| 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. |
- Niemi, MEK, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 3. |
- Arnau-Soler, A, et al.
(författare)
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Genome-wide by environment interaction studies of depressive symptoms and psychosocial stress in UK Biobank and Generation Scotland
- 2019
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Ingår i: Translational psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 9:1, s. 14-
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Tidskriftsartikel (refereegranskat)abstract
- Stress is associated with poorer physical and mental health. To improve our understanding of this link, we performed genome-wide association studies (GWAS) of depressive symptoms and genome-wide by environment interaction studies (GWEIS) of depressive symptoms and stressful life events (SLE) in two UK population-based cohorts (Generation Scotland and UK Biobank). No SNP was individually significant in either GWAS, but gene-based tests identified six genes associated with depressive symptoms in UK Biobank (DCC, ACSS3, DRD2, STAG1, FOXP2 and KYNU; p < 2.77 × 10−6). Two SNPs with genome-wide significant GxE effects were identified by GWEIS in Generation Scotland: rs12789145 (53-kb downstream PIWIL4; p = 4.95 × 10−9; total SLE) and rs17070072 (intronic to ZCCHC2; p = 1.46 × 10−8; dependent SLE). A third locus upstream CYLC2 (rs12000047 and rs12005200, p < 2.00 × 10−8; dependent SLE) when the joint effect of the SNP main and GxE effects was considered. GWEIS gene-based tests identified: MTNR1B with GxE effect with dependent SLE in Generation Scotland; and PHF2 with the joint effect in UK Biobank (p < 2.77 × 10−6). Polygenic risk scores (PRSs) analyses incorporating GxE effects improved the prediction of depressive symptom scores, when using weights derived from either the UK Biobank GWAS of depressive symptoms (p = 0.01) or the PGC GWAS of major depressive disorder (p = 5.91 × 10−3). Using an independent sample, PRS derived using GWEIS GxE effects provided evidence of shared aetiologies between depressive symptoms and schizotypal personality, heart disease and COPD. Further such studies are required and may result in improved treatments for depression and other stress-related conditions.
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| 4. |
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| 5. |
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| 6. |
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| 7. |
- Czamara, D, et al.
(författare)
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Integrated analysis of environmental and genetic influences on cord blood DNA methylation in new-borns
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 2548-
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Tidskriftsartikel (refereegranskat)abstract
- Epigenetic processes, including DNA methylation (DNAm), are among the mechanisms allowing integration of genetic and environmental factors to shape cellular function. While many studies have investigated either environmental or genetic contributions to DNAm, few have assessed their integrated effects. Here we examine the relative contributions of prenatal environmental factors and genotype on DNA methylation in neonatal blood at variably methylated regions (VMRs) in 4 independent cohorts (overall n = 2365). We use Akaike’s information criterion to test which factors best explain variability of methylation in the cohort-specific VMRs: several prenatal environmental factors (E), genotypes in cis (G), or their additive (G + E) or interaction (GxE) effects. Genetic and environmental factors in combination best explain DNAm at the majority of VMRs. The CpGs best explained by either G, G + E or GxE are functionally distinct. The enrichment of genetic variants from GxE models in GWAS for complex disorders supports their importance for disease risk.
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| 8. |
- de Jong, S, et al.
(författare)
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Applying polygenic risk scoring for psychiatric disorders to a large family with bipolar disorder and major depressive disorder
- 2018
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Ingår i: Communications biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 1, s. 163-
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Tidskriftsartikel (refereegranskat)abstract
- Psychiatric disorders are thought to have a complex genetic pathology consisting of interplay of common and rare variation. Traditionally, pedigrees are used to shed light on the latter only, while here we discuss the application of polygenic risk scores to also highlight patterns of common genetic risk. We analyze polygenic risk scores for psychiatric disorders in a large pedigree (n ~ 260) in which 30% of family members suffer from major depressive disorder or bipolar disorder. Studying patterns of assortative mating and anticipation, it appears increased polygenic risk is contributed by affected individuals who married into the family, resulting in an increasing genetic risk over generations. This may explain the observation of anticipation in mood disorders, whereby onset is earlier and the severity increases over the generations of a family. Joint analyses of rare and common variation may be a powerful way to understand the familial genetics of psychiatric disorders.
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| 9. |
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| 10. |
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| 11. |
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| 12. |
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| 13. |
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| 14. |
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| 15. |
- Bravo, L, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 16. |
- Tabiri, S, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 17. |
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| 18. |
- Arvanitis, D, et al.
(författare)
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Magnetic X-ray circular dichroism on in situ grown 3d magnetic thin films on surfaces
- 2001
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Ingår i: JOURNAL OF SYNCHROTRON RADIATION. - : MUNKSGAARD INT PUBL LTD. - 0909-0495. ; 8, s. 120-124
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Tidskriftsartikel (refereegranskat)abstract
- Epitaxic thin and ultrathin films on surfaces allow crystallographic phases that do not occur naturally in the bulk to be stabilized. They also offer new possibilities for an improved understanding of soft X-ray photoabsorption in magnetic systems. Data c
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| 19. |
- Bigdeli, TB, et al.
(författare)
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Genetic effects influencing risk for major depressive disorder in China and Europe
- 2017
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Ingår i: Translational psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 7:3, s. e1074-
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Tidskriftsartikel (refereegranskat)abstract
- Major depressive disorder (MDD) is a common, complex psychiatric disorder and a leading cause of disability worldwide. Despite twin studies indicating its modest heritability (~30–40%), extensive heterogeneity and a complex genetic architecture have complicated efforts to detect associated genetic risk variants. We combined single-nucleotide polymorphism (SNP) summary statistics from the CONVERGE and PGC studies of MDD, representing 10 502 Chinese (5282 cases and 5220 controls) and 18 663 European (9447 cases and 9215 controls) subjects. We determined the fraction of SNPs displaying consistent directions of effect, assessed the significance of polygenic risk scores and estimated the genetic correlation of MDD across ancestries. Subsequent trans-ancestry meta-analyses combined SNP-level evidence of association. Sign tests and polygenic score profiling weakly support an overlap of SNP effects between East Asian and European populations. We estimated the trans-ancestry genetic correlation of lifetime MDD as 0.33; female-only and recurrent MDD yielded estimates of 0.40 and 0.41, respectively. Common variants downstream of GPHN achieved genome-wide significance by Bayesian trans-ancestry meta-analysis (rs9323497; log10 Bayes Factor=8.08) but failed to replicate in an independent European sample (P=0.911). Gene-set enrichment analyses indicate enrichment of genes involved in neuronal development and axonal trafficking. We successfully demonstrate a partially shared polygenic basis of MDD in East Asian and European populations. Taken together, these findings support a complex etiology for MDD and possible population differences in predisposing genetic factors, with important implications for future genetic studies.
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| 20. |
- Campbell, PJ, et al.
(författare)
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Pan-cancer analysis of whole genomes
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 82-
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Tidskriftsartikel (refereegranskat)abstract
- Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1–3. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4–5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5,6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8,9; and evaluates a range of more-specialized features of cancer genomes8,10–18.
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| 21. |
- Davila, ME, et al.
(författare)
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Magnetic circular X-ray dichroism of metastable epitaxial Fe on Cu(100)
- 1999
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Ingår i: JOURNAL OF MAGNETISM AND MAGNETIC MATERIALS. - : ELSEVIER SCIENCE BV. - 0304-8853. ; 197, s. 120-122
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- We report L-edge Magnetic Circular X-Ray Dichroism measurements at 30 K of Fe deposited at 100 K on Cu (1 0 0) in the form of ultrathin films and a wedge. The orbital and spin moments of the wedge differ from those obtained for uniform thickness films. Fo
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| 22. |
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| 23. |
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| 24. |
- Dunn, JH, et al.
(författare)
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In situ MCD magnetometry in the ultrathin limit: Fe on Cu(100)
- 1997
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Ingår i: JOURNAL DE PHYSIQUE IV. - : EDITIONS PHYSIQUE. - 1155-4339. ; 7:C2, s. 383-387
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- By means of Magnetic Circular Dichroism in X-ray Absorption Spectroscopy we investigated the magnetic properties of fct Fe films stabilised by epitaxial growth on the Cu(100) surface. These are compared to bcc like Fe films. The films were characterised i
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| 25. |
- Dunn, JH, et al.
(författare)
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Influence of source coherence on X-ray absorption spectroscopy
- 2000
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Ingår i: PHYSICAL REVIEW LETTERS. - : AMERICAN PHYSICAL SOC. - 0031-9007. ; 84:5, s. 1031-1034
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Tidskriftsartikel (refereegranskat)abstract
- Core-level x-ray absorption spectroscopy measurements have bean performed at the L-3,L-2 edges of Fe and Co thin films. The degree of source coherence was varied using soft x rays from five different beam lines. We observe an increase of the L edge resona
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| 26. |
- Dunn, JH, et al.
(författare)
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Linear magnetic dichroism of thin Fe films on Cu(100)
- 1999
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Ingår i: JOURNAL OF ELECTRON SPECTROSCOPY AND RELATED PHENOMENA. - : ELSEVIER SCIENCE BV. - 0368-2048. ; 103, s. 463-466
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- A series of XPS measurements have been performed on the Fe/Cu(100) system. Using linearly polarised X-rays from an undulator source, magnetic information is evident in the spectra when the magnetisation direction is reversed. These measurements show that
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| 27. |
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| 28. |
- Dunn, JH, et al.
(författare)
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Magnetisation reorientation in ultra-thin Fe films on Cu(100) upon deposition of Co
- 2001
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Ingår i: JOURNAL OF SYNCHROTRON RADIATION. - : MUNKSGAARD INT PUBL LTD. - 0909-0495. ; 8, s. 463-465
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Tidskriftsartikel (refereegranskat)abstract
- Ultra thin films of Fe deposited on the (100) surface of a Cu single crystal exhibit a net perpendicular magnetic anisotropy. The addition of very low coverages of Co results in the easy magnetic direction reorienting into the film plane. This behavior is
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| 29. |
- Dunn, JH, et al.
(författare)
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Magnetism of thin Fe films on Cu(100)
- 1996
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Ingår i: PHYSICAL REVIEW B-CONDENSED MATTER. - : AMER INST PHYSICS. - 0163-1829. ; 54:16, s. 11157-11160
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Magnetic moments have been determined for the fct and bce structural phases of Fe, stabilized on the (100) surface of Cu, from magnetic-circular-dichroism measurements. For the thin fct films, the spin and orbital moments are greatly increased to 3.4(7)mu
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| 30. |
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| 31. |
- Hahlin, A, et al.
(författare)
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Structure and magnetism of ultrathin epitaxial Fe on Ag(100)
- 2006
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Ingår i: Physical Review B (Condensed Matter and Materials Physics). - 1098-0121 .- 1550-235X. ; 73:13
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Tidskriftsartikel (refereegranskat)abstract
- We have made in-situ investigations of ultrathin films of Fe grown on a Ag(100) single crystal. This system is known to exhibit a reorientation of the magnetization, dependent on both Fe thickness and temperature. X-ray absorption fine structure has been recorded for samples prepared in-situ, both in the near edge and in the extended x-ray absorption fine structure (EXAFS) region. Using x-ray magnetic circular dichroism we found that Fe films between 2-5 monolayers show an out-of-plane remanent magnetization. For thicker films the magnetization lies in-plane. By applying the magneto-optical sum rules we found an enhancement of the orbital moment (m(l)) for the out-of-plane phase, whereas the spin moment (m(s)) is unchanged. From the Fe L-edge EXAFS, we obtain information on the local crystallographic structure. A strong correlation between the local crystallographic structure and the magnetic properties is found for the Fe/Ag(100) system. Variations in the nearest neighbor distance of similar to 0.15 angstrom are observed when comparing 3 ML and 25 ML films. By comparison to simulations performed with the FEFF 8.10 code, we can identify a bcc structure for 6-25 ML Fe on Ag(100). For the 3 ML Fe film our simulations indicate strong deviations from any structure derived along the Bain path. We conclude that intermixing and distortion are important to describe the structure in this thickness range.
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| 32. |
- Khatri, C, et al.
(författare)
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Outcomes after perioperative SARS-CoV-2 infection in patients with proximal femoral fractures: an international cohort study
- 2021
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Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 11:11, s. e050830-
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Tidskriftsartikel (refereegranskat)abstract
- Studies have demonstrated high rates of mortality in people with proximal femoral fracture and SARS-CoV-2, but there is limited published data on the factors that influence mortality for clinicians to make informed treatment decisions. This study aims to report the 30-day mortality associated with perioperative infection of patients undergoing surgery for proximal femoral fractures and to examine the factors that influence mortality in a multivariate analysis.SettingProspective, international, multicentre, observational cohort study.ParticipantsPatients undergoing any operation for a proximal femoral fracture from 1 February to 30 April 2020 and with perioperative SARS-CoV-2 infection (either 7 days prior or 30-day postoperative).Primary outcome30-day mortality. Multivariate modelling was performed to identify factors associated with 30-day mortality.ResultsThis study reports included 1063 patients from 174 hospitals in 19 countries. Overall 30-day mortality was 29.4% (313/1063). In an adjusted model, 30-day mortality was associated with male gender (OR 2.29, 95% CI 1.68 to 3.13, p<0.001), age >80 years (OR 1.60, 95% CI 1.1 to 2.31, p=0.013), preoperative diagnosis of dementia (OR 1.57, 95% CI 1.15 to 2.16, p=0.005), kidney disease (OR 1.73, 95% CI 1.18 to 2.55, p=0.005) and congestive heart failure (OR 1.62, 95% CI 1.06 to 2.48, p=0.025). Mortality at 30 days was lower in patients with a preoperative diagnosis of SARS-CoV-2 (OR 0.6, 95% CI 0.6 (0.42 to 0.85), p=0.004). There was no difference in mortality in patients with an increase to delay in surgery (p=0.220) or type of anaesthetic given (p=0.787).ConclusionsPatients undergoing surgery for a proximal femoral fracture with a perioperative infection of SARS-CoV-2 have a high rate of mortality. This study would support the need for providing these patients with individualised medical and anaesthetic care, including medical optimisation before theatre. Careful preoperative counselling is needed for those with a proximal femoral fracture and SARS-CoV-2, especially those in the highest risk groups.Trial registration numberNCT04323644
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| 33. |
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| 34. |
- MAY, F, et al.
(författare)
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AN ANGLE-DEPENDENT MAGNETIC CIRCULAR X-RAY DICHROISM STUDY OF CO/CU(100) - EXPERIMENT VERSUS THEORY
- 1995
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Ingår i: JOURNAL OF PHYSICS-CONDENSED MATTER. - : IOP PUBLISHING LTD. - 0953-8984. ; 7:6, s. 1111-1119
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Values for the magnetic moments of 3d transition metals have been calculated from magnetic circular x-ray dichroism measurements using sum rules. In this work we reveal that these calculations are sensitive to a damping effect resulting from a decrease in
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| 35. |
- May, F, et al.
(författare)
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Magnetic coupling of Ni, Cu and Co bi- and trilayers probed by magnetic circular X-ray dichroism
- 1997
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Ingår i: JOURNAL DE PHYSIQUE IV. - : EDITIONS PHYSIQUE. - 1155-4339. ; 7:C2, s. 389-395
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Using magnetic circular X-ray dichroism (MCXD), Co/Ni, Cu/Co and Cu/Ni bilayers and Co/Cu/Ni and Ni/Cu/Co trilayers grown on a Cu(001) substrate were investigated. The Co layers were about 2 monolayers (Mi,) and the Ni layers were between 1.5 and 4.5 ML t
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| 36. |
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| 37. |
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| 38. |
- Shah, S, et al.
(författare)
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Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure
- 2020
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1, s. 163-
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Tidskriftsartikel (refereegranskat)abstract
- Heart failure (HF) is a leading cause of morbidity and mortality worldwide. A small proportion of HF cases are attributable to monogenic cardiomyopathies and existing genome-wide association studies (GWAS) have yielded only limited insights, leaving the observed heritability of HF largely unexplained. We report results from a GWAS meta-analysis of HF comprising 47,309 cases and 930,014 controls. Twelve independent variants at 11 genomic loci are associated with HF, all of which demonstrate one or more associations with coronary artery disease (CAD), atrial fibrillation, or reduced left ventricular function, suggesting shared genetic aetiology. Functional analysis of non-CAD-associated loci implicate genes involved in cardiac development (MYOZ1, SYNPO2L), protein homoeostasis (BAG3), and cellular senescence (CDKN1A). Mendelian randomisation analysis supports causal roles for several HF risk factors, and demonstrates CAD-independent effects for atrial fibrillation, body mass index, and hypertension. These findings extend our knowledge of the pathways underlying HF and may inform new therapeutic strategies.
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| 39. |
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| 40. |
- TISCHER, M, et al.
(författare)
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ENHANCEMENT OF ORBITAL MAGNETISM AT SURFACES - CO ON CU(100)
- 1995
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Ingår i: PHYSICAL REVIEW LETTERS. - : AMER INST PHYSICS. - 0031-9007. ; 75:8, s. 1602-1605
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- By combining magnetic circular x-ray dichroism experiments with first principles electronic structure calculations, we demonstrate that the orbital contribution to magnetism can be strongly enhanced at surfaces. This effect is illustrated for Co grown on
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| 41. |
- TISCHER, M, et al.
(författare)
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LOCAL MAGNETISM AND ELEMENT-SPECIFIC SUSCEPTIBILITY FOR NI/CU(100)
- 1995
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Ingår i: VACUUM. - : PERGAMON-ELSEVIER SCIENCE LTD. - 0042-207X. ; 46:8-10, s. 1211-1214
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- We report magnetic circular X-ray dichroism (MCXD) measurements of ultrathin Ni films grown on Cu(?OO). The Curie temperature of the films is determined by means of a.c. MXCD susceptibility, a technique that allows T-c to be probed precisely and unambiguo
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| 42. |
- Kanai, M, et al.
(författare)
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- 2023
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swepub:Mat__t
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