal article (peer-reviewed)abstract
- BACKGROUND Embolic strokes of undetermined source represent 20% of ischemic strokes and are associated with a high rate of recurrence. Anticoagulant treatment with rivaroxaban, an oral factor Xa inhibitor, may result in a lower risk of recurrent stroke than aspirin. We compared the efficacy and safety of rivaroxaban (at a daily dose of 15 mg) with aspirin (at a daily dose of 100 mg) for the prevention of recurrent stroke in patients with recent ischemic stroke that was presumed to be from cerebral embolism but without arterial stenosis, lacune, or an identified cardioembolic source. The primary efficacy outcome was the first recurrence of ischemic or hemorrhagic stroke or systemic embolism in a time-to-event analysis; the primary safety outcome was the rate of major bleeding. A total of 7213 participants were enrolled at 459 sites; 3609 patients were randomly assigned to receive rivaroxaban and 3604 to receive aspirin. Patients had been followed for a median of 11 months when the trial was terminated early because of a lack of benefit with regard to stroke risk and because of bleeding associated with rivaroxaban. The primary efficacy outcome occurred in 172 patients in the rivaroxaban group (annualized rate, 5.1%) and in 160 in the aspirin group (annualized rate, 4.8%) (hazard ratio, 1.07; 95% confidence interval [CI], 0.87 to 1.33; P=0.52). Recurrent ischemic stroke occurred in 158 patients in the rivaroxaban group (annualized rate, 4.7%) and in 156 in the aspirin group (annualized rate, 4.7%). Major bleeding occurred in 62 patients in the rivaroxaban group (annualized rate, 1.8%) and in 23 in the aspirin group (annualized rate, 0.7%) (hazard ratio, 2.72; 95% CI, 1.68 to 4.39; P<0.001). Rivaroxaban was not superior to aspirin with regard to the prevention of recurrent stroke after an initial embolic stroke of undetermined source and was associated with a higher risk of bleeding.
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31. |
- Hsu, Y. H., et al.
(author)
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Meta-Analysis of Genomewide Association Studies Reveals Genetic Variants for Hip Bone Geometry
- 2019
-
In: Journal of Bone and Mineral Research. - : Wiley. - 0884-0431 .- 1523-4681. ; 34:7, s. 1284-1296
-
Journal article (peer-reviewed)abstract
- Hip geometry is an important predictor of fracture. We performed a meta-analysis of GWAS studies in adults to identify genetic variants that are associated with proximal femur geometry phenotypes. We analyzed four phenotypes: (i) femoral neck length; (ii) neck-shaft angle; (iii) femoral neck width, and (iv) femoral neck section modulus, estimated from DXA scans using algorithms of hip structure analysis. In the Discovery stage, 10 cohort studies were included in the fixed-effect meta-analysis, with up to 18,719 men and women ages 16 to 93 years. Association analyses were performed with similar to 2.5 million polymorphisms under an additive model adjusted for age, body mass index, and height. Replication analyses of meta-GWAS significant loci (at adjusted genomewide significance [GWS], threshold p <= 2.6 x 10(-8)) were performed in seven additional cohorts in silico. We looked up SNPs associated in our analysis, for association with height, bone mineral density (BMD), and fracture. In meta-analysis (combined Discovery and Replication stages), GWS associations were found at 5p15 (IRX1 and ADAMTS16); 5q35 near FGFR4; at 12p11 (in CCDC91); 11q13 (near LRP5 and PPP6R3 (rs7102273)). Several hip geometry signals overlapped with BMD, including LRP5 (chr. 11). Chr. 11 SNP rs7102273 was associated with any-type fracture (p = 7.5 x 10(-5)). We used bone transcriptome data and discovered several significant eQTLs, including rs7102273 and PPP6R3 expression (p = 0.0007), and rs6556301 (intergenic, chr.5 near FGFR4) and PDLIM7 expression (p = 0.005). In conclusion, we found associations between several genes and hip geometry measures that explained 12% to 22% of heritability at different sites. The results provide a defined set of genes related to biological pathways relevant to BMD and etiology of bone fragility. (c) 2019 American Society for Bone and Mineral Research.
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32. |
- Laabei, M., et al.
(author)
-
Predicting the virulence of MRSA from its genome sequence
- 2014
-
In: Genome Research. - : Cold Spring Harbor Laboratory. - 1088-9051. ; 24:5, s. 839-849
-
Journal article (peer-reviewed)abstract
- Microbial virulence is a complex and often multifactorial phenotype, intricately linked to a pathogen's evolutionary trajectory. Toxicity, the ability to destroy host cell membranes, and adhesion, the ability to adhere to human tissues, are the major virulence factors of many bacterial pathogens, including Staphylococcus aureus. Here, we assayed the toxicity and adhesiveness of 90 MRSA (methicillin resistant S. aureus) isolates and found that while there was remarkably little variation in adhesion, toxicity varied by over an order of magnitude between isolates, suggesting different evolutionary selection pressures acting on these two traits. We performed a genome-wide association study (GWAS) and identified a large number of loci, as well as a putative network of epistatically interacting loci, that significantly associated with toxicity. Despite this apparent complexity in toxicity regulation, a predictive model based on a set of significant single nucleotide polymorphisms (SNPs) and insertion and deletions events (indels) showed a high degree of accuracy in predicting an isolate's toxicity solely from the genetic signature at these sites. Our results thus highlight the potential of using sequence data to determine clinically relevant parameters and have further implications for understanding the microbial virulence of this opportunistic pathogen.
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33. |
- Robinson-Cohen, Cassianne, et al.
(author)
-
Genetic Variants Associated with Circulating Parathyroid Hormone.
- 2017
-
In: Journal of the American Society of Nephrology : JASN. - 1533-3450. ; 28:5, s. 1553-1565
-
Journal article (peer-reviewed)abstract
- Parathyroid hormone (PTH) is a primary calcium regulatory hormone. Elevated serum PTH concentrations in primary and secondary hyperparathyroidism have been associated with bone disease, hypertension, and in some studies, cardiovascular mortality. Genetic causes of variation in circulating PTH concentrations are incompletely understood. We performed a genome-wide association study of serum PTH concentrations among 29,155 participants of European ancestry from 13 cohort studies (n=22,653 and n=6502 in discovery and replication analyses, respectively). We evaluated the association of single nucleotide polymorphisms (SNPs) with natural log-transformed PTH concentration adjusted for age, sex, season, study site, and principal components of ancestry. We discovered associations of SNPs from five independent regions with serum PTH concentration, including the strongest association with rs6127099 upstream of CYP24A1 (P=4.2 × 10(-53)), a gene that encodes the primary catabolic enzyme for 1,25-dihydroxyvitamin D and 25-dihydroxyvitamin D. Each additional copy of the minor allele at this SNP associated with 7% higher serum PTH concentration. The other SNPs associated with serum PTH concentration included rs4074995 within RGS14 (P=6.6 × 10(-17)), rs219779 adjacent to CLDN14 (P=3.5 × 10(-16)), rs4443100 near RTDR1 (P=8.7 × 10(-9)), and rs73186030 near CASR (P=4.8 × 10(-8)). Of these five SNPs, rs6127099, rs4074995, and rs219779 replicated. Thus, common genetic variants located near genes involved in vitamin D metabolism and calcium and renal phosphate transport associated with differences in circulating PTH concentrations. Future studies could identify the causal variants at these loci, and the clinical and functional relevance of these variants should be pursued.
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34. |
- Tubaro, M., et al.
(author)
-
Pre-hospital treatment of STEMI patients. A scientific statement of the working group acute cardiac care of the European society of cardiology
- 2011
-
In: Acute Cardiac Care. - : Informa Healthcare. - 1748-2941 .- 1748-295X. ; 13:2, s. 56-67
-
Journal article (peer-reviewed)abstract
- In ST-elevation myocardial infarction (STEMI) the pre-hospital phase is the most critical, as the administration of the most appropriate treatment in a timely manner is instrumental for mortality reduction. STEMI systems of care based on networks of medical institutions connected by an efficient emergency medical service are pivotal. The first steps are devoted to minimize the patients delay in seeking care, rapidly dispatch a properly staffed and equipped ambulance to make the diagnosis on scene, deliver initial drug therapy and transport the patient to the most appropriate (not necessarily the closest) cardiac facility. Primary PCI is the treatment of choice, but thrombolysis followed by coronary angiography and possibly PCI is a valid alternative, according to patients baseline risk, time from symptoms onset and primary PCI-related delay. Paramedics and nurses have an important role in pre-hospital STEMI care and their empowerment is essential to increase the eff ectiveness of the system. Strong cooperation between cardiologists and emergency medicine doctors is mandatory for optimal pre-hospital STEMI care. Scientific societies have an important role in guideline implementation as well as in developing quality indicators and performance measures; health care professionals must overcome existing barriers to optimal care together with political and administrative decision makers.
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35. |
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36. |
- Audet, J., et al.
(author)
-
Forest streams are important sources for nitrous oxide emissions
- 2020
-
In: Global Change Biology. - : Wiley. - 1354-1013 .- 1365-2486. ; 26:2, s. 629-641
-
Journal article (peer-reviewed)abstract
- Streams and river networks are increasingly recognized as significant sources for the greenhouse gas nitrous oxide (N2O). N2O is a transformation product of nitrogenous compounds in soil, sediment and water. Agricultural areas are considered a particular hotspot for emissions because of the large input of nitrogen (N) fertilizers applied on arable land. However, there is little information on N2O emissions from forest streams although they constitute a major part of the total stream network globally. Here, we compiled N2O concentration data from low-order streams (~1,000 observations from 172 stream sites) covering a large geographical gradient in Sweden from the temperate to the boreal zone and representing catchments with various degrees of agriculture and forest coverage. Our results showed that agricultural and forest streams had comparable N2O concentrations of 1.6±2.1 and 1.3±1.8µgN/L, respectively (mean±SD) despite higher total N (TN) concentrations in agricultural streams (1,520±1,640 vs. 780±600µgN/L). Although clear patterns linking N2O concentrations and environmental variables were difficult to discern, the percent saturation of N2O in the streams was positively correlated with stream concentration of TN and negatively correlated with pH. We speculate that the apparent contradiction between lower TN concentration but similar N2O concentrations in forest streams than in agricultural streams is due to the low pH (<6) in forest soils and streams which affects denitrification and yields higher N2O emissions. An estimate of the N2O emission from low-order streams at the national scale revealed that ~1.8×109g N2O-N are emitted annually in Sweden, with forest streams contributing about 80% of the total stream emission. Hence, our results provide evidence that forest streams can act as substantial N2O sources in the landscape with 800×109gCO2-eq emitted annually in Sweden, equivalent to 25% of the total N2O emissions from the Swedish agricultural sector. © 2019 The Authors. Global Change Biology published by John Wiley & Sons Ltd
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37. |
- Robinson-Cohen, Cassianne, et al.
(author)
-
Genetic Variants Associated with Circulating Fibroblast Growth Factor 23
- 2018
-
In: Journal of the American Society of Nephrology. - : AMER SOC NEPHROLOGY. - 1046-6673 .- 1533-3450. ; 29:10, s. 2583-2592
-
Journal article (peer-reviewed)abstract
- Background: Fibroblast growth factor 23 (FGF23), a bone-derived hormone that regulates phosphorus and vitamin D metabolism, contributes to the pathogenesis of mineral and bone disorders in CKD and is an emerging cardiovascular risk factor. Central elements of FGF23 regulation remain incompletely understood; genetic variation may help explain interindividual differences.Methods: We performed a meta-analysis of genome-wide association studies of circulating FGF23 concentrations among 16,624 participants of European ancestry from seven cohort studies, excluding participants with eGFR<30 ml/min per 1.73 m(2) to focus on FGF23 under normal conditions. We evaluated the association of single-nucleotide polymorphisms (SNPs) with natural log-transformed FGF23 concentration, adjusted for age, sex, study site, and principal components of ancestry. A second model additionally adjusted for BMI and eGFR.Results: We discovered 154 SNPs from five independent regions associated with FGF23 concentration. The SNP with the strongest association, rs17216707 (P=3.0x10(-24)), lies upstream of CYP24A1, which encodes the primary catabolic enzyme for 1,25-dihydroxyvitamin D and 25-hydroxyvitamin D. Each additional copy of the T allele at this locus is associated with 5% higher FGF23 concentration. Another locus strongly associated with variations in FGF23 concentration is rs11741640, within RGS14 and upstream of SLC34A1 (a gene involved in renal phosphate transport). Additional adjustment for BMI and eGFR did not materially alter the magnitude of these associations. Another top locus (within ABO, the ABO blood group transferase gene) was no longer statistically significant at the genome-wide level.Conclusions: Common genetic variants located near genes involved in vitamin D metabolism and renal phosphate transport are associated with differences in circulating FGF23 concentrations.
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38. |
- Wang, Thomas J, et al.
(author)
-
Common genetic determinants of vitamin D insufficiency: a genome-wide association study.
- 2010
-
In: Lancet. - 1474-547X. ; 376:9736, s. 180-8
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Vitamin D is crucial for maintenance of musculoskeletal health, and might also have a role in extraskeletal tissues. Determinants of circulating 25-hydroxyvitamin D concentrations include sun exposure and diet, but high heritability suggests that genetic factors could also play a part. We aimed to identify common genetic variants affecting vitamin D concentrations and risk of insufficiency. METHODS: We undertook a genome-wide association study of 25-hydroxyvitamin D concentrations in 33 996 individuals of European descent from 15 cohorts. Five epidemiological cohorts were designated as discovery cohorts (n=16 125), five as in-silico replication cohorts (n=9367), and five as de-novo replication cohorts (n=8504). 25-hydroxyvitamin D concentrations were measured by radioimmunoassay, chemiluminescent assay, ELISA, or mass spectrometry. Vitamin D insufficiency was defined as concentrations lower than 75 nmol/L or 50 nmol/L. We combined results of genome-wide analyses across cohorts using Z-score-weighted meta-analysis. Genotype scores were constructed for confirmed variants. FINDINGS: Variants at three loci reached genome-wide significance in discovery cohorts for association with 25-hydroxyvitamin D concentrations, and were confirmed in replication cohorts: 4p12 (overall p=1.9x10(-109) for rs2282679, in GC); 11q12 (p=2.1x10(-27) for rs12785878, near DHCR7); and 11p15 (p=3.3x10(-20) for rs10741657, near CYP2R1). Variants at an additional locus (20q13, CYP24A1) were genome-wide significant in the pooled sample (p=6.0x10(-10) for rs6013897). Participants with a genotype score (combining the three confirmed variants) in the highest quartile were at increased risk of having 25-hydroxyvitamin D concentrations lower than 75 nmol/L (OR 2.47, 95% CI 2.20-2.78, p=2.3x10(-48)) or lower than 50 nmol/L (1.92, 1.70-2.16, p=1.0x10(-26)) compared with those in the lowest quartile. INTERPRETATION: Variants near genes involved in cholesterol synthesis, hydroxylation, and vitamin D transport affect vitamin D status. Genetic variation at these loci identifies individuals who have substantially raised risk of vitamin D insufficiency. FUNDING: Full funding sources listed at end of paper (see Acknowledgments).
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39. |
- Cespedes, PF, et al.
(author)
-
T-cell trans-synaptic vesicles are distinct and carry greater effector content than constitutive extracellular vesicles
- 2022
-
In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1, s. 3460-
-
Journal article (peer-reviewed)abstract
- The immunological synapse is a molecular hub that facilitates the delivery of three activation signals, namely antigen, costimulation/corepression and cytokines, from antigen-presenting cells (APC) to T cells. T cells release a fourth class of signaling entities, trans-synaptic vesicles (tSV), to mediate bidirectional communication. Here we present bead-supported lipid bilayers (BSLB) as versatile synthetic APCs to capture, characterize and advance the understanding of tSV biogenesis. Specifically, the integration of juxtacrine signals, such as CD40 and antigen, results in the adaptive tailoring and release of tSV, which differ in size, yields and immune receptor cargo compared with steadily released extracellular vesicles (EVs). Focusing on CD40L+tSV as model effectors, we show that PD-L1 trans-presentation together with TSG101, ADAM10 and CD81 are key in determining CD40L vesicular release. Lastly, we find greater RNA-binding protein and microRNA content in tSV compared with EVs, supporting the specialized role of tSV as intercellular messengers.
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40. |
- Chiang, Cho-Han, et al.
(author)
-
Performance of the European Society of Cardiology 0/1-Hour, 0/2-Hour, and 0/3-Hour Algorithms for Rapid Triage of Acute Myocardial Infarction : An International Collaborative Meta-analysis
- 2022
-
In: Annals of Internal Medicine. - 0003-4819. ; 175:1, s. 101-113
-
Research review (peer-reviewed)abstract
- BACKGROUND: The 2020 European Society of Cardiology (ESC) guidelines recommend using the 0/1-hour and 0/2-hour algorithms over the 0/3-hour algorithm as the first and second choices of high-sensitivity cardiac troponin (hs-cTn)-based strategies for triage of patients with suspected acute myocardial infarction (AMI).PURPOSE: To evaluate the diagnostic accuracies of the ESC 0/1-hour, 0/2-hour, and 0/3-hour algorithms.DATA SOURCES: PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, and Scopus from 1 January 2011 to 31 December 2020. (PROSPERO: CRD42020216479).STUDY SELECTION: Prospective studies that evaluated the ESC 0/1-hour, 0/2-hour, or 0/3-hour algorithms in adult patients presenting with suspected AMI.DATA EXTRACTION: The primary outcome was index AMI. Twenty unique cohorts were identified. Primary data were obtained from investigators of 16 cohorts and aggregate data were extracted from 4 cohorts. Two independent authors assessed each study for methodological quality.DATA SYNTHESIS: A total of 32 studies (20 cohorts) with 30 066 patients were analyzed. The 0/1-hour algorithm had a pooled sensitivity of 99.1% (95% CI, 98.5% to 99.5%) and negative predictive value (NPV) of 99.8% (CI, 99.6% to 99.9%) for ruling out AMI. The 0/2-hour algorithm had a pooled sensitivity of 98.6% (CI, 97.2% to 99.3%) and NPV of 99.6% (CI, 99.4% to 99.8%). The 0/3-hour algorithm had a pooled sensitivity of 93.7% (CI, 87.4% to 97.0%) and NPV of 98.7% (CI, 97.7% to 99.3%). Sensitivity of the 0/3-hour algorithm was attenuated in studies that did not use clinical criteria (GRACE score <140 and pain-free) compared with studies that used clinical criteria (90.2% [CI, 82.9 to 94.6] vs. 98.4% [CI, 88.6 to 99.8]). All 3 algorithms had similar specificities and positive predictive values for ruling in AMI, but heterogeneity across studies was substantial. Diagnostic performance was similar across the hs-cTnT (Elecsys; Roche), hs-cTnI (Architect; Abbott), and hs-cTnI (Centaur/Atellica; Siemens) assays.LIMITATION: Diagnostic accuracy, inclusion and exclusion criteria, and cardiac troponin sampling time varied among studies.CONCLUSION: The ESC 0/1-hour and 0/2-hour algorithms have higher sensitivities and NPVs than the 0/3-hour algorithm for index AMI.PRIMARY FUNDING SOURCE: National Taiwan University Hospital.
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41. |
- Hambäck, P.A., et al.
(author)
-
Trade-offs and synergies in the design of multifunctional wetlands : A scaling issue
- 2023
-
In: Science of the Total Environment. - : Elsevier. - 0048-9697 .- 1879-1026. ; 862
-
Journal article (peer-reviewed)abstract
- Wetland area in agricultural landscapes has been heavily reduced to gain land for crop production, but in recent years there is increased societal recognition of the negative consequences from wetland loss on nutrient retention, biodiversity and a range of other benefits to humans. The current trend is therefore to re-establish wetlands, often with an aim to achieve the simultaneous delivery of multiple ecosystem services, i.e., multifunctionality. Here we review the literature on key objectives used to motivate wetland re-establishment in temperate agricultural landscapes (provision of flow regulation, nutrient retention, climate mitigation, biodiversity conservation and cultural ecosystem services), and their relationships to environmental properties, in order to identify potential for tradeoffs and synergies concerning the development of multifunctional wetlands. Through this process, we find that there is a need for a change in scale from a focus on single wetlands to wetlandscapes (multiple neighboring wetlands including their catchments and surrounding landscape features) if multiple societal and environmental goals are to be achieved. Finally, we discuss the key factors to be considered when planning for re-establishment of wetlands that can support achievement of a wide range of objectives at the landscape scale.
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42. |
- Hambäck, Peter A., et al.
(author)
-
Tradeoffs and synergies in wetland multifunctionality : A scaling issue
- 2023
-
In: Science of the Total Environment. - Amsterdam : Elsevier BV. - 0048-9697 .- 1879-1026. ; 862
-
Research review (peer-reviewed)abstract
- Wetland area in agricultural landscapes has been heavily reduced to gain land for crop production, but in recent years there is increased societal recognition of the negative consequences from wetland loss on nutrient retention, biodiversity and a range of other benefits to humans. The current trend is therefore to re-establish wetlands, often with an aim to achieve the simultaneous delivery of multiple ecosystem services, i.e., multifunctionality. Here we review the literature on key objectives used to motivate wetland re-establishment in temperate agricultural landscapes (provision of flow regulation, nutrient retention, climate mitigation, biodiversity conservation and cultural ecosystem services), and their relationships to environmental properties, in order to identify potential for tradeoffs and synergies concerning the development of multifunctional wetlands. Through this process, we find that there is a need for a change in scale from a focus on single wetlands to wetlandscapes (multiple neighboring wetlands including their catchments and surrounding landscape features) if multiple societal and environmental goals are to be achieved. Finally, we discuss the key factors to be considered when planning for re-establishment of wetlands that can support achievement of a wide range of objectives at the landscape scale.
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43. |
- Hepburn, Lucy, et al.
(author)
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A Spaetzle-like role for nerve growth factor beta in vertebrate immunity to Staphylococcus aureus
- 2014
-
In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 346:6209, s. 641-646
-
Journal article (peer-reviewed)abstract
- Many key components of innate immunity to infection are shared between Drosophila and humans. However, the fly Toll ligand Spaetzle is not thought to have a vertebrate equivalent. We have found that the structurally related cystine-knot protein, nerve growth factor β (NGFβ), plays an unexpected Spaetzle-like role in immunity to Staphylococcus aureus infection in chordates. Deleterious mutations of either human NGFβ or its high-affinity receptor tropomyosin-related kinase receptor A (TRKA) were associated with severe S. aureus infections. NGFβ was released by macrophages in response to S. aureus exoproteins through activation of the NOD-like receptors NLRP3 and NLRP4 and enhanced phagocytosis and superoxide-dependent killing, stimulated proinflammatory cytokine production, and promoted calcium-dependent neutrophil recruitment. TrkA knockdown in zebrafish increased susceptibility to S. aureus infection, confirming an evolutionarily conserved role for NGFβ-TRKA signaling in pathogen-specific host immunity.
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44. |
- Kasner, Scott E., et al.
(author)
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Characterization of Patients with Embolic Strokes of Undetermined Source in the NAVIGATE ESUS Randomized Trial
- 2018
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In: Journal of Stroke and Cerebrovascular Diseases. - : Elsevier BV. - 1052-3057. ; 27:6, s. 1673-1682
-
Journal article (peer-reviewed)abstract
- Background: The New Approach Rivaroxaban Inhibition of Factor Xa in a Global Trial vs. ASA to Prevent Embolism in Embolic Stroke of Undetermined Source (NAVIGATE-ESUS) trial is a randomized phase-III trial comparing rivaroxaban versus aspirin in patients with recent ESUS. Aims: We aimed to describe the baseline characteristics of this large ESUS cohort to explore relationships among key subgroups. Methods: We enrolled 7213 patients at 459 sites in 31 countries. Prespecified subgroups for primary safety and efficacy analyses included age, sex, race, global region, stroke or transient ischemic attack prior to qualifying event, time to randomization, hypertension, and diabetes mellitus. Results: Mean age was 66.9 ± 9.8 years; 24% were under 60 years. Older patients had more hypertension, coronary disease, and cancer. Strokes in older subjects were more frequently cortical and accompanied by radiographic evidence of prior infarction. Women comprised 38% of participants and were older than men. Patients from East Asia were oldest whereas those from Latin America were youngest. Patients in the Americas more frequently were on aspirin prior to the qualifying stroke. Acute cortical infarction was more common in the United States, Canada, and Western Europe, whereas prior radiographic infarctions were most common in East Asia. Approximately forty-five percent of subjects were enrolled within 30 days of the qualifying stroke, with earliest enrollments in Asia and Eastern Europe. Conclusions: NAVIGATE-ESUS is the largest randomized trial comparing antithrombotic strategies for secondary stroke prevention in patients with ESUS. The study population encompasses a broad array of patients across multiple continents and these subgroups provide ample opportunities for future research.
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45. |
- Lippman, Sheri A., et al.
(author)
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Village community mobilization is associated with reduced HIV incidence in young South African women participating in the HPTN 068 study cohort
- 2018
-
In: Journal of the International AIDS Society. - : John Wiley & Sons. - 1758-2652. ; 21:S7
-
Journal article (peer-reviewed)abstract
- Introduction: Adolescent girls and young women (AGYW) in South Africa bear a disproportionate burden of HIV. Community mobilization (CM), defined as community members taking collective action to achieve a common goal related to health, equity and rights, has been associated with increased HIV testing and condom use and has been called a ‘critical enabler’ for addressing the HIV epidemic. However, limited research has examined whether CM is associated with HIV incidence among AGYW.Methods: We examine the association of CM with incident HIV among AGYW (ages 13 to 21) enrolled in the HPTN 068 cohort in the Agincourt Health and socio‐Demographic Surveillance System, South Africa. This analysis includes 2292 participants residing in 26 villages where cross‐sectional, population‐based surveys were conducted to measure CM among 18‐ to 35‐year‐old residents in 2012 and 2014. HPTN 068 participants completed up to five annual visits that included an HIV test (2011 to 2016). Household‐level data were collected from AGYW parents/guardians and census data is updated annually. Mean village‐level CM scores were created using a validated community mobilization measure with seven components (social cohesion, social control, critical consciousness, shared concerns, organizations and networks, leadership and collective action). We used pooled generalized estimating equation regression with a Poisson distribution to estimate risk ratios (RR) for the association of village‐level CM score and CM components with incident HIV infection, accounting for village‐level clustering and adjusting for key covariates.Results: There were 194 incident infections over the follow‐up period. For every additional standard deviation of village‐level CM there was 12% lower HIV incidence (RR: 0.88, 95% CI: 0.79, 0.98) after adjusting for individual, household and community characteristics. CM components associated with lower HIV incidence included critical consciousness (RR: 0.88; CI: 0.79, 0.97) and leadership (RR: 0.87; CI: 0.79, 0.95); while not statistically significant, social cohesion (RR: 0.91; CI: 0.81, 1.01), shared concerns (RR: 0.90; CI: 0.81, 1.00), and organizations and networks (RR: 0.91; CI: 0.79, 1.03) may also play a protective role.Conclusions: These results suggest that having strong community social resources will reduce AGYW's risk of HIV acquisition. Work to mobilize communities, focusing on building social cohesion, shared concerns, critical consciousness, and effective and accountable leadership, can fortify prevention programming for AGYW.
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46. |
- MacPhail, Catherine, et al.
(author)
-
Process elements contributing to community mobilization for HIV risk reduction and gender equality in rural South Africa
- 2019
-
In: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 14:12
-
Journal article (peer-reviewed)abstract
- Community mobilization has been recognized as a critical enabler for HIV prevention and is employed for challenging gender inequalities. We worked together with community partners to implement the 'One Man Can' intervention in rural Mpumalanga, South Africa to promote gender equality and HIV risk reduction. During the intervention, we conducted longitudinal qualitative interviews and focus group discussions with community mobilizers (n = 26), volunteer community action team members (n = 22) and community members (n = 52) to explore their experience of being part of the intervention and their experiences of change associated with the intervention. The objective of the study was to examine processes of change in community mobilization for gender equity and HIV prevention. Our analysis showed that over time, participants referred to three key elements of their engagement with the intervention: developing respect for others; inter-personal communication; and empathy. These elements were viewed as assisting them in adopting a 'better life' and associated with behaviour change in the intervention's main focus areas of promoting gender equality and HIV risk reduction behaviours. We discuss how these concepts relate to the essential domains contained within our theoretical framework of community mobilization-specifically critical consciousness, shared concerns and social cohesion -, as demonstrated in this community. We interpret the focus on these key elements as significant indicators of communities engaging with the community mobilization process and initiating movement towards structural changes for HIV prevention.
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47. |
- Martinez, Arturo O., et al.
(author)
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Stellar and Planetary Parameters for K2's Late-type Dwarf Systems from C1 to C5
- 2017
-
In: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 837:1
-
Journal article (peer-reviewed)abstract
- The NASA K2 mission uses photometry to find planets transiting stars of various types. M dwarfs are of high interest since they host more short-period planets than any other type of main-sequence star and transiting planets around M dwarfs have deeper transits compared to other main-sequence stars. In this paper, we present stellar parameters from K and M dwarfs hosting transiting planet candidates discovered by our team. Using the SOFI spectrograph on the European Southern Observatory's New Technology Telescope, we obtained R approximate to 1000 J-, H-, and K-band (0.95-2.52 mu m) spectra of 34 late-type K2 planet and candidate planet host systems and 12 bright K4-M5 dwarfs with interferometrically measured radii and effective temperatures. Out of our 34 late-type K2 targets, we identify 27 of these stars as M dwarfs. We measure equivalent widths of spectral features, derive calibration relations using stars with interferometric measurements, and estimate stellar radii, effective temperatures, masses, and luminosities for the K2 planet hosts. Our calibrations provide radii and temperatures with median uncertainties of 0.059 R-circle dot (16.09%) and 160 K (4.33%), respectively. We then reassess the radii and equilibrium temperatures of known and candidate planets based on our spectroscopically derived stellar parameters. Since a planet's radius and equilibrium temperature depend on the parameters of its host star, our study provides more precise planetary parameters for planets and candidates orbiting late-type stars observed with K2. We find a median planet radius and an equilibrium temperature of approximately 3 R-circle plus and 500 K, respectively, with several systems (K2-18b and K2-72e) receiving near-Earth-like levels of incident irradiation.
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48. |
- Peacock, M., et al.
(author)
-
Global importance of methane emissions from drainage ditches and canals
- 2021
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In: Environmental Research Letters. - : IOP Publishing Ltd. - 1748-9326. ; 16:4
-
Journal article (peer-reviewed)abstract
- Globally, there are millions of kilometres of drainage ditches which have the potential to emit the powerful greenhouse gas methane (CH4), but these emissions are not reported in budgets of inland waters or drained lands. Here, we synthesise data to show that ditches spanning a global latitudinal gradient and across different land uses emit large quantities of CH4 to the atmosphere. Area-specific emissions are comparable to those from lakes, streams, reservoirs, and wetlands. While it is generally assumed that drainage negates terrestrial CH4 emissions, we find that CH4 emissions from ditches can, on average, offset similar to 10% of this reduction. Using global areas of drained land we show that ditches contribute 3.5 Tg CH4 yr(-1) (0.6-10.5 Tg CH4 yr(-1)); equivalent to 0.2%-3% of global anthropogenic CH4 emissions. A positive relationship between CH4 emissions and temperature was found, and emissions were highest from eutrophic ditches. We advocate the inclusion of ditch emissions in national GHG inventories, as neglecting them can lead to incorrect conclusions concerning the impact of drainage-based land management on CH4 budgets.
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49. |
- Peacock, M., et al.
(author)
-
Small artificial waterbodies are widespread and persistent emitters of methane and carbon dioxide
- 2021
-
In: Global Change Biology. - : Wiley. - 1354-1013 .- 1365-2486. ; 27:20, s. 5109-5123
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Journal article (peer-reviewed)abstract
- Inland waters play an active role in the global carbon cycle and emit large volumes of the greenhouse gases (GHGs), methane (CH4) and carbon dioxide (CO2). A considerable body of research has improved emissions estimates from lakes, reservoirs and rivers but recent attention has been drawn to the importance of small, artificial waterbodies as poorly quantified but potentially important emission hotspots. Of particular interest are emissions from drainage ditches and constructed ponds. These waterbody types are prevalent in many landscapes and their cumulative surface areas can be substantial. Furthermore, GHG emissions from constructed waterbodies are anthropogenic in origin and form part of national emissions reporting, whereas emissions from natural waterbodies do not (according to Intergovernmental Panel on Climate Change guidelines). Here, we present GHG data from two complementary studies covering a range of land uses. In the first, we measured emissions from nine ponds and seven ditches over a full year. Annual emissions varied considerably: 0.1-44.3 g CH4 m(-2) year(-1) and -36-4421 g CO2 m(-2) year(-1). In the second, we measured GHG concentrations in 96 ponds and 64 ditches across seven countries, covering subtropical, temperate and sub-arctic biomes. When CH4 emissions were converted to CO2 equivalents, 93% of waterbodies were GHG sources. In both studies, GHGs were positively related to nutrient status (C, N, P), and pond GHG concentrations were highest in smallest waterbodies. Ditch and pond emissions were larger per unit area when compared to equivalent natural systems (streams, natural ponds). We show that GHG emissions from natural systems should not be used as proxies for those from artificial waterbodies, and that artificial waterbodies have the potential to make a substantial but largely unquantified contribution to emissions from the Agriculture, Forestry and Other Land Use sector, and the global carbon cycle.
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- Pettifor, Audrey, et al.
(author)
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Community mobilization to modify harmful gender norms and reduce HIV risk : results from a community cluster randomized trial in South Africa
- 2018
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In: Journal of the International AIDS Society. - : John Wiley & Sons. - 1758-2652. ; 21:7
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Journal article (peer-reviewed)abstract
- Introduction: Community mobilization (CM) is increasingly recognized as critical to generating changes in social norms and behaviours needed to achieve reductions in HIV. We conducted a CM intervention to modify negative gender norms, particularly among men, in order to reduce associated HIV risk.Methods: Twenty two villages in the Agincourt Health and Socio-Demographic Surveillance Site in rural Mpumalanga, South Africa were randomized to either a theory-based, gender transformative, CM intervention or no intervention. Two cross-sectional, population-based surveys were conducted in 2012 (pre-intervention, n = 600 women; n = 581 men) and 2014 (pos-tintervention, n = 600 women; n = 575 men) among adults ages 18 to 35 years. We used an intent-to-treat (ITT) approach using survey regression cluster-adjusted standard errors to determine the intervention effect by trial arm on gender norms, measured using the Gender Equitable Mens Scale (GEMS), and secondary behavioural outcomes.Results: Among men, there was a significant 2.7 point increase (Beta Coefficient 95% CI: 0.62, 4.78, p = 0.01) in GEMS between those in intervention compared to control communities. We did not observe a significant difference in GEMS scores for women by trial arm. Among men and women in intervention communities, we did not observe significant differences in perpetration of intimate partner violence (IPV), condom use at last sex or hazardous drinking compared to control communities. The number of sex partners in the past 12 months (AOR 0.29, 95% CI 0.11 to 0.77) were significantly lower in women in intervention communities compared to control communities and IPV victimization was lower among women in intervention communities, but the reduction was not statistically significant (AOR 0.53, 95% CI 0.24 to 1.16).Conclusion: Community mobilization can reduce negative gender norms among men and has the potential to create environments that are more supportive of preventing IPV and reducing HIV risk behaviour. Nevertheless, we did not observe that changes in attitudes towards gender norms resulted in desired changes in risk behaviours suggesting that more time may be necessary to change behaviour or that the intervention may need to address behaviours more directly.
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