| 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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| 2. |
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| 3. |
- 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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| 4. |
- 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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| 6. |
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| 7. |
- 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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| 8. |
- Pulkkinen, T. I., et al.
(författare)
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Magnetospheric modes and solar wind energy coupling efficiency
- 2010
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Ingår i: Journal of Geophysical Research. - 0148-0227 .- 2156-2202. ; 115:3, s. A03207-
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Tidskriftsartikel (refereegranskat)abstract
- Using observations and two different global MHD simulations, we demonstrate that the solar wind speed controls the magnetospheric response such that the higher the speed, the more dynamic and irregular is the magnetospheric response. For similar level of driving solar wind electric field, the magnetospheric modes can be organized in terms of speed: Low speed produces steady convection events, intermediate speeds result in periodic sawtooth oscillations, and high speeds drive large geomagnetic storms. We show that the control parameter of energy transfer and coupling is the electric field along the large-scale X line. We demonstrate using global MHD simulations that for slowly varying interplanetary magnetic field (IMF), the reconnection line is tilted approximately by an angle theta/2, where theta is the IMF clock angle. Then, for clock angles away from northward, the magnetospheric energy entry and response scale with the electric field along the reconnection line (E-PAR), rather than the traditionally used E-Y. If we define the energy coupling efficiency as response/E-PAR, we can show it to be independent of the IMF clock angle and only weakly dependent on the solar wind dynamic pressure. These results demonstrate the ability of the localized reconnection line to control the energy input through the entire magnetopause.
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| 9. |
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| 11. |
- 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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| 12. |
- 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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| 13. |
- 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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| 15. |
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| 17. |
- 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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| 18. |
- 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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| 19. |
- Frier, Emily M, et al.
(författare)
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Consortium for the Study of Pregnancy Treatments (Co-OPT): An international birth cohort to study the effects of antenatal corticosteroids.
- 2023
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Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 18:3
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Tidskriftsartikel (refereegranskat)abstract
- Antenatal corticosteroids (ACS) are widely prescribed to improve outcomes following preterm birth. Significant knowledge gaps surround their safety, long-term effects, optimal timing and dosage. Almost half of women given ACS give birth outside the "therapeutic window" and have not delivered over 7 days later. Overtreatment with ACS is a concern, as evidence accumulates of risks of unnecessary ACS exposure.The Consortium for the Study of Pregnancy Treatments (Co-OPT) was established to address research questions surrounding safety of medications in pregnancy. We created an international birth cohort containing information on ACS exposure and pregnancy and neonatal outcomes by combining data from four national/provincial birth registers and one hospital database, and follow-up through linked population-level data from death registers and electronic health records.The Co-OPT ACS cohort contains 2.28 million pregnancies and babies, born in Finland, Iceland, Israel, Canada and Scotland, between 1990 and 2019. Births from 22 to 45 weeks' gestation were included; 92.9% were at term (≥ 37 completed weeks). 3.6% of babies were exposed to ACS (67.0% and 77.9% of singleton and multiple births before 34 weeks, respectively). Rates of ACS exposure increased across the study period. Of all ACS-exposed babies, 26.8% were born at term. Longitudinal childhood data were available for 1.64 million live births. Follow-up includes diagnoses of a range of physical and mental disorders from the Finnish Hospital Register, diagnoses of mental, behavioural, and neurodevelopmental disorders from the Icelandic Patient Registers, and preschool reviews from the Scottish Child Health Surveillance Programme. The Co-OPT ACS cohort is the largest international birth cohort to date with data on ACS exposure and maternal, perinatal and childhood outcomes. Its large scale will enable assessment of important rare outcomes such as perinatal mortality, and comprehensive evaluation of the short- and long-term safety and efficacy of ACS.
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| 23. |
- 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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