| 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. |
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| 3. |
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| 4. |
- Bellenguez, C, et al.
(författare)
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New insights into the genetic etiology of Alzheimer's disease and related dementias
- 2022
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 54:4, s. 412-436
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Tidskriftsartikel (refereegranskat)abstract
- Characterization of the genetic landscape of Alzheimer’s disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/‘proxy’ AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele.
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| 9. |
- Kim, Jae-Young, et al.
(författare)
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Event Horizon Telescope imaging of the archetypal blazar 3C 279 at an extreme 20 microarcsecond resolution
- 2020
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 640
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Tidskriftsartikel (refereegranskat)abstract
- 3C 279 is an archetypal blazar with a prominent radio jet that show broadband flux density variability across the entire electromagnetic spectrum. We use an ultra-high angular resolution technique - global Very Long Baseline Interferometry (VLBI) at 1.3mm (230 GHz) - to resolve the innermost jet of 3C 279 in order to study its fine-scale morphology close to the jet base where highly variable-ray emission is thought to originate, according to various models. The source was observed during four days in April 2017 with the Event Horizon Telescope at 230 GHz, including the phased Atacama Large Millimeter/submillimeter Array, at an angular resolution of ∼20 μas (at a redshift of z = 0:536 this corresponds to ∼0:13 pc ∼ 1700 Schwarzschild radii with a black hole mass MBH = 8 × 108 M⊙). Imaging and model-fitting techniques were applied to the data to parameterize the fine-scale source structure and its variation.We find a multicomponent inner jet morphology with the northernmost component elongated perpendicular to the direction of the jet, as imaged at longer wavelengths. The elongated nuclear structure is consistent on all four observing days and across diffierent imaging methods and model-fitting techniques, and therefore appears robust. Owing to its compactness and brightness, we associate the northern nuclear structure as the VLBI "core". This morphology can be interpreted as either a broad resolved jet base or a spatially bent jet.We also find significant day-to-day variations in the closure phases, which appear most pronounced on the triangles with the longest baselines. Our analysis shows that this variation is related to a systematic change of the source structure. Two inner jet components move non-radially at apparent speeds of ∼15 c and ∼20 c (∼1:3 and ∼1:7 μas day-1, respectively), which more strongly supports the scenario of traveling shocks or instabilities in a bent, possibly rotating jet. The observed apparent speeds are also coincident with the 3C 279 large-scale jet kinematics observed at longer (cm) wavelengths, suggesting no significant jet acceleration between the 1.3mm core and the outer jet. The intrinsic brightness temperature of the jet components are ≤1010 K, a magnitude or more lower than typical values seen at ≥7mm wavelengths. The low brightness temperature and morphological complexity suggest that the core region of 3C 279 becomes optically thin at short (mm) wavelengths.
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| 10. |
- Wang, Li-San, et al.
(författare)
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Rarity of the Alzheimer Disease-Protective APP A673T Variant in the United States.
- 2015
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Ingår i: JAMA neurology. - : American Medical Association (AMA). - 2168-6157 .- 2168-6149. ; 72:2
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Tidskriftsartikel (refereegranskat)abstract
- Recently, a rare variant in the amyloid precursor protein gene (APP) was described in a population from Iceland. This variant, in which alanine is replaced by threonine at position 673 (A673T), appears to protect against late-onset Alzheimer disease (AD). We evaluated the frequency of this variant in AD cases and cognitively normal controls to determine whether this variant will significantly contribute to risk assessment in individuals in the United States.
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| 11. |
- Akiyama, Kazunori, et al.
(författare)
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The persistent shadow of the supermassive black hole of M 87: I. Observations, calibration, imaging, and analysis*
- 2024
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Ingår i: Astronomy and Astrophysics. - 0004-6361 .- 1432-0746. ; 681
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Tidskriftsartikel (refereegranskat)abstract
- In April 2019, the Event Horizon Telescope (EHT) Collaboration reported the first-ever event-horizon-scale images of a black hole, resolving the central compact radio source in the giant elliptical galaxy M 87. These images reveal a ring with a southerly brightness distribution and a diameter of ∼42 μas, consistent with the predicted size and shape of a shadow produced by the gravitationally lensed emission around a supermassive black hole. These results were obtained as part of the April 2017 EHT observation campaign, using a global very long baseline interferometric radio array operating at a wavelength of 1.3 mm. Here, we present results based on the second EHT observing campaign, taking place in April 2018 with an improved array, wider frequency coverage, and increased bandwidth. In particular, the additional baselines provided by the Greenland telescope improved the coverage of the array. Multiyear EHT observations provide independent snapshots of the horizon-scale emission, allowing us to confirm the persistence, size, and shape of the black hole shadow, and constrain the intrinsic structural variability of the accretion flow. We have confirmed the presence of an asymmetric ring structure, brighter in the southwest, with a median diameter of 43.3-3.1+1.5 μas. The diameter of the 2018 ring is remarkably consistent with the diameter obtained from the previous 2017 observations. On the other hand, the position angle of the brightness asymmetry in 2018 is shifted by about 30 relative to 2017. The perennial persistence of the ring and its diameter robustly support the interpretation that the ring is formed by lensed emission surrounding a Kerr black hole with a mass ∼6.5× 109M. The significant change in the ring brightness asymmetry implies a spin axis that is more consistent with the position angle of the large-scale jet.
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| 12. |
- Zhou, XP, et al.
(författare)
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Non-coding variability at the APOE locus contributes to the Alzheimer's risk
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 3310-
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Tidskriftsartikel (refereegranskat)abstract
- Alzheimer’s disease (AD) is a leading cause of mortality in the elderly. While the coding change of APOE-ε4 is a key risk factor for late-onset AD and has been believed to be the only risk factor in the APOE locus, it does not fully explain the risk effect conferred by the locus. Here, we report the identification of AD causal variants in PVRL2 and APOC1 regions in proximity to APOE and define common risk haplotypes independent of APOE-ε4 coding change. These risk haplotypes are associated with changes of AD-related endophenotypes including cognitive performance, and altered expression of APOE and its nearby genes in the human brain and blood. High-throughput genome-wide chromosome conformation capture analysis further supports the roles of these risk haplotypes in modulating chromatin states and gene expression in the brain. Our findings provide compelling evidence for additional risk factors in the APOE locus that contribute to AD pathogenesis.
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| 13. |
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| 14. |
- Grazian, A., et al.
(författare)
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Lyman continuum escape fraction of faint galaxies at z similar to 3.3 in the CANDELS/GOODS-North, EGS, and COSMOS fields with LBC
- 2017
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 602
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Tidskriftsartikel (refereegranskat)abstract
- Context. The reionization of the Universe is one of the most important topics of present-day astrophysical research. The most plausible candidates for the reionization process are star-forming galaxies, which according to the predictions of the majority of the theoretical and semi-analytical models should dominate the H I ionizing background at z greater than or similar to 3. Aims. We measure the Lyman continuum escape fraction, which is one of the key parameters used to compute the contribution of star-forming galaxies to the UV background. It provides the ratio between the photons produced at lambda <= 912 angstrom rest-frame and those that are able to reach the inter-galactic medium, i.e. that are not absorbed by the neutral hydrogen or by the dust of the galaxy's inter-stellar medium. Methods. We used ultra-deep U-band imaging (U = 30.2 mag at 1 sigma) from Large Binocular Camera at the Large Binocular Telescope (LBC/LBT) in the CANDELS/GOODS-North field and deep imaging in the COSMOS and EGS fields in order to estimate the Lyman continuum escape fraction of 69 star-forming galaxies with secure spectroscopic redshifts at 3.27 <= z <= 3.40 to faint magnitude limits (L = 0.2L*, or equivalently M-1500 similar to -19). The narrow redshift range implies that the LBC U-band filter exclusively samples the lambda <= 912 angstrom rest-frame wavelengths. Results. We measured through stacks a stringent upper limit (<1.7% at 1 sigma) for the relative escape fraction of H I ionizing photons from bright galaxies (L > L*), while for the faint population (L = 0.2L*) the limit to the escape fraction is less than or similar to 10%. We computed the contribution of star-forming galaxies to the observed UV background at z similar to 3 and find that it is not sufficient to keep the Universe ionized at these redshifts unless their escape fraction increases significantly (>= 10%) at low luminosities (M-1500 >= -19). Conclusions. We compare our results on the Lyman continuum escape fraction of high-z galaxies with recent estimates in the literature, and discuss future prospects to shed light on the end of the Dark Ages. In the future, strong gravitational lensing will be fundamental in order to measure the Lyman continuum escape fraction down to faint magnitudes (M-1500 similar to -16) that are inaccessible with the present instrumentation on blank fields. These results will be important in order to quantify the role of faint galaxies to the reionization budget.
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| 15. |
- Jones, Lesley, et al.
(författare)
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Convergent genetic and expression data implicate immunity in Alzheimer's disease
- 2015
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Ingår i: Alzheimer's & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 11:6, s. 658-671
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Tidskriftsartikel (refereegranskat)abstract
- Background: Late-onset Alzheimer's disease (AD) is heritable with 20 genes showing genome-wide association in the International Genomics of Alzheimer's Project (IGAP). To identify the biology underlying the disease, we extended these genetic data in a pathway analysis. Methods: The ALIGATOR and GSEA algorithms were used in the IGAP data to identify associated functional pathways and correlated gene expression networks in human brain. Results: ALIGATOR identified an excess of curated biological pathways showing enrichment of association. Enriched areas of biology included the immune response (P = 3.27 X 10(-12) after multiple testing correction for pathways), regulation of endocytosis (P = 1.31 X 10(-11)), cholesterol transport (P = 2.96 X 10(-9)), and proteasome-ubiquitin activity (P = 1.34 X 10(-6)). Correlated gene expression analysis identified four significant network modules, all related to the immune response (corrected P = .002-.05). Conclusions: The immime response, regulation of endocytosis, cholesterol transport, and protein ubiquitination represent prime targets for AD therapeutics.
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| 16. |
- Escott-Price, Valentina, et al.
(författare)
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Gene-Wide Analysis Detects Two New Susceptibility Genes for Alzheimer's Disease
- 2014
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:6, s. e94661-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Alzheimer's disease is a common debilitating dementia with known heritability, for which 20 late onset susceptibility loci have been identified, but more remain to be discovered. This study sought to identify new susceptibility genes, using an alternative gene-wide analytical approach which tests for patterns of association within genes, in the powerful genome-wide association dataset of the International Genomics of Alzheimer's Project Consortium, comprising over 7 m genotypes from 25,580 Alzheimer's cases and 48,466 controls. Principal Findings: In addition to earlier reported genes, we detected genome-wide significant loci on chromosomes 8 (TP53INP1, p = 1.4x10(-6)) and 14 (IGHV1-67 p = 7.9x10(-8)) which indexed novel susceptibility loci. Significance: The additional genes identified in this study, have an array of functions previously implicated in Alzheimer's disease, including aspects of energy metabolism, protein degradation and the immune system and add further weight to these pathways as potential therapeutic targets in Alzheimer's disease.
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| 24. |
- Goodall, Rhys E. A., et al.
(författare)
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Rapid discovery of stable materials by coordinate-free coarse graining
- 2022
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Ingår i: Science Advances. - : AMER ASSOC ADVANCEMENT SCIENCE. - 2375-2548. ; 8:30
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Tidskriftsartikel (refereegranskat)abstract
- A fundamental challenge in materials science pertains to elucidating the relationship between stoichiometry, stability, structure, and property. Recent advances have shown that machine learning can be used to learn such relationships, allowing the stability and functional properties of materials to be accurately predicted. However, most of these approaches use atomic coordinates as input and are thus bottlenecked by crystal structure identification when investigating previously unidentified materials. Our approach solves this bottleneck by coarse-graining the infinite search space of atomic coordinates into a combinatorially enumerable search space. The key idea is to use Wyckoff representations, coordinate-free sets of symmetry-related positions in a crystal, as the input to a machine learning model. Our model demonstrates exceptionally high precision in finding unknown theoretically stable materials, identifying 1569 materials that lie below the known convex hull of previously calculated materials from just 5675 ab initio calculations. Our approach opens up fundamental advances in computational materials discovery.
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| 25. |
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| 26. |
- Lu, R.S., et al.
(författare)
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A ring-like accretion structure in M87 connecting its black hole and jet
- 2023
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Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 616:7958, s. 686-690
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Tidskriftsartikel (refereegranskat)abstract
- The nearby radio galaxy M87 is a prime target for studying black hole accretion and jet formation1,2. Event Horizon Telescope observations of M87 in 2017, at a wavelength of 1.3 mm, revealed a ring-like structure, which was interpreted as gravitationally lensed emission around a central black hole3. Here we report images of M87 obtained in 2018, at a wavelength of 3.5 mm, showing that the compact radio core is spatially resolved. High-resolution imaging shows a ring-like structure of [Formula: see text] Schwarzschild radii in diameter, approximately 50% larger than that seen at 1.3 mm. The outer edge at 3.5 mm is also larger than that at 1.3 mm. This larger and thicker ring indicates a substantial contribution from the accretion flow with absorption effects, in addition to the gravitationally lensed ring-like emission. The images show that the edge-brightened jet connects to the accretion flow of the black hole. Close to the black hole, the emission profile of the jet-launching region is wider than the expected profile of a black-hole-driven jet, suggesting the possible presence of a wind associated with the accretion flow.
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| 27. |
- Mooij, Wolf M., et al.
(författare)
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Serving many at once : How a database approach can create unity in dynamical ecosystem modelling
- 2014
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Ingår i: Environmental Modelling & Software. - : Elsevier BV. - 1364-8152 .- 1873-6726. ; 61, s. 266-273
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Tidskriftsartikel (refereegranskat)abstract
- Simulation modelling in ecology is a field that is becoming increasingly compartmentalized. Here we propose a Database Approach To Modelling (DATM) to create unity in dynamical ecosystem modelling with differential equations. In this approach the storage of ecological knowledge is independent of the language and platform in which the model will be run. To create an instance of the model, the information in the database is translated and augmented with the language and platform specifics. This process is automated so that a new instance can be created each time the database is updated. We describe the approach using the simple Lotka-Volterra model and the complex ecosystem model for shallow lakes PCLake, which we automatically implement in the frameworks OSIRIS, GRIND for MATLAB, ACSL, R, DUFLOW and DELWAQ. A clear advantage of working in a database is the overview it provides. The simplicity of the approach only adds to its elegance.
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| 32. |
- Baird, Denis A., et al.
(författare)
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Identification of Novel Loci Associated With Hip Shape : A Meta-Analysis of Genomewide Association Studies.
- 2019
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Ingår i: Journal of Bone and Mineral Research. - : Wiley-Blackwell. - 0884-0431 .- 1523-4681. ; 34:2, s. 241-251
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Tidskriftsartikel (refereegranskat)abstract
- We aimed to report the first genomewide association study (GWAS) meta-analysis of dual-energy X-ray absorptiometry (DXA)-derived hip shape, which is thought to be related to the risk of both hip osteoarthritis and hip fracture. Ten hip shape modes (HSMs) were derived by statistical shape modeling using SHAPE software, from hip DXA scans in the Avon Longitudinal Study of Parents and Children (ALSPAC; adult females), TwinsUK (mixed sex), Framingham Osteoporosis Study (FOS; mixed), Osteoporotic Fractures in Men study (MrOS), and Study of Osteoporotic Fractures (SOF; females) (total N = 15,934). Associations were adjusted for age, sex, and ancestry. Five genomewide significant (p < 5 × 10-9 , adjusted for 10 independent outcomes) single-nucleotide polymorphisms (SNPs) were associated with HSM1, and three SNPs with HSM2. One SNP, in high linkage disequilibrium with rs2158915 associated with HSM1, was associated with HSM5 at genomewide significance. In a look-up of previous GWASs, three of the identified SNPs were associated with hip osteoarthritis, one with hip fracture, and five with height. Seven SNPs were within 200 kb of genes involved in endochondral bone formation, namely SOX9, PTHrP, RUNX1, NKX3-2, FGFR4, DICER1, and HHIP. The SNP adjacent to DICER1 also showed osteoblast cis-regulatory activity of GSC, in which mutations have previously been reported to cause hip dysplasia. For three of the lead SNPs, SNPs in high LD (r2 > 0.5) were identified, which intersected with open chromatin sites as detected by ATAC-seq performed on embryonic mouse proximal femora. In conclusion, we identified eight SNPs independently associated with hip shape, most of which were associated with height and/or mapped close to endochondral bone formation genes, consistent with a contribution of processes involved in limb growth to hip shape and pathological sequelae. These findings raise the possibility that genetic studies of hip shape might help in understanding potential pathways involved in hip osteoarthritis and hip fracture. © 2018 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals, Inc.
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| 33. |
- Baunsgaard, C. B., et al.
(författare)
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EXOSKELETON GAIT TRAINING AFTER SPINAL CORD INJURY: AN EXPLORATORY STUDY ON SECONDARY HEALTH CONDITIONS
- 2018
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Ingår i: Journal of Rehabilitation Medicine. - : Medical Journals Sweden AB. - 1650-1977 .- 1651-2081. ; 50:9, s. 806-813
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To explore changes in pain, spasticity, range of motion, activities of daily living, bowel and lower urinary tract function and quality of life of individuals with spinal cord injury following robotic exoskeleton gait training. Methods: Three training sessions per week for 8 weeks using an Ekso GT robotic exoskeleton (Ekso Bionics). Included were individuals with recent (<1 year) or chronic (>1 year) injury, paraplegia and tetraplegia, complete and incomplete injury, men and women. Results: Fifty-two participants completed the training protocol. Pain was reported by 52% of participants during the week prior to training and 17% during training, but no change occurred longitudinally. Spasticity decreased after a training session compared with before the training session (p< 0.001), but not longitudinally. Chronically injured participants increased Spinal Cord Independence Measure (SCIM III) from 73 to 74 (p= 0.008) and improved life satisfaction (p= 0.036) over 8 weeks of training. Recently injured participants increased SCIM III from 62 to 70 (p<0.001), but no significant change occurred in life satisfaction. Range of motion, bowel and lower urinary function did not change over time. Conclusion: Training seemed not to provoke new pain. Spasticity decreased after a single training session. SCIM III and quality of life increased longitudinally for subsets of participants.
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| 34. |
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| 35. |
- Lill, Christina M., et al.
(författare)
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Closing the case of APOE in multiple sclerosis : no association with disease risk in over 29 000 subjects
- 2012
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Ingår i: Journal of Medical Genetics. - : BMJ. - 0022-2593 .- 1468-6244. ; 49:9, s. 558-562
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Tidskriftsartikel (refereegranskat)abstract
- Background Single nucleotide polymorphisms (SNPs) rs429358 (ε4) and rs7412 (ε2), both invoking changes in the amino-acid sequence of the apolipoprotein E (APOE) gene, have previously been tested for association with multiple sclerosis (MS) risk. However, none of these studies was sufficiently powered to detect modest effect sizes at acceptable type-I error rates. As both SNPs are only imperfectly captured on commonly used microarray genotyping platforms, their evaluation in the context of genome-wide association studies has been hindered until recently.Methods We genotyped 12 740 subjects hitherto not studied for their APOE status, imputed raw genotype data from 8739 subjects from five independent genome-wide association studies datasets using the most recent high-resolution reference panels, and extracted genotype data for 8265 subjects from previous candidate gene assessments.Results Despite sufficient power to detect associations at genome-wide significance thresholds across a range of ORs, our analyses did not support a role of rs429358 or rs7412 on MS susceptibility. This included meta-analyses of the combined data across 13 913 MS cases and 15 831 controls (OR=0.95, p=0.259, and OR 1.07, p=0.0569, for rs429358 and rs7412, respectively).Conclusion Given the large sample size of our analyses, it is unlikely that the two APOE missense SNPs studied here exert any relevant effects on MS susceptibility.
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| 36. |
- Perez-Cueto, Federico J. A., et al.
(författare)
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How barriers towards plant-based food consumption differ according to dietary lifestyle : findings from a consumer survey in 10 EU countries
- 2022
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Ingår i: International Journal of Gastronomy and Food Science. - : Elsevier. - 1878-450X .- 1878-4518. ; 29
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Tidskriftsartikel (refereegranskat)abstract
- A diet shift towards a more plant-based food consumption is advocated for sustainable, health and ethical reasons. Still, a diet change remains a societal challenge. The objective of this paper is to identify how barriers towards plant-based food consumption are experienced according to dietary lifestyle in 10 European countries. A pan-EU consumer survey was conducted as part of Smart Protein Project. In total 7590 answers were obtained (49.5% women). Omnivores were more likely to score higher in the barriers to diet shift than vegetarians, vegans or flexitarians. Large effect sizes (Eta squared >0.1) were observed for the following barriers a) the lay belief that humans are meant to eat lots of animal-based meat; b) the expectation that plant-based food products would not be tasty enough; c) and the experience of not enjoying such products. Medium effect sizes (Eta sq. > 0.06) were observed for variables addressing nutrition related barriers “would not be filling enough” and “I would not get energy or strength from these products”. Promotion of plant-based food consumption should be targeted according to diet lifestyle, with focus on their sensory characteristics and on addressing cultural (lay) beliefs e.g. through knowledge sharing.
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| 37. |
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| 38. |
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| 39. |
- van Gerven, Luuk P. A., et al.
(författare)
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Advantages of concurrent use of multiple software frameworks in water quality modelling using a database approach
- 2015
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Ingår i: Fundamental and Applied Limnology. - : Schweizerbart. - 1863-9135. ; 186:1-2, s. 5-20
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Tidskriftsartikel (refereegranskat)abstract
- Water quality modelling deals with multidisciplinary questions ranging from fundamental to applied. Addressing this broad range of questions requires multiple analysis techniques and therefore multiple frameworks. Through the recently developed database approach to modelling (DATM), it has become possible to run a model in multiple software frameworks without much overhead. Here we apply DATM to the ecosystem model for ditches PCDitch and its twin model for shallow lakes PCLake. Using DATM, we run these models in six frameworks (ACSL, DELWAQ, DUFLOW, GRIND for MATLAB, OSIRIS and R), and report on the possible model analyses with tools provided by each framework. We conclude that the dynamic link between frameworks and models resulting from DATM has the following main advantages: it allows one to use the framework one is familiar with for most model analyses and eases switching between frameworks for complementary model analyses, including the switch between a 0-D and 1-D to 3-D setting. Moreover, the strength of each framework - including runtime performance - can now be easily exploited. We envision that a community-based further development of the concept can contribute to the future development of water quality modelling, not only by addressing multidisciplinary questions but also by facilitating the exchange of models and process formulations within the community of water quality modellers.
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| 40. |
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| 41. |
- Boulakh, L., et al.
(författare)
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Nationwide Incidence of Thyroid Eye Disease and Cumulative Incidence of Strabismus and Surgical Interventions in Denmark
- 2022
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Ingår i: Jama Ophthalmology. - : American Medical Association (AMA). - 2168-6165. ; 140:7, s. 667-673
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE Thyroid eye disease (TED) is a serious condition that can cause proptosis and strabismus and, in rare cases, lead to blindness. Incidence data for TED and strabismus and surgical interventions after TED are sparce. OBJECTIVE To investigate the nationwide incidence of TED, strabismus, and surgical interventions associated with TED. DESIGN, SETTING, AND PARTICIPANTS A Danish nationwide registry-based cohort study between 2000, which marks the beginning of uniform coding for the decompression surgery nationwide, and 2018. The cohort consisted of a mean 4.3 million people aged 18 to 100 years with no prior TED diagnosis each year. Total observation time was 8.22 x 10(7) person-years (women, 4.18 x 10(7) person-years; men, 4.04 x 10(7) person-years). MAIN OUTCOME MEASURES The annual numeric and age-standardized incidence of hospital-treated TED and cumulative incidence of strabismus, strabismus surgery, and orbital decompression surgery in patients with TED. The incidence was stratified by sex, thyroid diagnosis, and age. RESULTS A total of 4106 incident diagnoses of TED were identified during 19 years among 3344 women (81.4%) and 762 men (18.6%). The mean numeric annual nationwide incidence rate of TED was 5,0 per 100 000 person-years overall, 8.0 per 100 000 person-years in women, and 1.9 per 100 000 person-years in men, resulting in a 4:1 ratio of women to men with TED. The age-standardized incidence was similar. The mean (SD) age at onset was 51.3 (14.5) years. At the time of TED diagnosis, 611 patients (14.9%) were euthyroid, 477 (11.6%) were hypothyroid, and 3018 (73.5%) were hyperthyroid. In patients with TED who were euthyroid, the 4-year cumulative incidence was 41% for antithyroid medication and 13% for L-thyroxine. In patients with TED, the 4-year cumulative incidence for strabismus was 10%. The 4-year cumulative incidence of surgical interventions after TED was 8% for strabismus surgery and 5% for orbital decompression. At 4 years, strabismus surgery was more common in men (13.3%; 95% CI, 10.75-15.86) than in women (7.2%; 95% CI, 6.24-8.08), and the absolute difference was 6.1% (95% CI, 3.42-8.14; P < .001). CONCLUSIONS AND RELEVANCE This study in Denmark provides nationwide empirical incidence of TED and strabismus and surgical interventions after TED that required inpatient or outpatient hospital treatment, and might be used for patient information and health care planning.
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| 42. |
- Bryan, Jim, et al.
(författare)
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The local Gromov-Witten theory of curves
- 2008
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Ingår i: Journal of The American Mathematical Society. - 0894-0347 .- 1088-6834. ; 21:1, s. 101-136
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Tidskriftsartikel (refereegranskat)
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| 43. |
- Faber, Catherine, et al.
(författare)
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Three-dimensional structure of a human Fab with high affinity for tetanus toxoid
- 1998
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Ingår i: Immunotechnology. - 1380-2933. ; 3:4, s. 253-270
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Tidskriftsartikel (refereegranskat)abstract
- Background: The wide range of antibody specificity and affinity results from the differing shapes and chemical compositions of their binding sites. These shapes range from discrete grooves in antibodies elicited by linear oligomers of nucleotides and carbohydrates to shallow depressions or flat surfaces for accommodation of proteins: peptides and large organic compounds. Objectives: To determine the Fab structure of a high-affinity human antitoxin antibody. To explore structural features which enable the antibody to bind to intact tetanus toxoid, peptides derived from the sequence of the natural immunogen and antigenic mimics identified by combinatorial chemistry. To explain why this Fab shows a remarkable tendency to produce crystals consistently diffracting to d spacings of 1.7-1.8 Å. To use this information to engineer a strong tendency to crystallize into the design of other Fabs. Study design: The protein was crystallized in hanging or sitting drops by a microseeding technique in polyethylene glycol (PEG) 8000. Crystals were subjected to X-ray analysis and the three-dimensional structure of the Fab was determined by the molecular replacement method. Interactive computer graphics were employed to fit models to electron density maps, survey the structure in multiple views and discover the crystal packing motif of the protein. Results: Exceptionally large single crystals of this protein have been obtained, one measuring 5 x 3 x 2 mm (l x w x d). The latter was cut into six irregular pieces, each retaining the features of the original in diffracting to high resolution (1.8 Å) with little decay in the X-ray beam. In an individual Fab, the active site is relatively flat and it seems likely that the protein antigen and derivative peptides are tightly held on the outer surface without significant penetration into the interior. There is no free space to accommodate even a dipeptide between V(H) and V(L). One of the unique features of the B7-15A2 Fab is a large aliphatic ridge dominating the center of the active site. The CDR3 of the H chain contributes significantly to this ridge, as well as to adjoining regions projected to be important for the docking of the antigen. Both the ease of crystallization and the favorable diffraction properties are mainly attributable to the tight packing of the protein molecules in the crystal lattice. Discussion: The B7-15A2 active site provides a stable and well defined platform for high affinity docking of proteins, peptides and their mimotopes. The advantages for future developments are suggested by the analysis of the crystal properties. It should be possible to incorporate the features promoting crystallization, close packing and resistance to radiation damage into engineered human antibodies without altering the desired specificities and affinities of their active sites.
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| 44. |
- Faber, Felix A., et al.
(författare)
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Machine Learning Energies of 2 Million Elpasolite (AB2D6) Crystals
- 2016
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Ingår i: Physical Review Letters. - : American Physical Society. - 0031-9007 .- 1079-7114. ; 117:13
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Tidskriftsartikel (refereegranskat)abstract
- Elpasolite is the predominant quaternary crystal structure (AlNaK2F6 prototype) reported in the Inorganic Crystal Structure Database. We develop a machine learning model to calculate density functional theory quality formation energies of all ∼2×106 pristine ABC2D6 elpasolite crystals that can be made up from main-group elements (up to bismuth). Our model’s accuracy can be improved systematically, reaching a mean absolute error of 0.1 eV/atom for a training set consisting of 10×103 crystals. Important bonding trends are revealed: fluoride is best suited to fit the coordination of the D site, which lowers the formation energy whereas the opposite is found for carbon. The bonding contribution of the elements A and B is very small on average. Low formation energies result from A and B being late elements from group II, C being a late (group I) element, and D being fluoride. Out of 2×106 crystals, 90 unique structures are predicted to be on the convex hull—among which is NFAl2Ca6, with a peculiar stoichiometry and a negative atomic oxidation state for Al.
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| 45. |
- Faber, Ilona, et al.
(författare)
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Associations among social engagement, meal‐related behaviour, satisfaction with food‐related life and wellbeing in Danish older adults living alone
- 2022
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Ingår i: Nutrition Bulletin. - : John Wiley & Sons. - 1471-9827 .- 1467-3010. ; 47:3, s. 346-355
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Tidskriftsartikel (refereegranskat)abstract
- The present study aimed at exploring associations among meal-related behaviour, social engagement factors, satisfaction with food-related life (SWFL) to assess food-related wellbeing and subjective wellbeing in Danish older adults living alone. Three hundred and eighty-eight older adults aged 65–75 years from six Danish municipalities completed an online or article-based survey addressing home cooking, commensality, loneliness, SWFL and subjective wellbeing. Home cooking frequency and self-perceived cooking skills were positively associated with SWFL but not with subjective wellbeing. Commensality was positively associated with SWFL but was not associated with subjective wellbeing. The level of loneliness was negatively associated with SWFL and with subjective wellbeing. Satisfaction with food-related life and subjective health status were positively associated with subjective wellbeing. Male and female respondents did not differ in meal-related behaviour, social engagement factors, SWFL and wellbeing. While the cross-sectional nature of this study does not allow for the direction of causality to be determined, these results suggest that older adults living alone could benefit from a higher frequency of home-cooked meals, a higher level of self-perceived cooking skills and commensality to support SWFL. A higher level of SWFL could, in turn, lead to a higher level of wellbeing.
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| 46. |
- Faber, Ilona, et al.
(författare)
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Relevant characteristics of food products based on alternative proteins according to European consumers
- 2021
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Ingår i: Journal of the Science of Food and Agriculture. - : John Wiley & Sons. - 0022-5142 .- 1097-0010.
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The objective of this study was to evaluate the importance attributed by consumers in Denmark (DK), Germany (DE) and Spain (ES) and across dietary lifestyles to the characteristics of different types of foods based on alternative proteins. Data were collected through a web-based survey (15 November to 16 December 2019). A total of 872 completed questionnaires from DK (n = 258), DE (n = 296) and ES (n = 318) were obtained.RESULTS: Four segments according to frequency of animal- and plant-based food consumption were identified: (i) no animal, high plant; (ii) low animal, high plant; (iii) moderate animal and plant; and (iv) high animal, moderate plant. Across all segments, foods based on legumes/pulses as well as plant-based spreads and products that do not resemble meat in taste and texture were of interest. Segment 4 was more in favour of ‘health’ as an important factor in new food products, whereas segment 1 was more likely to consider ‘animal friendly’, ‘minimally processed’, ‘environmentally friendly’ and ‘produced with minimum CO2 emissions’ as key aspects. Furthermore, familiarity was of minor importance across the segments. This could indicate an opening for new, innovative plant-based alternatives that have their own identity.CONCLUSION: An overall interest exists towards innovative food products based on plant protein, specifically legumes/pulses, among consumers in the three countries and across different dietary lifestyles.
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| 47. |
- Faber, Ilona, et al.
(författare)
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The mediating role of barriers and trust on the intentions to consume plant-based foods in Europe
- 2024
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Ingår i: Food Quality and Preference. - : Elsevier. - 0950-3293 .- 1873-6343. ; 114
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Tidskriftsartikel (refereegranskat)abstract
- Plant-based food alternatives have increased in popularity, particularly plant-based meat alternatives, while plant-based cheese alternatives less so. However, their acceptance remains low in Europe. Food choice motives (FCM) and trust towards alternative proteins may contribute to purchasing plant-based food alternatives, while other FCM and barriers can hinder this. The present study aimed to investigate whether FCM focused on “Environment & ethics” and “Intrinsic product quality” are associated with behavioural intentions towards plant-based meat and cheese alternatives, and specifically investigating the mediating role of perceived barriers to plant-based food consumption and trust towards plant-based alternative proteins. A survey was conducted in 10 European countries (AT, DE, DK, ES, FR, IT, NL, PL, RO, UK) with quotas on age and gender (N = 7588). Partial Least Squares Structural Equation Modelling (PLS-SEM) was used to determine factors associated with behavioural intentions towards plant-based meat and cheese alternatives. Results showed that “environmental & ethical” motives are positively associated with intentions to consume plant-based alternatives to meat (in 6/10 countries) and cheese (in 8/10 countries). “Intrinsic product quality” motives were not directly associated with behavioural intentions towards plant-based meat alternatives. However, country differences were observed for effects of “Intrinsic product quality”. Perceived barriers to plant-based food consumption and trust towards plant-based alternative proteins play a significant mediating role among all 10 countries. The implications are that environmental and ethical motivations could contribute to effectively promoting plant-based alternatives to meat and dairy. High sensory quality for plant-based meat and cheese alternatives is needed to build trust.
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| 48. |
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| 49. |
- Faber, Zachary J, et al.
(författare)
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The genomic landscape of core-binding factor acute myeloid leukemias
- 2016
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 48, s. 1551-1556
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Tidskriftsartikel (refereegranskat)abstract
- Acute myeloid leukemia (AML) comprises a heterogeneous group of leukemias frequently defined by recurrent cytogenetic abnormalities, including rearrangements involving the core-binding factor (CBF) transcriptional complex. To better understand the genomic landscape of CBF-AMLs, we analyzed both pediatric (n = 87) and adult (n = 78) samples, including cases with RUNX1-RUNX1T1 (n = 85) or CBFB-MYH11 (n = 80) rearrangements, by whole-genome or whole-exome sequencing. In addition to known mutations in the Ras pathway, we identified recurrent stabilizing mutations in CCND2, suggesting a previously unappreciated cooperating pathway in CBF-AML. Outside of signaling alterations, RUNX1-RUNX1T1 and CBFB-MYH11 AMLs demonstrated remarkably different spectra of cooperating mutations, as RUNX1-RUNX1T1 cases harbored recurrent mutations in DHX15 and ZBTB7A, as well as an enrichment of mutations in epigenetic regulators, including ASXL2 and the cohesin complex. This detailed analysis provides insights into the pathogenesis and development of CBF-AML, while highlighting dramatic differences in the landscapes of cooperating mutations for these related AML subtypes.
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| 50. |
- Fahrenholtz, I. L., et al.
(författare)
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Within-day energy deficiency and reproductive function in female endurance athletes
- 2018
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Ingår i: Scandinavian Journal of Medicine and Science in Sports. - : Wiley-Blackwell. - 0905-7188 .- 1600-0838. ; 28:3, s. 1139-1146
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Tidskriftsartikel (refereegranskat)abstract
- We aimed to estimate and compare within-day energy balance (WDEB) in athletes with eumenorrhea and menstrual dysfunction (MD) with similar 24-hour energy availability/energy balance (EA/EB). Furthermore, to investigate whether within-day energy deficiency is associated with resting metabolic rate (RMR), body composition, S-cortisol, estradiol, T-3, and fasting blood glucose. We reanalyzed 7-day dietary intake and energy expenditure data in 25 elite endurance athletes with eumenorrhea (n=10) and MD (n=15) from a group of 45 subjects where those with disordered eating behaviors (n=11), MD not related to low EA (n=5), and low dietary record validity (n=4) had been excluded. Besides gynecological examination and disordered eating evaluation, the protocol included RMR measurement; assessment of body composition by dual-energy X-ray absorptiometry, blood plasma analysis, and calculation of WDEB in 1-hour intervals. Subjects with MD spent more hours in a catabolic state compared to eumenorrheic athletes; WDEB<0kcal: 23.0hour (20.8-23.4) vs 21.1hour (4.7-22.3), P=.048; WDEB<-300kcal: 21.8hour (17.8-22.4) vs 17.6hour (3.9-20.9), P=.043, although similar 24-hour EA: 35.6 (11.6) vs 41.3 (12.7) kcal/kg FFM/d, (P=.269), and EB: -659 (551) vs -313 (596) kcal/d, (P=.160). Hours with WDEB <0kcal and <-300kcal were inversely associated with RMRratio (r=-.487, P=.013, r=-.472, P=.018), and estradiol (r=-.433, P=.034, r=-.516, P=.009), and positively associated with cortisol (r=.442, P=.027, r=.463, P=.019). In conclusion, although similar 24-hour EA/EB, the reanalysis revealed that MD athletes spent more time in a catabolic state compared to eumenorrheic athletes. Within-day energy deficiency was associated with clinical markers of metabolic disturbances.
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