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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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- Wang, J., et al.
(författare)
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Final report of the CCQM-K145 : Toxic and essential elements in bovine liver
- 2020
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Ingår i: Metrologia. - : IOP Publishing Ltd. - 0026-1394 .- 1681-7575. ; 57:1 A
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Tidskriftsartikel (refereegranskat)abstract
- Liver plays a major role in metabolism and acts as a source of energy for the body by storing glycogen. With the growing interest and investigation in the biological effects in recent years, it is important and necessary to develop accurate and comparable analytical methods for elements in bio-samples. It has, however, been 10 years since the tissue sample (bovine liver) of CCQM-K49 key comparison. The purpose of CCQM-K145 is to ensure the comparable and traceable measurement results for essential and toxic elements such as P, S, Zn, Mn, Ni, Mo, Sr, Cr, Co, Pb, As and Hg in bovine liver among NMIs and other designated measurement bodies worldwide. The comparison was agreed by IAWG as 6th IAWG Benchmarking Exercise with Zn and Ni as exemplary elements at the meeting in Korea in the early October 2016. The results of CCQM-K145 are expected to cover the measurement capability and support CMCs claiming for inorganic elements in the similar biological tissue materials and food samples. 30 NMIs and DIs registered in CCQM-K145. With respect to the methodology, a variety of techniques such as IDMS, ICP-OES, ICP-MS(non-ID), AAS and NAA were adopted by the participants. For Zn, Ni, Sr, Pb and Hg measurements, most participants chose ID-ICP-MS method, which showed the better performance in terms of consistency and reliability of the measurement results. In aspect of the traceability for the measurement results in CCQM-K145, most participants used their own (in house) CRMs or other NMI's CRMs to guarantee trace to SI unit. Most participants used similar matrix CRMs for quality control or method validation. Base on different statistic way to calculate the reference mass fraction values and associated uncertainties for each measurand, removal of the suspected extreme values, and discussion at the IAWG meetings, the median values are proposed as the KCRV for Zn, Ni, Mn, Mo, Cr, Pb and Hg; the arithmetic mean values are proposed as the KCRV for P, S, Sr, Co and As. In general, the performances of the majority of CCQM-K145 participants are very good, illustrating their measurement capabilities for Zn, Ni, P, S, Mn, Mo, Sr, Cr, As, Co, Pb and Hg in a complex biological tissue matrix. Bovine liver contains many kinds of nutrients and microelements, it can be regarded as a typical representative material of biological tissue and food. In CCQM-K145, the analytes involved alkali metals and transition elements, metalloids/semi-metals and non metals with a range of mass fraction from mg/g to μg/kg. CCQM-K145 also tested the ability of NMIs/DIs to determine elements that were easy to be lost and polluted, and interfered significantly. The chemical pretreatment methods of samples used in the comparison is suitable for general food and biological matrix samples. A variety of measurement methods used in the comparison represent the main instrumental technology for elemental analysis. Therefore, for supporting CMC claim, CCQM-K145 is readily applicable to measurement of more elements in a wide range of biological materials (including liquids and solids) and meat products. Main text To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by the CCQM, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).
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- Heuer, V. B., et al.
(författare)
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Temperature limits to deep subseafloor life in the Nankai Trough subduction zone
- 2020
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 370:6521, s. 1230-1234
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Tidskriftsartikel (refereegranskat)abstract
- Microorganisms in marine subsurface sediments substantially contribute to global biomass. Sediments warmer than 40 degrees C account for roughly half the marine sediment volume, but the processes mediated by microbial populations in these hard-to-access environments are poorly understood. We investigated microbial life in up to 1.2-kilometer-deep and up to 120 degrees C hot sediments in the Nankai Trough subduction zone. Above 45 degrees C, concentrations of vegetative cells drop two orders of magnitude and endospores become more than 6000 times more abundant than vegetative cells. Methane is biologically produced and oxidized until sediments reach 80 degrees to 85 degrees C. In 100 degrees to 120 degrees C sediments, isotopic evidence and increased cell concentrations demonstrate the activity of acetate-degrading hyperthermophiles. Above 45 degrees C, populated zones alternate with zones up to 192 meters thick where microbes were undetectable.
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- Screaton, E., et al.
(författare)
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Interactions between deformation and fluids in the frontal thrust region of the NanTroSEIZE transect offshore the Kii Peninsula, Japan : Results from IODP Expedition 316 Sites C0006 and C0007
- 2009
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Ingår i: Geochemistry Geophysics Geosystems. - 1525-2027. ; 10, s. Q0AD01-
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Tidskriftsartikel (refereegranskat)abstract
- Integrated Ocean Drilling Program (IODP) Expedition 316 Sites C0006 and C0007 examined the deformation front of the Nankai accretionary prism offshore the Kii Peninsula, Japan. In the drilling area, the frontal thrust shows unusual behavior as compared to other regions of the Nankai Trough. Drilling results, integrated with observations from seismic reflection profiles, suggest that the frontal thrust has been active since similar to 0.78-0.436 Ma and accommodated similar to 13 to 34% of the estimated plate convergence during that time. The remainder has likely been distributed among out-of-sequence thrusts further landward and/or accommodated through diffuse shortening. Unlike results of previous drilling on the Nankai margin, porosity data provide no indication of undercompaction beneath thrust faults. Furthermore, pore water geochemistry data lack clear indicators of fluid flow from depth. These differences may be related to coarser material with higher permeability or more complex patterns of faulting that could potentially provide more avenues for fluid escape. In turn, fluid pressures may affect deformation. Well-drained, sand-rich material under the frontal thrust could have increased fault strength and helped to maintain a large taper angle near the toe. Recent resumption of normal frontal imbrication is inferred from seismic reflection data. Associated decollement propagation into weaker sediments at depth may help explain evidence for recent slope failures within the frontal thrust region. This evidence consists of seafloor bathymetry, normal faults documented in cores, and low porosities in near surface sediments that suggest removal of overlying material. Overall, results provide insight into the complex interactions between incoming materials, deformation, and fluids in the frontal thrust region.
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| 9. |
- Inagaki-Kawata, Y, et al.
(författare)
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Genetic and clinical landscape of breast cancers with germline BRCA1/2 variants
- 2020
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Ingår i: Communications biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1, s. 578-
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Tidskriftsartikel (refereegranskat)abstract
- The genetic and clinical characteristics of breast tumors with germline variants, including their association with biallelic inactivation through loss-of-heterozygosity (LOH) and second somatic mutations, remain elusive. We analyzed germline variants of 11 breast cancer susceptibility genes for 1,995 Japanese breast cancer patients, and identified 101 (5.1%) pathogenic variants, including 62 BRCA2 and 15 BRCA1 mutations. Genetic analysis of 64 BRCA1/2-mutated tumors including TCGA dataset tumors, revealed an association of biallelic inactivation with more extensive deletions, copy neutral LOH, gain with LOH and younger onset. Strikingly, TP53 and RB1 mutations were frequently observed in BRCA1- (94%) and BRCA2- (9.7%) mutated tumors with biallelic inactivation. Inactivation of TP53 and RB1 together with BRCA1 and BRCA2, respectively, involved LOH of chromosomes 17 and 13. Notably, BRCA1/2 tumors without biallelic inactivation were indistinguishable from those without germline variants. Our study highlights the heterogeneity and unique clonal selection pattern in breast cancers with germline variants.
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