1. |
- Munn-Chernoff, M. A., et al.
(författare)
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Shared genetic risk between eating disorder- and substance-use-related phenotypes: Evidence from genome-wide association studies
- 2021
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Ingår i: Addiction Biology. - : Wiley. - 1355-6215 .- 1369-1600. ; 26:1
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Tidskriftsartikel (refereegranskat)abstract
- Eating disorders and substance use disorders frequently co-occur. Twin studies reveal shared genetic variance between liabilities to eating disorders and substance use, with the strongest associations between symptoms of bulimia nervosa and problem alcohol use (genetic correlation [r(g)], twin-based = 0.23-0.53). We estimated the genetic correlation between eating disorder and substance use and disorder phenotypes using data from genome-wide association studies (GWAS). Four eating disorder phenotypes (anorexia nervosa [AN], AN with binge eating, AN without binge eating, and a bulimia nervosa factor score), and eight substance-use-related phenotypes (drinks per week, alcohol use disorder [AUD], smoking initiation, current smoking, cigarettes per day, nicotine dependence, cannabis initiation, and cannabis use disorder) from eight studies were included. Significant genetic correlations were adjusted for variants associated with major depressive disorder and schizophrenia. Total study sample sizes per phenotype ranged from similar to 2400 to similar to 537 000 individuals. We used linkage disequilibrium score regression to calculate single nucleotide polymorphism-based genetic correlations between eating disorder- and substance-use-related phenotypes. Significant positive genetic associations emerged between AUD and AN (r(g) = 0.18; false discovery rate q = 0.0006), cannabis initiation and AN (r(g) = 0.23; q < 0.0001), and cannabis initiation and AN with binge eating (r(g) = 0.27; q = 0.0016). Conversely, significant negative genetic correlations were observed between three nondiagnostic smoking phenotypes (smoking initiation, current smoking, and cigarettes per day) and AN without binge eating (r(gs) = -0.19 to -0.23; qs < 0.04). The genetic correlation between AUD and AN was no longer significant after co-varying for major depressive disorder loci. The patterns of association between eating disorder- and substance-use-related phenotypes highlights the potentially complex and substance-specific relationships among these behaviors.
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3. |
- Bartels, M., et al.
(författare)
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Childhood aggression and the co-occurrence of behavioural and emotional problems: results across ages 3-16years from multiple raters in six cohorts in the EU-ACTION project
- 2018
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Ingår i: European Child & Adolescent Psychiatry. - : Springer Science and Business Media LLC. - 1018-8827 .- 1435-165X. ; 27:9, s. 1105-1121
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Tidskriftsartikel (refereegranskat)abstract
- Childhood aggression and its resulting consequences inflict a huge burden on affected children, their relatives, teachers, peers and society as a whole. Aggression during childhood rarely occurs in isolation and is correlated with other symptoms of childhood psychopathology. In this paper, we aim to describe and improve the understanding of the co-occurrence of aggression with other forms of childhood psychopathology. We focus on the co-occurrence of aggression and other childhood behavioural and emotional problems, including other externalising problems, attention problems and anxiety-depression. The data were brought together within the EU-ACTION (Aggression in Children: unravelling gene-environment interplay to inform Treatment and InterventiON strategies) project. We analysed the co-occurrence of aggression and other childhood behavioural and emotional problems as a function of the child's age (ages 3 through 16years), gender, the person rating the behaviour (father, mother or self) and assessment instrument. The data came from six large population-based European cohort studies from the Netherlands (2x), the UK, Finland and Sweden (2x). Multiple assessment instruments, including the Child Behaviour Checklist (CBCL), the Strengths and Difficulties Questionnaire (SDQ) and Multidimensional Peer Nomination Inventory (MPNI), were used. There was a good representation of boys and girls in each age category, with data for 30,523 3- to 4-year-olds (49.5% boys), 20,958 5- to 6-year-olds (49.6% boys), 18,291 7- to 8-year-olds (49.0% boys), 27,218 9- to 10-year-olds (49.4% boys), 18,543 12- to 13-year-olds (48.9% boys) and 10,088 15- to 16-year-olds (46.6% boys). We replicated the well-established gender differences in average aggression scores at most ages for parental ratings. The gender differences decreased with age and were not present for self-reports. Aggression co-occurred with the majority of other behavioural and social problems, from both externalising and internalising domains. At each age, the co-occurrence was particularly prevalent for aggression and oppositional and ADHD-related problems, with correlations of around 0.5 in general. Aggression also showed substantial associations with anxiety-depression and other internalizing symptoms (correlations around 0.4). Co-occurrence for self-reported problems was somewhat higher than for parental reports, but we found neither rater differences, nor differences across assessment instruments in co-occurrence patterns. There were large similarities in co-occurrence patterns across the different European countries. Finally, co-occurrence was generally stable across age and sex, and if any change was observed, it indicated stronger correlations when children grew older. We present an online tool to visualise these associations as a function of rater, gender, instrument and cohort. In addition, we present a description of the full EU-ACTION projects, its first results and the future perspectives.
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4. |
- Berthomier, M., et al.
(författare)
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Alfven : magnetosphere-ionosphere connection explorers
- 2012
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Ingår i: Experimental astronomy. - Dordrecht : Springer. - 0922-6435 .- 1572-9508. ; 33:2-3, s. 445-489
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Tidskriftsartikel (refereegranskat)abstract
- The aurorae are dynamic, luminous displays that grace the night skies of Earth's high latitude regions. The solar wind emanating from the Sun is their ultimate energy source, but the chain of plasma physical processes leading to auroral displays is complex. The special conditions at the interface between the solar wind-driven magnetosphere and the ionospheric environment at the top of Earth's atmosphere play a central role. In this Auroral Acceleration Region (AAR) persistent electric fields directed along the magnetic field accelerate magnetospheric electrons to the high energies needed to excite luminosity when they hit the atmosphere. The "ideal magnetohydrodynamics" description of space plasmas which is useful in much of the magnetosphere cannot be used to understand the AAR. The AAR has been studied by a small number of single spacecraft missions which revealed an environment rich in wave-particle interactions, plasma turbulence, and nonlinear acceleration processes, acting on a variety of spatio-temporal scales. The pioneering 4-spacecraft Cluster magnetospheric research mission is now fortuitously visiting the AAR, but its particle instruments are too slow to allow resolve many of the key plasma physics phenomena. The Alfv,n concept is designed specifically to take the next step in studying the aurora, by making the crucial high-time resolution, multi-scale measurements in the AAR, needed to address the key science questions of auroral plasma physics. The new knowledge that the mission will produce will find application in studies of the Sun, the processes that accelerate the solar wind and that produce aurora on other planets.
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5. |
- Laitinen, T, et al.
(författare)
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Characterization of a common susceptibility locus for asthma-related traits
- 2004
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Ingår i: Science (New York, N.Y.). - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 304:5668, s. 300-304
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Tidskriftsartikel (refereegranskat)abstract
- Susceptibility to asthma depends on variation at an unknown number of genetic loci. To identify susceptibility genes on chromosome 7p, we adopted a hierarchical genotyping design, leading to the identification of a 133-kilobase risk-conferring segment containing two genes. One of these coded for an orphan G protein–coupled receptor named GPRA (G protein–coupled receptor for asthma susceptibility), which showed distinct distribution of protein isoforms between bronchial biopsies from healthy and asthmatic individuals. In three cohorts from Finland and Canada, single nucleotide polymorphism–tagged haplotypes associated with high serum immunoglobulin E or asthma. The murine ortholog of GPRA was up-regulated in a mouse model of ovalbumin-induced inflammation. Together, these data implicate GPRA in the pathogenesis of atopy and asthma.
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7. |
- Neumann, A, et al.
(författare)
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A genome-wide association study of total child psychiatric problems scores
- 2022
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Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 17:8, s. e0273116-
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Tidskriftsartikel (refereegranskat)abstract
- Substantial genetic correlations have been reported across psychiatric disorders and numerous cross-disorder genetic variants have been detected. To identify the genetic variants underlying general psychopathology in childhood, we performed a genome-wide association study using a total psychiatric problem score. We analyzed 6,844,199 common SNPs in 38,418 school-aged children from 20 population-based cohorts participating in the EAGLE consortium. The SNP heritability of total psychiatric problems was 5.4% (SE = 0.01) and two loci reached genome-wide significance: rs10767094 and rs202005905. We also observed an association of SBF2, a gene associated with neuroticism in previous GWAS, with total psychiatric problems. The genetic effects underlying the total score were shared with common psychiatric disorders only (attention-deficit/hyperactivity disorder, anxiety, depression, insomnia) (rG > 0.49), but not with autism or the less common adult disorders (schizophrenia, bipolar disorder, or eating disorders) (rG < 0.01). Importantly, the total psychiatric problem score also showed at least a moderate genetic correlation with intelligence, educational attainment, wellbeing, smoking, and body fat (rG > 0.29). The results suggest that many common genetic variants are associated with childhood psychiatric symptoms and related phenotypes in general instead of with specific symptoms. Further research is needed to establish causality and pleiotropic mechanisms between related traits.
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11. |
- Czamara, D, et al.
(författare)
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Integrated analysis of environmental and genetic influences on cord blood DNA methylation in new-borns
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 2548-
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Tidskriftsartikel (refereegranskat)abstract
- Epigenetic processes, including DNA methylation (DNAm), are among the mechanisms allowing integration of genetic and environmental factors to shape cellular function. While many studies have investigated either environmental or genetic contributions to DNAm, few have assessed their integrated effects. Here we examine the relative contributions of prenatal environmental factors and genotype on DNA methylation in neonatal blood at variably methylated regions (VMRs) in 4 independent cohorts (overall n = 2365). We use Akaike’s information criterion to test which factors best explain variability of methylation in the cohort-specific VMRs: several prenatal environmental factors (E), genotypes in cis (G), or their additive (G + E) or interaction (GxE) effects. Genetic and environmental factors in combination best explain DNAm at the majority of VMRs. The CpGs best explained by either G, G + E or GxE are functionally distinct. The enrichment of genetic variants from GxE models in GWAS for complex disorders supports their importance for disease risk.
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12. |
- de Mello, V. D. F., et al.
(författare)
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Link between plasma ceramides, inflammation and insulin resistance : association with serum IL-6 concentration in patients with coronary heart disease
- 2009
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Ingår i: Diabetologia. - : Springer. - 0012-186X .- 1432-0428. ; 52:12, s. 2612-2615
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Tidskriftsartikel (refereegranskat)abstract
- AIMS/HYPOTHESIS: Ceramides and IL-6 have a role in immune-inflammatory responses and cardiovascular diseases, and are suggested to be involved in insulin and glucose metabolism. We sought to assess the associations of circulating levels of IL-6, TNF-alpha and high-sensitivity C reactive protein (hsCRP), which are inflammatory markers related to insulin resistance (IR), with the plasma lipid metabolites ceramides and diacylglycerols (DAG) in patients with CHD.METHODS: Cross-sectional analyses were carried out on data from 33 patients with CHD. Serum levels of the inflammatory markers and plasma lipid metabolites (lipidomics approach performed by ultra-performance liquid chromatography coupled to electrospray ionisation MS) were measured at the same time point as insulin resistance (IR) (HOMA-IR index).RESULTS: Serum circulating levels of IL-6 were strongly correlated with plasma ceramide concentrations (r = 0.59, p < 0.001). Adjustments for serum TNF-alpha or hsCRP levels, smoking, BMI, age, sex or HOMA-IR did not change the results (p < 0.001). After adjustments for the effect of serum inflammatory markers (TNF-alpha or hsCRP), HOMA-IR and BMI the correlation between plasma DAG and serum IL-6 (r = 0.33) was also significant (p < 0.03). In a linear regression model, circulating levels of both ceramides and TNF-alpha had a significant independent influence on circulating levels of IL-6, altogether accounting for 41% of its variation (p < 0.001).CONCLUSIONS/INTERPRETATION: Our results strongly suggest that the link between ceramides, IR and inflammation is related to the inflammatory marker IL-6. Ceramides may contribute to the induction of inflammation involved in IR states that frequently coexist with CHD.
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13. |
- Duursma, R. A., et al.
(författare)
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Contributions of climate, leaf area index and leaf physiology to variation in gross primary production of six coniferous forests across Europe: a model-based analysis
- 2009
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Ingår i: Tree Physiology. - : Oxford University Press (OUP). - 1758-4469 .- 0829-318X. ; 29:5, s. 621-639
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Tidskriftsartikel (refereegranskat)abstract
- Gross primary production (GPP) is the primary source of all carbon fluxes in the ecosystem. Understanding, variation in this flux is vital to understanding variation in the carbon sink of forest ecosystems, and this would serve as input to forest production models. Using GPP derived from eddy-covariance (EC) Measurements, it is now possible to determine the most important factor to scale GPP across sites. We use long-term EC measurements for six coniferous forest stands in Europe, for a total of 25 site-years, located oil a gradient between Southern France and northern Finland. Eddy-derived GPP varied threefold across the six sites, peak ecosystem leaf area index (LAI) (all-sided) varied from 4 to 22 m(2) m(-2) and mean annual temperature varied from - 1 to 13 degrees C. A process-based model operating at a half-hourly time-step was parameterized with available information for each site, and explained 71-96% in variation between daily totals of GPP within site-years and 62% of annual total GPP across site-years. Using the parameterized model, we performed two simulation experiments: weather datasets were interchanged between sites, so that the model was used to predict GPP at some site using data from either a different year or a different site. The resulting bias in GPP prediction was related to several aggregated weather variables and was found to be closely related to the change in the effective temperature sum or mean annual temperature. High R(2)s resulted even when using weather datasets from unrelated sites, providing a cautionary note on the interpretation of R-2 ill model comparisons. A second experiment interchanged stand-structure information between sites. and the resulting bias was strongly related to the difference in LAI, or the difference in integrated absorbed light. Across the six sites. variation in mean annual temperature had more effect on simulated GPP than the variation in LAI. but both were important determinants of GPP. A sensitivity analysis of leaf physiology parameters showed that the quantum yield was the most influential parameter on annual GPP, followed by a parameter controlling the seasonality of photosynthesis and photosynthetic capacity. Overall, the results are promising for the development of a parsimonious model of GPP.
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16. |
- Horbury, T., et al.
(författare)
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Cross-scale : A multi-spacecraft mission to study cross-scale coupling in space plasmas
- 2006
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Ingår i: European Space Agency, (Special Publication) ESA SP. ; , s. 561-568
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Konferensbidrag (refereegranskat)abstract
- Collisionless astrophysical plasmas exhibit complexity on many scales: if we are to understand their properties and effects, we must measure this complexity. We can identify a small number of processes and phenomena, one of which is dominant in almost every space plasma region of interest: shocks, reconnection and turbulence. These processes act to transfer energy between locations, scales and modes. However, this transfer is characterised by variability and 3D structure on at least three scales: electron kinetic, ion kinetic and fluid. It is the nonlinear interaction between physical processes at these scales that is the key to understanding these phenomena and predicting their effects. However, current and planned multi-spacecraft missions such as Cluster and MMS only study variations on one scale in 3D at any given time - we must measure the three scales simultaneously fully to understand the energy transfer processes. We propose a mission, called Cross-Scale, to study these processes. Cross-Scale would comprise three nested groups, each consisting of up to four spacecraft. Each group would have a different spacecraft separation, at approximately the electron and ion gyroradii, and a larger MHD scale. We would therefore be able to measure variations on all three important physical scales, simultaneously, for the first time. The spacecraft would fly in formation through key regions of near-Earth space: The solar wind, bowshock, magnetosheath, magnetopause and magnetotail.
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17. |
- Lockwood, M, et al.
(författare)
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Coordinated Cluster and ground-based instrument observations of transient changes in the magnetopause boundary layer during an interval of predominantly northward IMF : relation to reconnection pulses and FTE signatures
- 2001
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Ingår i: Annales Geophysicae. - : Copernicus GmbH. - 0992-7689 .- 1432-0576. ; 19:10-12, s. 1613-1640
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Forskningsöversikt (refereegranskat)abstract
- We study a series of transient entries into the low-latitude boundary layer (LLBL) of all four Cluster spacecraft during an outbound pass through the mid-afternoon magnetopause ([X(GSM), Y(GSM), Z(GSM)] approximate to [2, 7, 9] R(E)). The events take place during an interval of northward IMF, as seen in the data from the ACE satellite and lagged by a propagation delay of 75 min that is well-defined by two separate studies: (1) the magnetospheric variations prior to the northward turning (Lockwood et al., 2001, this issue) and (2) the field clock angle seen by Cluster after it had emerged into the magnetosheath (Opgenoorth et al., 2001, this issue). With an additional lag of 16.5 min, the transient LLBL events cor-relate well with swings of the IMF clock angle (in GSM) to near 90degrees. Most of this additional lag is explained by ground-based observations, which reveal signatures of transient reconnection in the pre-noon sector that then take 10-15 min to propagate eastward to 15 MLT, where they are observed by Cluster. The eastward phase speed of these signatures agrees very well with the motion deduced by the cross-correlation of the signatures seen on the four Cluster spacecraft. The evidence that these events are reconnection pulses includes: transient erosion of the noon 630 nm (cusp/cleft) aurora to lower latitudes; transient and travelling enhancements of the flow into the polar cap, imaged by the AMIE technique; and poleward-moving events moving into the polar cap, seen by the EISCAT Svalbard Radar (ESR). A pass of the DMSP-F15 satellite reveals that the open field lines near noon have been opened for some time: the more recently opened field lines were found closer to dusk where the flow transient and the poleward-moving event intersected the satellite pass. The events at Cluster have ion and electron characteristics predicted and observed by Lockwood and Hapgood (1998) for a Flux Transfer Event (FTE), with allowance for magnetospheric ion reflection at Alfvenic disturbances in the magnetopause reconnection layer. Like FTEs, the events are about 1 R(E) in their direction of motion and show a rise in the magnetic field strength, but unlike FTEs, in general, they show no pressure excess in their core and hence, no characteristic bipolar signature in the boundary-normal component. However, most of the events were observed when the magnetic field was southward, i.e. on the edge of the interior magnetic cusp, or when the field was parallel to the magnetic equatorial plane. Only when the satellite begins to emerge from the exterior boundary (when the field was northward), do the events start to show a pressure excess in their core and the consequent bipolar signature. We identify the events as the first observations of FTEs at middle altitudes.
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18. |
- Middeldorp, Christel M., et al.
(författare)
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The Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia : design, results and future prospects
- 2019
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Ingår i: European Journal of Epidemiology. - : Springer Science and Business Media LLC. - 0393-2990 .- 1573-7284. ; 34:3, s. 279-300
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Tidskriftsartikel (refereegranskat)abstract
- The impact of many unfavorable childhood traits or diseases, such as low birth weight and mental disorders, is not limited to childhood and adolescence, as they are also associated with poor outcomes in adulthood, such as cardiovascular disease. Insight into the genetic etiology of childhood and adolescent traits and disorders may therefore provide new perspectives, not only on how to improve wellbeing during childhood, but also how to prevent later adverse outcomes. To achieve the sample sizes required for genetic research, the Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia were established. The majority of the participating cohorts are longitudinal population-based samples, but other cohorts with data on early childhood phenotypes are also involved. Cohorts often have a broad focus and collect(ed) data on various somatic and psychiatric traits as well as environmental factors. Genetic variants have been successfully identified for multiple traits, for example, birth weight, atopic dermatitis, childhood BMI, allergic sensitization, and pubertal growth. Furthermore, the results have shown that genetic factors also partly underlie the association with adult traits. As sample sizes are still increasing, it is expected that future analyses will identify additional variants. This, in combination with the development of innovative statistical methods, will provide detailed insight on the mechanisms underlying the transition from childhood to adult disorders. Both consortia welcome new collaborations. Policies and contact details are available from the corresponding authors of this manuscript and/or the consortium websites.
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20. |
- Sundén, Henrik, 1978, et al.
(författare)
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Synthesis and Biological Evaluation of Second-Generation Tropanol-Based Androgen Receptor Modulators
- 2015
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Ingår i: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 1520-4804 .- 0022-2623. ; 58:3, s. 1569-1574
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Tidskriftsartikel (refereegranskat)abstract
- To circumvent antiandrogen resistance in prostate cancer, antiandrogens effective for both the androgen receptor (AR) and AR mutants are required. The AR antagonists in this study originate from previous findings, which showed that subtle differences in substitution pattern lead to a conformational change that alters the ligand activity, rendering an agonist to an antagonist. We have identified small yet potent tropanol-based ligands possessing significant antiandrogenic activity with both wild-type AR and the two most common AR ligand binding domain (LBD) mutants.
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22. |
- Alho, Markku, et al.
(författare)
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Hybrid modeling of cometary plasma environments : II. Remote-sensing of a cometary bow shock
- 2019
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 630
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Tidskriftsartikel (refereegranskat)abstract
- Context. The ESA Rosetta probe has not seen direct evidence of a fully formed bow shock at comet 67P/Churyumov–Gerasimenko (67P). Ion spectrometer measurements of cometary pickup ions measured in the vicinity of the nucleus of 67P are available and may contain signatures of the large-scale plasma environment.Aims. The aim is to investigate the possibility of using pickup ion signatures to infer the existence or nonexistence of a bow shock-like structure and possibly other large-scale plasma environment features.Methods. A numerical plasma model in the hybrid plasma description was used to model the plasma environment of a comet. Simulated pickup ion spectra were generated for different interplanetary magnetic field conditions. The results were interpreted through test particle tracing in the hybrid simulation solutions.Results. Features of the observed pickup ion energy spectrum were reproduced, and the model was used to interpret the observation to be consistent with a shock-like structure. We identify (1) a spectral break related to the bow shock, (2) a mechanism for generating the spectral break, and (3) a dependency of the energy of the spectral break on the interplanetary magnetic field magnitude and bow shock standoff distance.
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23. |
- Amm, O., Janhunen, P., Kauristie, K., Opgenoorth, H.J., Pulkkinen, T.I. and Viljanen, A.
(författare)
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Mesoscale ionospheric electrodynamics observed with the MIRACLE network: 1. Analysis of a pseudobreakup spiral.
- 2001
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Ingår i: Journal of Geophysical Research. ; 106:111, s. 24675-24690
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Tidskriftsartikel (refereegranskat)abstract
- A short-lived auroral spiral is observed on February 3, 1999, around 2204 UT, using the Multi-Instrument Array for Ionosphere-Magnetosphere Coupling Studies (MIRACLE) network of ground-based instruments in Fennoscandia, which consists of magnetometers, co
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24. |
- Andreeova, K., et al.
(författare)
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Shock propagation in the magnetosphere : Observations and MHD simulations compared
- 2008
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Ingår i: Journal of Geophysical Research. - 0148-0227 .- 2156-2202. ; 113:A9, s. A09224-
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Tidskriftsartikel (refereegranskat)abstract
- We examine the propagation of disturbances in the Earth's magnetosphere caused by fast forward shock interaction with the magnetopause. Our statistical study and event analyses show that the propagation speeds are larger in the magnetosphere than in the solar wind and are larger in the nightside magnetosphere than in the dayside magnetosphere. A case study of a double shock during 9 November 2002 is examined both observationally and using the GUMICS-4 global MHD simulation. Tracing the disturbance propagation allows us to confirm that the MHD simulation results are in good agreement with the in situ observations. The simulation results show that the propagation of the disturbance occurs in the antisunward direction at all clock angles simultaneously. However, changes in the magnetosheath are largest at high latitudes, while in the magnetotail the largest variations are seen in the plasma sheet.
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25. |
- Apatenkov, S. V., et al.
(författare)
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Multi-spacecraft observation of plasma dipolarization/injection in the inner magnetosphere
- 2007
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Ingår i: Annales Geophysicae. - 0992-7689 .- 1432-0576. ; 25:3, s. 801-814
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Tidskriftsartikel (refereegranskat)abstract
- Addressing the origin of the energetic particle injections into the inner magnetosphere, we investigate the 23 February 2004 substorm using a favorable constellation of four Cluster (near perigee), LANL and Geotail spacecraft. Both an energy-dispersed and a dispersionless injection were observed by Cluster crossing the plasma sheet horn, which mapped to 9-12 R-E in the equatorial plane close to the midnight meridian. Two associated narrow equatorward auroral tongues/streamers propagating from the oval poleward boundary could be discerned in the global images obtained by IMAGE/WIC. As compared to the energy-dispersed event, the dispersionless injection front has important distinctions consequently repeated at 4 spacecraft: a simultaneous increase in electron fluxes at energies similar to 1.300 keV, similar to 25 nT increase in B-Z and a local increase by a factor 1.5-1.7 in plasma pressure. The injected plasma was primarily of solar wind origin. We evaluated the change in the injected flux tube configuration during the dipolarization by fitting flux increases observed by the PEACE and RAPID instruments, assuming adiabatic heating and the Liouville theorem. Mapping the locations of the injection front detected by the four spacecraft to the equatorial plane, we estimated the injection front thickness to be similar to 1 R-E and the earthward propagation speed to be similar to 200-400km/s (at 9-12 RE). Based on observed injection properties, we suggest that it is the underpopulated flux tubes (bubbles with enhanced magnetic field and sharp inner front propagating earthward), which accelerate and transport particles into the strong-field dipolar region.
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26. |
- Bergh, Camilla, et al.
(författare)
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Increased risk of revision in patients with non-traumatic femoral head necrosis.
- 2014
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Ingår i: Acta orthopaedica. - : Medical Journals Sweden AB. - 1745-3682 .- 1745-3674. ; 85:1, s. 11-17
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose Previous studies of patients who have undergone total hip arthroplasty (THA) due to femoral head necrosis (FHN) have shown an increased risk of revision compared to cases with primary osteoarthritis (POA), but recent studies have suggested that this procedure is not associated with poor outcome. We compared the risk of revision after operation with THA due to FHN or POA in the Nordic Arthroplasty Register Association (NARA) database including Denmark, Finland, Norway, and Sweden. Patients and methods 427,806 THAs performed between 1995 and 2011 were included. The relative risk of revision for any reason, for aseptic loosening, dislocation, deep infection, and periprosthetic fracture was studied before and after adjustment for covariates using Cox regression models. Results 416,217 hips with POA (mean age 69 (SD 10), 59% females) and 11,589 with FHN (mean age 65 (SD 16), 58% females) were registered. The mean follow-up was 6.3 (SD 4.3) years. After 2 years of observation, 1.7% in the POA group and 3.0% in the FHN group had been revised. The corresponding proportions after 16 years of observation were 4.2% and 6.1%, respectively. The 16-year survival in the 2 groups was 86% (95% CI: 86-86) and 77% (CI: 74-80). After adjusting for covariates, the relative risk (RR) of revision for any reason was higher in patients with FHN for both periods studied (up to 2 years: RR = 1.44, 95% CI: 1.34-1.54; p < 0.001; and 2-16 years: RR = 1.25, 1.14-1.38; p < 0.001). Interpretation Patients with FHN had an overall increased risk of revision. This increased risk persisted over the entire period of observation and covered more or less all of the 4 most common reasons for revision.
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28. |
- de Mello, Vanessa D. F., et al.
(författare)
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The effect of fatty or lean fish intake on inflammatory gene expression in peripheral blood mononuclear cells of patients with coronary heart disease
- 2009
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Ingår i: European Journal of Nutrition. - : Steinkopff-Verlag. - 1436-6207 .- 1436-6215. ; 48:8, s. 447-455
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Little is known about the effect of fish consumption on gene expression of inflammation-related genes in immune cells in coronary heart disease (CHD).AIM OF THE STUDY: We sought to evaluate the effect of a fatty fish (FF) or a lean fish (LF) diet on the modulation of inflammatory and endothelial function-related genes in peripheral blood mononuclear cells (PBMCs) of subjects with CHD, and its association with serum fatty acid (FA) profile and lipid metabolic compounds.METHODS: Data from 27 patients randomized into an 8-week FF (n = 10; mean +/- SD: 4.3 +/- 0.4 portions of fish per week), LF (n = 11; 4.7 +/- 1.1 portions of fish per week), or control diet (n = 6; 0.6 +/- 0.4 portions of fish per week) were analyzed. The mRNA expression was measured using real-time PCR.RESULTS: The effect of the intervention on the mRNA expression of the genes studied did not differ among groups. In the FF group, however, the decrease in arachidonic acid to eicosapentaenoic acid (AA:EPA) ratio in cholesterol ester and phospholipid fractions strongly correlated with the change in IL1B mRNA levels (r (s) = 0.60, P = 0.06 and r (s) = 0.86, P = 0.002, respectively). In the LF group, the decrease in palmitic acid and total saturated FAs in cholesterol esters correlated with the change in intercellular cell adhesion molecule-1 (ICAM1) expression (r (s) = 0.64, P = 0.04 for both). Circulating levels of soluble ICAM-1 decreased only in the LF group (P < 0.05).CONCLUSIONS: The intake of FF or LF diet did not alter the expression of inflammatory and endothelial function-related genes in PBMCs of patients with CHD. However, the decrease in AA:EPA ratio in serum lipids in the FF group may induce an anti-inflammatory response at mRNA levels in PBMCs. A LF diet might benefit endothelial function, possibly mediated by the changes in serum FA composition.
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29. |
- Dimmock, Andrew P., et al.
(författare)
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Direct evidence of nonstationary collisionless shocks in space plasmas
- 2019
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Ingår i: Science Advances. - : AMER ASSOC ADVANCEMENT SCIENCE. - 2375-2548. ; 5:2
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Tidskriftsartikel (refereegranskat)abstract
- Collisionless shocks are ubiquitous throughout the universe: around stars, supernova remnants, active galactic nuclei, binary systems, comets, and planets. Key information is carried by electromagnetic emissions from particles accelerated by high Mach number collisionless shocks. These shocks are intrinsically nonstationary, and the characteristic physical scales responsible for particle acceleration remain unknown. Quantifying these scales is crucial, as it affects the fundamental process of redistributing upstream plasma kinetic energy into other degrees of freedom-particularly electron thermalization. Direct in situ measurements of nonstationary shock dynamics have not been reported. Thus, the model that best describes this process has remained unknown. Here, we present direct evidence demonstrating that the transition to nonstationarity is associated with electron-scale field structures inside the shock ramp.
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30. |
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31. |
- Hietala, H., et al.
(författare)
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Supermagnetosonic Jets behind a Collisionless Quasiparallel Shock
- 2009
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Ingår i: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 103:24, s. 245001-
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Tidskriftsartikel (refereegranskat)abstract
- The downstream region of a collisionless quasiparallel shock is structured containing bulk flows with high kinetic energy density from a previously unidentified source. We present Cluster multispacecraft measurements of this type of supermagnetosonic jet as well as of a weak secondary shock front within the sheath, that allow us to propose the following generation mechanism for the jets: The local curvature variations inherent to quasiparallel shocks can create fast, deflected jets accompanied by density variations in the downstream region. If the speed of the jet is super(magneto)sonic in the reference frame of the obstacle, a second shock front forms in the sheath closer to the obstacle. Our results can be applied to collisionless quasiparallel shocks in many plasma environments.
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32. |
- Hill, S. C., et al.
(författare)
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Magnetospheric Sources of Theta Aurora: A Case Study Comparing Observations With SWMF Global Simulation
- 2024
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Ingår i: Geophysical Research Letters. - : American Geophysical Union (AGU). - 0094-8276 .- 1944-8007. ; 51:10
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Tidskriftsartikel (refereegranskat)abstract
- We present the first high resolution global MHD with coupled inner magnetosphere simulation results of an observed theta aurora event. We use the Space Weather Modeling Framework in the Geospace configuration, which produces accurate field aligned current closure in the ionosphere that is integral to theta aurora formation. At the location of the observed theta aurora, the simulation produces a narrow channel of Joule heating along both open and closed field lines, and between a pair of oppositely directed field-aligned current sheets in the ionosphere. We demonstrate that this Joule heating pattern that we identify as theta aurora maps to a reconnection region at the magnetotail flanks as well as in the distant magnetotail. The theta aurora maps to a cross-tail current disruption and field-aligned current source region in a highly twisted magnetotail.
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36. |
- Karlsson, SBP, et al.
(författare)
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Solar wind control of magnetospheric energy content: Substorm quenching and multiple onsets
- 2000
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Ingår i: JOURNAL OF GEOPHYSICAL RESEARCH-SPACE PHYSICS. - : AMER GEOPHYSICAL UNION. - 0148-0227. ; 105:A3, s. 5335-5356
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Tidskriftsartikel (refereegranskat)abstract
- In this paper we report coordinated multispacecraft and ground-based observations of a double substorm onset close to Scandinavia on November 17, 1996. The Wind and the Geotail spacecraft, which were located in the solar wind and the subsolar magnetosheat
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37. |
- Kaurisitie, K., Syrjsuo, M., Amm, O., Viljanen, A., Pulkkinen, T.I. and Opgenoorth, H.J.
(författare)
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A statistical study of evening sectorarcs and electrojets.
- 2001
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Ingår i: Advances in Space Research. ; 28, s. 16045-1610
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Tidskriftsartikel (refereegranskat)abstract
- We present results of a statistical study of evening sector auroral arcs associated with electrojets. The study (including similar to 1000 all-sky camera (ASC) frames) is based on data of the MIRACLE instrument network. An automatic search engine is used
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41. |
- Kumar, Anmol, et al.
(författare)
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GDNF Overexpression from the Native Locus Reveals its Role in the Nigrostriatal Dopaminergic System Function
- 2015
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Ingår i: PLOS Genetics. - : PLoS. - 1553-7390 .- 1553-7404. ; 11:12
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Tidskriftsartikel (refereegranskat)abstract
- Degeneration of nigrostriatal dopaminergic system is the principal lesion in Parkinson's disease. Because glial cell line-derived neurotrophic factor (GDNF) promotes survival of dopamine neurons in vitro and in vivo, intracranial delivery of GDNF has been attempted for Parkinson's disease treatment but with variable success. For improving GDNF-based therapies, knowledge on physiological role of endogenous GDNF at the sites of its expression is important. However, due to limitations of existing genetic model systems, such knowledge is scarce. Here, we report that prevention of transcription of Gdnf 3'UTR in Gdnf endogenous locus yields GDNF hypermorphic mice with increased, but spatially unchanged GDNF expression, enabling analysis of postnatal GDNF function. We found that increased level of GDNF in the central nervous system increases the number of adult dopamine neurons in the substantia nigra pars compacta and the number of dopaminergic terminals in the dorsal striatum. At the functional level, GDNF levels increased striatal tissue dopamine levels and augmented striatal dopamine release and re-uptake. In a proteasome inhibitor lactacystin-induced model of Parkinson's disease GDNF hypermorphic mice were protected from the reduction in striatal dopamine and failure of dopaminergic system function. Importantly, adverse phenotypic effects associated with spatially unregulated GDNF applications were not observed. Enhanced GDNF levels up-regulated striatal dopamine transporter activity by at least five fold resulting in enhanced susceptibility to 6-OHDA, a toxin transported into dopamine neurons by DAT. Further, we report how GDNF levels regulate kidney development and identify microRNAs miR-9, miR-96, miR-133, and miR-146a as negative regulators of GDNF expression via interaction with Gdnf 3'UTR in vitro. Our results reveal the role of GDNF in nigrostriatal dopamine system postnatal development and adult function, and highlight the importance of correct spatial expression of GDNF. Furthermore, our results suggest that 3'UTR targeting may constitute a useful tool in analyzing gene function.
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42. |
- Laari, S., et al.
(författare)
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Memory decline in young stroke survivors during a 9-year follow-up: A cohort study
- 2022
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Ingår i: Frontiers in Neurology. - : Frontiers Media SA. - 1664-2295. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- IntroductionA decade after stroke, young stroke survivors continue to suffer from cognitive impairment. However, it is not known whether this long-term cognitive outcome is caused in part by further cognitive decline or solely by incomplete recovery from the acute effects of ischemic stroke. We studied changes in three cognitive domains over a 9-year follow-up period after first-ever and only ischemic stroke. Patients and methodsIn this prospective, two-center cohort study, we recruited consecutive 18-65 year-old patients with acute stroke between 2007 and 2009, along with demographically matched stroke-free controls. We performed comprehensive neuropsychological assessments at 3 months, 2, and 9 years after stroke, and we also performed neurological examinations at the time of inclusion and at the 9-year follow-up. We assessed the associations among stroke, follow-up time and long-term cognitive outcomes using repeated-measures analysis of variance. ResultsThe subjects comprised 85 patients who had had their first-ever and only ischemic stroke (mean age 53 years at inclusion), along with 31 stroke-free demographic controls. We compared the cognitive changes in patients to those in controls over a 9-year follow-up. After initial recovery between 3 months and 2 years after stroke, patients showed a decline in memory between 2 and 9 years after stroke compared to controls within the same time interval (immediate recall p < 0.001; delayed recall p < 0.001; list learning p < 0.001). Other than memory, we found no difference in cognitive changes between poststroke patients and controls. DiscussionOur main finding was memory decline over a decade in young first-ever stroke patients with no further stroke or neurodegenerative disease. Our study extends the previous results of further memory decline in elderly stroke survivors to young stroke survivors. ConclusionYoung stroke survivors might be at risk of memory decline over the decade following the stroke.
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43. |
- Lakka, A., et al.
(författare)
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The Cross-Polar Cap Saturation in GUMICS-4 During High Solar Wind Driving
- 2018
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Ingår i: Journal of Geophysical Research - Space Physics. - 2169-9380 .- 2169-9402. ; 123:5, s. 3320-3332
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Tidskriftsartikel (refereegranskat)abstract
- It is well known that the Earth's ionospheric cross‐polar cap potential (CPCP) saturates as a response to the solar wind (SW) driver especially when the level of driving is high and the interplanetary magnetic field is oriented southward. Moreover, previous studies have shown that the upstream Alfvén Mach number may be an important factor in the saturation effect. While the CPCP is often viewed as a measure of the SW‐magnetosphere‐ionosphere coupling, the processes associated with the nonlinearity of the coupling remain an open issue. We use fourth edition of the Grand Unified Magnetosphere‐Ionosphere Coupling Simulation (GUMICS‐4) and artificial SW data to mimic weak and strong driving in order to study the CPCP response to a wide range of interplanetary magnetic field magnitudes (3.5–30 nT) and upstream Alfvén Mach number values (1.2–22). The results provide the first overview of the CPCP saturation in GUMICS‐4 and show that the onset of saturation is strongly dependent on the upstream Alfvén Mach number and the physical processes responsible for the saturation effect might take place both in the Earth's magnetosheath and in the upstream SW.
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45. |
- Makela, K. T., et al.
(författare)
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Countrywise results of total hip replacement An analysis of 438,733 hips based on the Nordic Arthroplasty Register Association database
- 2014
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Ingår i: Acta Orthopaedica. - : Medical Journals Sweden AB. - 1745-3674 .- 1745-3682. ; 85:2, s. 107-116
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose An earlier Nordic Arthroplasty Register Association (NARA) report on 280,201 total hip replacements (THRs) based on data from 1995-2006, from Sweden, Norway, and Denmark, was published in 2009. The present study assessed THR survival according to country, based on the NARA database with the Finnish data included. Material and methods 438,733 THRs performed during the period 1995-2011 in Sweden, Denmark, Norway, and Finland were included. Kaplan-Meier survival analysis was used to calculate survival probabilities with 95% confidence interval (CI). Cox multiple regression, with adjustment for age, sex, and diagnosis, was used to analyze implant survival with revision for any reason as endpoint. Results The 15-year survival, with any revision as an endpoint, for all THRs was 86% (CI: 85.7-86.9) in Denmark, 88% (CI: 87.6-88.3) in Sweden, 87% (CI: 86.4-87.4) in Norway, and 84% (CI: 82.9-84.1) in Finland. Revision risk for all THRs was less in Sweden than in the 3 other countries during the first 5 years. However, revision risk for uncemented THR was less in Denmark than in Sweden during the sixth (HR = 0.53, CI: 0.34-0.82), seventh (HR = 0.60, CI: 0.37-0.97), and ninth (HR = 0.59, CI: 0.36-0.98) year of follow-up. Interpretation The differences in THR survival rates were considerable, with inferior results in Finland. Brand-level comparison of THRs in Nordic countries will be required.
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48. |
- Pulkkinen, Karoliina, et al.
(författare)
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The value of values in climate science
- 2022
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Ingår i: Nature Climate Change. - : Springer Nature. - 1758-678X .- 1758-6798. ; 12:1, s. 4-6
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Tidskriftsartikel (refereegranskat)
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