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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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- Sugita, S., et al.
(författare)
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The geomorphology, color, and thermal properties of Ryugu: Implications for parent-body processes
- 2019
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Ingår i: Science. - : AAAS. - 0036-8075 .- 1095-9203. ; 364:6437
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Tidskriftsartikel (refereegranskat)abstract
- Asteroids fall to Earth in the form of meteorites, but these provide little information about their origins. The Japanese mission Hayabusa2 is designed to collect samples directly from the surface of an asteroid and return them to Earth for laboratory analysis. Three papers in this issue describe the Hayabusa2 team's study of the near-Earth carbonaceous asteroid 162173 Ryugu, at which the spacecraft arrived in June 2018 (see the Perspective by Wurm). Watanabeet al.measured the asteroid's mass, shape, and density, showing that it is a “rubble pile” of loose rocks, formed into a spinning-top shape during a prior period of rapid spin. They also identified suitable landing sites for sample collection. Kitazatoet al.used near-infrared spectroscopy to find ubiquitous hydrated minerals on the surface and compared Ryugu with known types of carbonaceous meteorite. Sugitaet al.describe Ryugu's geological features and surface colors and combined results from all three papers to constrain the asteroid's formation process. Ryugu probably formed by reaccumulation of rubble ejected by impact from a larger asteroid. These results provide necessary context to understand the samples collected by Hayabusa2, which are expected to arrive on Earth in December 2020.Science, this issue p.268, p.272, p.eaaw0422; see also p.230
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- Iwata, S., et al.
(författare)
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Therapeutic hypothermia can be induced and maintained using either commercial water bottles or a "phase changing material'' mattress in a newborn piglet model
- 2009
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Ingår i: Archives of Disease in Childhood. - : BMJ. - 0003-9888 .- 1468-2044. ; 94:5, s. 387-391
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Tidskriftsartikel (refereegranskat)abstract
- Background: Therapeutic hypothermia, a safe and effective treatment for neonatal encephalopathy in an intensive care setting, is not available in low-resource settings. Aims/Methods: To assess two low-tech, low-cost cooling devices for use in low-resource settings: (i) commercially available water bottles filled with tepid water (25 degrees C); (ii) a mattress made of phase changing material (PCM) with a melting point of 32 degrees C (PCM works as a heat buffer at this temperature). Eleven anaesthetised newborn piglets were studied following transient hypoxia-ischaemia. The cooling device was applied 2-26 h after hypoxia-ischaemia with a target rectal temperature (T-rectal) of 33-34 degrees C. T-rectal undershoot was adjusted using cotton blankets; the cooling device was renewed when T-rectal rose above 35 degrees C. T-rectal data during cooling were dichotomised (within or without target) to assess: (a) the total period within the target T-rectal range; (b) the stability and fluctuation of T-rectal during cooling. Results: Therapeutic hypothermia was achieved with both water bottles (n=5) and the PCM mattress (n=6). The mean (SD) time to reach target T-rectal was 1.8 (0.5) h with water bottles and 1.9 (0.3) h with PCM. PCM cooling led to a longer period within the target T-rectal range (p<0.01) and more stable cooling (p<0.05). Water bottle cooling required device renewal (in four out of five piglets). Conclusion: Simple, low-tech cooling devices can induce and maintain therapeutic hypothermia effectively in a porcine model of neonatal encephalopathy, although frequent fine tuning by adjusting the number of blankets insulating the piglet was required to maintain a stable temperature. PCM may induce more stable cooling compared with water bottles.
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- Sakaguchi, M., et al.
(författare)
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FoxK1 and FoxK2 in insulin regulation of cellular and mitochondrial metabolism
- 2019
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- A major target of insulin signaling is the FoxO family of Forkhead transcription factors, which translocate from the nucleus to the cytoplasm following insulin-stimulated phosphorylation. Here we show that the Forkhead transcription factors FoxK1 and FoxK2 are also downstream targets of insulin action, but that following insulin stimulation, they translocate from the cytoplasm to nucleus, reciprocal to the translocation of FoxO1. FoxK1/FoxK2 translocation to the nucleus is dependent on the Akt-mTOR pathway, while its localization to the cytoplasm in the basal state is dependent on GSK3. Knockdown of FoxK1 and FoxK2 in liver cells results in upregulation of genes related to apoptosis and down-regulation of genes involved in cell cycle and lipid metabolism. This is associated with decreased cell proliferation and altered mitochondrial fatty acid metabolism. Thus, FoxK1/K2 are reciprocally regulated to FoxO1 following insulin stimulation and play a critical role in the control of apoptosis, metabolism and mitochondrial function.
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- Schoehe, S., et al.
(författare)
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Free-charge carrier parameters of n-type, p-type and compensated InN:Mg determined by infrared spectroscopic ellipsometry
- 2014
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Ingår i: Thin Solid Films. - : Elsevier. - 0040-6090 .- 1879-2731. ; 571, s. 384-388
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Tidskriftsartikel (refereegranskat)abstract
- Infrared spectroscopic ellipsometry is applied to investigate the free-charge carrier properties of Mg-doped InN films. Two representative sets of In-polar InN grown by molecular beam epitaxy with Mg concentrations ranging from 1.2 x 10(17) cm(-3) to 8 x 10(20) cm(-3) are compared. P-type conductivity is indicated for the Mg concentration range of 1 x 10(18) cm(-3) to 9 x 10(19) cm(-3) from a systematic investigation of the longitudinal optical phonon plasmon broadening and the mobility parameter in dependence of the Mg concentration. A parameterized model that accounts for the phonon-plasmon coupling is applied to determine the free-charge carrier concentration and mobility parameters in the doped bulk InN layer as well as the GaN template and undoped InN buffer layer for each sample. The free-charge carrier properties in the second sample set are consistent with the results determined in a comprehensive analysis of the first sample set reported earlier [Schoche et al., J. Appl. Phys. 113, 013502 (2013)]. In the second set, two samples with Mg concentration of 2.3 x 10(20) cm(-3) are identified as compensated n-type InN with very low electron concentrations which are suitable for further investigation of intrinsic material properties that are typically governed by high electron concentrations even in undoped InN. The compensated n-type InN samples can be clearly distinguished from the p-type conductive material of similar plasma frequencies by strongly reduced phonon plasmon broadening.
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