| 1. |
- 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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| 2. |
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| 3. |
- 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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| 4. |
- O'Connor, C. M., et al.
(författare)
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Effect of nesiritide in patients with acute decompensated heart failure
- 2011
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Ingår i: The New England journal of medicine. - : Massachusetts Medical Society. - 0028-4793 .- 1533-4406. ; 365:1, s. 32-43
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Nesiritide is approved in the United States for early relief of dyspnea in patients with acute heart failure. Previous meta-analyses have raised questions regarding renal toxicity and the mortality associated with this agent. METHODS: We randomly assigned 7141 patients who were hospitalized with acute heart failure to receive either nesiritide or placebo for 24 to 168 hours in addition to standard care. Coprimary end points were the change in dyspnea at 6 and 24 hours, as measured on a 7-point Likert scale, and the composite end point of rehospitalization for heart failure or death within 30 days. RESULTS: Patients randomly assigned to nesiritide, as compared with those assigned to placebo, more frequently reported markedly or moderately improved dyspnea at 6 hours (44.5% vs. 42.1%, P=0.03) and 24 hours (68.2% vs. 66.1%, P=0.007), but the prespecified level for significance (P
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| 5. |
- 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 .- 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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| 6. |
- 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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| 7. |
- Müller, T D, et al.
(författare)
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Ghrelin.
- 2015
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Ingår i: Molecular metabolism. - : Elsevier BV. - 2212-8778. ; 4:6, s. 437-60
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Tidskriftsartikel (refereegranskat)abstract
- The gastrointestinal peptide hormone ghrelin was discovered in 1999 as the endogenous ligand of the growth hormone secretagogue receptor. Increasing evidence supports more complicated and nuanced roles for the hormone, which go beyond the regulation of systemic energy metabolism.
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| 8. |
- Anker, A., et al.
(författare)
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Neutrino vertex reconstruction with in-ice radio detectors using surface reflections and implications for the neutrino energy resolution
- 2019
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Ingår i: Journal of Cosmology and Astroparticle Physics. - : IOP PUBLISHING LTD. - 1475-7516. ; :11
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Tidskriftsartikel (refereegranskat)abstract
- Ultra high energy neutrinos (E-nu >10(16.5) eV) are efficiently measured via radio signals following a neutrino interaction in ice. An antenna placed O(15 m) below the ice surface will measure two signals for the vast majority of events (90% at E-nu = 10(18) eV): a direct pulse and a second delayed pulse from a reflection off the ice surface. This allows for a unique identification of neutrinos against backgrounds arriving from above. Furthermore, the time delay between the direct and reflected signal (D'n'R) correlates with the distance to the neutrino interaction vertex, a crucial quantity to determine the neutrino energy. In a simulation study, we derive the relation between time delay and distance and study the corresponding experimental uncertainties in estimating neutrino energies. We find that the resulting contribution to the energy resolution is well below the natural limit set by the unknown inelasticity in the initial neutrino interaction. We present an in-situ measurement that proves the experimental feasibility of this technique. Continuous monitoring of the local snow accumulation in the vicinity of the transmit and receive antennas using this technique provide a precision of O(1mm) in surface elevation, which is much better than that needed to apply the D'n'R technique to neutrinos.
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| 9. |
- Cowie, M. R., et al.
(författare)
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New medicinal products for chronic heart failure: advances in clinical trial design and efficacy assessment
- 2017
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Ingår i: European Journal of Heart Failure. - : Wiley. - 1388-9842. ; 19:6, s. 718-727
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Tidskriftsartikel (refereegranskat)abstract
- Despite the availability of a number of different classes of therapeutic agents with proven efficacy in heart failure, the clinical course of heart failure patients is characterized by a reduction in life expectancy, a progressive decline in health-related quality of life and functional status, as well as a high risk of hospitalization. New approaches are needed to address the unmet medical needs of this patient population. The European Medicines Agency (EMA) is undertaking a revision of its Guideline on Clinical Investigation of Medicinal Products for the Treatment of Chronic Heart Failure. The draft version of the Guideline was released for public consultation in January 2016. The Cardiovascular Round Table of the European Society of Cardiology (ESC), in partnership with the Heart Failure Association of the ESC, convened a dedicated two-day workshop to discuss three main topic areas of major interest in the field and addressed in this draft EMA guideline: (i) assessment of efficacy (i.e. endpoint selection and statistical analysis); (ii) clinical trial design (i.e. issues pertaining to patient population, optimal medical therapy, run-in period); and (iii) research approaches for testing novel therapeutic principles (i.e. cell therapy). This paper summarizes the key outputs from the workshop, reviews areas of expert consensus, and identifies gaps that require further research or discussion. Collaboration between regulators, industry, clinical trialists, cardiologists, health technology assessment bodies, payers, and patient organizations is critical to address the ongoing challenge of heart failure and to ensure the development and market access of new therapeutics in a scientifically robust, practical and safe way.
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| 10. |
- Anker, A., et al.
(författare)
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A search for cosmogenic neutrinos with the ARIANNA test bed using 4.5 years of data
- 2020
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Ingår i: Journal of Cosmology and Astroparticle Physics. - : IOP PUBLISHING LTD. - 1475-7516. ; :3
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Tidskriftsartikel (refereegranskat)abstract
- The primary mission of the ARIANNA ultra-high energy neutrino telescope is to uncover astrophysical sources of neutrinos with energies greater than 10(16) eV. A pilot array, consisting of seven ARIANNA stations located on the surface of the Ross Ice Shelf in Antarctica, was commissioned in November 2014. We report on the search for astrophysical neutrinos using data collected between November 2014 and February 2019. A straight-forward template matching analysis yielded no neutrino candidates, with a signal efficiency of 79%. We find a 90% confidence upper limit on the diffuse neutrino flux of E-2 Phi = 1.7 x 10(-6) GeV cm(-2) s(-1) sr(-1) for a decade wide logarithmic bin centered at a neutrino energy of 10(18),eV, which is an order of magnitude improvement compared to the previous limit reported by the ARIANNA collaboration. The ARIANNA stations, including purpose built cosmic-ray stations at the Moore's Bay site and demonstrator stations at the South Pole, have operated reliably. Sustained operation at two distinct sites confirms that the flexible and adaptable architecture can be deployed in any deep ice, radio quiet environment. We show that the scientific capabilities, technical innovations, and logistical requirements of ARIANNA are sufficiently well understood to serve as the basis for large area radio-based neutrino telescope with a wide field-of-view.
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