| 1. |
- Campbell, PJ, et al.
(author)
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Pan-cancer analysis of whole genomes
- 2020
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In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 82-
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Journal article (peer-reviewed)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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| 2. |
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| 3. |
- Bar, N., et al.
(author)
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A reference map of potential determinants for the human serum metabolome
- 2020
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In: Nature. - : Nature Research. - 0028-0836 .- 1476-4687. ; 588:7836, s. 135-140
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Journal article (peer-reviewed)abstract
- The serum metabolome contains a plethora of biomarkers and causative agents of various diseases, some of which are endogenously produced and some that have been taken up from the environment1. The origins of specific compounds are known, including metabolites that are highly heritable2,3, or those that are influenced by the gut microbiome4, by lifestyle choices such as smoking5, or by diet6. However, the key determinants of most metabolites are still poorly understood. Here we measured the levels of 1,251 metabolites in serum samples from a unique and deeply phenotyped healthy human cohort of 491 individuals. We applied machine-learning algorithms to predict metabolite levels in held-out individuals on the basis of host genetics, gut microbiome, clinical parameters, diet, lifestyle and anthropometric measurements, and obtained statistically significant predictions for more than 76% of the profiled metabolites. Diet and microbiome had the strongest predictive power, and each explained hundreds of metabolites—in some cases, explaining more than 50% of the observed variance. We further validated microbiome-related predictions by showing a high replication rate in two geographically independent cohorts7,8 that were not available to us when we trained the algorithms. We used feature attribution analysis9 to reveal specific dietary and bacterial interactions. We further demonstrate that some of these interactions might be causal, as some metabolites that we predicted to be positively associated with bread were found to increase after a randomized clinical trial of bread intervention. Overall, our results reveal potential determinants of more than 800 metabolites, paving the way towards a mechanistic understanding of alterations in metabolites under different conditions and to designing interventions for manipulating the levels of circulating metabolites.
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| 4. |
- Andres, E., et al.
(author)
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Selected recent results from AMANDA
- 2001
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In: ICHEP 2000. Proceedings of the 30th International Conference on High Energy Physics. - : World Scientific. ; , s. 965-968
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Conference paper (peer-reviewed)abstract
- We present a selection of results based on data taken in 1997 with the 302-PMT Antarctic Muon and Neutrino Detector Array-B10 ("AMANDA-B10") array. Atmospheric neutrinos created in the northern hemisphere are observed indirectly through their charged current interactions which produce relativistic, Cherenkov-light-emitting upgoing muons in the South Pole ice cap. The reconstructed angular distribution of these events is in good agreement with expectation and demonstrates the viability of this ice-based device as a neutrino telescope. Studies of nearly vertical upgoing muons limit the available parameter space for WIMP dark matter under the assumption that WIMPS are trapped in the earth's gravitational potential well and annihilate with one another near the earth's center.
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| 5. |
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| 6. |
- Karle, A., et al.
(author)
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Observation of high energy atmospheric neutrinos with AMANDA
- 2000
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In: AIP Conference Proceedings. - : American Institute of Physics (AIP). ; , s. 823-827
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Conference paper (peer-reviewed)abstract
- In 1997 the Antarctic Muon and Neutrino Detector Array (AMANDA) started operating with 10 strings. In an analysis of data taken during the first year of operation 188 atmospheric neutrino candidates were found. Their zenith angle distribution agrees with expectations based on Monte Carlo simulations. A preliminary upper limit is given on a diffuse flux of high energy neutrinos of astrophysical origin.
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| 7. |
- Wilman, H. R., et al.
(author)
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Genetic studies of abdominal MRI data identify genes regulating hepcidin as major determinants of liver iron concentration
- 2019
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In: Journal of Hepatology. - : Elsevier. - 0168-8278 .- 1600-0641. ; 71:3, s. 594-602
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Journal article (peer-reviewed)abstract
- Background & Aims: Excess liver iron content is common and is linked to the risk of hepatic and extrahepatic diseases. We aimed to identify genetic variants influencing liver iron content and use genetics to understand its link to other traits and diseases. Methods: First, we performed a genome-wide association study (GWAS) in 8,289 individuals from UK Biobank, whose liver iron level had been quantified by magnetic resonance imaging, before validating our findings in an independent cohort (n = 1,513 from IMI DIRECT). Second, we used Mendelian randomisation to test the causal effects of 25 predominantly metabolic traits on liver iron content. Third, we tested phenome-wide associations between liver iron variants and 770 traits and disease outcomes. Results: We identified 3 independent genetic variants (rs1800562 [C282Y] and rs1799945 [H63D] in HFE and rs855791 [V736A] in TMPRSS6) associated with liver iron content that reached the GWAS significance threshold (p <5 × 10−8). The 2 HFE variants account for ∼85% of all cases of hereditary haemochromatosis. Mendelian randomisation analysis provided evidence that higher central obesity plays a causal role in increased liver iron content. Phenome-wide association analysis demonstrated shared aetiopathogenic mechanisms for elevated liver iron, high blood pressure, cirrhosis, malignancies, neuropsychiatric and rheumatological conditions, while also highlighting inverse associations with anaemias, lipidaemias and ischaemic heart disease. Conclusion: Our study provides genetic evidence that mechanisms underlying higher liver iron content are likely systemic rather than organ specific, that higher central obesity is causally associated with higher liver iron, and that liver iron shares common aetiology with multiple metabolic and non-metabolic diseases. Lay summary: Excess liver iron content is common and is associated with liver diseases and metabolic diseases including diabetes, high blood pressure, and heart disease. We identified 3 genetic variants that are linked to an increased risk of developing higher liver iron content. We show that the same genetic variants are linked to higher risk of many diseases, but they may also be associated with some health advantages. Finally, we use genetic variants associated with waist-to-hip ratio as a tool to show that central obesity is causally associated with increased liver iron content.
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| 13. |
- Barwick, S. W., et al.
(author)
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Initial results from the AMANDA high-energy neutrino detector
- 1998
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In: High-energy physics. Proceedings, 29th International Conference, ICHEP'98, Vancouver, Canada, July 23-29, 1998. Vol. 1, 2. ; , s. 1447-1452
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Conference paper (peer-reviewed)
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| 14. |
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| 15. |
- Halzen, F., et al.
(author)
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From the first neutrino telescope, the antarctic muon and neutrino detector array AMANDA, to the IceCube observatory
- 1999
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In: Proceedings of the 26th International Cosmic Ray Conference, August 17-25, 1999, Salt Lake City : Invited, Rapporteur, and Highlight Papers. - : American Institute of Physics (AIP). ; , s. 428-431
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Conference paper (peer-reviewed)
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| 16. |
- Miller, T. C., et al.
(author)
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Particle astrophysics in antarctica
- 1996
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In: International School of Cosmic Ray Astrophysics: 10th Course: Toward the Millennium in Astrophysics: Problems and Prospects 16-26 Jun 1996. Erice, Italy. ; , s. 157-166
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Conference paper (peer-reviewed)
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| 17. |
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| 18. |
- Bergstrom, L., et al.
(author)
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The AMANDA experiment : Status and prospects for indirect dark matter detection
- 1996
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In: The identification of dark matter. Proceedings, 1st International Workshop, Sheffield, UK, September 8-12, 1996. ; , s. 521-528
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Conference paper (peer-reviewed)abstract
- At the AMANDA South Pole site, four new holes were drilled to depths 2050m to 2180 m and instrumented with 86 photomultipliers (PMTs) at depths1520-2000 m. Of these PMTs 79 are working, with 4-ns timing resolutionand noise rates 300 to 600 Hz. Various diagnostic devices were deployedand are working. An observed factor 60 increase in scattering length anda sharpening of the distribution of arrival times of laser pulses relative tomeasurements at 800-1000 m showed that bubbles are absent below 1500 m.Absorption lengths are 100 to 150 m at wavelengths in the blue and UV to337 nm. Muon coincidences are seen between the SPASE air shower arrayand the AMANDA PMTs at 800-1000 m and 1500-1900 m. The muon trackrate is 30 Hz for 8-fold triggers and 10 Hz for 10-fold triggers. The presentarray is the nucleus for a future expanded array. The potential of AMANDAfor SUSY dark matter search through the detection of high-energy neutrinosfrom the centre of the Sun or Earth is discussed.
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| 19. |
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| 20. |
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| 21. |
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| 22. |
- Heggebo, L. C., et al.
(author)
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Investigating survival, quality of life and cognition in PROton versus photon therapy for IDH-mutated diffuse grade 2 and 3 GLIOmas (PRO-GLIO): a randomised controlled trial in Norway and Sweden
- 2023
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In: Bmj Open. - : BMJ. - 2044-6055. ; 13:3
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Journal article (peer-reviewed)abstract
- IntroductionThe use of proton therapy increases globally despite a lack of randomised controlled trials demonstrating its efficacy and safety. Proton therapy enables sparing of non-neoplastic tissue from radiation. This is principally beneficial and holds promise of reduced long-term side effects. However, the sparing of seemingly non-cancerous tissue is not necessarily positive for isocitrate dehydrogenase (IDH)-mutated diffuse gliomas grade 2-3, which have a diffuse growth pattern. With their relatively good prognosis, yet incurable nature, therapy needs to be delicately balanced to achieve a maximal survival benefit combined with an optimised quality of life.Methods and analysisPRO-GLIO (PROton versus photon therapy in IDH-mutated diffuse grade 2 and 3 GLIOmas) is an open-label, multicentre, randomised phase III non-inferiority study. 224 patients aged 18-65 years with IDH-mutated diffuse gliomas grade 2-3 from Norway and Sweden will be randomised 1:1 to radiotherapy delivered with protons (experimental arm) or photons (standard arm). First intervention-free survival at 2 years is the primary endpoint. Key secondary endpoints are fatigue and cognitive impairment, both at 2 years. Additional secondary outcomes include several survival measures, health-related quality of life parameters and health economy endpoints.Ethics and disseminationTo implement proton therapy as part of standard of care for patients with IDH-mutated diffuse gliomas grade 2-3, it should be deemed safe. With its randomised controlled design testing proton versus photon therapy, PRO-GLIO will provide important information for this patient population concerning safety, cognition, fatigue and other quality of life parameters. As proton therapy is considerably more costly than its photon counterpart, cost-effectiveness will also be evaluated. PRO-GLIO is approved by ethical committees in Norway (Regional Committee for Medical & Health Research Ethics) and Sweden (The Swedish Ethical Review Authority) and patient inclusion has commenced. Trial results will be published in international peer-reviewed journals, relevant conferences, national and international meetings and expert forums.Trial registration numberClinicalTrials.gov Registry (NCT05190172).
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| 23. |
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| 24. |
- Hulth, P. O., et al.
(author)
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The AMANDA experiment
- 1996
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In: Neutrino '96. Proceedings, 17th International Conference on Neutrino Physics and Astrophysics, Helsinki, Finland, June 13-19, 1996. ; , s. 518-523
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Conference paper (peer-reviewed)abstract
- At the AMANDA South Pole site, four new holes were drilled to depths 2050 m to 2180 m and instrumented with 86 photomultipliers (PMTs) at depths 1520-2000 m. Of these PMTs 79 are working, with 4-ns timing resolution and noise rates 300 to 600 Hz. Various diagnostic devices were deployed and are working. An observed factor 60 increase in scattering length and a sharpening of the distribution of arrival times of laser pulses relative to measurements at 800-1000 m showed that bubbles are absent below 1500 m. Absorption lengths are 100 to 150 m at wavelengths in the blue and UV to 337 nm. Muon coincidences are seen between the SPASE air shower array and the AMANDA PMTs at 800-1000 m and 1500-1900 m. The muon track rate is 30 Hz for 8-fold triggers and 10 Hz for 10-fold triggers. The present array is the nucleus for a future expanded array.
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| 25. |
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