| 1. |
- Aad, G, et al.
(författare)
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- 2015
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swepub:Mat__t
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| 2. |
- 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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| 3. |
- Bennedbaek, M., et al.
(författare)
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Phylogenetic analysis of HIV-1 shows frequent cross-country transmission and local population expansions
- 2021
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Ingår i: Virus Evolution. - : Oxford University Press (OUP). - 2057-1577. ; 7:2
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Tidskriftsartikel (refereegranskat)abstract
- Understanding of pandemics depends on the characterization of pathogen collections from well-defined and demographically diverse cohorts. Since its emergence in Congo almost a century ago, Human Immunodeficiency Virus Type 1 (HIV-1) has geographically spread and genetically diversified into distinct viral subtypes. Phylogenetic analysis can be used to reconstruct the ancestry of the virus to better understand the origin and distribution of subtypes. We sequenced two 3.6-kb amplicons of HIV-1 genomes from 3,197 participants in a clinical trial with consistent and uniform sampling at sites across 35 countries and analyzed our data with another 2,632 genomes that comprehensively reflect the HIV-1 genetic diversity. We used maximum likelihood phylogenetic analysis coupled with geographical information to infer the state of ancestors. The majority of our sequenced genomes (n=2,501) were either pure subtypes (A-D, F, and G) or CRF01_AE. The diversity and distribution of subtypes across geographical regions differed; USA showed the most homogenous subtype population, whereas African samples were most diverse. We delineated transmission of the four most prevalent subtypes in our dataset (A, B, C, and CRF01_AE), and our results suggest both continuous and frequent transmission of HIV-1 over country borders, as well as single transmission events being the seed of endemic population expansions. Overall, we show that coupling of genetic and geographical information of HIV-1 can be used to understand the origin and spread of pandemic pathogens.
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| 4. |
- Gorshunov, B. P., et al.
(författare)
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Subterahertz electrodynamics of (TMTSF)(2)X (X = ClO4, PF6) salts
- 2013
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Ingår i: Journal of Experimental and Theoretical Physics. - 1063-7761 .- 1090-6509. ; 116:3, s. 460-466
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Tidskriftsartikel (refereegranskat)abstract
- The terahertz-subterahertz spectra of the complex permittivity and dynamic conductivity of polycrystalline (TMTSF)(2)ClO4 and (TMTSF)(2)PF6 samples are measured quantitatively. The spectra of (TMTSF)(2)ClO4 have absorption lines at frequencies of 7 and 30 cm(-1). The obtained temperature dependences of the line parameters in the range 5-300 K cast some doubt on the earlier concept of their phonon origin. An excitation is detected at temperatures below 20 K in the frequency range near 30 cm(-1), and its nature is related to the activation of a transverse acoustic phonon caused by the folding of the Brillouin zone due to the ordering of noncentrosymmetrical anions below 20 K. An increase in the carrier relaxation rate is found in this temperature range, which indicates a close relation between the electron and phonon subsystems in (TMTSF)(2)ClO4. Sings of additional low-energy excitations that should manifest themselves at frequencies below 1-2 cm(-1) are detected. (TMTSF)(2)PF6 containing centrosymmetrical anions has no absorption lines in the frequency range 3-20 cm(-1) and the temperature range 5-300 K.
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| 5. |
- Lontchi, Jackson, et al.
(författare)
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Optimization of Back Contact Grid Size in Al2O3-Rear-Passivated Ultrathin CIGS PV Cells by 2-D Simulations
- 2020
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Ingår i: IEEE Journal of Photovoltaics. - 2156-3381 .- 2156-3403. ; 10:6, s. 1908-1917
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Tidskriftsartikel (refereegranskat)abstract
- We present a simulation strategy using ATLAS-2D to optimize the back-contact hole grid (i.e., size and pitch of openings) of the Al 2 O 3 -rear-passivation layer in ultrathin Cu(In,Ga)Se 2 photovoltaic cells. We first discuss and compare our simulation model with a series of experimental nonpassivated and passivated cells to decouple the crucial passivation parameters. The simulation results follow the experimental trends, highlighting the beneficial effects of the passivation on the cell performances. Furthermore, it stresses the influence of the passivation quality at the Al 2 O 3 /Cu(In,Ga)Se 2 (CIGS) interface and of the contact resistance at the Mo/CIGS interface within the openings. Further simulations quantify significant improvements in short-circuit current and open-circuit voltage for different sizes of openings in the Al 2 O 3 layer, relative to an excellent passivation quality (i.e., high density of negative charges in the passivation layer). However, a degradation is predicted for a poor passivation (i.e., low density of such charges) or a high contact resistance. Consequently, we point out an optimum in efficiency when varying the opening widths at fixed hole-pitch and fixed contact resistance. At equivalent contact resistance, simulations predict that the sizes of the pitch and openings can be increased without optimal performance losses when maintaining a width to pitch ratio around 0.2. This simulation trends have been confirmed by a series of experiments, indicating that it is crucial to care about the dimensions of the opening grid and the contact resistance of passivated cells. These simulation results provide significant insights for optimal cell design and characterizations of passivated UT-CIGS PV cells.
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| 6. |
- Zhukova, Nataliya, et al.
(författare)
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WNT activation by lithium abrogates TP53 mutation associated radiation resistance in medulloblastoma
- 2014
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Ingår i: Acta neuropathologica communications. - : Springer Science and Business Media LLC. - 2051-5960. ; 2
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Tidskriftsartikel (refereegranskat)abstract
- TP53 mutations confer subgroup specific poor survival for children with medulloblastoma. We hypothesized that WNT activation which is associated with improved survival for such children abrogates TP53 related radioresistance and can be used to sensitize TP53 mutant tumors for radiation. We examined the subgroup-specific role of TP53 mutations in a cohort of 314 patients treated with radiation. TP53 wild-type or mutant human medulloblastoma cell-lines and normal neural stem cells were used to test radioresistance of TP53 mutations and the radiosensitizing effect of WNT activation on tumors and the developing brain. Children with WNT/TP53 mutant medulloblastoma had higher 5-year survival than those with SHH/TP53 mutant tumours (100% and 36.6%±8.7%, respectively (p<0.001)). Introduction of TP53 mutation into medulloblastoma cells induced radioresistance (survival fractions at 2Gy (SF2) of 89%±2% vs. 57.4%±1.8% (p<0.01)). In contrast, beta-catenin mutation sensitized TP53 mutant cells to radiation (p<0.05). Lithium, an activator of the WNT pathway, sensitized TP53 mutant medulloblastoma to radiation (SF2 of 43.5%±1.5% in lithium treated cells vs. 56.6±3% (p<0.01)) accompanied by increased number of gammaH2AX foci. Normal neural stem cells were protected from lithium induced radiation damage (SF2 of 33%±8% for lithium treated cells vs. 27%±3% for untreated controls (p=0.05). Poor survival of patients with TP53 mutant medulloblastoma may be related to radiation resistance. Since constitutive activation of the WNT pathway by lithium sensitizes TP53 mutant medulloblastoma cells and protect normal neural stem cells from radiation, this oral drug may represent an attractive novel therapy for high-risk medulloblastomas.
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