| 1. |
- Anney, R. J. L., et al.
(författare)
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Meta-analysis of GWAS of over 16,000 individuals with autism spectrum disorder highlights a novel locus at 10q24.32 and a significant overlap with schizophrenia
- 2017
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Ingår i: Molecular Autism. - : Springer Science and Business Media LLC. - 2040-2392. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Background: Over the past decade genome-wide association studies (GWAS) have been applied to aid in the understanding of the biology of traits. The success of this approach is governed by the underlying effect sizes carried by the true risk variants and the corresponding statistical power to observe such effects given the study design and sample size under investigation. Previous ASD GWAS have identified genome-wide significant (GWS) risk loci; however, these studies were of only of low statistical power to identify GWS loci at the lower effect sizes (odds ratio (OR) < 1.15). Methods: We conducted a large-scale coordinated international collaboration to combine independent genotyping data to improve the statistical power and aid in robust discovery of GWS loci. This study uses genome-wide genotyping data from a discovery sample (7387 ASD cases and 8567 controls) followed by meta-analysis of summary statistics from two replication sets (7783 ASD cases and 11359 controls; and 1369 ASD cases and 137308 controls). Results: We observe a GWS locus at 10q24.32 that overlaps several genes including PITX3, which encodes a transcription factor identified as playing a role in neuronal differentiation and CUEDC2 previously reported to be associated with social skills in an independent population cohort. We also observe overlap with regions previously implicated in schizophrenia which was further supported by a strong genetic correlation between these disorders (Rg = 0.23; P= 9 x10(-6)). We further combined these Psychiatric Genomics Consortium (PGC) ASD GWAS data with the recent PGC schizophrenia GWAS to identify additional regions which may be important in a common neurodevelopmental phenotype and identified 12 novel GWS loci. These include loci previously implicated in ASD such as FOXP1 at 3p13, ATP2B2 at 3p25.3, and a 'neurodevelopmental hub' on chromosome 8p11.23. Conclusions: This study is an important step in the ongoing endeavour to identify the loci which underpin the common variant signal in ASD. In addition to novel GWS loci, we have identified a significant genetic correlation with schizophrenia and association of ASD with several neurodevelopmental- related genes such as EXT1, ASTN2, MACROD2, and HDAC4.
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| 2. |
- Arking, D. E., et al.
(författare)
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Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization
- 2014
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 46:8, s. 826-836
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Tidskriftsartikel (refereegranskat)abstract
- The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼ 8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD. © 2014 Nature America, Inc.
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| 3. |
- Weiner, D. J., et al.
(författare)
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Polygenic transmission disequilibrium confirms that common and rare variation act additively to create risk for autism spectrum disorders
- 2017
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 49:7
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Tidskriftsartikel (refereegranskat)abstract
- Autism spectrum disorder (ASD) risk is influenced by common polygenic and de novo variation. We aimed to clarify the influence of polygenic risk for ASD and to identify subgroups of ASD cases, including those with strongly acting de novo variants, in which polygenic risk is relevant. Using a novel approach called the polygenic transmission disequilibrium test and data from 6,454 families with a child with ASD, we show that polygenic risk for ASD, schizophrenia, and greater educational attainment is over-transmitted to children with ASD. These findings hold independent of proband IQ. We find that polygenic variation contributes additively to risk in ASD cases who carry a strongly acting de novo variant. Lastly, we show that elements of polygenic risk are independent and differ in their relationship with phenotype. These results confirm that the genetic influences on ASD are additive and suggest that they create risk through at least partially distinct etiologic pathways.
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| 4. |
- Aad, G., et al.
(författare)
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Commissioning of the ATLAS Muon Spectrometer with cosmic rays
- 2010
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Ingår i: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044 .- 1434-6052. ; 70:3, s. 875-916
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Tidskriftsartikel (refereegranskat)abstract
- The ATLAS detector at the Large Hadron Collider has collected several hundred million cosmic ray events during 2008 and 2009. These data were used to commission the Muon Spectrometer and to study the performance of the trigger and tracking chambers, their alignment, the detector control system, the data acquisition and the analysis programs. We present the performance in the relevant parameters that determine the quality of the muon measurement. We discuss the single element efficiency, resolution and noise rates, the calibration method of the detector response and of the alignment system, the track reconstruction efficiency and the momentum measurement. The results show that the detector is close to the design performance and that the Muon Spectrometer is ready to detect muons produced in high energy proton-proton collisions.
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| 5. |
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| 6. |
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| 7. |
- Aad, G., et al.
(författare)
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Readiness of the ATLAS Tile Calorimeter for LHC collisions
- 2010
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Ingår i: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044 .- 1434-6052. ; 70:4, s. 1193-1236
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Tidskriftsartikel (refereegranskat)abstract
- The Tile hadronic calorimeter of the ATLAS detector has undergone extensive testing in the experimental hall since its installation in late 2005. The readout, control and calibration systems have been fully operational since 2007 and the detector has successfully collected data from the LHC single beams in 2008 and first collisions in 2009. This paper gives an overview of the Tile Calorimeter performance as measured using random triggers, calibration data, data from cosmic ray muons and single beam data. The detector operation status, noise characteristics and performance of the calibration systems are presented, as well as the validation of the timing and energy calibration carried out with minimum ionising cosmic ray muons data. The calibration systems' precision is well below the design value of 1%. The determination of the global energy scale was performed with an uncertainty of 4%.
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| 8. |
- Aad, G., et al.
(författare)
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Studies of the performance of the ATLAS detector using cosmic-ray muons
- 2011
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Ingår i: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044 .- 1434-6052. ; 71:3
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Tidskriftsartikel (refereegranskat)abstract
- Muons from cosmic-ray interactions in the atmosphere provide a high-statistics source of particles that can be used to study the performance and calibration of the ATLAS detector. Cosmic-ray muons can penetrate to the cavern and deposit energy in all detector subsystems. Such events have played an important role in the commissioning of the detector since the start of the installation phase in 2005 and were particularly important for understanding the detector performance in the time prior to the arrival of the first LHC beams. Global cosmic-ray runs were undertaken in both 2008 and 2009 and these data have been used through to the early phases of collision data-taking as a tool for calibration, alignment and detector monitoring. These large datasets have also been used for detector performance studies, including investigations that rely on the combined performance of different subsystems. This paper presents the results of performance studies related to combined tracking, lepton identification and the reconstruction of jets and missing transverse energy. Results are compared to expectations based on a cosmic-ray event generator and a full simulation of the detector response.
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| 9. |
- Aad, G., et al.
(författare)
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The ATLAS Inner Detector commissioning and calibration
- 2010
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Ingår i: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044 .- 1434-6052. ; 70:3, s. 787-821
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Tidskriftsartikel (refereegranskat)abstract
- The ATLAS Inner Detector is a composite tracking system consisting of silicon pixels, silicon strips and straw tubes in a 2 T magnetic field. Its installation was completed in August 2008 and the detector took part in data-taking with single LHC beams and cosmic rays. The initial detector operation, hardware commissioning and in-situ calibrations are described. Tracking performance has been measured with 7.6 million cosmic-ray events, collected using a tracking trigger and reconstructed with modular pattern-recognition and fitting software. The intrinsic hit efficiency and tracking trigger efficiencies are close to 100%. Lorentz angle measurements for both electrons and holes, specific energy-loss calibration and transition radiation turn-on measurements have been performed. Different alignment techniques have been used to reconstruct the detector geometry. After the initial alignment, a transverse impact parameter resolution of 22.1 +/- 0.9 mu m and a relative momentum resolution sigma (p) /p=(4.83 +/- 0.16)x10(-4) GeV(-1)xp (T) have been measured for high momentum tracks.
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| 10. |
- Aad, G., et al.
(författare)
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The ATLAS Simulation Infrastructure
- 2010
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Ingår i: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044 .- 1434-6052. ; 70:3, s. 823-874
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Tidskriftsartikel (refereegranskat)abstract
- The simulation software for the ATLAS Experiment at the Large Hadron Collider is being used for large-scale production of events on the LHC Computing Grid. This simulation requires many components, from the generators that simulate particle collisions, through packages simulating the response of the various detectors and triggers. All of these components come together under the ATLAS simulation infrastructure. In this paper, that infrastructure is discussed, including that supporting the detector description, interfacing the event generation, and combining the GEANT4 simulation of the response of the individual detectors. Also described are the tools allowing the software validation, performance testing, and the validation of the simulated output against known physics processes.
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| 11. |
- Chew, D M, et al.
(författare)
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The tectonothermal evolution and provenance of the Tyrone Central Inlier, Ireland: Grampian imbrication of an outboard Laurentian microcontinent?
- 2008
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Ingår i: Journal of the Geological Society. - : Geological Society of London. - 2041-479X .- 0016-7649. ; 165:3, s. 675-685
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Tidskriftsartikel (refereegranskat)abstract
- The Tyrone Central Inlier is a metamorphic terrane of uncertain affinity situated outboard of the main Dalradian outcrop (south of the Fair Head-Clew Bay Line) and could represent sub-arc basement to part of the enigmatic Midland Valley Terrane. Using a combination of isotopic, structural and petrographic evidence, the tectonothermal evolution of the Tyrone Central Inlier was investigated. Sillimanite-bearing 14 metamorphic assemblages (c. 670 degrees C, 6.8 kbar) and leucosomes in paragneisses are cut by granite pegmatites, which post-date two deformation fabrics. The leucosomes yield a weighted average Pb-207/Ph-206 zircon age of 467 +/- 12 Ma whereas the main fabric yields a Ar-40-Ar-39 biotite cooling age of 468 +/- 1.4 Ma. The pegmatites yield 457 +/- 7 Ma and 458 +/- 7 Ma Rb-Sr muscovite-feldspar ages and Ar-40-Ar-39 step-heating plateaux of 466 +/- 1 Ma and 468 +/- 1 Ma, respectively. The metasedimentary rocks yield Palaeoproterozoic Sm-Nd model ages and laser ablation inductively coupled plasma mass spectrometry detrital zircon U-Pb analyses from a psammitic gneiss yield age populations at 1.05-1.2, 1.5, 1.8, 2.7 and 3.1 Ga. Combined, these data permit correlation of the Tyrone Central Inlier with either the Argyll or the Southern Highland Group of the Dalradian Supergroup. The inlier was thus part of Laurentia onto which the Tyrone ophiolite was obducted.
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| 12. |
- Correa, D. F., et al.
(författare)
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Geographic patterns of tree dispersal modes in Amazonia and their ecological correlates
- 2023
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Ingår i: Global Ecology and Biogeography. - : Wiley. - 1466-822X .- 1466-8238. ; 32:1, s. 49-69
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Tidskriftsartikel (refereegranskat)abstract
- Aim To investigate the geographic patterns and ecological correlates in the geographic distribution of the most common tree dispersal modes in Amazonia (endozoochory, synzoochory, anemochory and hydrochory). We examined if the proportional abundance of these dispersal modes could be explained by the availability of dispersal agents (disperser-availability hypothesis) and/or the availability of resources for constructing zoochorous fruits (resource-availability hypothesis). Time period Tree-inventory plots established between 1934 and 2019. Major taxa studied Trees with a diameter at breast height (DBH) >= 9.55 cm. Location Amazonia, here defined as the lowland rain forests of the Amazon River basin and the Guiana Shield. Methods We assigned dispersal modes to a total of 5433 species and morphospecies within 1877 tree-inventory plots across terra-firme, seasonally flooded, and permanently flooded forests. We investigated geographic patterns in the proportional abundance of dispersal modes. We performed an abundance-weighted mean pairwise distance (MPD) test and fit generalized linear models (GLMs) to explain the geographic distribution of dispersal modes. Results Anemochory was significantly, positively associated with mean annual wind speed, and hydrochory was significantly higher in flooded forests. Dispersal modes did not consistently show significant associations with the availability of resources for constructing zoochorous fruits. A lower dissimilarity in dispersal modes, resulting from a higher dominance of endozoochory, occurred in terra-firme forests (excluding podzols) compared to flooded forests. Main conclusions The disperser-availability hypothesis was well supported for abiotic dispersal modes (anemochory and hydrochory). The availability of resources for constructing zoochorous fruits seems an unlikely explanation for the distribution of dispersal modes in Amazonia. The association between frugivores and the proportional abundance of zoochory requires further research, as tree recruitment not only depends on dispersal vectors but also on conditions that favour or limit seedling recruitment across forest types.
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| 13. |
- Deng, X. H., et al.
(författare)
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Dynamics and waves near multiple magnetic null points in reconnection diffusion region
- 2009
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Ingår i: Journal of Geophysical Research. - : Blackwell Publishing. - 0148-0227 .- 2156-2202. ; 114:7
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Tidskriftsartikel (refereegranskat)abstract
- Identifying the magnetic structure in the region where the magnetic field lines break and how reconnection happens is crucial to improving our understanding of three-dimensional reconnection. Here we show the in situ observation of magnetic null structures in the diffusion region, the dynamics, and the associated waves. Possible spiral null pair has been identified near the diffusion region. There is a close relation among the null points, the bipolar signature of the Z component of the magnetic field, and enhancement of the flux of energetic electrons up to 100 keV. Near the null structures, whistler-mode waves were identified by both the polarity and the power law of the spectrum of electric and magnetic fields. It is found that the angle between the fans of the nulls is quite close to the theoretically estimated maximum value of the group-velocity cone angle for the whistler wave regime of reconnection.
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| 14. |
- Ilhan, Emre, et al.
(författare)
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What is the definition of acute episodic and chronic pain in critically ill neonates and infants? A global, four-stage consensus and validation study
- 2022
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Ingår i: BMJ Open. - : BMJ Publishing Group Ltd. - 2044-6055. ; 12:3
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To define and validate types of pain in critically ill neonates and infants by researchers and clinicians working in the neonatal intensive care unit (NICU) and high dependency unit (HDU).Design: A qualitative descriptive mixed-methods design.Procedure/s: Each stage of the study was built on and confirmed the previous stages. Stage 1 was an expert panel to develop definitions; stage 2 was a different expert panel made up of neonatal clinicians to propose clinical characteristics associated with the definitions from stage 1; stage 3 was a focus group of neonatal clinicians to provide clinical case scenarios associated with each definition and clinical characteristics; and stage 4 was a survey administered to neonatal clinicians internationally to test the validity of the definitions using the clinical case scenarios.Results: In stage 1, the panel (n=10) developed consensus definitions for acute episodic pain and chronic pain in neonates and infants. In stage 2, a panel (n=8) established clinical characteristics that may be associated with each definition. In stage 3, a focus group (n=11) created clinical case scenarios of neonates and infants with acute episodic pain, chronic pain and no pain using the definitions and clinical characteristics. In stage 4, the survey (n=182) revealed that the definitions allowed an excellent level of discrimination between case scenarios that described neonates and infants with acute episodic pain and chronic pain (area under the receiver operating characteristic=0.87 and 0.89, respectively).Conclusions: This four-stage study enabled the development of consensus-based and clinically valid definitions of acute episodic pain and chronic pain. There is a need to define and validate other pain types to inform a taxonomy of pain experienced by neonates and infants in the NICU and HDU.
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| 15. |
- Jernström, Helena, et al.
(författare)
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Pregnancy and risk of early breast cancer in carriers of BRCA1 and BRCA2
- 1999
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Ingår i: The Lancet. - 1474-547X. ; 354:9193, s. 1846-1850
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Early age at first full-term pregnancy and increasing parity are associated with a reduced risk of breast cancer. However, whether pregnancy decreases the risk of early-onset hereditary breast cancer is unknown. There is concern that pregnancy may increase breast-cancer risk in carriers of BRCA1 and BRCA2 germline mutations. We aimed to establish whether pregnancy is a risk factor for hereditary breast cancer. METHODS: We did a matched case-control study of breast cancer in women who carry deleterious BRCA1 or BRCA2 mutations. Cases were carriers who developed breast cancer by age 40 years, and controls were carriers of the same age without breast cancer, or who were diagnosed with breast cancer after age 40 years. Women who had undergone preventive mastectomy, hysterectomy, or oophorectomy, or who were diagnosed with ovarian cancer before the age at which breast cancer was diagnosed in the matched case were excluded. Information about pregnancies and pregnancy outcome was derived from a questionnaire completed by women in the course of genetic counselling. FINDINGS: A higher proportion of cases than controls had had a full term pregnancy (173/236 vs 146/236; odds ratio 1.71 [95% CI 1.13-2.62], p=0.01). The mean number of births was also greater for cases than for controls (1.62 vs 1.38, p=0.04). The risk increased with the number of births and did not diminish with time since last pregnancy. There were no significant differences in age at first birth or age at last birth between cases and controls. INTERPRETATION: Carriers of the BRCA1 and BRCA2 mutations who have children are significantly more likely to develop breast cancer by age 40 than carriers who are nulliparous. Each pregnancy is associated with an increased cancer risk. An early first pregnancy does not confer protection for carriers of BRCA1 or BRCA2 mutations.
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| 16. |
- Kirkland, C. L., et al.
(författare)
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The Finnmarkian Orogeny revisited: An isotopic investigation in eastern Finnmark, Arctic Norway
- 2008
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Ingår i: Tectonophysics. - : Elsevier BV. - 0040-1951. ; 460:1-4, s. 158-177
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Forskningsöversikt (refereegranskat)abstract
- The Scandinavian Caleclonides have been viewed as resulting from either a single Silurian (i.e. Scandian) event or from polycyclic orogenies involving several collisions on the margin of Baltica. Early studies of the Kalak Nappe Complex (KNC) in Finnmark, Arctic Norway, led to the hypothesis of an Early Cambrian-Early Ordovician (520-480 Ma) Finnmarkian Crogeny, though the nature of this tectonic event remains enigmatic. In this contribution we have employed in situ UV laser ablation Ar-Ar dating of fine-grained phyllite and schist from the eastern Caledonides of Arctic Norway to investigate the presence of pre-Scandian tectonometamorphic events. U-Th-Pb detrital zircon and whole rock Sm-Nd analyses have been used to test the regional stratigraphic correlations of these metasedimentary rocks. These results indicate that the Berlevag Formation within the Tanafjord Nappe, previously assumed to be part of the KNC, was deposited after 1872 Ma and prior to a low temperature hydrothermal event at 555 +/- 15 Ma. It has a likely provenance on the Baltica continent, lacks any Grenville-Sveconorwegian detrital zircons, and thus cannot be part of the KNC which contains abundant detritus in this age range. Instead the Berlevag Formation is interpreted as part of the Laksefjord Nappe Complex, which structurally underlies the KNC. Laser-ablation argon-argon dating also shows that late Caledonian (i.e. Scandian) tectonometamorphism affected both the KNC and its immediate footwall at c. 425 +/- 15 Ma. This is corroborated by a step-heating argon-argon muscovite age of 424 +/- 3 Ma which is interpreted as dating cooling. However, within two samples from the KNC, an earlier (Middle-Late Cambrian) metamorphic event is also recorded. A biotite-grade schist yielded an Ar-Ar inverse isochron age of 506 +/- 17 Ma from whole rock surfaces, in which the mineral domains are too fine-grained to date individually. An early generation of muscovite from a coarser-grained amphibolite-facies sample yielded an inverse isochron of 498 +/- 13 Ma. Both isochron ages have atmospheric argon intercept values. Previous studies have documented similar Cambrian ages in the Caledonian nappes below the KNC. These results suggest correlative tectonometamorphic events in the eastern KNC and its footwall at c. 500 Ma. This Cambrian event may reflect the arrival of the Kalak Nappe Complex as a previously constructed exotic mobile belt onto the margin of Baltica. Combined with recent studies from the western Kalak Nappe Complex, the results do not support the traditional constraint on the Finnmarkian Orogeny sensu stricto. However they vindicate classic tectonic models involving a Cambrian accretion event. (c) 2008 Elsevier B.V. All rights reserved.
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| 17. |
- Pease, Victoria, et al.
(författare)
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Baltica in the Cryogenian, 850-650 Ma
- 2008
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Ingår i: Precambrian Research. - : Elsevier BV. - 0301-9268 .- 1872-7433. ; 160:1-2, s. 46-65
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Forskningsöversikt (refereegranskat)abstract
- This new tectonic synthesis provides a framework for understanding the dynamic evolution of Baltica and for constraining tectonic correlations within the context of the Neoproterozoic break-up of Rodinia–Pannotia. Cryogenian Baltica is described with respect to five geographic regions: the northwest, northeast, east, south, and southwest (modern coordinates). These geographic regions define three principal Cryogenian tectonic margins: a rifting northwestern margin, a passive northeastern margin, and a poorly understood southern margin. The northwest region is characterized by Neoproterozoic to lower Ordovician sedimentary successions deposited on Archean to late Mesoproterozoic crystalline complexes, reworked during Caledonian orogenesis. Lare Neoproterozoic to lower Ordovician sedimentary strata record the change from an alluvial setting to a marine environment, and eventually to a partially starved (?) turbidite basin. They document rifting from the Rodinian-Pannotian supercontinent, which was unsuccessful until ca. 620–550 Ma when voluminous dikes and mafic/ultramafic complexes were intruded. Baltica's northeastern and eastern regions document episodic intracratonic rifting throughout the Mesoproterozoic, followed by pericontinental passive margin deposition throughout the Cryogenian. In the northeast platformal and deeper-water basin deposits are preserved, whereas the eastern region was later affected by Paleozoic rifting and preserves only shelf deposits. The northeastern and eastern regions define Baltica's Cryogenian northeastern tectonic margin, which was an ocean-facing passive margin of the Rodinia–Pannotia supercontinent. It remained a passive margin until the onset of Timanian orogenesis at ca. 615 Ma, approximately synchronous with the time of Rodinia–Pannotia rifting. Baltica's southern and southwestern regions remain enigmatic and controversial. Precambrian basement is generally hidden beneath thick successions of Ediacaran and younger platform sediments. Similarities between these regions exist, however, and suggest that they may share a similar tectonic evolution in the Cryogenian and therefore define the southern tectonic margin of Baltica at this time. Paleo- to Mesoproterozic basement was affected by Neoproterozoic and younger tectonism, including Cryogenian (?) and Ediacaran rifting. This was followed by Ediacaran (ca. 550 Ma) passive margin sediment deposition at the time of Rodinia–Pannotia break-up, until Early Paleozoic accretion of allochthonous terranes record the transition from rifting to a compressional regime. Paleomagnetic and paleontological data are consistent with Baltica and Laurentia drifting together between ca. 750 and 550 Ma, when they had similar apparent polar wander paths. Microfossil assemblages along the eastern margin of Laurentia and the western margin of Baltica (modern coordinates), suggest proximity between these two margins at this time. At ca. 550 Ma, Laurentia and Baltica separated, consistent with paleomagnetic, paleontological, and geological data, and a late break-up for Rodinia–Pannotia.
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| 18. |
- Sliz, E., et al.
(författare)
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Evidence of a causal effect of genetic tendency to gain muscle mass on uterine leiomyomata
- 2023
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 14:1
-
Tidskriftsartikel (refereegranskat)abstract
- Uterine leiomyomata (UL) are the most common tumours of the female genital tract and the primary cause of surgical removal of the uterus. Genetic factors contribute to UL susceptibility. To add understanding to the heritable genetic risk factors, we conduct a genome-wide association study (GWAS) of UL in up to 426,558 European women from FinnGen and a previous UL meta-GWAS. In addition to the 50 known UL loci, we identify 22 loci that have not been associated with UL in prior studies. UL-associated loci harbour genes enriched for development, growth, and cellular senescence. Of particular interest are the smooth muscle cell differentiation and proliferation-regulating genes functioning on the myocardin-cyclin dependent kinase inhibitor 1A pathway. Our results further suggest that genetic predisposition to increased fat-free mass may be causally related to higher UL risk, underscoring the involvement of altered muscle tissue biology in UL pathophysiology. Overall, our findings add to the understanding of the genetic pathways underlying UL, which may aid in developing novel therapeutics.
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| 19. |
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| 20. |
- Aad, G., et al.
(författare)
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- 2013
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swepub:Mat__t (refereegranskat)
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| 21. |
- Aad, G., et al.
(författare)
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- 2012
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Tidskriftsartikel (refereegranskat)
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| 22. |
- Aad, G., et al.
(författare)
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- 2010
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swepub:Mat__t
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| 23. |
- Aad, G., et al.
(författare)
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- 2011
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swepub:Mat__t
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| 24. |
- Aad, G., et al.
(författare)
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- 2012
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swepub:Mat__t (refereegranskat)
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| 25. |
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| 26. |
- Aad, G., et al.
(författare)
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- 2010
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swepub:Mat__t
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| 27. |
- Aad, G., et al.
(författare)
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- 2010
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swepub:Mat__t
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| 28. |
- Aad, G., et al.
(författare)
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- 2010
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swepub:Mat__t
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