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- Ruilope, LM, et al.
(author)
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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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In: American journal of nephrology. - : S. Karger AG. - 1421-9670 .- 0250-8095. ; 50:5, s. 345-356
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Journal article (peer-reviewed)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. |
- Ferreira, Mjv, et al.
(author)
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Poster Session 3 : Tuesday 5 May 2015, 08
- 2015
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In: European Heart Journal Cardiovascular Imaging. - : Oxford University Press (OUP). - 2047-2404 .- 2047-2412. ; 16 Suppl 1
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Journal article (peer-reviewed)
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- Hellberg, F, et al.
(author)
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Investigating the breakup dynamics of dihydrogen sulfide ions recombining with electrons
- 2005
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In: Journal of Chemical Physics. - : AIP Publishing. - 0021-9606 .- 1089-7690. ; 122:22, s. 224314-
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Journal article (peer-reviewed)abstract
- This paper presents results concerning measurements of the dissociative recombination (DR) of dihydrogen sulfide ions. In combination with the ion storage ring CRYRING an imaging technique was used to investigate the breakup dynamics of the three-body channel in the DR of (SD2+)-S-32. The two energetically available product channels S(P-3)+2D(S-2) and S(D-1)+2D(S-2) were both populated, with a branching fraction of the ground-state channel of 0.6(0.1). Information about the angle between the two deuterium atoms upon dissociation was obtained together with information about how the available kinetic energy was distributed between the two light fragments. The recombination cross sections as functions of energy in the interval of 1 meV to 0.3 eV in the center-of-mass frame are presented for (SH2+)-S-34. The thermal rate coefficient for the DR of (SH2+)-S-34 was determined to be (4.8 +/- 1.0)x10(-7)(T/300)(-0.72 +/- 0.1) cm(3) s(-1) over this interval.
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| 14. |
- Hellberg, I., et al.
(author)
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3D analysis and grading of calcifications from ex vivo human meniscus
- 2023
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In: Osteoarthritis and Cartilage. - : Elsevier BV. - 1063-4584. ; 31:4, s. 482-492
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Journal article (peer-reviewed)abstract
- Objective: Meniscal calcifications are associated with the pathogenesis of knee osteoarthritis (OA). We propose a micro-computed tomography (μCT) based 3D analysis of meniscal calcifications ex vivo, including a new grading system. Method: Human medial and lateral menisci were obtained from 10 patients having total knee replacement for medial compartment OA and 10 deceased donors without knee OA (healthy references). The samples were fixed; one subsection was imaged with μCT, and the adjacent tissue was processed for histological evaluation. Calcifications were examined from the reconstructed 3D μCT images, and a new grading system was developed. To validate the grading system, meniscal calcification volumes (CVM) were quantitatively analyzed and compared between the calcification grades. Furthermore, we estimated the relationship between histopathological degeneration and the calcification severity. Results: 3D μCT images depict calcifications in every sample, including diminutive calcifications that are not visible in histology. In the new grading system, starting from grade 2, each grade results in a CVM that is 20.3 times higher (95% CI 13.3–30.5) than in the previous grade. However, there was no apparent difference in CVM between grades 1 and 2. The calcification grades appear to increase with the increasing histopathological degeneration, although histopathological degeneration is also observed with small calcification grades. Conclusions: 3D μCT grading of meniscal calcifications is feasible. Interestingly, it seems that there are two patterns of degeneration in the menisci of our sample set: 1) with diminutive calcifications (calcification grades 1–2), and 2) with large to widespread calcifications (calcification grades 3–5).
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- Thacher, J. D., et al.
(author)
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Tobacco smoke exposure in early life and adolescence in relation to lung function
- 2018
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In: European Respiratory Journal. - : European Respiratory Society (ERS). - 0903-1936 .- 1399-3003. ; 51:6
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Journal article (peer-reviewed)abstract
- Maternal smoking during pregnancy is associated with impaired lung function among young children, but less is known about long-term effects and the impact of adolescents' own smoking. We investigated the influence of maternal smoking during pregnancy, secondhand smoke exposure and adolescent smoking on lung function at age 16 years. The BAMSE (Barn/Child, Allergy, Milieu, Stockholm, Epidemiology) birth cohort collected information on participants' tobacco smoke exposure through repeated questionnaires, and measured saliva cotinine concentrations at age 16 years. Participants performed spirometry and impulse oscillometry (IOS) at age 16 years (n=2295). Exposure to maternal smoking during pregnancy was associated with reduced forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ratio of -1.1% (95% CI -2.0 to -0.2%). IOS demonstrated greater resistance at 5-20 Hz (R5-20) in participants exposed to maternal smoking during pregnancy. Adolescents who smoked had reduced FEV1/FVC ratios of -0.9% (95% CI -1.8 to -0.1%) and increased resistance of 6.5 Pa.L-1.s (95% CI 0.7 to 12.2 Pa.L-1.s) in R5-20. Comparable associations for FEV1/FVC ratio were observed for cotinine concentrations, using. 12 ng.mL(-1) as a cut-off for adolescent smoking. Maternal smoking during pregnancy was associated with lower FEV1/FVC ratios and increased airway resistance. In addition, adolescent smoking appears to be associated with reduced FEV1/FVC ratios and increased peripheral airway resistance.
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| 17. |
- Thomas, R. D., et al.
(author)
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Hot Water from Cold. The Dissociative Recombination of Water Cluster Ions
- 2010
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In: Journal of Physical Chemistry A. - : American Chemical Society (ACS). - 1089-5639 .- 1520-5215. ; 114:14, s. 4843-4846
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Journal article (peer-reviewed)abstract
- Dissociative recombination of the Zundel cation D(5)O(2)(+) almost exclusively produces D + 2 D(2)O with a maximum kinetic energy release of 5.1 eV. An imaging technique is used to investigate the distribution of the available reaction energy among these products. Analysis shows that as much as 4 eV can be stored internally by the molecular fragments, with a preference for producing highly excited molecular fragments, and that the deuteron shows a nonrandom distribution of kinetic energies. A possible mechanism and the implications for these observations are addressed.
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| 26. |
- Hult, Annika, et al.
(author)
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Blood group genotype analysis for the quality improvement of reagent test red blood cells
- 2005
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In: Vox Sanguinis. - : Wiley. - 1423-0410 .- 0042-9007. ; 88:4, s. 265-270
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Journal article (peer-reviewed)abstract
- Background and Objectives Reagent red blood cells (RBCs) for antibody detection should express certain important antigens as a double dose, that is, the donors must be homozygous for the corresponding alleles. Traditionally, dose is determined by serological typing and known allele frequencies. However, RHD zygosity cannot be predicted serologically owing to the absence of an antithetical antigen, and FY zygosity is confounded by two variant haplotypes, FY*0 and FY*X. Furthermore, lack of reagents hampers our ability to type for some clinically important antigen pairs such as Do(a)/Do(b). Materials and Methods Genomic DNA was isolated from reagent RBC samples. Established, validated methods were used to determine the RHD, FY, and DO genotypes. Results Three of 52 D+ samples gave results that differed from the predicted genotype: two presumed (RR1)-R-1 samples and an (RR2)-R-2 sample were shown to be R(1)r" and R(2)r', respectively. Five of 59 samples that were from presumed homozygotes for either FY*A or FY*B were heterozygous, together with either FY*X (three samples) or FY*0 (two samples). Seventy-five samples tested for DO were DO*A/A (n = 14), DO*A/B (n = 39), or DO*B/B (n = 22). Conclusions The results show that serologically determined RhD and Duffy phenotypes of reagent RBCs are unreliable and that antigens we thought were represented as a double dose were single dose. The addition of Dombrock genotyping provides information which is useful in antibody identification. We conclude that selected genotype analyses are a valuable quality assurance measure to ensure that reagent RBCs comply with national and international recommendations for test sensitivity.
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| 27. |
- Irshaid, N M, et al.
(author)
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Phenotype prediction by DNA-based typing of clinically significant blood group systems in Jordanian blood donors.
- 2002
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In: Vox Sanguinis. - : Wiley. - 1423-0410 .- 0042-9007. ; 83:1, s. 55-62
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Journal article (peer-reviewed)abstract
- BACKGROUND AND OBJECTIVES: During the past 10 years several DNA-typing methods have been developed to complement routine serological typing for determination of polymorphisms in the ABO, RH, KEL, JK and FY blood group genes. However, the molecular basis of blood groups can differ widely between ethnic groups. The purpose of this study was to evaluate selected DNA-based methods for phenotype prediction in a population not previously investigated. MATERIALS AND METHODS: Blood samples from a random sample of Jordanian blood donors were collected and red cells isolated from these blood samples were phenotyped for common ABO (n = 150) and KEL/FY/JK (n = 90) antigens. RHD-negative and -positive donors were selected for RH typing (n = 120 and 30, respectively). DNA was prepared and blood group genotyping performed according to selected methods in current use. Discordant samples required further investigation by extended serology and DNA sequencing. RESULTS: The degree of concordance between phenotype and genotype was high, but some exceptions were noted. Two of 14 A2/A2B samples lacked all mutations associated with known A2 alleles of the ABO system. RH typing revealed four samples with the c(cyt48) marker, causing false-positive RHC typing. A single D-negative sample was positive for D-specific exon 10 markers. The RHD pseudogene was not found in the 150 donors tested. Nine samples revealed discrepancies that were associated with unknown silent or weakly expressing Fyb-like alleles. CONCLUSIONS: With the exception of the FY system, we conclude that the molecular background of the clinically important blood group antigens studied here is similar to that reported for Caucasoids.
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