| 1. |
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Overview of the JET results
- 2015
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Ingår i: Nuclear Fusion. - : IOP Publishing. - 0029-5515 .- 1741-4326. ; 55:10
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Tidskriftsartikel (refereegranskat)
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| 2. |
- Campbell, PJ, et al.
(författare)
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Pan-cancer analysis of whole genomes
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 82-
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Tidskriftsartikel (refereegranskat)abstract
- Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1–3. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4–5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5,6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8,9; and evaluates a range of more-specialized features of cancer genomes8,10–18.
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| 3. |
- Block, Michael, et al.
(författare)
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Research of the NUSTAR departments : SHE departments and HIM SHE section
- 2020
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Ingår i: GSI-FAIR Scientific Report 2019 : An overview of the 2019 achievements in science and technology - An overview of the 2019 achievements in science and technology. ; , s. 53-59
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- The SHE departments devoted to the research of superheavy elements, operate the recoil separators SHIP and TASCA and their ancillary installations including SHIPTRAP and a laser spectroscopy setup at SHIP as well as chemistry and nuclear spectroscopy setups at TASCA. In 2019, the activities at GSI focused on the UNILAC beamtime within the FAIR Phase-0 program and on the analysis of data obtained in prior beamtimes. At HIM, the advancement of actinide sample preparation, manipulation, and characterization for various applications was most central. In addition, technical developments, for example for single-ion mass measurements, have been performed.
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| 4. |
- Götz, S., et al.
(författare)
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Rapid extraction of short-lived isotopes from a buffer gas cell for use in gas-phase chemistry experiments, Part II : On-line studies with short-lived accelerator-produced radionuclides
- 2021
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Ingår i: Nuclear Instruments and Methods in Physics Research, Section B: Beam Interactions with Materials and Atoms. - : Elsevier BV. - 0168-583X. ; 507, s. 27-35
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Tidskriftsartikel (refereegranskat)abstract
- A novel combination of advanced gas-chromatography and detection systems coupled to a buffer-gas cell was characterized on-line to allow gas-phase chemical studies of accelerator-produced short-lived α-decaying mercury, francium, and astatine isotopes. These were produced in 40Ar- and 48Ca-induced nuclear fusion–evaporation reactions, subsequently isolated in the recoil separators MARS at Texas A&M University, USA, and TASCA at GSI Darmstadt, Germany, before being thermalized in a buffer-gas-stopping cell. From the latter, the nuclear reaction products were extracted into gas-phase chromatographic systems, suitable for registering α-decaying short-lived radionuclides, such as isotopes of superheavy elements. Efficiencies of 21(3)% for 204-209Fr were reached for the extraction into the optimized miniCOMPACT gas-chromatography setup, indicating that this technique enables the identification of isotopes of volatile as well as non-volatile elements. These studies guide the path towards chemical investigations of superheavy elements beyond flerovium, which are out of reach with currently used setups.
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| 5. |
- Angelopoulos, V., et al.
(författare)
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First Results from the THEMIS Mission
- 2008
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Ingår i: Space Science Reviews. - : Springer Science and Business Media LLC. - 0038-6308 .- 1572-9672. ; 141:1-4, s. 453-476
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Forskningsöversikt (refereegranskat)abstract
- THEMIS was launched on February 17, 2007 to determine the trigger and large-scale evolution of substorms. During the first seven months of the mission the five satellites coasted near their injection orbit to avoid differential precession in anticipation of orbit placement, which started in September 2007 and led to a commencement of the baseline mission in December 2007. During the coast phase the probes were put into a string-of-pearls configuration at 100 s of km to 2 R-E along-track separations, which provided a unique view of the magnetosphere and enabled an unprecedented dataset in anticipation of the first tail season. In this paper we describe the first THEMIS substorm observations, captured during instrument commissioning on March 23, 2007. THEMIS measured the rapid expansion of the plasma sheet at a speed that is commensurate with the simultaneous expansion of the auroras on the ground. These are the first unequivocal observations of the rapid westward expansion process in space and on the ground. Aided by the remote sensing technique at energetic particle boundaries and combined with ancillary measurements and MHD simulations, they allow determination and mapping of space currents. These measurements show the power of the THEMIS instrumentation in the tail and the radiation belts. We also present THEMIS Flux Transfer Events (FTE) observations at the magnetopause, which demonstrate the importance of multi-point observations there and the quality of the THEMIS instrumentation in that region of space.
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| 6. |
- Thanabalasingham, G., et al.
(författare)
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A large multi-centre European study validates high-sensitivity C-reactive protein (hsCRP) as a clinical biomarker for the diagnosis of diabetes subtypes
- 2011
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 1432-0428 .- 0012-186X. ; 54:11, s. 2801-2810
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Tidskriftsartikel (refereegranskat)abstract
- An accurate molecular diagnosis of diabetes subtype confers clinical benefits; however, many individuals with monogenic diabetes remain undiagnosed. Biomarkers could help to prioritise patients for genetic investigation. We recently demonstrated that high-sensitivity C-reactive protein (hsCRP) levels are lower in UK patients with hepatocyte nuclear factor 1 alpha (HNF1A)-MODY than in other diabetes subtypes. In this large multi-centre study we aimed to assess the clinical validity of hsCRP as a diagnostic biomarker, examine the genotype-phenotype relationship and compare different hsCRP assays. High-sensitivity CRP levels were analysed in individuals with HNF1A-MODY (n = 457), glucokinase (GCK)-MODY (n = 404), hepatocyte nuclear factor 4 alpha (HNF4A)-MODY (n = 54) and type 2 diabetes (n = 582) from seven European centres. Three common assays for hsCRP analysis were evaluated. We excluded 121 participants (8.1%) with hsCRP values > 10 mg/l. The discriminative power of hsCRP with respect to diabetes aetiology was assessed by receiver operating characteristic curve-derived C-statistic. In all centres and irrespective of the assay method, meta-analysis confirmed significantly lower hsCRP levels in those with HNF1A-MODY than in those with other aetiologies (z score -21.8, p < 5 x 10(-105)). HNF1A-MODY cases with missense mutations had lower hsCRP levels than those with truncating mutations (0.03 vs 0.08 mg/l, p < 5 x 10(-5)). High-sensitivity CRP values between assays were strongly correlated (r (2) a parts per thousand yenaEuro parts per thousand 0.91, p a parts per thousand currency signaEuro parts per thousand 1 x 10(-5)). Across the seven centres, the C-statistic for distinguishing HNF1A-MODY from young adult-onset type 2 diabetes ranged from 0.79 to 0.97, indicating high discriminative accuracy. In the largest study to date, we have established that hsCRP is a clinically valid biomarker for HNF1A-MODY in European populations. Given the modest costs and wide availability, hsCRP could translate rapidly into clinical practice, considerably improving diagnosis rates in monogenic diabetes.
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| 7. |
- Bärebring, Linnea, et al.
(författare)
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Use of bioelectrical impedance analysis to monitor changes in fat-free mass during recovery from colorectal cancer– a validation study
- 2020
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Ingår i: Clinical Nutrition ESPEN. - : Elsevier BV. - 2405-4577. ; 40, s. 201-207
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Tidskriftsartikel (refereegranskat)abstract
- Background & aims: Although previous research show high correlation between fat-free mass (FFM) measured by bioelectrical impedance analysis (BIA) and dual-energy X-ray absorptiometry (DXA), the validity of BIA to track longitudinal changes in FFM is uncertain. Thus, the aim of this study was to validate the ability of BIA to assess changes in FFM during 6 months of recovery from non-metastatic colorectal cancer (CRC). Methods: A total of 136 women and men (50–80 years) with stage I-III CRC and a wide range of baseline FFM (35.7–73.5 kg) were included in the study. Body composition was measured at study baseline within 2–9 months of surgery and again 6 months later. Whole-body BIA FFM estimates (FFMBIA) were calculated using three different equations (manufacturer's, Schols' and Gray's) before comparison to FFM estimates obtained by DXA (FFMDXA). Results: Correlation between changes in FFMBIA and FFMDXA was intermediate regardless of equation (r ≈ 0.6). The difference in change of FFMBIA was significant compared to FFMDXA, using all three equations and BIA overestimated both loss and gain. However, BIA showed 100% sensitivity and about 90% specificity to identify individuals with ≥5% loss in FFM, using all three equations. Sensitivity of FFMBIA to detect a smaller loss of FFM (60–76%) or a gain in FFM of ≥5% (33–62%) was poor. Conclusion: In a well-nourished population of non-metastatic CRC patients, a single-frequency whole-body BIA device yielded imprecise data on changes in FFM, regardless of equation. BIA is thus not a valid option for quantifying changes in FFM in individuals. However, BIA could be used to identify patients with loss in FFM ≥5% in this population. The validity of BIA to monitor changes in FFM warrants further investigation before implementation in clinical praxis. © 2020 The Author(s)
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| 8. |
- Giacoppo, F., et al.
(författare)
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Recent upgrades of the SHIPTRAP setup : On the finish line towards direct mass spectroscopy of superheavy elements
- 2017
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Ingår i: Acta Physica Polonica B. - 0587-4254. ; 48:3, s. 423-429
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Tidskriftsartikel (refereegranskat)abstract
- With the Penning-trap mass spectrometer SHIPTRAP at GSI, Darmstadt, it is possible to investigate exotic nuclei in the region of the heaviest elements. Few years ago, challenging experiments led to the direct measurements of the masses of neutron-deficient isotopes with Z = 102; 103 around N = 152. Thanks to recent advances in cooling and ion-manipulation techniques, a major technical upgrade of the setup has been recently accomplished to boost its efficiency. At present, the gap to reach more rare and shorter-lived species at the limits of the nuclear landscape has been narrowed.
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| 9. |
- Heyes, S. Burnett, et al.
(författare)
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Mental Imagery-Based Training to Modify Mood and Cognitive Bias in Adolescents : Effects of Valence and Perspective
- 2017
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Ingår i: Cognitive Therapy and Research. - : SPRINGER/PLENUM PUBLISHERS. - 0147-5916 .- 1573-2819. ; 41:1, s. 73-88
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Tidskriftsartikel (refereegranskat)abstract
- Mental imagery has a powerful impact on emotion and cognitive processing in adults, and is implicated in emotional disorders. Research suggests the perspective adopted in mental imagery modulates its emotional impact. However, little is known about the impact of mental imagery in adolescence, despite adolescence being the key time for the onset of emotional dysfunction. We administered computerised positive versus mixed valence picture-word mental imagery training to male adolescent participants (N = 60, aged 11-16 years) across separate field and observer perspective sessions. Positive mood increased more following positive than mixed imagery; pleasantness ratings of ambiguous pictures increased following positive versus mixed imagery generated from field but not observer perspective; negative interpretation bias on a novel scrambled sentences task was smaller following positive than mixed imagery particularly when imagery was generated from field perspective. These findings suggest positive mental imagery generation alters mood and cognition in male adolescents, with the latter moderated by imagery perspective. Identifying key components of such training, such as imagery perspective, extends understanding of the relationship between mental imagery, mood, and cognition in adolescence.
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| 10. |
- Neerland, B. E., et al.
(författare)
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Alpha-2-adrenergic receptor agonists for the prevention of delirium and cognitive decline after open heart surgery (ALPHA2PREVENT): protocol for a multicentre randomised controlled trial
- 2022
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Ingår i: Bmj Open. - : BMJ. - 2044-6055. ; 12:6
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Tidskriftsartikel (refereegranskat)abstract
- Introduction Postoperative delirium is common in older cardiac surgery patients and associated with negative short-term and long-term outcomes. The alpha-2-adrenergic receptor agonist dexmedetomidine shows promise as prophylaxis and treatment for delirium in intensive care units (ICU) and postoperative settings. Clonidine has similar pharmacological properties and can be administered both parenterally and orally. We aim to study whether repurposing of clonidine can represent a novel treatment option for delirium, and the possible effects of dexmedetomidine and clonidine on long-term cognitive trajectories, motor activity patterns and biomarkers of neuronal injury, and whether these effects are associated with frailty status. Methods and analysis This five-centre, double-blind randomised controlled trial will include 900 cardiac surgery patients aged 70+ years. Participants will be randomised 1:1:1 to dexmedetomidine or clonidine or placebo. The study drug will be given as a continuous intravenous infusion from the start of cardiopulmonary bypass, at a rate of 0.4 mu g/kg/hour. The infusion rate will be decreased to 0.2 mu g/kg/hour postoperatively and be continued until discharge from the ICU or 24 hours postoperatively, whichever happens first. Primary end point is the 7-day cumulative incidence of postoperative delirium (Diagnostic and Statistical Manual of Mental Disorders, fifth edition). Secondary end points include the composite end point of coma, delirium or death, in addition to delirium severity and motor activity patterns, levels of circulating biomarkers of neuronal injury, cognitive function and frailty status 1 and 6 months after surgery. Ethics and dissemination This trial is approved by the Regional Committee for Ethics in Medical Research in Norway (South-East Norway) and by the Norwegian Medicines Agency. Dissemination plans include publication in peer-reviewed medical journals and presentation at scientific meetings.
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