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- Ruilope, LM, et al.
(författare)
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Design and Baseline Characteristics of the Finerenone in Reducing Cardiovascular Mortality and Morbidity in Diabetic Kidney Disease Trial
- 2019
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Ingår i: American journal of nephrology. - : S. Karger AG. - 1421-9670 .- 0250-8095. ; 50:5, s. 345-356
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Tidskriftsartikel (refereegranskat)abstract
- <b><i>Background:</i></b> Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. <b><i>Patients and</i></b> <b><i>Methods:</i></b> The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate ≥25 mL/min/1.73 m<sup>2</sup> and albuminuria (urinary albumin-to-creatinine ratio ≥30 to ≤5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level α = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. <b><i>Conclusions:</i></b> FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049.
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- Shimwell, T. W., et al.
(författare)
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The LOFAR Two-metre Sky Survey: II. First data release
- 2019
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 622
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Forskningsöversikt (refereegranskat)abstract
- The LOFAR Two-metre Sky Survey (LoTSS) is an ongoing sensitive, high-resolution 120-168 MHz survey of the entire northern sky for which observations are now 20% complete. We present our first full-quality public data release. For this data release 424 square degrees, or 2% of the eventual coverage, in the region of the HETDEX Spring Field (right ascension 10h45m00s to 15h30m00s and declination 45°00′00″ to 57°00′00″) were mapped using a fully automated direction-dependent calibration and imaging pipeline that we developed. A total of 325 694 sources are detected with a signal of at least five times the noise, and the source density is a factor of ∼10 higher than the most sensitive existing very wide-area radio-continuum surveys. The median sensitivity is S144 MHz = 71 μJy beam -1 and the point-source completeness is 90% at an integrated flux density of 0.45 mJy. The resolution of the images is 6″ and the positional accuracy is within 0.2″. This data release consists of a catalogue containing location, flux, and shape estimates together with 58 mosaic images that cover the catalogued area. In this paper we provide an overview of the data release with a focus on the processing of the LOFAR data and the characteristics of the resulting images. In two accompanying papers we provide the radio source associations and deblending and, where possible, the optical identifications of the radio sources together with the photometric redshifts and properties of the host galaxies. These data release papers are published together with a further ∼20 articles that highlight the scientific potential of LoTSS.
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- Stewart, A. J., et al.
(författare)
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LOFAR MSSS : detection of a low-frequency radio transient in 400 h of monitoring of the North Celestial Pole
- 2016
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 456:3, s. 2321-2342
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Tidskriftsartikel (refereegranskat)abstract
- We present the results of a four-month campaign searching for low-frequency radio transients near the North Celestial Pole with the Low-Frequency Array (LOFAR), as part of the Multifrequency Snapshot Sky Survey (MSSS). The data were recorded between 2011 December and 2012 April and comprised 2149 11-min snapshots, each covering 175 deg2. We have found one convincing candidate astrophysical transient, with a duration of a few minutes and a flux density at 60 MHz of 15–25 Jy. The transient does not repeat and has no obvious optical or high-energy counterpart, as a result of which its nature is unclear. The detection of this event implies a transient rate at 60 MHz of 3.9−3.7+14.7×10−4" style="position: relative;" tabindex="0" id="MathJax-Element-1-Frame" class="MathJax">3.9+14.7−3.7×10−4 d−1 deg−2, and a transient surface density of 1.5 × 10−5 deg−2, at a 7.9-Jy limiting flux density and ∼10-min time-scale. The campaign data were also searched for transients at a range of other time-scales, from 0.5 to 297 min, which allowed us to place a range of limits on transient rates at 60 MHz as a function of observation duration.
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| 8. |
- Buitink, S., et al.
(författare)
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A large light-mass component of cosmic rays at 1017–1017.5 electronvolts from radio observations
- 2016
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 531:7592, s. 70-73
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Tidskriftsartikel (refereegranskat)abstract
- Cosmic rays are the highest-energy particles found in nature. Measurements of the mass composition of cosmic rays with energies of 1017–1018 electronvolts are essential to understanding whether they have galactic or extragalactic sources. It has also been proposed that the astrophysical neutrino signal1 comes from accelerators capable of producing cosmic rays of these energies2. Cosmic rays initiate air showers—cascades of secondary particles in the atmosphere—and their masses can be inferred from measurements of the atmospheric depth of the shower maximum3 (Xmax; the depth of the air shower when it contains the most particles) or of the composition of shower particles reaching the ground4. Current measurements5 have either high uncertainty, or a low duty cycle and a high energy threshold. Radio detection of cosmic rays6, 7, 8 is a rapidly developing technique9 for determining Xmax (refs 10, 11) with a duty cycle of, in principle, nearly 100 per cent. The radiation is generated by the separation of relativistic electrons and positrons in the geomagnetic field and a negative charge excess in the shower front6, 12. Here we report radio measurements of Xmax with a mean uncertainty of 16 grams per square centimetre for air showers initiated by cosmic rays with energies of 1017–1017.5 electronvolts. This high resolution in Xmax enables us to determine the mass spectrum of the cosmic rays: we find a mixed composition, with a light-mass fraction (protons and helium nuclei) of about 80 per cent. Unless, contrary to current expectations, the extragalactic component of cosmic rays contributes substantially to the total flux below 1017.5 electronvolts, our measurements indicate the existence of an additional galactic component, to account for the light composition that we measured in the 1017–1017.5 electronvolt range.
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- Fresard, Laure, et al.
(författare)
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Identification of rare-disease genes using blood transcriptome sequencing and large control cohorts
- 2019
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Ingår i: Nature Medicine. - : NATURE PUBLISHING GROUP. - 1078-8956 .- 1546-170X. ; 25:6, s. 911-919
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Tidskriftsartikel (refereegranskat)abstract
- It is estimated that 350 million individuals worldwide suffer from rare diseases, which are predominantly caused by mutation in a single gene(1). The current molecular diagnostic rate is estimated at 50%, with whole-exome sequencing (WES) among the most successful approaches(2-5). For patients in whom WES is uninformative, RNA sequencing (RNA-seq) has shown diagnostic utility in specific tissues and diseases(6-8). This includes muscle biopsies from patients with undiagnosed rare muscle disorders(6,9), and cultured fibroblasts from patients with mitochondrial disorders(7). However, for many individuals, biopsies are not performed for clinical care, and tissues are difficult to access. We sought to assess the utility of RNA-seq from blood as a diagnostic tool for rare diseases of different pathophysiologies. We generated whole-blood RNA-seq from 94 individuals with undiagnosed rare diseases spanning 16 diverse disease categories. We developed a robust approach to compare data from these individuals with large sets of RNA-seq data for controls (n = 1,594 unrelated controls and n = 49 family members) and demonstrated the impacts of expression, splicing, gene and variant filtering strategies on disease gene identification. Across our cohort, we observed that RNA-seq yields a 7.5% diagnostic rate, and an additional 16.7% with improved candidate gene resolution.
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| 10. |
- Shimwell, T. W., et al.
(författare)
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The LOFAR Two-metre Sky Survey: I. Survey description and preliminary data release
- 2017
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 598, s. Art no A104-
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Tidskriftsartikel (refereegranskat)abstract
- The LOFAR Two-metre Sky Survey (LoTSS) is a deep 120-168 MHz imaging survey that will eventually cover the entire northern sky. Each of the 3170 pointings will be observed for 8 h, which, at most declinations, is sufficient to produce ~5? resolution images with a sensitivity of ~100 ?Jy/beam and accomplish the main scientific aims of the survey, which are to explore the formation and evolution of massive black holes, galaxies, clusters of galaxies and large-scale structure. Owing to the compact core and long baselines of LOFAR, the images provide excellent sensitivity to both highly extended and compact emission. For legacy value, the data are archived at high spectral and time resolution to facilitate subarcsecond imaging and spectral line studies. In this paper we provide an overview of the LoTSS. We outline the survey strategy, the observational status, the current calibration techniques, a preliminary data release, and the anticipated scientific impact. The preliminary images that we have released were created using a fully automated but direction-independent calibration strategy and are significantly more sensitive than those produced by any existing large-Area low-frequency survey. In excess of 44 000 sources are detected in the images that have a resolution of 25?, typical noise levels of less than 0.5 mJy/beam, and cover an area of over 350 square degrees in the region of the HETDEX Spring Field (right ascension 10h45m00s to 15h30m00s and declination 45°00?00? to 57°00?00?).
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