| 1. |
- Aad, G., et al.
(författare)
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- 2013
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Tidskriftsartikel (refereegranskat)
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| 2. |
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- 2017
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Ingår i: Physical Review D. - 2470-0010 .- 2470-0029. ; 96:2
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Tidskriftsartikel (refereegranskat)
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| 3. |
- Munn-Chernoff, M. A., et al.
(författare)
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Shared genetic risk between eating disorder- and substance-use-related phenotypes: Evidence from genome-wide association studies
- 2021
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Ingår i: Addiction Biology. - : Wiley. - 1355-6215 .- 1369-1600. ; 26:1
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Tidskriftsartikel (refereegranskat)abstract
- Eating disorders and substance use disorders frequently co-occur. Twin studies reveal shared genetic variance between liabilities to eating disorders and substance use, with the strongest associations between symptoms of bulimia nervosa and problem alcohol use (genetic correlation [r(g)], twin-based = 0.23-0.53). We estimated the genetic correlation between eating disorder and substance use and disorder phenotypes using data from genome-wide association studies (GWAS). Four eating disorder phenotypes (anorexia nervosa [AN], AN with binge eating, AN without binge eating, and a bulimia nervosa factor score), and eight substance-use-related phenotypes (drinks per week, alcohol use disorder [AUD], smoking initiation, current smoking, cigarettes per day, nicotine dependence, cannabis initiation, and cannabis use disorder) from eight studies were included. Significant genetic correlations were adjusted for variants associated with major depressive disorder and schizophrenia. Total study sample sizes per phenotype ranged from similar to 2400 to similar to 537 000 individuals. We used linkage disequilibrium score regression to calculate single nucleotide polymorphism-based genetic correlations between eating disorder- and substance-use-related phenotypes. Significant positive genetic associations emerged between AUD and AN (r(g) = 0.18; false discovery rate q = 0.0006), cannabis initiation and AN (r(g) = 0.23; q < 0.0001), and cannabis initiation and AN with binge eating (r(g) = 0.27; q = 0.0016). Conversely, significant negative genetic correlations were observed between three nondiagnostic smoking phenotypes (smoking initiation, current smoking, and cigarettes per day) and AN without binge eating (r(gs) = -0.19 to -0.23; qs < 0.04). The genetic correlation between AUD and AN was no longer significant after co-varying for major depressive disorder loci. The patterns of association between eating disorder- and substance-use-related phenotypes highlights the potentially complex and substance-specific relationships among these behaviors.
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| 4. |
- Aguilar, J. A., et al.
(författare)
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Triboelectric backgrounds to radio-based polar ultra-high energy neutrino (UHEN) experiments
- 2023
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Ingår i: Astroparticle physics. - : Elsevier. - 0927-6505 .- 1873-2852. ; 145
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Tidskriftsartikel (refereegranskat)abstract
- In the hopes of observing the highest-energy neutrinos (E> 1 EeV) populating the Universe, both past (RICE, AURA, ANITA) and current (RNO-G, ARIANNA, ARA and TAROGE-M) polar-sited experiments exploit the impulsive radio emission produced by neutrino interactions. In such experiments, rare single event candidates must be unambiguously identified above backgrounds. Background rejection strategies to date primarily target thermal noise fluctuations and also impulsive radio-frequency signals of anthropogenic origin. In this paper, we consider the possibility that 'fake' neutrino signals may also be generated naturally via the `triboelectric effect' This broadly describes any process in which force applied at a boundary layer results in displacement of surface charge, leading to the production of an electrostatic potential difference AV. Wind blowing over granular surfaces such as snow can induce such a potential difference, with subsequent coronal discharge. Discharges over timescales as short as nanoseconds can then lead to radio-frequency emissions at characteristic MHz-GHz frequencies. Using data from various past (RICE, AURA, SATRA, ANITA) and current (RNO G, ARIANNA and ARA) neutrino experiments, we find evidence for such backgrounds, which are generally characterized by: (a) a threshold wind velocity which likely depends on the experimental trigger criteria and layout; for the experiments considered herein, this value is typically O(10 m/s), (b) frequency spectra generally shifted to the low-end of the frequency regime to which current radio experiments are typically sensitive (100-200 MHz), (c) for the strongest background signals, an apparent preference for discharges from above-surface structures, although the presence of more isotropic, lower amplitude triboelectric discharges cannot be excluded.
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| 5. |
- Tierney, W., et al.
(författare)
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A creative destruction approach to replication : Implicit work and sex morality across cultures
- 2021
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Ingår i: Journal of Experimental Social Psychology. - : Elsevier BV. - 0022-1031 .- 1096-0465. ; 93
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Tidskriftsartikel (refereegranskat)abstract
- How can we maximize what is learned from a replication study? In the creative destruction approach to replication, the original hypothesis is compared not only to the null hypothesis, but also to predictions derived from multiple alternative theoretical accounts of the phenomenon. To this end, new populations and measures are included in the design in addition to the original ones, to help determine which theory best accounts for the results across multiple key outcomes and contexts. The present pre-registered empirical project compared the Implicit Puritanism account of intuitive work and sex morality to theories positing regional, religious, and social class differences; explicit rather than implicit cultural differences in values; self-expression vs. survival values as a key cultural fault line; the general moralization of work; and false positive effects. Contradicting Implicit Puritanism's core theoretical claim of a distinct American work morality, a number of targeted findings replicated across multiple comparison cultures, whereas several failed to replicate in all samples and were identified as likely false positives. No support emerged for theories predicting regional variability and specific individual-differences moderators (religious affiliation, religiosity, and education level). Overall, the results provide evidence that work is intuitively moralized across cultures.
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| 6. |
- Adolph, C., et al.
(författare)
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Interplay among transversity induced asymmetries in hadron leptoproduction
- 2016
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Ingår i: Physics Letters B. - : Elsevier BV. - 0370-2693 .- 1873-2445. ; 753, s. 406-411
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Tidskriftsartikel (refereegranskat)abstract
- In the fragmentation of a transversely polarized quark several left-right asymmetries are possible for the hadrons in the jet. When only one unpolarized hadron is selected, it exhibits an azimuthal modulation known as the Collins effect. When a pair of oppositely charged hadrons is observed, three asymmetries can be considered, a di-hadron asymmetry and two single hadron asymmetries. In lepton deep inelastic scattering on transversely polarized nucleons all these asymmetries are coupled with the transversity distribution. From the high statistics COMPASS data on oppositely charged hadron-pair production we have investigated for the first time the dependence of these three asymmetries on the difference of the azimuthal angles of the two hadrons. The similarity of transversity induced single and di-hadron asymmetries is discussed. A new analysis of the data allows quantitative relationships to be established among them, providing for the first time strong experimental indication that the underlying fragmentation mechanisms are all driven by a common physical process.
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| 7. |
- Abazov, V. M., et al.
(författare)
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Jet energy scale determination in the DO experiment
- 2014
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Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier BV. - 0168-9002 .- 1872-9576. ; 763, s. 442-475
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Tidskriftsartikel (refereegranskat)abstract
- The calibration of jet energy measured in the DO detector is presented, based on p (p) over bar collisions at a center-of-mass energy of 1.96 TeV at the Fermilab Tevatron collider, jet energies are measured using a sampling calorimeter composed of uranium and liquid argon as the passive and active media, respectively. This paper describes the energy calibration of jets performed with gamma+jet, Z+jet and dilet events, with jet transverse momentum p(T) > 6 GeV and pseudorapidity range vertical bar eta vertical bar < 3.6, The corrections are measured separately for data and simulation, achieving a precision of 1.4-1.8% for jets in the central part of the calorimeter ancl up to 3.5% for the jets with pseudorapidity vertical bar eta vertical bar = 3.0. Specific corrections are extracted to enhance the description of jet energy in simulation and in particular of the effects due to the flavor of the parton originating the jet, correcting biases up to 3-4% in jets with low PT originating from gluons and up to 6-8% in jets from b quarks. Published by Elsevier B.V.
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| 8. |
- Abazov, V. M., et al.
(författare)
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Measurement of spin correlation between top and antitop quarks produced in p(p)over-bar collisions at root s=1.96 TeV
- 2016
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Ingår i: Physics Letters B. - : Elsevier BV. - 0370-2693 .- 1873-2445. ; 757, s. 199-206
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Tidskriftsartikel (refereegranskat)abstract
- We present a measurement of the correlation between the spins of t and (t) over bar quarks produced in proton-antiproton collisions at the Tevatron Collider at a center-of-mass energy of 1.96 TeV. We apply a matrix element technique to dilepton and single-lepton+jets final states in data accumulated with the DO detector that correspond to an integrated luminosity of 9.7 fb(-1). The measured value of the correlation coefficient in the off-diagonal basis, O-off = 0.89 +/- 0.22 (stat + syst), is in agreement with the standard model prediction, and represents evidence for a top-antitop quark spin correlation difference from zero at a level of 4.2 standard deviations.
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| 9. |
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| 10. |
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| 11. |
- Shrine, N, et al.
(författare)
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Multi-ancestry genome-wide association analyses improve resolution of genes and pathways influencing lung function and chronic obstructive pulmonary disease risk
- 2023
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 55:3, s. 410-
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Tidskriftsartikel (refereegranskat)abstract
- Lung-function impairment underlies chronic obstructive pulmonary disease (COPD) and predicts mortality. In the largest multi-ancestry genome-wide association meta-analysis of lung function to date, comprising 580,869 participants, we identified 1,020 independent association signals implicating 559 genes supported by ≥2 criteria from a systematic variant-to-gene mapping framework. These genes were enriched in 29 pathways. Individual variants showed heterogeneity across ancestries, age and smoking groups, and collectively as a genetic risk score showed strong association with COPD across ancestry groups. We undertook phenome-wide association studies for selected associated variants as well as trait and pathway-specific genetic risk scores to infer possible consequences of intervening in pathways underlying lung function. We highlight new putative causal variants, genes, proteins and pathways, including those targeted by existing drugs. These findings bring us closer to understanding the mechanisms underlying lung function and COPD, and should inform functional genomics experiments and potentially future COPD therapies.
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| 12. |
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| 13. |
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| 14. |
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| 15. |
- Haas, Brian J., et al.
(författare)
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Genome sequence and analysis of the Irish potato famine pathogen Phytophthora infestans
- 2009
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 461:7262, s. 393-398
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Tidskriftsartikel (refereegranskat)abstract
- Phytophthora infestans is the most destructive pathogen of potato and a model organism for the oomycetes, a distinct lineage of fungus-like eukaryotes that are related to organisms such as brown algae and diatoms. As the agent of the Irish potato famine in the mid-nineteenth century, P. infestans has had a tremendous effect on human history, resulting in famine and population displacement(1). To this day, it affects world agriculture by causing the most destructive disease of potato, the fourth largest food crop and a critical alternative to the major cereal crops for feeding the world's population(1). Current annual worldwide potato crop losses due to late blight are conservatively estimated at $6.7 billion(2). Management of this devastating pathogen is challenged by its remarkable speed of adaptation to control strategies such as genetically resistant cultivars(3,4). Here we report the sequence of the P. infestans genome, which at similar to 240 megabases (Mb) is by far the largest and most complex genome sequenced so far in the chromalveolates. Its expansion results from a proliferation of repetitive DNA accounting for similar to 74% of the genome. Comparison with two other Phytophthora genomes showed rapid turnover and extensive expansion of specific families of secreted disease effector proteins, including many genes that are induced during infection or are predicted to have activities that alter host physiology. These fast-evolving effector genes are localized to highly dynamic and expanded regions of the P. infestans genome. This probably plays a crucial part in the rapid adaptability of the pathogen to host plants and underpins its evolutionary potential.
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| 16. |
- Jang, Seon-Kyeong, et al.
(författare)
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Rare genetic variants explain missing heritability in smoking.
- 2022
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Ingår i: Nature human behaviour. - : Springer Science and Business Media LLC. - 2397-3374. ; 6:11, s. 1577-1586
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Tidskriftsartikel (refereegranskat)abstract
- Common genetic variants explain less variation in complex phenotypes than inferred from family-based studies, and there is a debate on the source of this 'missing heritability'. We investigated the contribution of rare genetic variants to tobacco use with whole-genome sequences from up to 26,257 unrelated individuals of European ancestries and 11,743 individuals of African ancestries. Across four smoking traits, single-nucleotide-polymorphism-based heritability ([Formula: see text]) was estimated from 0.13 to 0.28 (s.e., 0.10-0.13) in European ancestries, with 35-74% of it attributable to rare variants with minor allele frequencies between 0.01% and 1%. These heritability estimates are 1.5-4 times higher than past estimates based on common variants alone and accounted for 60% to 100% of our pedigree-based estimates of narrow-sense heritability ([Formula: see text], 0.18-0.34). In the African ancestry samples, [Formula: see text] was estimated from 0.03 to 0.33 (s.e., 0.09-0.14) across the four smoking traits. These results suggest that rare variants are important contributors to the heritability of smoking.
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| 17. |
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| 18. |
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| 19. |
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| 20. |
- Aguilar, J. A., et al.
(författare)
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Design and sensitivity of the Radio Neutrino Observatory in Greenland (RNO-G)
- 2021
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Ingår i: Journal of Instrumentation. - : Institute of Physics Publishing (IOPP). - 1748-0221. ; 16:3
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Tidskriftsartikel (refereegranskat)abstract
- This article presents the design of the Radio Neutrino Observatory Greenland (RNO-G) and discusses its scientific prospects. Using an array of radio sensors, RNO-G seeks to measure neutrinos above 10 PeV by exploiting the Askaryan effect in neutrino-induced cascades in ice. We discuss the experimental considerations that drive the design of RNO-G, present first measurements of the hardware that is to be deployed and discuss the projected sensitivity of the instrument. RNO-G will be the first production-scale radio detector for in-ice neutrino signals.
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| 21. |
- Aguilar, J. A., et al.
(författare)
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Hardware Development for the Radio Neutrino Observatory in Greenland (RNO-G)
- 2022
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Ingår i: 37th International Cosmic Ray Conference, ICRC2021. - Trieste, Italy : Proceedings of Science.
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Konferensbidrag (refereegranskat)abstract
- The Radio Neutrino Observatory in Greenland (RNO-G) is designed to make the first observations of ultra-high energy neutrinos at energies above 10 PeV, playing a unique role in multi-messenger astrophysics as the world's largest in-ice Askaryan radio detection array. The experiment will be composed of 35 autonomous stations deployed over a 5 x 6 km grid near NSF Summit Station in Greenland. The electronics chain of each station is optimized for sensitivity and low power, incorporating 150 - 600 MHz RF antennas at both the surface and in ice boreholes, low-noise amplifiers, custom RF-over-fiber systems, and an FPGA-based phased array trigger. Each station will consume 25 W of power, allowing for a live time of 70% from a solar power system. The communications system is composed of a high-bandwidth LTE network and an ultra-low power LoRaWAN network. I will also present on the calibration and DAQ systems, as well as status of the first deployment of 10 stations in Summer 2021.
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| 22. |
- Aguilar, J. A., et al.
(författare)
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In situ, broadband measurement of the radio frequency attenuation length at Summit Station, Greenland
- 2022
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Ingår i: Journal of Glaciology. - : Cambridge University Press. - 0022-1430 .- 1727-5652. ; 68:272, s. 1234-1242
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Tidskriftsartikel (refereegranskat)abstract
- Over the last 25 years, radiowave detection of neutrino-generated signals, using cold polar ice as the neutrino target, has emerged as perhaps the most promising technique for detection of extragalactic ultra-high energy neutrinos (corresponding to neutrino energies in excess of 0.01 Joules, or 10(17) electron volts). During the summer of 2021 and in tandem with the initial deployment of the Radio Neutrino Observatory in Greenland (RNO-G), we conducted radioglaciological measurements at Summit Station, Greenland to refine our understanding of the ice target. We report the result of one such measurement, the radio-frequency electric field attenuation length L-alpha. We find an approximately linear dependence of L-alpha on frequency with the best fit of the average field attenuation for the upper 1500 m of ice: < L-alpha > = ((1154 +/- 121) - (0.81 +/- 0.14) (v/MHz)) m for frequencies v is an element of [145 - 3501 MHz.
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| 23. |
- Aguilar, J. A., et al.
(författare)
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Reconstructing the neutrino energy for in-ice radio detectors
- 2022
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Ingår i: European Physical Journal C. - : Springer Nature. - 1434-6044 .- 1434-6052. ; 82:2
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Tidskriftsartikel (refereegranskat)abstract
- Since summer 2021, the Radio Neutrino Observatory in Greenland (RNO-G) is searching for astrophysical neutrinos at energies > 10 PeV by detecting the radio emission from particle showers in the ice around Summit Station, Greenland. We present an extensive simulation study that shows how RNO-G will be able to measure the energy of such particle cascades, which will in turn be used to estimate the energy of the incoming neutrino that caused them. The location of the neutrino interaction is determined using the differences in arrival times between channels and the electric field of the radio signal is reconstructed using a novel approach based on Information Field Theory. Based on these properties, the shower energy can be estimated. We show that this method can achieve an uncertainty of 13% on the logarithm of the shower energy after modest quality cuts and estimate how this can constrain the energy of the neutrino. The method presented in this paper is applicable to all similar radio neutrino detectors, such as the proposed radio array of IceCube-Gen2.
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| 24. |
- Anker, A., et al.
(författare)
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Probing the angular and polarization reconstruction of the ARIANNA detector at the South Pole
- 2020
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Ingår i: Journal of Instrumentation. - : IOP PUBLISHING LTD. - 1748-0221. ; 15:9
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Tidskriftsartikel (refereegranskat)abstract
- The sources of ultra-high energy (UHE) cosmic rays, which can have energies up to 10(20) eV, remain a mystery. UHE neutrinos may provide important clues to understanding the nature of cosmic-ray sources. ARIANNA aims to detect UHE neutrinos via radio (Askaryan) emission from particle showers when a neutrino interacts with ice, which is an efficient method for neutrinos with energies between 10(16) eV and 10(20) eV. The ARIANNA radio detectors are located in Antarctic ice just beneath the surface. Neutrino observation requires that radio pulses propagate to the antennas at the surface with minimum distortion by the ice and firn medium. Using the residual hole from the South Pole Ice Core Project, radio pulses were emitted from a transmitter located up to 1.7 km below the snow surface. By measuring these signals with an ARIANNA surface station, the angular and polarization reconstruction abilities are quantified, which are required to measure the direction of the neutrino. After deconvolving the raw signals for the detector response and attenuation from propagation through the ice, the signal pulses show no significant distortion and agree with a reference measurement of the emitter made in an anechoic chamber. Furthermore, the signal pulses reveal no significant birefringence for our tested geometry of mostly vertical ice propagation. The origin of the transmitted radio pulse was measured with an angular resolution of 0.37 degrees indicating that the neutrino direction can be determined with good precision if the polarization of the radio-pulse can be well determined. In the present study we obtained a resolution of the polarization vector of 2.7 degrees. Neither measurement show a significant offset relative to expectation.
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| 25. |
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| 26. |
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| 27. |
- Marina, Neyssa M., et al.
(författare)
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Comparison of MAPIE versus MAP in patients with a poor response to preoperative chemotherapy for newly diagnosed high-grade osteosarcoma (EURAMOS-1) : an open-label, international, randomised controlled trial
- 2016
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Ingår i: The Lancet Oncology. - 1470-2045. ; 17:10, s. 1396-1408
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Tidskriftsartikel (refereegranskat)abstract
- Background We designed the EURAMOS-1 trial to investigate whether intensified postoperative chemotherapy for patients whose tumour showed a poor response to preoperative chemotherapy (≥10% viable tumour) improved event-free survival in patients with high-grade osteosarcoma. Methods EURAMOS-1 was an open-label, international, phase 3 randomised, controlled trial. Consenting patients with newly diagnosed, resectable, high-grade osteosarcoma aged 40 years or younger were eligible for randomisation. Patients were randomly assigned (1:1) to receive either postoperative cisplatin, doxorubicin, and methotrexate (MAP) or MAP plus ifosfamide and etoposide (MAPIE) using concealed permuted blocks with three stratification factors: trial group; location of tumour (proximal femur or proximal humerus vs other limb vs axial skeleton); and presence of metastases (no vs yes or possible). The MAP regimen consisted of cisplatin 120 mg/m2, doxorubicin 37·5 mg/m2 per day on days 1 and 2 (on weeks 1 and 6) followed 3 weeks later by high-dose methotrexate 12 g/m2 over 4 h. The MAPIE regimen consisted of MAP as a base regimen, with the addition of high-dose ifosfamide (14 g/m2) at 2·8 g/m2 per day with equidose mesna uroprotection, followed by etoposide 100 mg/m2 per day over 1 h on days 1–5. The primary outcome measure was event-free survival measured in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT00134030. Findings Between April 14, 2005, and June 30, 2011, 2260 patients were registered from 325 sites in 17 countries. 618 patients with poor response were randomly assigned; 310 to receive MAP and 308 to receive MAPIE. Median follow-up was 62·1 months (IQR 46·6–76·6); 62·3 months (IQR 46·9–77·1) for the MAP group and 61·1 months (IQR 46·5–75·3) for the MAPIE group. 307 event-free survival events were reported (153 in the MAP group vs 154 in the MAPIE group). 193 deaths were reported (101 in the MAP group vs 92 in the MAPIE group). Event-free survival did not differ between treatment groups (hazard ratio [HR] 0·98 [95% CI 0·78–1·23]); hazards were non-proportional (p=0·0003). The most common grade 3–4 adverse events were neutropenia (268 [89%] patients in MAP vs 268 [90%] in MAPIE), thrombocytopenia (231 [78% in MAP vs 248 [83%] in MAPIE), and febrile neutropenia without documented infection (149 [50%] in MAP vs 217 [73%] in MAPIE). MAPIE was associated with more frequent grade 4 non-haematological toxicity than MAP (35 [12%] of 301 in the MAP group vs 71 [24%] of 298 in the MAPIE group). Two patients died during postoperative therapy, one from infection (although their absolute neutrophil count was normal), which was definitely related to their MAP treatment (specifically doxorubicin and cisplatin), and one from left ventricular systolic dysfunction, which was probably related to MAPIE treatment (specifically doxorubicin). One suspected unexpected serious adverse reaction was reported in the MAP group: bone marrow infarction due to methotrexate. Interpretation EURAMOS-1 results do not support the addition of ifosfamide and etoposide to postoperative chemotherapy in patients with poorly responding osteosarcoma because its administration was associated with increased toxicity without improving event-free survival. The results define standard of care for this population. New strategies are required to improve outcomes in this setting. Funding UK Medical Research Council, National Cancer Institute, European Science Foundation, St Anna Kinderkrebsforschung, Fonds National de la Recherche Scientifique, Fonds voor Wetenschappelijk Onderzoek-Vlaanderen, Parents Organization, Danish Medical Research Council, Academy of Finland, Deutsche Forschungsgemeinschaft, Deutsche Krebshilfe, Federal Ministry of Education and Research, Semmelweis Foundation, ZonMw (Council for Medical Research), Research Council of Norway, Scandinavian Sarcoma Group, Swiss Paediatric Oncology Group, Cancer Research UK, National Institute for Health Research, University College London Hospitals, and Biomedical Research Centre.
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| 28. |
- Pleunis, Z., et al.
(författare)
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LOFAR Detection of 110-188MHz emission and frequency-dependent activity from FRB20180916B
- 2021
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Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8213 .- 2041-8205. ; 911:1
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Tidskriftsartikel (refereegranskat)abstract
- The object FRB 20180916B is a well-studied repeating fast radio burst source. Its proximity (∼150 Mpc), along with detailed studies of the bursts, has revealed many clues about its nature, including a 16.3 day periodicity in its activity. Here we report on the detection of 18 bursts using LOFAR at 110-188 MHz, by far the lowest-frequency detections of any FRB to date. Some bursts are seen down to the lowest observed frequency of 110 MHz, suggesting that their spectra extend even lower. These observations provide an order-of-magnitude stronger constraint on the optical depth due to freëCfree absorption in the source's local environment. The absence of circular polarization and nearly flat polarization angle curves are consistent with burst properties seen at 300-1700 MHz. Compared with higher frequencies, the larger burst widths (∼40-160 ms at 150 MHz) and lower linear polarization fractions are likely due to scattering. We find ∼2-3 rad m variations in the Faraday rotation measure that may be correlated with the activity cycle of the source. We compare the LOFAR burst arrival times to those of 38 previously published and 22 newly detected bursts from the uGMRT (200-450 MHz) and CHIME/FRB (400-800 MHz). Simultaneous observations show five CHIME/FRB bursts when no emission is detected by LOFAR. We find that the burst activity is systematically delayed toward lower frequencies by about 3 days from 600 to 150 MHz. We discuss these results in the context of a model in which FRB 20180916B is an interacting binary system featuring a neutron star and high-mass stellar companion.
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| 29. |
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| 30. |
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| 31. |
- Anker, A., et al.
(författare)
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Improving sensitivity of the ARIANNA detector by rejecting thermal noise with deep learning
- 2022
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Ingår i: Journal of Instrumentation. - : IOP Publishing. - 1748-0221. ; 17:3
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Tidskriftsartikel (refereegranskat)abstract
- The ARIANNA experiment is an Askaryan detector designed to record radio signals induced by neutrino interactions in the Antarctic ice. Because of the low neutrino flux at high energies (E-nu > 10(16 )eV), the physics output is limited by statistics. Hence, an increase in sensitivity significantly improves the interpretation of data and offers the ability to probe new parameter spaces. The amplitudes of the trigger threshold are limited by the rate of triggering on unavoidable thermal noise fluctuations. We present a real-time thermal noise rejection algorithm that enables the trigger thresholds to be lowered, which increases the sensitivity to neutrinos by up to a factor of two (depending on energy) compared to the current ARIANNA capabilities. A deep learning discriminator, based on a Convolutional Neural Network (CNN), is implemented to identify and remove thermal events in real time. We describe a CNN trained on MC data that runs on the current ARIANNA microcomputer and retains 95% of the neutrino signal at a thermal noise rejection factor of 10(5), compared to a template matching procedure which reaches only 10(2) for the same signal efficiency. Then the results are verified in a lab measurement by feeding in generated neutrino-like signal pulses and thermal noise directly into the ARIANNA data acquisition system. Lastly, the same CNN is used to classify cosmic-rays events to make sure they are not rejected. The network classified 102 out of 104 cosmic-ray events as signal.
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| 32. |
- Anker, A., et al.
(författare)
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Measuring the polarization reconstruction resolution of the ARIANNA neutrino detector with cosmic rays
- 2022
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Ingår i: Journal of Cosmology and Astroparticle Physics. - : IOP Publishing. - 1475-7516. ; :4
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Tidskriftsartikel (refereegranskat)abstract
- The ARIANNA detector is designed to detect neutrinos with energies above 10(17) eV. Due to the similarities in generated radio signals, cosmic rays are often used as test beams for neutrino detectors. Some ARIANNA detector stations are equipped with antennas capable of detecting air showers. Since the radio emission properties of air showers are well understood, and the polarization of the radio signal can be predicted from the arrival direction, cosmic rays can be used as a proxy to assess the reconstruction capabilities of the ARIANNA neutrino detector. We report on dedicated efforts of reconstructing the polarization of cosmic-ray radio pulses. After correcting for difference in hardware, the two stations used in this study showed similar performance in terms of event rate and agreed with simulation. Subselecting high quality cosmic rays, the polarizations of these cosmic rays were reconstructed with a resolution of 2.5 degrees (68% containment), which agrees with the expected value obtained from simulation. A large fraction of this resolution originates from uncertainties in the predicted polarization because of the contribution of the subdominant Askaryan effect in addition to the dominant geomagnetic emission. Subselecting events with a zenith angle greater than 70 degrees removes most influence of the Askaryan emission, and, with limited statistics, we found the polarization uncertainty is reduced to 1.3 degrees (68% containment).
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| 33. |
- Dawson, K. S., et al.
(författare)
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An Intensive Hubble Space Telescope Survey for z>1 Type Ia Supernovae by Targeting Galaxy Clusters
- 2009
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Ingår i: Astronomical Journal. - : American Astronomical Society. - 0004-6256 .- 1538-3881. ; 138, s. 1271-1283
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Tidskriftsartikel (refereegranskat)abstract
- We present a new survey strategy to discover and study high-redshift Type Ia supernovae (SNe Ia) using the Hubble Space Telescope (HST). By targeting massive galaxy clusters at 0.9 < z < 1.5, we obtain a twofold improvement in the efficiency of finding SNe compared to an HST field survey and a factor of 3 improvement in the total yield of SN detections in relatively dust-free red-sequence galaxies. In total, sixteen SNe were discovered at z>0.95, nine of which were in galaxy clusters. This strategy provides an SN sample that can be used to decouple the effects of host-galaxy extinction and intrinsic color in high-redshift SNe, thereby reducing one of the largest systematic uncertainties in SN cosmology. Based on observations made with the NASA/ESA Hubble Space Telescope and obtained from the data archive at the Space Telescope Institute. STScI is operated by the Association of Universities for Research in Astronomy, Inc. under the NASA contract NAS 5-26555. The observations are associated with program 10496.
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| 34. |
- Hoshino, Ayuko, et al.
(författare)
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Extracellular Vesicle and Particle Biomarkers Define Multiple Human Cancers
- 2020
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Ingår i: Cell. - : CELL PRESS. - 0092-8674 .- 1097-4172. ; 182:4, s. 1044-
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Tidskriftsartikel (refereegranskat)abstract
- There is an unmet clinical need for improved tissue and liquid biopsy tools for cancer detection. We investigated the proteomic profile of extracellular vesicles and particles (EVPs) in 426 human samples from tissue explants (TEs), plasma, and other bodily fluids. Among traditional exosome markers, CD9, HSPA8, ALIX, and HSP90AB1 represent pan-EVP markers, while ACTB, MSN, and RAP1B are novel pan-EVP markers. To confirm that EVPs are ideal diagnostic tools, we analyzed proteomes of TE- (n =151) and plasma-derived (n =120) EVPs. Comparison of TE EVPs identified proteins (e.g., VCAN, TNC, and THBS2) that distinguish tumors from normal tissues with 90% sensitivity/94% specificity. Machine-learning classification of plasma-derived EVP cargo, including immunoglobulins, revealed 95% sensitivity/90% specificity in detecting cancer Finally, we defined a panel of tumor-type-specific EVP proteins in TEs and plasma, which can classify tumors of unknown primary origin. Thus, EVP proteins can serve as reliable biomarkers for cancer detection and determining cancer type.
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| 35. |
- Shrine, Nick, et al.
(författare)
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New genetic signals for lung function highlight pathways and chronic obstructive pulmonary disease associations across multiple ancestries
- 2019
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 51:3, s. 481-493
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Tidskriftsartikel (refereegranskat)abstract
- Reduced lung function predicts mortality and is key to the diagnosis of chronic obstructive pulmonary disease (COPD). In a genome-wide association study in 400,102 individuals of European ancestry, we define 279 lung function signals, 139 of which are new. In combination, these variants strongly predict COPD in independent populations. Furthermore, the combined effect of these variants showed generalizability across smokers and never smokers, and across ancestral groups. We highlight biological pathways, known and potential drug targets for COPD and, in phenome-wide association studies, autoimmune-related and other pleiotropic effects of lung function-associated variants. This new genetic evidence has potential to improve future preventive and therapeutic strategies for COPD.
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| 36. |
- Suzuki, N., et al.
(författare)
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THE HUBBLE SPACE TELESCOPE CLUSTER SUPERNOVA SURVEY. V. IMPROVING THE DARK- ENERGY CONSTRAINTS ABOVE z > 1 AND BUILDING AN EARLY-TYPE-HOSTED SUPERNOVA SAMPLE
- 2012
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 746:1
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Tidskriftsartikel (refereegranskat)abstract
- We present Advanced Camera for Surveys, NICMOS, and Keck adaptive-optics-assisted photometry of 20 Type Ia supernovae (SNe Ia) from the Hubble Space Telescope (HST) Cluster Supernova Survey. The SNe Ia were discovered over the redshift interval 0.623 < z < 1.415. Of these SNe Ia, 14 pass our strict selection cuts and are used in combination with the world's sample of SNe Ia to derive the best current constraints on dark energy. Of our new SNe Ia, 10 are beyond redshift z = 1, thereby nearly doubling the statistical weight of HST-discovered SNe Ia beyond this redshift. Our detailed analysis corrects for the recently identified correlation between SN Ia luminosity and host galaxy mass and corrects the NICMOS zero point at the count rates appropriate for very distant SNe Ia. Adding these SNe improves the best combined constraint on dark-energy density,rho(DE)(z), at redshifts 1.0 < z < 1.6 by 18% (including systematic errors). For a flat. CDM universe, we find Omega(A) = 0.729 +/- 0.014 (68% confidence level (CL) including systematic errors). For a flat wCDM model, we measure a constant dark-energy equation-of-state parameter w = -1.013(-0.073)(+0.068) (68% CL). Curvature is constrained to similar to 0.7% in the owCDM model and to similar to 2% in a model in which dark energy is allowed to vary with parameters w(0) and w(a). Further tightening the constraints on the time evolution of dark energy will require several improvements, including high-quality multi-passband photometry of a sample of several dozenz > 1 SNe Ia. We describe how such a sample could be efficiently obtained by targeting cluster fields with WFC3 on board HST. The updated supernova Union2.1 compilation of 580 SNe is available at http://supernova.lbl.gov/Union.
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| 37. |
- Zicha, S., et al.
(författare)
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Comparative analytical performance of multiple plasma A beta 42 and A beta 40 assays and their ability to predict positron emission tomography amyloid positivity
- 2022
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Ingår i: Alzheimers & Dementia. - : Wiley. - 1552-5260 .- 1552-5279.
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Tidskriftsartikel (refereegranskat)abstract
- Introduction This report details the approach taken to providing a dataset allowing for analyses on the performance of recently developed assays of amyloid beta (A beta) peptides in plasma and the extent to which they improve the prediction of amyloid positivity. Methods Alzheimer's Disease Neuroimaging Initiative plasma samples with corresponding amyloid positron emission tomography (PET) data were run on six plasma A beta assays. Statistical tests were performed to determine whether the plasma A beta measures significantly improved the area under the receiver operating characteristic curve for predicting amyloid PET status compared to age and apolipoprotein E (APOE) genotype. Results The age and APOE genotype model predicted amyloid status with an area under the curve (AUC) of 0.75. Three assays improved AUCs to 0.81, 0.81, and 0.84 (P < .05, uncorrected for multiple comparisons). Discussion Measurement of A beta in plasma contributes to addressing the amyloid component of the ATN (amyloid/tau/neurodegeneration) framework and could be a first step before or in place of a PET or cerebrospinal fluid screening study. Highlights The Foundation of the National Institutes of Health Biomarkers Consortium evaluated six plasma amyloid beta (A beta) assays using Alzheimer's Disease Neuroimaging Initiative samples. Three assays improved prediction of amyloid status over age and apolipoprotein E (APOE) genotype. Plasma A beta 42/40 predicted amyloid positron emission tomography status better than A beta 42 or A beta 40 alone.
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| 38. |
- Barbary, K., et al.
(författare)
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Discovery of an Unusual Optical Transient with the Hubble Space Telescope
- 2009
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 690, s. 1358-1362
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Tidskriftsartikel (refereegranskat)abstract
- We present observations of SCP 06F6, an unusual optical transient discovered during the Hubble Space Telescope Cluster Supernova Survey. The transient brightened over a period of ~100 days, reached a peak magnitude of ~ 21.0 in both i 775 and z 850, and then declined over a similar timescale. There is no host galaxy or progenitor star detected at the location of the transient to a 3σ upper limit of i 775 >= 26.4 and z 850 >= 26.1, giving a corresponding lower limit on the flux increase of a factor of ~ 120. Multiple spectra show five broad absorption bands between 4100 Å and 6500 Å, and a mostly featureless continuum longward of 6500 Å. The shape of the light curve is inconsistent with microlensing. The transient's spectrum, in addition to being inconsistent with all known supernova types, does not match any spectrum in the Sloan Digital Sky Survey database. We suggest that the transient may be one of a new class. Based in part on observations made with the NASA/ESA Hubble Space Telescope, obtained from the data archive at the Space Telescope Science Institute (STScI). STScI is operated by the Association of Universities for Research in Astronomy (AURA), Inc. under the NASA contract NAS 5-26555. The observations are associated with program GO-10496. Based in part on observations obtained at the European Southern Observatory under ESO program 077.A-0110. Based in part on observations collected at Subaru Telescope, which is operated by the National Astronomical Observatory of Japan. Some of the data presented herein were obtained at the W.M. Keck Observatory, which is operated as a scientific partnership among the California Institute of Technology, the University of California, and NASA.
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| 39. |
- Bhat, N. D. R., et al.
(författare)
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Observations of Low-frequency Radio Emission from Millisecond Pulsars and Multipath Propagation in the Interstellar Medium
- 2018
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Ingår i: Astrophysical Journal, Supplement Series. - : American Astronomical Society. - 1538-4365 .- 0067-0049. ; 238:1
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Tidskriftsartikel (refereegranskat)abstract
- Studying the gravitational-wave sky with pulsar timing arrays (PTAs) is a key science goal for the Square Kilometre Array (SKA) and its pathfinder telescopes. With current PTAs reaching sub-microsecond timing precision, making accurate measurements of interstellar propagation effects and mitigating them effectively has become increasingly important to realize PTA goals. As these effects are much stronger at longer wavelengths, low-frequency observations are most appealing for characterizing the interstellar medium (ISM) along the sight lines toward PTA pulsars. The Murchison Widefield Array (MWA) and the Engineering Development Array (EDA), which utilizes MWA technologies, present promising opportunities for undertaking such studies, particularly for PTA pulsars located in the southern sky. Such pulsars are also the prime targets for PTA efforts planned with the South African MeerKAT, and eventually with the SKA. In this paper we report on observations of two bright southern millisecond pulsars, PSR J0437-4715 and PSR J2145-0750, made with these facilities; MWA observations sampled multiple frequencies across the 80-250 MHz frequency range, while the EDA provided direct-sampled baseband data to yield a large instantaneous usable bandwidth of similar to 200 MHz. Using these exploratory observations, we investigate various aspects relating to pulsar emission and ISM properties, such as spectral evolution of the mean pulse shape, scintillation as a function of frequency, chromaticity in interstellar dispersion, and flux density spectra at low frequencies. Systematic and regular monitoring observations will help ascertain the role of low-frequency measurements in PTA experiments, while simultaneously providing a detailed characterization of the ISM toward the pulsars, which will be useful in devising optimal observing strategies for future PTA experiments.
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| 40. |
- Bielack, Stefan S, et al.
(författare)
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Methotrexate, Doxorubicin, and Cisplatin (MAP) Plus Maintenance Pegylated Interferon Alfa-2b Versus MAP Alone in Patients With Resectable High-Grade Osteosarcoma and Good Histologic Response to Preoperative MAP: First Results of the EURAMOS-1 Good Response Randomized Controlled Trial
- 2015
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Ingår i: Journal of Clinical Oncology. - 1527-7755. ; 33:20, s. 2279-2287
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Tidskriftsartikel (refereegranskat)abstract
- Purpose EURAMOS-1, an international randomized controlled trial, investigated maintenance therapy with pegylated interferon alfa-2b (IFN-α-2b) in patients whose osteosarcoma showed good histologic response (good response) to induction chemotherapy. Patients and Methods At diagnosis, patients age ≤ 40 years with resectable high-grade osteosarcoma were registered. Eligibility after surgery for good response random assignment included ≥ two cycles of preoperative MAP (methotrexate, doxorubicin, and cisplatin), macroscopically complete surgery of primary tumor, < 10% viable tumor, and no disease progression. These patients were randomly assigned to four additional cycles MAP with or without IFN-α-2b (0.5 to 1.0 μg/kg per week subcutaneously, after chemotherapy until 2 years postregistration). Outcome measures were event-free survival (EFS; primary) and overall survival and toxicity (secondary). Results Good response was reported in 1,041 of 2,260 registered patients; 716 consented to random assignment (MAP, n = 359; MAP plus IFN-α-2b, n = 357), with baseline characteristics balanced by arm. A total of 271 of 357 started IFN-α-2b; 105 stopped early, and 38 continued to receive treatment at data freeze. Refusal and toxicity were the main reasons for never starting IFN-α-2b and for stopping prematurely, respectively. Median IFN-α-2b duration, if started, was 67 weeks. A total of 133 of 268 patients who started IFN-α-2b and provided toxicity information reported grade ≥ 3 toxicity during IFN-α-2b treatment. With median follow-up of 44 months, 3-year EFS for all 716 randomly assigned patients was 76% (95% CI, 72% to 79%); 174 EFS events were reported (MAP, n = 93; MAP plus IFN-α-2b, n = 81). Hazard ratio was 0.83 (95% CI, 0.61 to 1.12; P = .214) from an adjusted Cox model. Conclusion At the preplanned analysis time, MAP plus IFN-α-2b was not statistically different from MAP alone. A considerable proportion of patients never started IFN-α-2b or stopped prematurely. Long-term follow-up for events and survival continues.
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| 41. |
- Bigdeli, TB, et al.
(författare)
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Contributions of common genetic variants to risk of schizophrenia among individuals of African and Latino ancestry
- 2020
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Ingår i: Molecular psychiatry. - : Springer Science and Business Media LLC. - 1476-5578 .- 1359-4184. ; 25:10, s. 2455-2467
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Tidskriftsartikel (refereegranskat)abstract
- Schizophrenia is a common, chronic and debilitating neuropsychiatric syndrome affecting tens of millions of individuals worldwide. While rare genetic variants play a role in the etiology of schizophrenia, most of the currently explained liability is within common variation, suggesting that variation predating the human diaspora out of Africa harbors a large fraction of the common variant attributable heritability. However, common variant association studies in schizophrenia have concentrated mainly on cohorts of European descent. We describe genome-wide association studies of 6152 cases and 3918 controls of admixed African ancestry, and of 1234 cases and 3090 controls of Latino ancestry, representing the largest such study in these populations to date. Combining results from the samples with African ancestry with summary statistics from the Psychiatric Genomics Consortium (PGC) study of schizophrenia yielded seven newly genome-wide significant loci, and we identified an additional eight loci by incorporating the results from samples with Latino ancestry. Leveraging population differences in patterns of linkage disequilibrium, we achieve improved fine-mapping resolution at 22 previously reported and 4 newly significant loci. Polygenic risk score profiling revealed improved prediction based on trans-ancestry meta-analysis results for admixed African (Nagelkerke’s R2 = 0.032; liability R2 = 0.017; P < 10−52), Latino (Nagelkerke’s R2 = 0.089; liability R2 = 0.021; P < 10−58), and European individuals (Nagelkerke’s R2 = 0.089; liability R2 = 0.037; P < 10−113), further highlighting the advantages of incorporating data from diverse human populations.
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| 42. |
- Duggan, D., et al.
(författare)
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Two genome-wide association studies of aggressive prostate cancer implicate putative prostate tumor suppressor gene DAB2IP
- 2007
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 99:24, s. 1836-1844
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Tidskriftsartikel (refereegranskat)abstract
- Background: The consistent finding of a genetic susceptibility to prostate cancer suggests that there are germline sequence variants predisposing individuals to this disease. These variants could be useful in screening and treatment. Methods: We performed an exploratory genome-wide association scan in 498 men with aggressive prostate cancer and 494 control subjects selected from a population-based case-control study in Sweden. We combined the results of this scan with those for aggressive prostate cancer from the publicly available Cancer Genetic Markers of Susceptibility (CGEMS) Study. Single-nucleotide polymorphisms (SNPs) that showed statistically significant associations with the risk of aggressive prostate cancer based on two-sided allele tests were tested for their association with aggressive prostate cancer in two independent study populations composed of individuals of European or African American descent using one-sided tests and the genetic model (dominant or additive) associated with the lowest value in the exploratory study. Results: Among the approximately 60000 SNPs that were common to our study and CGEMS, we identified seven that had a similar (positive or negative) and statistically significant (P<.01) association with the risk of aggressive prostate cancer in both studies. Analysis of the distribution of these SNPs among 1032 prostate cancer patients and 571 control subjects of European descent indicated that one, rs1571801, located in the DAB2IP gene, which encodes a novel Ras GTPase-activating protein and putative prostate tumor suppressor, was associated with aggressive prostate cancer (one-sided P value =. 004). The association was also statistically significant in an African American study population that included 210 prostate cancer patients and 346 control subjects (one-sided P value =. 02). Conclusion: A genetic variant in DAB2IP may be associated with the risk of aggressive prostate cancer and should be evaluated further.
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| 43. |
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| 44. |
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| 45. |
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| 46. |
- Nordin, J., et al.
(författare)
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Lensed Type Ia supernovae as probes of cluster mass models
- 2014
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 440:3, s. 2742-2754
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Tidskriftsartikel (refereegranskat)abstract
- Using three magnified Type Ia supernovae (SNe Ia) detected behind CLASH (Cluster Lensing and Supernovae with Hubble) clusters, we perform a first pilot study to see whether standardizable candles can be used to calibrate cluster mass maps created from strong lensing observations. Such calibrations will be crucial when next-generation Hubble Space Telescope cluster surveys (e.g. Frontier) provide magnification maps that will, in turn, form the basis for the exploration of the high-redshift Universe. We classify SNe using combined photometric and spectroscopic observations, finding two of the three to be clearly of Type Ia and the third probable. The SNe exhibit significant amplification, up to a factor of 1.7 at similar to 5 Sigma significance (SN-L2). We conducted this as a blind study to avoid fine-tuning of parameters, finding a mean amplification difference between SNe and the cluster lensing models of 0.09 +/- 0.09(stat) +/- 0.05(sys) mag. This impressive agreement suggests no tension between cluster mass models and high-redshift-standardized SNe Ia. However, the measured statistical dispersion of Sigma(mu) = 0.21 mag appeared large compared to the dispersion expected based on statistical uncertainties (0.14). Further work with the SN and cluster lensing models, post-unblinding, reduced the measured dispersion to Sigma(mu) = 0.12. An explicit choice should thus be made as to whether SNe are used unblinded to improve the model, or blinded to test the model. As the lensed SN samples grow larger, this technique will allow improved constraints on assumptions regarding e.g. the structure of the dark matter halo.
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| 47. |
- Rubin, D., et al.
(författare)
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Precision Measurement of The Most Distant Spectroscopically Confirmed Supernova Ia with the Hubble Space Telescope
- 2013
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 763:1, s. 35-
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Tidskriftsartikel (refereegranskat)abstract
- We report the discovery of a redshift 1.71 supernova in the GOODS-North field. The Hubble Space Telescope (HST) ACS spectrum has almost negligible contamination from the host or neighboring galaxies. Although the rest-frame-sampled range is too blue to include any Si II line, a principal component analysis allows us to confirm it as a Type Ia supernova with 92% confidence. A recent serendipitous archival HST WFC3 grism spectrum contributed a key element of the confirmation by giving a host-galaxy redshift of 1.713 +/- 0.007. In addition to being the most distant SN Ia with spectroscopic confirmation, this is the most distant Ia with a precision color measurement. We present the ACS WFC and NICMOS 2 photometry and ACS and WFC3 spectroscopy. Our derived supernova distance is in agreement with the prediction of CDM.
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| 48. |
- Sakornsakolpat, Phuwanat, et al.
(författare)
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Genetic landscape of chronic obstructive pulmonary disease identifies heterogeneous cell-type and phenotype associations
- 2019
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 51:3, s. 494-505
-
Tidskriftsartikel (refereegranskat)abstract
- Chronic obstructive pulmonary disease (COPD) is the leading cause of respiratory mortality worldwide. Genetic risk loci provide new insights into disease pathogenesis. We performed a genome-wide association study in 35,735 cases and 222,076 controls from the UK Biobank and additional studies from the International COPD Genetics Consortium. We identified 82 loci associated with P < 5 x 10-8; 47 of these were previously described in association with either COPD or population-based measures of lung function. Of the remaining 35 new loci, 13 were associated with lung function in 79,055 individuals from the SpiroMeta consortium. Using gene expression and regulation data, we identified functional enrichment of COPD risk loci in lung tissue, smooth muscle, and several lung cell types. We found 14 COPD loci shared with either asthma or pulmonary fibrosis. COPD genetic risk loci clustered into groups based on associations with quantitative imaging features and comorbidities. Our analyses provide further support for the genetic susceptibility and heterogeneity of COPD.
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| 49. |
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| 50. |
- Werth, V, et al.
(författare)
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BIIB059, A HUMANIZED MONOCLONAL ANTIBODY TARGETING BDCA2 ON PLASMACYTOID DENDRITIC CELLS (PDC), SHOWS DOSE-RELATED EFFICACY IN THE PHASE 2 LILAC STUDY IN PATIENTS (PTS) WITH ACTIVE CUTANEOUS LUPUS ERYTHEMATOSUS (CLE)
- 2020
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Ingår i: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ. - 0003-4967 .- 1468-2060. ; 79, s. 120-121
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- CLE represents an unmet medical need with no approved therapy. BIIB059, a humanized monoclonal antibody, binds to BDCA2 and inhibits pro-inflammatory mediators production, including type I interferons. BIIB059 was evaluated in Phase 1 studiesNCT02106897andNCT03224793. LILAC is a 2-part Phase 2 study: Part A enrolled SLE pts; Part B enrolled pts with active CLE (NCT02847598).Objectives:Evaluate efficacy and safety of BIIB059 in pts enrolled in Part B at Week 16, end of treatment (EOT) period.Methods:Pts with active CLE, SCLE and/or CCLE and adjudicated Cutaneous Lupus Disease Area and Severity Index – Activity (CLASI-A) ≥8 were enrolled and randomized to receive either BIIB059 (50, 150 or 450 mg) or placebo (PBO) s.c. Q4W. Primary endpoint was dose response defined by % change in CLASI-A score from baseline (BL) to Week 16. Secondary endpoints included CLASI-50 response rate and ≥ 7-point reduction in CLASI-A score from baseline to EOT. Adverse events and serious adverse events were recorded throughout the study.Results:132 pts with active CLE were randomized. The study met its primary endpoint, demonstrating a dose response (p= 0.0005) and a statistically significant difference in % change from BL in CLASI-A score in BIIB059-treated pts vs PBO. Table 1 and Table 2 summarize efficacy and safety results, respectively.Table 1.Efficacy EndpointsBIIB059PBO50 mg150 mg450 mgLS Mean (SE)LS Mean (SE)LSMD*from PBO (95% CI)P val.LS Mean(SE)LSMD*from PBO (95% CI)P val.LS Mean(SE)LSMD*from PBO (95% CI)P val.Primary EndpointCLASI-A % change from BL-14.5 (6.4)-40.8 (7.5)-26.3 (-45.7; -7.0)0.008-47.9 (7.4)-33.5 (-52.7; -14.3)0.001-43.5 (5.5)-28.0 (-44.5; -11.5)0.001Secondary Endpointsn(%)n(%)LSMD*from PBO (95% CI)P val.n(%)LSMD*from PBO (95% CI)P val.n(%)LSMD*from PBO (95% CI)P val.Prop. of participants achieving CLASI 507/32 (21.9%)10/26 (38.5%)15.8% (-7; 39)0.13311/25 (44.0%)21 (-2.8; 45)0.05920/43 (46.5%)23 (3; 44)0.024Prop. of participants achieving a ≥7-point CLASI-A reduction from BL7/32 (21.9%)9/26 (34.6%)12.3 (-11.3; 35.8)0.22812/25 (48.0%)22.2 (-2.0; 46.3)0.05518/43 (41.8%)16.8 (-6.7; 40.4)0.048*LSMD=LS Mean DifferencePBOBIIB059OVERALLN=3350 mgN=26150 mgN=25450 mgN=48PooledN=99N=132Any Event, n(%)18 (54.5)17 (65.4)12 (48)33 (68.8)62 (62.6)80 (60.6)SeverityMild11 (33.3)11 (42.3)8 (32.0)19 (39.6)38 (38.4)49 (37.1)Moderate4 (12.1)6 (23.1)3 (12.0)12 (25.0)21 (21.2)25 (18.9)Severe3 (9.1)01 (4.0)2 (4.2)3 (3.0)6 (4.5)Related events6 (18.2)9 (34.6)4 (16.0)16 (33.3)29 (29.3)35 (26.5)Serious events2 (6.1)03 (12.0)2 (4.2)5 (5.1)7 (5.3)Related serious events1 (3.0)01 (4.0)1 (2.1)2 (2.0)3 (2.3)Events leading to drug withdrawal01 (3.8)1 (4.0)1 (2.1)3 (3.0)3 (2.3)Events leading to study withdrawal0001 (2.1)1 (1.0)1 (0.8)Fatal events000000Conclusion:BIIB059 administration to pts with active CLE resulted in statistically significant dose-related improvement in disease activity vs PBO with no untoward safety signals. Further development of BIIB059 in CLE is warranted.Disclosure of Interests:Victoria Werth Grant/research support from: Biogen, Celgene, Gilead, Janssen, Viela, Consultant of: Biogen, Gilead, Janssen, Abbvie, GSK, Resolve, AstraZeneca, Amgen, Eli Lilly, EMD Serono, BMS, Viela, Kyowa Kirin, Richard Furie Grant/research support from: AstraZeneca, Biogen, Consultant of: AstraZeneca, Biogen, Juanita Romero-Diaz Consultant of: Biogen, Sandra Navarra Speakers bureau: Astellas, Novartis, Pfizer, Johnson & Johnson, Abbvie, Kenneth Kalunian Grant/research support from: Pfizer, Lupus Research Alliance, Sanford Consortium, Consultant of: Genentech, Nektar, BMS, Janssen, AstraZeneca, Biogen, Vielabio, Equillium, Eli Lilly, ILTOO, Abbvie, Amgen, Roche, Gilead, Ronald van Vollenhoven Grant/research support from: AbbVie, Arthrogen, Bristol-Myers Squibb, GlaxoSmithKline, Lilly, Pfizer, and UCB, Consultant of: AbbVie, AstraZeneca, Biotest, Bristol-Myers Squibb, Celgene, GSK, Janssen, Lilly, Medac, Merck, Novartis, Pfizer, Roche, and UCB, Filippa Nyberg Consultant of: Biogen, Benjamin Kaffenberger Grant/research support from: Amgen, Biogen, InflaRx, Veloce Biopharmaceuticals, Dermatology Foundation, Saira Sheikh: None declared, Goran Radunovic: None declared, XIAOBI HUANG Shareholder of: Biogen, Employee of: Biogen, HUA CARROLL Shareholder of: Biogen, Employee of: Biogen, Francois Gaudreault Shareholder of: Biogen, Employee of: Biogen, Adam Meyers Shareholder of: Biogen, Employee of: Biogen, Catherine Barbey Shareholder of: Biogen, Employee of: Biogen, Cristina Musselli Shareholder of: Biogen, Employee of: Biogen, NATHALIE FRANCHIMONT Shareholder of: Biogen, Employee of: Biogen
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