| 1. |
- Clark, DW, et al.
(författare)
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Associations of autozygosity with a broad range of human phenotypes
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 4957-
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Tidskriftsartikel (refereegranskat)abstract
- In many species, the offspring of related parents suffer reduced reproductive success, a phenomenon known as inbreeding depression. In humans, the importance of this effect has remained unclear, partly because reproduction between close relatives is both rare and frequently associated with confounding social factors. Here, using genomic inbreeding coefficients (FROH) for >1.4 million individuals, we show that FROH is significantly associated (p < 0.0005) with apparently deleterious changes in 32 out of 100 traits analysed. These changes are associated with runs of homozygosity (ROH), but not with common variant homozygosity, suggesting that genetic variants associated with inbreeding depression are predominantly rare. The effect on fertility is striking: FROH equivalent to the offspring of first cousins is associated with a 55% decrease [95% CI 44–66%] in the odds of having children. Finally, the effects of FROH are confirmed within full-sibling pairs, where the variation in FROH is independent of all environmental confounding.
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| 2. |
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| 3. |
- Saevarsdottir, KS, et al.
(författare)
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Illness severity and risk of mental morbidities among patients recovering from COVID-19: a cross-sectional study in the Icelandic population
- 2021
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Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 11:7, s. e049967-
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Tidskriftsartikel (refereegranskat)abstract
- To test if patients recovering from COVID-19 are at increased risk of mental morbidities and to what extent such risk is exacerbated by illness severity.DesignPopulation-based cross-sectional study.SettingIceland.ParticipantsA total of 22 861 individuals were recruited through invitations to existing nationwide cohorts and a social media campaign from 24 April to 22 July 2020, of which 373 were patients recovering from COVID-19.Main outcome measuresSymptoms of depression (Patient Health Questionnaire), anxiety (General Anxiety Disorder Scale) and posttraumatic stress disorder (PTSD; modified Primary Care PTSD Screen for DSM-5) above screening thresholds. Adjusting for multiple covariates and comorbidities, multivariable Poisson regression was used to assess the association between COVID-19 severity and mental morbidities.ResultsCompared with individuals without a diagnosis of COVID-19, patients recovering from COVID-19 had increased risk of depression (22.1% vs 16.2%; adjusted relative risk (aRR) 1.48, 95% CI 1.20 to 1.82) and PTSD (19.5% vs 15.6%; aRR 1.38, 95% CI 1.09 to 1.75) but not anxiety (13.1% vs 11.3%; aRR 1.24, 95% CI 0.93 to 1.64). Elevated relative risks were limited to patients recovering from COVID-19 that were 40 years or older and were particularly high among individuals with university education. Among patients recovering from COVID-19, symptoms of depression were particularly common among those in the highest, compared with the lowest tertile of influenza-like symptom burden (47.1% vs 5.8%; aRR 6.42, 95% CI 2.77 to 14.87), among patients confined to bed for 7 days or longer compared with those never confined to bed (33.3% vs 10.9%; aRR 3.67, 95% CI 1.97 to 6.86) and among patients hospitalised for COVID-19 compared with those never admitted to hospital (48.1% vs 19.9%; aRR 2.72, 95% CI 1.67 to 4.44).ConclusionsSevere disease course is associated with increased risk of depression and PTSD among patients recovering from COVID-19.
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| 4. |
- Sigmundsson, F., et al.
(författare)
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Segmented lateral dyke growth in a rifting event at Bardarbunga volcanic system, Iceland
- 2015
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 517:7533
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Tidskriftsartikel (refereegranskat)abstract
- Crust at many divergent plate boundaries forms primarily by the injection of vertical sheet-like dykes, some tens of kilometres long(1). Previous models of rifting events indicate either lateral dyke growth away from a feeding source, with propagation rates decreasing as the dyke lengthens(2-4), or magma flowing vertically into dykes from an underlying source(5,6), with the role of topography on the evolution of lateral dykes not clear. Here we show how a recent segmented dyke intrusion in the Bardarbunga volcanic system grew laterally for more than 45 kilometres at a variable rate, with topography influencing the direction of propagation. Barriers at the ends of each segment were overcome by the build-up of pressure in the dyke end; then a new segment formed and dyke lengthening temporarily peaked. The dyke evolution, which occurred primarily over 14 days, was revealed by propagating seismicity, ground deformation mapped by Global Positioning System(GPS), interferometric analysis of satellite radar images (InSAR), and graben formation. The strike of the dyke segments varies from an initially radial direction away from the Bardarbunga caldera, towards alignment with that expected from regional stress at the distal end. A model minimizing the combined strain and gravitational potential energy explains the propagation path. Dyke opening and seismicity focused at the most distal segment at any given time, and were simultaneous with magma source deflation and slow collapse at the Bardarbunga caldera, accompanied by a series of magnitude M > 5 earthquakes. Dyke growth was slowed down by an effusive fissure eruption near the end of the dyke. Lateral dyke growth with segment barrier breaking by pressure build-up in the dyke distal end explains how focused upwelling of magma under central volcanoes is effectively redistributed over long distances to create new upper crust at divergent plate boundaries.
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| 5. |
- Wuttke, Matthias, et al.
(författare)
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A catalog of genetic loci associated with kidney function from analyses of a million individuals
- 2019
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Ingår i: Nature Genetics. - : NATURE PUBLISHING GROUP. - 1061-4036 .- 1546-1718. ; 51:6, s. 957-972
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Tidskriftsartikel (refereegranskat)abstract
- Chronic kidney disease (CKD) is responsible for a public health burden with multi-systemic complications. Through transancestry meta-analysis of genome-wide association studies of estimated glomerular filtration rate (eGFR) and independent replication (n = 1,046,070), we identified 264 associated loci (166 new). Of these,147 were likely to be relevant for kidney function on the basis of associations with the alternative kidney function marker blood urea nitrogen (n = 416,178). Pathway and enrichment analyses, including mouse models with renal phenotypes, support the kidney as the main target organ. A genetic risk score for lower eGFR was associated with clinically diagnosed CKD in 452,264 independent individuals. Colocalization analyses of associations with eGFR among 783,978 European-ancestry individuals and gene expression across 46 human tissues, including tubulo-interstitial and glomerular kidney compartments, identified 17 genes differentially expressed in kidney. Fine-mapping highlighted missense driver variants in 11 genes and kidney-specific regulatory variants. These results provide a comprehensive priority list of molecular targets for translational research.
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| 6. |
- Baldi, A., et al.
(författare)
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Mg/Ti multilayers : Structural and hydrogen absorption properties
- 2010
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Ingår i: Physical Review B. Condensed Matter and Materials Physics. - 1098-0121 .- 1550-235X. ; 81:22, s. 224203-
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Tidskriftsartikel (refereegranskat)abstract
- Mg-Ti alloys have uncommon optical and hydrogen absorbing properties, originating from a "spinodal-like" microstructure with a small degree of chemical short-range order in the atomic distribution. In the present study we artificially engineer short-range order by depositing Pd-capped Mg/Ti multilayers with different periodicities. Notwithstanding the large lattice mismatch between Mg and Ti, the as-deposited metallic multilayers show good structural coherence. On exposure to H-2 gas a two-step hydrogenation process occurs with the Ti layers forming the hydride before Mg. From in situ measurements of the bilayer thickness Lambda at different hydrogen pressures, we observe large out-of-plane expansions of Mg and Ti layers on hydrogenation, indicating strong plastic deformations in the films and a consequent shortening of the coherence length. On unloading at room temperature in air, hydrogen atoms remain trapped in the Ti layers due to kinetic constraints. Such loading/unloading sequence can be explained in terms of the different thermodynamic properties of hydrogen in Mg and Ti, as shown by diffusion calculations on a model multilayered systems. Absorption isotherms measured by hydrogenography can be interpreted as a result of the elastic clamping arising from strongly bonded Mg/Pd and broken Mg/Ti interfaces.
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| 7. |
- Eiteneer, D., et al.
(författare)
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Depth-Resolved Composition and Electronic Structure of Buried Layers and Interfaces in a LaNiO3/SrTiO3 Superlatticefroni Soft- and Hard-X-ray Standing-Wave Angle-Resolved Photoemission
- 2016
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Ingår i: Journal of Electron Spectroscopy and Related Phenomena. - : Elsevier BV. - 0368-2048 .- 1873-2526. ; 211, s. 70-81
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Tidskriftsartikel (refereegranskat)abstract
- LaNiO3 (LNO) is an intriguing member of the rare-earth nickelates in exhibiting a metal-insulator transition for a critical film thickness of about 4 unit cells [Son et al., Appl. Phys. Lett. 96, 062114 (2010)]; however, such thin films also show a transition to a metallic state in superlattices with SrTiO3 (STO) [Son et al., Appl. Phys. Lett. 97, 202109 (2010)]. In order to better understand this transition, we have studied a strained LNO/STO superlattice with 10 repeats of [4 unit-cell LNO/3 unit-cell STO] grown on an (LaAlO3)(0.3)(Sr2AlTaO6)(0.7) substrate using soft x-ray standing-wave-excited angle-resolved photoemission (SWARPES), together with soft- and hard- x-ray photoemission-measurements of core levels and densities-of-states valence spectra. The experimental results are compared with state-of-the-art density functional theory (DFT) calculations of band structures and densities of states. Using core-level rocking curves and x-ray optical modeling to assess the position of the standing wave, SWARPES measurements are carried out for various incidence angles and used to determine interface-specific changes in momentum-resolved electronic structure. We further show that the momentum-resolved behavior of the Ni 3d e(g) and t(2g) states near the Fermi level, as well as those at the bottom of the valence bands, is very similar to recently published SWARPES results for a related La0.7Sr0.3MnO3/SrTiO3 superlattice that was-studied using the same technique (Gray et al., Europhysics Letters 104, 17004 (2013)), which further validates this experimental approach and our conclusions. Our conclusions are also supported in several ways by comparison to DFT calculations for the parent materials and the superlattice, including layer-resolved density-of-states results.
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| 8. |
- Estrada, Karol, et al.
(författare)
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Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture.
- 2012
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 44:5, s. 491-501
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Tidskriftsartikel (refereegranskat)abstract
- Bone mineral density (BMD) is the most widely used predictor of fracture risk. We performed the largest meta-analysis to date on lumbar spine and femoral neck BMD, including 17 genome-wide association studies and 32,961 individuals of European and east Asian ancestry. We tested the top BMD-associated markers for replication in 50,933 independent subjects and for association with risk of low-trauma fracture in 31,016 individuals with a history of fracture (cases) and 102,444 controls. We identified 56 loci (32 new) associated with BMD at genome-wide significance (P < 5 × 10(-8)). Several of these factors cluster within the RANK-RANKL-OPG, mesenchymal stem cell differentiation, endochondral ossification and Wnt signaling pathways. However, we also discovered loci that were localized to genes not known to have a role in bone biology. Fourteen BMD-associated loci were also associated with fracture risk (P < 5 × 10(-4), Bonferroni corrected), of which six reached P < 5 × 10(-8), including at 18p11.21 (FAM210A), 7q21.3 (SLC25A13), 11q13.2 (LRP5), 4q22.1 (MEPE), 2p16.2 (SPTBN1) and 10q21.1 (DKK1). These findings shed light on the genetic architecture and pathophysiological mechanisms underlying BMD variation and fracture susceptibility.
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| 9. |
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| 10. |
- Koopman, J J E, et al.
(författare)
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Senescence rates in patients with end-stage renal disease: a critical appraisal of the Gompertz model.
- 2011
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Ingår i: Aging Cell. - : Wiley. - 1474-9726 .- 1474-9718. ; Dec, s. 233-238
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Tidskriftsartikel (refereegranskat)abstract
- The most frequently used model to describe the exponential increase in mortality rate over age is the Gompertz equation. Logarithmically transformed, the equation conforms to a straight line, of which the slope has been interpreted as the rate of senescence. Earlier, we proposed the derivative function of the Gompertz equation as a superior descriptor of senescence rate. Here, we tested both measures of the rate of senescence in a population of patients with end-stage renal disease. It is clinical dogma that patients on dialysis experience accelerated senescence, whereas those with a functional kidney transplant have mortality rates comparable to the general population. Therefore, we calculated the age-specific mortality rates for European patients on dialysis (n=274,221; follow-up=594,767 person-years), for European patients with a functioning kidney transplant (n=61,286; follow-up=345,024 person-years), and for the general European population. We found higher mortality rates, but a smaller slope of logarithmical mortality curve for patients on dialysis compared to both patients with a functioning kidney transplant and the general population (p<0.001). A classical interpretation of the Gompertz model would imply that the rate of senescence in patients on dialysis is lower than in patients with a functioning transplant and lower than in the general population. In contrast, the derivative function of the Gompertz equation yielded highest senescence rates for patients on dialysis, whereas the rate was similar in patients with a functioning transplant and the general population. We conclude that the rate of senescence is better described by the derivative function of the Gompertz equation.
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| 11. |
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| 12. |
- Andersson, K. G., et al.
(författare)
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Parametric improvement for the ingestion dose module of the European ARGOS and RODOS decision support systems
- 2011
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Ingår i: Radioprotection. - : EDP Sciences. - 0033-8451 .- 1769-700X. ; 46
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Tidskriftsartikel (refereegranskat)abstract
- The European decision support systems ARGOS and RODOS rely on the ECOSYS model for prognoses of ingestion doses. ECOSYS needs an update of various parameter values to provide reliable estimates. This paper reports on some results of a Nordic initiative to derive parameter values that are specific to Nordic conditions, as well as to improve generic parameter values in ECOSYS, taking into account the host of useful measurement data accumulated since ECOSYS was created. © 2011 EDP Sciences.
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| 13. |
- Andersson, Kasper G, et al.
(författare)
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Revision of deposition and weathering parameters for the ingestion dose module (ECOSYS) of the ARGOS and RODOS decision support systems.
- 2011
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Ingår i: Journal of environmental radioactivity. - : Elsevier BV. - 1879-1700 .- 0265-931X.
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Tidskriftsartikel (refereegranskat)abstract
- The ECOSYS model is the ingestion dose model integrated in the ARGOS and RODOS decision support systems for nuclear emergency management. The parameters used in this model have however not been updated in recent years, where the level of knowledge on various environmental processes has increased considerably. A Nordic work group has carried out a series of evaluations of the general validity of current ECOSYS default parameters. This paper specifically discusses the parameter revisions required with respect to the modelling of deposition and natural weathering of contaminants on agricultural crops, to enable the trustworthy prognostic modelling that is essential to ensure justification and optimisation of countermeasure strategies. New modelling approaches are outlined, since it was found that current ECOSYS approaches for deposition and natural weathering could lead to large prognostic errors.
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| 14. |
- Azofeifa, D. E., et al.
(författare)
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Temperature-and hydrogen-induced changes in the optical properties of Pd capped V thin films
- 2012
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Ingår i: Physica Scripta. - : IOP Publishing. - 0031-8949 .- 1402-4896. ; 86:6, s. 065702-
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Tidskriftsartikel (refereegranskat)abstract
- Optical properties of V thin films deposited on MgO substrates have been obtained from spectrophotometric measurements. The V films were coated with a thin Pd layer to protect them from oxidation and to favor absorption of atomic hydrogen. Electrical resistance was recorded while hydrogen pressure was increased slowly up to 750mbar keeping the temperature constant. Simultaneously, visible and near-infrared transmittance spectra of this Pd/V/MgO system were measured. The spectra were numerically inverted to obtain the spectral behavior of the Pd and V dielectric functions at 22 and 140 degrees C. Hydrogen concentrations were first determined from the combined effect of hydrogen content on the electrical resistance and on the optical direct transmission of the system. Then, determination of these concentrations was improved using retrieved values of the absorption coefficients of the hydrides and taking into account the structural change of V and the volumetric expansion of Pd. Good agreement is established when considering qualitative correlations between spectral features of the optimized PdHy and VHx dielectric functions and band structure calculations and densities of states for these two transition metal hydrides.
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| 15. |
- Bergsteinsson, Hjörleifur G., et al.
(författare)
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Heat load forecasting using adaptive temporal hierarchies
- 2021
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Ingår i: Applied Energy. - : Elsevier BV. - 0306-2619. ; 292
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Tidskriftsartikel (refereegranskat)abstract
- Heat load forecasts are crucial for energy operators in order to optimize the energy production at district heating plants for the coming hours. Furthermore, forecasts of heat load are needed for optimized control of the district heating network since a lower temperature reduces the heat loss, but the required heat supply at the end-users puts a lower limit on the temperature level. Consequently, improving the accuracy of heat load forecasts leads to savings and reduced heat loss by enabling improved control of the network and an optimized production schedule at the plant. This paper proposes the use of temporal hierarchies to enhance the accuracy of heat load forecasts in district heating. Usually, forecasts are only made at the temporal aggregation level that is the most important for the system. However, forecasts for multiple aggregation levels can be reconciled and lead to more accurate forecasts at essentially all aggregation levels. Here it is important that the auto- and cross-covariance between forecast errors at the different aggregation levels are taken into account. This paper suggests a novel framework using temporal hierarchies and adaptive estimation to improve heat load forecast accuracy by optimally combining forecasts from multiple aggregation levels using a reconciliation process. The weights for the reconciliation are computed using an adaptively estimated covariance matrix with a full structure, enabling the process to share time-varying information both within and between aggregation levels. The case study shows that the proposed framework improves the heat load forecast accuracy by 15% compared to commercial state-of-the-art operational forecasts.
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| 16. |
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| 17. |
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| 18. |
- Conlon, C. S., et al.
(författare)
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Hard x-ray standing-wave photoemission insights into the structure of an epitaxial Fe/MgO multilayer magnetic tunnel junction
- 2019
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Ingår i: Journal of Applied Physics. - : AIP Publishing. - 0021-8979 .- 1089-7550. ; 126:7
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Tidskriftsartikel (refereegranskat)abstract
- The Fe/MgO magnetic tunnel junction is a classic spintronic system, with current importance technologically and interest for future innovation. The key magnetic properties are linked directly to the structure of hard-to-access buried interfaces, and the Fe and MgO components near the surface are unstable when exposed to air, making a deeper probing, nondestructive, in-situ measurement ideal for this system. We have thus applied hard x-ray photoemission spectroscopy (HXPS) and standing-wave (SW) HXPS in the few kilo-electron-volt energy range to probe the structure of an epitaxially grown MgO/Fe superlattice. The superlattice consists of 9 repeats of MgO grown on Fe by magnetron sputtering on an MgO(001) substrate, with a protective Al2O3 capping layer. We determine through SW-HXPS that 8 of the 9 repeats are similar and ordered, with a period of 33 +/- 4 angstrom, with the minor presence of FeO at the interfaces and a significantly distorted top bilayer with ca. 3 times the oxidation of the lower layers at the top MgO/Fe interface. There is evidence of asymmetrical oxidation on the top and bottom of the Fe layers. We find agreement with dark-field scanning transmission electron microscope (STEM) and x-ray reflectivity measurements. Through the STEM measurements, we confirm an overall epitaxial stack with dislocations and warping at the interfaces of ca. 5 angstrom. We also note a distinct difference in the top bilayer, especially MgO, with possible Fe inclusions. We thus demonstrate that SW-HXPS can be used to probe deep buried interfaces of novel magnetic devices with few-angstrom precision.
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| 19. |
- de Boer, Hugo J., et al.
(författare)
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Botanical Repellents and Pesticides Traditionally Used Against Hematophagous Invertebrates in Lao People's Democratic Republic : A Comparative Study of Plants Used in 66 Villages
- 2010
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Ingår i: Journal of medical entomology. - 0022-2585 .- 1938-2928. ; 47:3, s. 400-414
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Tidskriftsartikel (refereegranskat)abstract
- Hematophagous parasites such as leeches, ticks, mites, lice, bedbugs, mosquitoes, and myiasis-producing fly larvae are common health problems in Lao People's Democratic Republic. Several arthropod-borne infections, e.g., malaria, dengue fever, and Japanese encephalitis, are endemic there. Effective vector control methods including the use of pesticides, insecticide-treated bed nets, and synthetic and plant-based repellents are important means of control against such invertebrates and the pathogens they may transmit or directly cause. In this study, we documented traditional knowledge on plants that are used to repel or kill hematophagous arthropods, including mosquitoes, bedbugs, human lice, mites and ticks, fly larvae, and blood-sucking leeches. Structured interviews were carried out in 66 villages comprising 17 ethnic groups, covering a range of cultures, throughout Lao People's Democratic Republic. A total of 92 plant species was recorded as traditional repellents (including plants for pesticidal usages) in 123 different plant-ectoparasite combinations. The number and species of plants, and animal taxa repelled (or killed) per plant species differed per region, village, and ethnic group. Traditional use was confirmed in the scientific literature for 74 of these plant species, and for an additional 13 species using literature on closely related species. The use of botanical repellents and pesticides from many plant species is common and widespread in the Lao countryside. In the future, the identification of the active components in certain plants to develop more optimal, inexpensive repellents, insecticides, acaricides, or antileech compounds as alternatives to synthetic repellents/pesticides against blood-feeding insects, ticks, mites, and leeches is warranted.
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| 20. |
- Delanaye, Pierre, et al.
(författare)
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CKD : A Call for an Age-Adapted Definition
- 2019
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Ingår i: Journal of the American Society of Nephrology. - 1046-6673. ; 30:10, s. 1785-1805
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Forskningsöversikt (refereegranskat)abstract
- Current criteria for the diagnosis of CKD in adults include persistent signs of kidney damage, such as increased urine albumin-to-creatinine ratio or a GFR below the threshold of 60 ml/min per 1.73 m2 This threshold has important caveats because it does not separate kidney disease from kidney aging, and therefore does not hold for all ages. In an extensive review of the literature, we found that GFR declines with healthy aging without any overt signs of compensation (such as elevated single-nephron GFR) or kidney damage. Older living kidney donors, who are carefully selected based on good health, have a lower predonation GFR compared with younger donors. Furthermore, the results from the large meta-analyses conducted by the CKD Prognosis Consortium and from numerous other studies indicate that the GFR threshold above which the risk of mortality is increased is not consistent across all ages. Among younger persons, mortality is increased at GFR <75 ml/min per 1.73 m2, whereas in elderly people it is increased at levels <45 ml/min per 1.73 m2 Therefore, we suggest that amending the CKD definition to include age-specific thresholds for GFR. The implications of an updated definition are far reaching. Having fewer healthy elderly individuals diagnosed with CKD could help reduce inappropriate care and its associated adverse effects. Global prevalence estimates for CKD would be substantially reduced. Also, using an age-specific threshold for younger persons might lead to earlier identification of CKD onset for such individuals, at a point when progressive kidney damage may still be preventable.
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| 21. |
- Elmunzer, B. Joseph, et al.
(författare)
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Prolonged Gastrointestinal Manifestations After Recovery From COVID-19
- 2024
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Ingår i: Clinical Gastroenterology and Hepatology. - 1542-3565 .- 1542-7714. ; 22:5
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Tidskriftsartikel (refereegranskat)abstract
- Background & Aims: Acute enteric infections are well known to result in long-term gastrointestinal (GI) disorders. Although COVID-19 is principally a respiratory illness, it demonstrates significant GI tropism, possibly predisposing to prolonged gut manifestations. We aimed to examine the long-term GI impact of hospitalization with COVID-19. Methods: Nested within a large-scale observational cohort study of patients hospitalized with COVID-19 across North America, we performed a follow-up survey of 530 survivors 12–18 months later to assess for persistent GI symptoms and their severity, and for the development of disorders of gut-brain interaction (DGBIs). Eligible patients were identified at the study site level and surveyed electronically. The survey instrument included the Rome IV Diagnostic Questionnaire for DGBI, a rating scale of 24 COVID-related symptoms, the Gastrointestinal Symptoms Rating Scale, and the Impact of Events–Revised trauma symptom questionnaire (a measure of posttraumatic stress associated with the illness experience). A regression analysis was performed to explore the factors associated with GI symptom severity at follow-up. Results: Of the 530 invited patients, 116 responded (52.6% females; mean age, 55.2 years), and 73 of those (60.3%) met criteria for 1 or more Rome IV DGBI at follow-up, higher than the prevalence in the US general population (P <. 0001). Among patients who experienced COVID-related GI symptoms during the index hospitalization (abdominal pain, nausea, vomiting, or diarrhea), 42.1% retained at least 1 of these symptoms at follow-up; in comparison, 89.8% of respondents retained any (GI or non-GI) COVID-related symptom. The number of moderate or severe GI symptoms experienced during the initial COVID-19 illness by self-report correlated with the development of DGBI and severity of GI symptoms at follow-up. Posttraumatic stress disorder (Impact of Events–Revised score ≥33) related to the COVID-19 illness experience was identified in 41.4% of respondents and those individuals had higher DGBI prevalence and GI symptom severity. Regression analysis revealed that higher psychological trauma score (Impact of Events–Revised) was the strongest predictor of GI symptom severity at follow-up. Conclusions: In this follow-up survey of patients 12–18 months after hospitalization with COVID-19, there was a high prevalence of DGBIs and persistent GI symptoms. Prolonged GI manifestations were associated with the severity of GI symptoms during hospitalization and with the degree of psychological trauma related to the illness experience.
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| 22. |
- Gutierrez, Jahir M., et al.
(författare)
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Genome-scale reconstructions of the mammalian secretory pathway predict metabolic costs and limitations of protein secretion
- 2020
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723 .- 2041-1723. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- In mammalian cells, >25% of synthesized proteins are exported through the secretory pathway. The pathway complexity, however, obfuscates its impact on the secretion of different proteins. Unraveling its impact on diverse proteins is particularly important for biopharmaceutical production. Here we delineate the core secretory pathway functions and integrate them with genome-scale metabolic reconstructions of human, mouse, and Chinese hamster ovary cells. The resulting reconstructions enable the computation of energetic costs and machinery demands of each secreted protein. By integrating additional omics data, we find that highly secretory cells have adapted to reduce expression and secretion of other expensive host cell proteins. Furthermore, we predict metabolic costs and maximum productivities of biotherapeutic proteins and identify protein features that most significantly impact protein secretion. Finally, the model successfully predicts the increase in secretion of a monoclonal antibody after silencing a highly expressed selection marker. This work represents a knowledgebase of the mammalian secretory pathway that serves as a novel tool for systems biotechnology.
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| 23. |
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| 24. |
- Herrgård, Markus J, et al.
(författare)
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A consensus yeast metabolic network reconstruction obtained from a community approach to systems biology
- 2008
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Ingår i: Nature Biotechnology. ; 26:10, s. 1155-1160
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Tidskriftsartikel (refereegranskat)abstract
- Genomic data allow the large-scale manual or semi-automated assembly of metabolic network reconstructions, which provide highly curated organism-specific knowledge bases. Although several genome-scale network reconstructions describe Saccharomyces cerevisiae metabolism, they differ in scope and content, and use different terminologies to describe the same chemical entities. This make comparisons between them difficult and underscores the desirability of a consolidated metabolic network that collects and formalizes the 'community knowledge' of yeast metabolism. We describe how we have produced a consensus metabolic network reconstruction for S. cerevisiae. In drafting it, we placed special emphasis on referencing molecules to persistent databases or using database-independent forms, such as SMILES or InChl strings, as this permits their chemical structure to be represented unambiguously and in a manner that permits automated reasoning. The reconstruction is readily available via a publicly accessible database and in the Systems Biology Markup Language (http://www.comp-sys-bio.org/yeastnet). It can be maintained as a resource that serves as a common denominator for studying the systems biology of yeast. Similar strategies should benefit communities studying genome-scale metabolic networks of other organisms.
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| 25. |
- Hruskova, Zdenka, et al.
(författare)
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Characteristics and Outcomes of Patients With Systemic Sclerosis (Scleroderma) Requiring Renal Replacement Therapy in Europe: Results From the ERA-EDTA Registry
- 2019
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Ingår i: American Journal of Kidney Diseases. - : W B SAUNDERS CO-ELSEVIER INC. - 0272-6386 .- 1523-6838. ; 73:2, s. 184-193
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Tidskriftsartikel (refereegranskat)abstract
- Rationale amp; Objective: Data for outcomes of patients with end-stage renal disease (ESRD) secondary to systemic sclerosis (scleroderma) requiring renal replacement therapy (RRT) are limited. We examined the incidence and prevalence of ESRD due to scleroderma in Europe and the outcomes among these patients following initiation of RRT. Study Design: Registry study of incidence and prevalence and a matched cohort study of clinical outcomes. Setting amp; Participants: Patients represented in any of 19 renal registries that provided data to the European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) Registry between 2002 and 2013. Predictor: Scleroderma as the identified cause of ESRD. Outcomes: Incidence and prevalence of ESRD from scleroderma. Recovery from RRT dependence, patient survival after ESRD, and graft survival after kidney transplantation. Analytical Approach: Incidence and prevalence were calculated using population data from the European Union and standardized to population characteristics in 2005. Patient and graft survival were compared with 2 age- and sex-matched control groups without scleroderma: (1) diabetes mellitus as the cause of ESRD and (2) conditions other than diabetes mellitus as the cause of ESRD. Survival analyses were performed using Kaplan-Meier analysis and Cox regression. Results: 342 patients with scleroderma (0.14% of all incident RRT patients) were included. Between 2002 and 2013, the range of adjusted annual incidence and prevalence rates of RRT for ESRD due to scleroderma were 0.11 to 0.26 and 0.73 to 0.95 per million population, respectively. Recovery of independent kidney function was greatest in the scleroderma group (7.6% vs 0.7% in diabetes mellitus and 2.0% in other primary kidney diseases control group patients, both Pamp;lt;0.001), though time required to achieve recovery was longer. The 5-year survival probability from day 91 of RRT among patients with scleroderma was 38.9% (95% CI, 32.0%-45.8%), whereas 5-year posttransplantation patient survival and 5-year allograft survival were 88.2% (95% CI, 75.3%-94.6%) and 72.4% (95% CI, 55.0%-84.0%), respectively. Adjusted mortality from day 91 on RRT was higher among patients with scleroderma than observed in both control groups (HRs of 1.25 [95% CI, 1.05-1.48] and 2.00 [95% CI, 1.69-2.39]). In contrast, patient and graft survival after kidney transplantation did not differ between patients with scleroderma and control groups. Limitations: No data for extrarenal manifestations, treatment, or recurrence. Conclusions: Survival of patients with scleroderma who receive dialysis for more than 90 days was worse than for those with other causes of ESRD. Patient survival after transplantation was similar to that observed among patients with ESRD due to other conditions. Patients with scleroderma had a higher rate of recovery from RRT dependence than controls.
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| 26. |
- Jaenson, T. G. T., et al.
(författare)
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Evaluation of extracts and oils of mosquito (Diptera : Culicidae) repellent plants from Sweden and Guinea-Bissau
- 2006
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Ingår i: Journal of medical entomology. - : Oxford University Press (OUP). - 0022-2585 .- 1938-2928. ; 43:1, s. 113-119
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Tidskriftsartikel (refereegranskat)abstract
- In laboratory tests, ethyl acetate extracts of Hyptis, suaveolens Poit. from Guinea-Bissau and Rhododendon tomentosum (Stokes) H. Harmaja (formerly Ledum palustre L.) and Myrica gale L. significantly reduced probing activity of Aedes aegypti (L.). In the field in southern Sweden, extracts of leaves of R. tomentosum, M. gale, and Achillea millefolium L. significantly reduced biting by Aedes mosquitoes. Volatile compounds from M. gale, R. tomentosum, A. millefolium, and H. suaveolens were collected by solid phase microextraction (SPME). Alternatively, compounds in the plants were subjected to extraction by organic solvents of different polarities or by steam distillation and collection by SPME. Compounds collected were identified by gas chromatography-mass spectrometry. Leaves of H. suaveolens contained mainly beta-caryophyllene, bergamotene, and terpinolene. The volatile fraction of an ethyl acetate extract of H. suaveolens was collected by SPME and included beta-caryophyllene, (-) -sabinene, beta-pinene, limonene, alpha-pinene, and bergamotene. The main volatiles detected were alpha-pinene, alpha-phellandrene, myrcene, and limonene from M. gale leaves or inflorescences; pcymene, sabinene, and terpinyl acetate from leaves of R. tornentoston; and (-)-germacrene D, beta-pinene, sabinene, and alpha-pinene from A. millefolium leaves or inflorescences. The selected plant species contained numerous volatiles known to have insecticidal, acaricidal, pesticidal, and/orinsect repellent properties.
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| 27. |
- Jaenson, T. G. T., et al.
(författare)
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Evaluation of extracts and oils of tick-repellent plants from Sweden
- 2005
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Ingår i: Medical and Veterinary Entomology. - : Wiley. - 0269-283X .- 1365-2915. ; 19:4, s. 345-352
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Tidskriftsartikel (refereegranskat)abstract
- Leaves of Myrica gale Linnaeus (Myricaceae), Rhododendron tomentosum (Stokes) H. Harmaja (formerly Ledum palustre Linnaeus: Ericaceae) and Artemisia absinthium Linnaeus (Asteraceae) were extracted with organic solvents of different polarities and the essential oils of leaves were obtained by steam distillation. The extracts or oils were tested in the laboratory for repellency against host-seeking nymphs of Ixodes ricinus Linnaeus (Acari: Ixodidae). Rhododendron tomentosum oil, 10%, diluted in acetone, exhibited 95% repellency; R. tomentosum and A. absinthium extracts in ethyl acetate, > 70% repellency; A. absinthium extract in hexane, similar to 62% repellency; and M. gale oil, 10%, similar to 50% repellency on I. ricinus nymphs. Compounds in the leaf extracts or in the oils were collected by solid phase microextraction (SPME) and identified by gas chromatography-mass spectrometry (GC-MS) and/or MS. Characteristic volatiles detected from oil or extract of M. gale were the monoterpenes 1,8-cineole, alpha-terpineol, 4-terpineol and thujenol; and of R. tomentosum myrcene and palustrol. Characteristic volatiles from leaf extracts of A. absinthium were sabinene, oxygenated monoterpenes, e.g. thujenol and linalool, and geranyl acetate. Each plant species synthesized numerous volatiles known to exhibit acaricidal, insecticidal, 'pesticidal' and/or arthropod repellent properties. These plants may be useful sources of chemicals for the control of arthropods of medical, veterinary or agricultural importance.
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| 28. |
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| 29. |
- Jonsdottir, G. M., et al.
(författare)
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RT-HIL hardware prototyping of synchrophasor and active load-based power system oscillation damping controllers
- 2016
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Ingår i: IEEE Power and Energy Society General Meeting. - : IEEE. - 9781509041688
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Konferensbidrag (refereegranskat)abstract
- The Icelandic power system is characterized by two areas that oscillate against each other during stressed system operation, and may lead to an islanding of system. Conventional stabilizing methods are being used to their full capacity, thus new options are being explored to prevent system break-ups. There is potential in exploiting large industrial loads to enhance system stability. In this paper a hardware prototype of a synchrophasor-based active load controller for oscillation damping is presented. The performance of the controller is analysed using Real-Time Hardware-in-the-Loop (RT-HIL) approach.
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| 30. |
- Jung, Christian, et al.
(författare)
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A comparison of very old patients admitted to intensive care unit after acute versus elective surgery or intervention
- 2019
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Ingår i: Journal of critical care. - : W B SAUNDERS CO-ELSEVIER INC. - 0883-9441 .- 1557-8615. ; 52, s. 141-148
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Tidskriftsartikel (refereegranskat)abstract
- Background: We aimed to evaluate differences in outcome between patients admitted to intensive care unit (ICU) after elective versus acute surgery in a multinational cohort of very old patients (80 years; VIP). Predictors of mortality, with special emphasis on frailty, were assessed.Methods: In total, 5063 VIPs were induded in this analysis, 922 were admitted after elective surgery or intervention, 4141 acutely, with 402 after acute surgery. Differences were calculated using Mann-Whitney-U test and Wilcoxon test. Univariate and multivariable logistic regression were used to assess associations with mortality.Results: Compared patients admitted after acute surgery, patients admitted after elective surgery suffered less often from frailty as defined as CFS (28% vs 46%; p < 0.001), evidenced lower SOFA scores (4 +/- 5 vs 7 +/- 7; p < 0.001). Presence of frailty (CFS >4) was associated with significantly increased mortality both in elective surgery patients (7% vs 12%; p = 0.01), in acute surgery (7% vs 12%; p = 0.02).Conclusions: VIPs admitted to ICU after elective surgery evidenced favorable outcome over patients after acute surgery even after correction for relevant confounders. Frailty might be used to guide clinicians in risk stratification in both patients admitted after elective and acute surgery.
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| 31. |
- Keqi, A., et al.
(författare)
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Electronic structure of the dilute magnetic semiconductor Ga1-xMnxP from hard x-ray photoelectron spectroscopy and angle-resolved photoemission
- 2018
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Ingår i: Physical Review B. - 2469-9950 .- 2469-9969. ; 97:15
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Tidskriftsartikel (refereegranskat)abstract
- We have investigated the electronic structure of the dilute magnetic semiconductor (DMS) Ga0.98Mn0.02P and compared it to that of an undoped GaP reference sample, using hard x-ray photoelectron spectroscopy (HXPS) and hard x-ray angle-resolved photoemission spectroscopy (HARPES) at energies of about 3 keV. We present experimental data, as well as theoretical calculations, to understand the role of the Mn dopant in the emergence of ferromagnetism in this material. Both core-level spectra and angle-resolved or angle-integrated valence spectra are discussed. In particular, the HARPES experimental data are compared to free-electron final-state model calculations and to more accurate one-step photoemission theory. The experimental results show differences between Ga0.98Mn0.02P and GaP in both angle-resolved and angle-integrated valence spectra. The Ga0.98Mn0.02P bands are broadened due to the presence of Mn impurities that disturb the long-range translational order of the host GaP crystal. Mn-induced changes of the electronic structure are observed over the entire valence band range, including the presence of a distinct impurity band close to the valence-band maximum of the DMS. These experimental results are in good agreement with the one-step photoemission calculations and a prior HARPES study of Ga0.97Mn0.03As and GaAs [Gray et al., Nat. Mater. 11, 957 (2012)], demonstrating the strong similarity between these two materials. The Mn 2p and 3s core-level spectra also reveal an essentially identical state in doping both GaAs and GaP.
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| 32. |
- Kiemeney, Lambertus A, et al.
(författare)
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A sequence variant at 4p16.3 confers susceptibility to urinary bladder cancer.
- 2010
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 42:5, s. 415-9
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Tidskriftsartikel (refereegranskat)abstract
- Previously, we reported germline DNA variants associated with risk of urinary bladder cancer (UBC) in Dutch and Icelandic subjects. Here we expanded the Icelandic sample set and tested the top 20 markers from the combined analysis in several European case-control sample sets, with a total of 4,739 cases and 45,549 controls. The T allele of rs798766 on 4p16.3 was found to associate with UBC (odds ratio = 1.24, P = 9.9 x 10(-12)). rs798766 is located in an intron of TACC3, 70 kb from FGFR3, which often harbors activating somatic mutations in low-grade, noninvasive UBC. Notably, rs798766[T] shows stronger association with low-grade and low-stage UBC than with more aggressive forms of the disease and is associated with higher risk of recurrence in low-grade stage Ta tumors. The frequency of rs798766[T] is higher in Ta tumors that carry an activating mutation in FGFR3 than in Ta tumors with wild-type FGFR3. Our results show a link between germline variants, somatic mutations of FGFR3 and risk of UBC.
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| 33. |
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| 34. |
- Lischner, Johannes, et al.
(författare)
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Accurate determination of the valence band edge in hard x-ray photoemission spectra using GW theory
- 2016
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Ingår i: Journal of Applied Physics. - : AIP Publishing. - 0021-8979 .- 1089-7550. ; 119:16
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Tidskriftsartikel (refereegranskat)abstract
- We introduce a new method for determining accurate values of the valence-band maximum in x-ray photoemission spectra. Specifically, we align the sharpest peak in the valence-band region of the experimental spectrum with the corresponding feature of a theoretical valence-band density of states curve from ab initio GW theory calculations. This method is particularly useful for soft and hard x-ray photoemission studies of materials with a mixture of valence-band characters, where strong matrix element effects can render standard methods for extracting the valence-band maximum unreliable. We apply our method to hydrogen-terminated boron-doped diamond, which is a promising substrate material for novel solar cell devices. By carrying out photoemission experiments with variable light polarizations, we verify the accuracy of our analysis and the general validity of the method. Published by AIP Publishing.
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| 35. |
- Magnusson, E., et al.
(författare)
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Development of a subglacial lake monitored with radio-echo sounding: case study from the eastern Skafta cauldron in the Vatnajokull ice cap, Iceland
- 2021
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Ingår i: Cryosphere. - : Copernicus GmbH. - 1994-0416. ; 15:8, s. 3731-3749
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Tidskriftsartikel (refereegranskat)abstract
- We present repeated radio-echo sounding (RES, 5 MHz) on a profile grid over the eastern Skafta cauldron (ESC) in Vatnajokull ice cap, Iceland. The ESC is a similar to 3 km wide and 50-150 m deep ice cauldron created and maintained by subglacial geothermal activity of similar to 1GW. Beneath the cauldron and 200-400 m thick ice, water accumulates in a subglacial lake and is released semi-regularly in jokulhlaups. The RES record consists of annual surveys conducted at the beginning of every summer during the period 2014-2020. Comparison of the RES surveys reveals variable lake area (0.5-4.1 km(2)) and enables traced reflections from the lake roof to be distinguished from bedrock reflections. This allows construction of a digital elevation model (DEM) of the bedrock in the area, further constrained by two borehole measurements at the cauldron centre. It also allows creation of lake thickness maps and an estimate of lake volume at the time of each survey, which we compare with lowering patterns and released water volumes obtained from pre- and post-jokulhlaup surface DEMs. The estimated lake volume was 250 GL (gigalitres = 10(6) m(3)) in June 2015, but 320 +/- 20 GL drained from the ESC in October 2015. In June 2018, RES profiles revealed a lake volume of 185 GL, while 220 +/- 30 GL were released in a jokulhlaup in August 2018. Considering the water accumulation over the periods between RES surveys and jokulhlaups, this indicates 10 %-20% uncertainty in the RES-derived volumes at times when significant jokulhlaups may be expected.
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| 36. |
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| 37. |
- Oei, Ling, et al.
(författare)
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A genome-wide copy number association study of osteoporotic fractures points to the 6p25.1 locus
- 2014
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Ingår i: Journal of Medical Genetics. - : BMJ Publishing Group. - 0022-2593 .- 1468-6244. ; 51:2, s. 122-131
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Osteoporosis is a systemic skeletal disease characterised by reduced bone mineral density and increased susceptibility to fracture; these traits are highly heritable. Both common and rare copy number variants (CNVs) potentially affect the function of genes and may influence disease risk.AIM: To identify CNVs associated with osteoporotic bone fracture risk.METHOD: We performed a genome-wide CNV association study in 5178 individuals from a prospective cohort in the Netherlands, including 809 osteoporotic fracture cases, and performed in silico lookups and de novo genotyping to replicate in several independent studies.RESULTS: A rare (population prevalence 0.14%, 95% CI 0.03% to 0.24%) 210 kb deletion located on chromosome 6p25.1 was associated with the risk of fracture (OR 32.58, 95% CI 3.95 to 1488.89; p=8.69×10(-5)). We performed an in silico meta-analysis in four studies with CNV microarray data and the association with fracture risk was replicated (OR 3.11, 95% CI 1.01 to 8.22; p=0.02). The prevalence of this deletion showed geographic diversity, being absent in additional samples from Australia, Canada, Poland, Iceland, Denmark, and Sweden, but present in the Netherlands (0.34%), Spain (0.33%), USA (0.23%), England (0.15%), Scotland (0.10%), and Ireland (0.06%), with insufficient evidence for association with fracture risk.CONCLUSIONS: These results suggest that deletions in the 6p25.1 locus may predispose to higher risk of fracture in a subset of populations of European origin; larger and geographically restricted studies will be needed to confirm this regional association. This is a first step towards the evaluation of the role of rare CNVs in osteoporosis.
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| 38. |
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| 39. |
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| 40. |
- Pippias, Maria, et al.
(författare)
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Long-term Kidney Transplant Outcomes in Primary Glomerulonephritis: Analysis From the ERA-EDTA Registry
- 2016
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Ingår i: Transplantation. - : LIPPINCOTT WILLIAMS & WILKINS. - 0041-1337 .- 1534-6080. ; 100:9, s. 1955-1962
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Tidskriftsartikel (refereegranskat)abstract
- Background We evaluated the 15-year kidney allograft survival in patients with primary glomerulonephritis and determined if the risk of graft loss varied with donor source within each glomerulonephritis group. Methods Using data from the European Renal Association-European Dialysis and Transplant Association Registry, Kaplan-Meier, competing risk, and Cox regression analyses were performed on adult, first kidney transplant recipients during 1991 to 2010 (n = 14 383). Follow-up was set to December 31, 2011. Adjustments for pretransplant dialysis duration, sex, country, and transplant era were made. Death-adjusted graft survival was assessed in patients with glomerulonephritis and compared with those with autosomal dominant polycystic kidney disease (ADPKD), in which the native kidney disease cannot recur. Additionally, death-adjusted graft survival was compared between living and deceased donor transplants within each glomerulonephritis group. Results All glomerulonephritides had a 15-year death-adjusted graft survival probability above 55%. The 15-year risk of death-adjusted graft failure compared to ADPKD ranged from 1.17 (95% confidence interval [95% CI], 1.05-1.31) for immunoglobulin A nephropathy to 2.09 (95% CI, 1.56-2.78) for membranoproliferative glomerulonephritis type II. The expected survival benefits of living over deceased donor transplants were not present in membranoproliferative glomerulonephritis type I (adjusted hazard ratios [HRa], 1.08; 95% CI, 0.73-1.60) or type II (HRa, 0.90; 95% CI, 0.32-2.52) but present in immunoglobulin A nephropathy (HRa, 0.74; 95% CI, 0.59-0.92), membranous nephropathy (HRa, 0.47; 95% CI, 0.29-0.75), and focal segmental glomerulosclerosis (HRa, 0.69; 95% CI, 0.45-1.06). Conclusions This large European study shows favorable long-term kidney graft survival in all primary glomerulonephritides, although this remains lower than graft survival in ADPKD, and confirms that the reluctance to use living donors in some primary glomerulonephritides remains unfounded. These data will further inform prospective renal transplant recipients and donors during pretransplant counselling.
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| 41. |
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| 42. |
- Singh-Bhalla, Guneeta, et al.
(författare)
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Unexpected termination switching and polarity compensation in LaAlO3/SrTiO3 heterostructures
- 2018
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Ingår i: Physical Review Materials. - : AMER PHYSICAL SOC. - 2475-9953. ; 2:11
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Tidskriftsartikel (refereegranskat)abstract
- Polar crystals composed of charged ionic planes cannot exist in nature without acquiring surface changes to balance an ever-growing dipole. The necessary changes can manifest structurally or electronically as observed in semiconductors and ferroelectric materials through screening charges and/or domain wall formation. In the case of prototypical polar complex oxides such as the LaAlO3/SrTiO3 system the nature of screening charges for different interface terminations is not symmetric. Electron accumulation is observed near the LaAlO3/TiO2-SrTiO3 interface, while the LaAlO3/SrO-SrTiO3 stack is insulating. Here, we observe evidence for an asymmetry in the surface chemical termination for nominally stoichiometric LaAlO3 films in contact with the two different surface layers of SrTiO3 crystals, TiO2 and SrO. Using several element-specific probes, we find that the surface termination of LaAlO3 remains AlO2 irrespective of the starting termination of SrTiO3 substrate surface. We use a combination of cross-plane tunneling measurements and first-principles calculations to understand the effects of this unexpected termination on band alignments and polarity compensation of LaAlO3/SrTiO3 heterostructures. An asymmetry in LaAlO3 polarity compensation and resulting electronic properties will fundamentally limit atomic level control of oxide heterostructures.
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| 43. |
- Stel, Vianda S., et al.
(författare)
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International comparison of trends in patients commencing renal replacement therapy by primary renal disease
- 2019
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Ingår i: Nephrology. - : Wiley. - 1320-5358 .- 1440-1797. ; 24:10, s. 1064-1076
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Tidskriftsartikel (refereegranskat)abstract
- Aim: To examine international time trends in the incidence of renal replacement therapy (RRT) for end-stage renal disease (ESRD) by primary renal disease (PRD). Methods: Renal registries reporting on patients starting RRT per million population for ESRD by PRD from 2005 to 2014, were identified by internet search and literature review. The average annual percentage change (AAPC) with a 95% confidence interval (CI) of the time trends was computed using Joinpoint regression. Results: There was a significant decrease in the incidence of RRT for ESRD due to diabetes mellitus (DM) in Europe (AAPC = −0.9; 95%CI −1.3; −0.5) and to hypertension/renal vascular disease (HT/RVD) in Australia (AAPC = −1.8; 95%CI −3.3; −0.3), Canada (AAPC = −2.9; 95%CI −4.4; −1.5) and Europe (AAPC = −1.1; 95%CI −2.1; −0.0). A decrease or stabilization was observed for glomerulonephritis in all regions and for autosomal dominant polycystic kidney disease (ADPKD) in all regions except for Malaysia and the Republic of Korea. An increase of 5.2–16.3% was observed for DM, HT/RVD and ADPKD in Malaysia and the Republic of Korea. Conclusion: Large international differences exist in the trends in incidence of RRT by primary renal disease. Mapping of these international trends is the first step in defining the causes and successful preventative measures of CKD.
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| 44. |
- Thiele, I., et al.
(författare)
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A community-driven global reconstruction of human metabolism
- 2013
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Ingår i: Nature Biotechnology. - : Springer Science and Business Media LLC. - 1087-0156 .- 1546-1696. ; 31:5, s. 419-
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Tidskriftsartikel (refereegranskat)abstract
- Multiple models of human metabolism have been reconstructed, but each represents only a subset of our knowledge. Here we describe Recon 2, a community-driven, consensus 'metabolic reconstruction', which is the most comprehensive representation of human metabolism that is applicable to computational modeling. Compared with its predecessors, the reconstruction has improved topological and functional features, including similar to 2x more reactions and similar to 1.7x more unique metabolites. Using Recon 2 we predicted changes in metabolite biomarkers for 49 inborn errors of metabolism with 77% accuracy when compared to experimental data. Mapping metabolomic data and drug information onto Recon 2 demonstrates its potential for integrating and analyzing diverse data types. Using protein expression data, we automatically generated a compendium of 65 cell type-specific models, providing a basis for manual curation or investigation of cell-specific metabolic properties. Recon 2 will facilitate many future biomedical studies and is freely available at http://humanmetabolism.org/.
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| 45. |
- van Wijk, Xander M., et al.
(författare)
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Whole-Genome Sequencing of Invasion-Resistant Cells Identifies Laminin α2 as a Host Factor for Bacterial Invasion
- 2017
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Ingår i: mBio. - : American Society for Microbiology. - 2161-2129 .- 2150-7511. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- To understand the role of glycosaminoglycans in bacterial cellular invasion, xylosyltransferase-deficient mutants of Chinese hamster ovary (CHO) cells were created using clustered regularly interspaced short palindromic repeat (CRISPR) and CRISPR-associated gene 9 (CRISPR-cas9) gene targeting. When these mutants were compared to the pgsA745 cell line, a CHO xylosyltransferase mutant generated previously using chemical mutagenesis, an unexpected result was obtained. Bacterial invasion of pgsA745 cells by group B Streptococcus (GBS), group A Streptococcus, and Staphylococcus aureus was markedly reduced compared to the invasion of wild-type cells, but newly generated CRISPR-cas9 mutants were only resistant to GBS. Invasion of pgsA745 cells was not restored by transfection with xylosyltransferase, suggesting that an additional mutation conferring panresistance to multiple bacteria was present in pgsA745 cells. Whole-genome sequencing and transcriptome sequencing (RNA-Seq) uncovered a deletion in the gene encoding the laminin subunit alpha 2 (Lama2) that eliminated much of domain L4a. Silencing of the long Lama2 isoform in wild-type cells strongly reduced bacterial invasion, whereas transfection with human LAMA2 cDNA significantly enhanced invasion in pgsA745 cells. The addition of exogenous laminin-alpha 2 beta 1 gamma 1/laminin-alpha 2 beta 2 gamma 1 strongly increased bacterial invasion in CHO cells, as well as in human alveolar basal epithelial and human brain microvascular endothelial cells. Thus, the L4a domain in laminin alpha 2 is important for cellular invasion by a number of bacterial pathogens. IMPORTANCE Pathogenic bacteria penetrate host cellular barriers by attachment to extracellular matrix molecules, such as proteoglycans, laminins, and collagens, leading to invasion of epithelial and endothelial cells. Here, we show that cellular invasion by the human pathogens group B Streptococcus, group A Streptococcus, and Staphylococcus aureus depends on a specific domain of the laminin alpha 2 subunit. This finding may provide new leads for the molecular pathogenesis of these bacteria and the development of novel antimicrobial drugs.
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| 46. |
- Wahlstrom, I., et al.
(författare)
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Projected climate change impact on a coastal sea-As significant as all current pressures combined
- 2022
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Ingår i: Global Change Biology. - : Wiley. - 1354-1013 .- 1365-2486. ; 28:17, s. 5310-5319
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Tidskriftsartikel (refereegranskat)abstract
- Climate change influences the ocean's physical and biogeochemical conditions, causing additional pressures on marine environments and ecosystems, now and in the future. Such changes occur in environments that already today suffer under pressures from, for example, eutrophication, pollution, shipping, and more. We demonstrate how to implement climate change into regional marine spatial planning by introducing data of future temperature, salinity, and sea ice cover from regional ocean climate model projections to an existing cumulative impact model. This makes it possible to assess climate change impact in relation to pre-existing cumulative impact from current human activities. Results indicate that end-of-century projected climate change alone is a threat of the same magnitude as the combination of all current pressures to the marine environment. These findings give marine planners and policymakers forewarning on how future climate change may impact marine ecosystems, across space, emission scenarios, and in relation to other pressures.
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