| 1. |
- 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. |
- Dork, T, et al.
(författare)
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Two truncating variants in FANCC and breast cancer risk
- 2019
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1, s. 12524-
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Tidskriftsartikel (refereegranskat)abstract
- Fanconi anemia (FA) is a genetically heterogeneous disorder with 22 disease-causing genes reported to date. In some FA genes, monoallelic mutations have been found to be associated with breast cancer risk, while the risk associations of others remain unknown. The gene for FA type C, FANCC, has been proposed as a breast cancer susceptibility gene based on epidemiological and sequencing studies. We used the Oncoarray project to genotype two truncating FANCC variants (p.R185X and p.R548X) in 64,760 breast cancer cases and 49,793 controls of European descent. FANCC mutations were observed in 25 cases (14 with p.R185X, 11 with p.R548X) and 26 controls (18 with p.R185X, 8 with p.R548X). There was no evidence of an association with the risk of breast cancer, neither overall (odds ratio 0.77, 95%CI 0.44–1.33, p = 0.4) nor by histology, hormone receptor status, age or family history. We conclude that the breast cancer risk association of these two FANCC variants, if any, is much smaller than for BRCA1, BRCA2 or PALB2 mutations. If this applies to all truncating variants in FANCC it would suggest there are differences between FA genes in their roles on breast cancer risk and demonstrates the merit of large consortia for clarifying risk associations of rare variants.
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| 4. |
- Hasan, A, et al.
(författare)
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World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for Biological Treatment of Schizophrenia : Part 1: Update 2012 on the acute treatment of schizophrenia and the management of treatment resistance.
- 2012
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Ingår i: The World Journal of Biological Psychiatry. - : Informa UK Limited. - 1562-2975 .- 1814-1412. ; 13:5, s. 318-378
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Tidskriftsartikel (refereegranskat)abstract
- These updated guidelines are based on a first edition of the World Federation of Societies of Biological Psychiatry Guidelines for Biological Treatment of Schizophrenia published in 2005. For this 2012 revision, all available publications pertaining to the biological treatment of schizophrenia were reviewed systematically to allow for an evidence-based update. These guidelines provide evidence-based practice recommendations that are clinically and scientifically meaningful and these guidelines are intended to be used by all physicians diagnosing and treating people suffering from schizophrenia. Based on the first version of these guidelines, a systematic review of the MEDLINE/PUBMED database and the Cochrane Library, in addition to data extraction from national treatment guidelines, has been performed for this update. The identified literature was evaluated with respect to the strength of evidence for its efficacy and then categorised into six levels of evidence (A–F; Bandelow et al. 2008b, World J Biol Psychiatry 9:242). This first part of the updated guidelines covers the general descriptions of antipsychotics and their side effects, the biological treatment of acute schizophrenia and the management of treatment-resistant schizophrenia.
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| 5. |
- Maeda, Y., et al.
(författare)
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Differential cross section and analyzing power measurements for (n)over-right-arrowd elastic scattering at 248 MeV
- 2007
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Ingår i: Physical Review C. Nuclear Physics. - 0556-2813 .- 1089-490X. ; 76:1, s. 014004-
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Tidskriftsartikel (refereegranskat)abstract
- The differential cross sections and vector analyzing powers for nd elastic scattering at E-n=248 MeV were measured for 10 degrees-180 degrees in the center-of-mass (c.m.) system. To cover the wide angular range, the experiments were performed separately by using two different setups for forward and backward angles. The data are compared with theoretical results based on Faddeev calculations with realistic nucleon-nucleon (NN) forces such as AV18, CD Bonn, and Nijmegen I and II, and their combinations with the three-nucleon forces (3NFs), such as Tucson-Melbourne 99 (TM99), Urbana IX, and the coupled-channel potential with Delta-isobar excitation. Large discrepancies are found between the experimental cross sections and theory with only 2N forces for theta(c.m.)>90 degrees. The inclusion of 3NFs brings the theoretical cross sections closer to the data but only partially explains this discrepancy. For the analyzing power, no significant improvement is found when 3NFs are included. Relativistic corrections are shown to be small for both the cross sections and the analyzing powers at this energy. For the cross sections, these effects are mostly seen in the very backward angles. Compared with the pd cross section data, quite significant differences are observed at all scattering angles that cannot be explained only by the Coulomb interaction, which is usually significant at small angles.
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| 6. |
- Bahr, A., et al.
(författare)
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Non-reactive HiPIMS deposition of NbCx thin films : Effect of the target power density on structure-mechanical properties
- 2022
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Ingår i: Surface & Coatings Technology. - : Elsevier. - 0257-8972 .- 1879-3347. ; 444
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Tidskriftsartikel (refereegranskat)abstract
- The exceptional mechanical properties of transition metal carbide coatings are known to be governed by the carbon content and its morphological distribution. Here, we verify the influence of the target peak power density on the chemical composition, microstructure, and mechanical properties of NbCx coatings grown by non-reactive high-power impulse magnetron sputtering (HiPIMS). By tuning the pulse parameters, the power density can be increased from 0.11 to 1.48 kW/cm2 leading to a decrease in the C/Nb ratio from 1.52 to 0.99 within the films - proven by combined elastic backscattering and time-of-flight elastic recoil detection analysis. This decrease in the C/Nb ratio is accompanied by microstructural changes from nanocomposite morphologies with an average grain size of 6.6 +/- 2.5 nm at 0.13 kW/cm2 into more columnar structures with an average column width of 65.2 +/- 18.7 nm at 1.48 kW/cm2. Independent from the C/Nb ratio, all films exhibit a single face-centered cubic structure. The mechanical properties correlate with the enhanced growth behavior dominated by ions at higher peak power densities and the varied C/Nb ratios. A maximum in hardness and fracture toughness of H = 38.7 +/- 3.6 GPa and KIc = 2.78 +/- 0.13 MPa center dot m1/2 (at 3.2 GPa residual compressive stress), is obtained for the nearly stoichiometric NbC coating exhibiting C/Nb ratio of 1.06.
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| 9. |
- Frieler, Katja, et al.
(författare)
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Scenario setup and forcing data for impact model evaluation and impact attribution within the third round of the Inter-Sectoral Impact Model Intercomparison Project (ISIMIP3a)
- 2024
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Ingår i: Geoscientific Model Development. - : Copernicus Publications. - 1991-959X .- 1991-9603. ; 17:1, s. 1-51
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Tidskriftsartikel (refereegranskat)abstract
- This paper describes the rationale and the protocol of the first component of the third simulation round of the Inter-Sectoral Impact Model Intercomparison Project (ISIMIP3a, http://www.isimip.org, last access: 2 November 2023) and the associated set of climate-related and direct human forcing data (CRF and DHF, respectively). The observation-based climate-related forcings for the first time include high-resolution observational climate forcings derived by orographic downscaling, monthly to hourly coastal water levels, and wind fields associated with historical tropical cyclones. The DHFs include land use patterns, population densities, information about water and agricultural management, and fishing intensities. The ISIMIP3a impact model simulations driven by these observation-based climate-related and direct human forcings are designed to test to what degree the impact models can explain observed changes in natural and human systems. In a second set of ISIMIP3a experiments the participating impact models are forced by the same DHFs but a counterfactual set of atmospheric forcings and coastal water levels where observed trends have been removed. These experiments are designed to allow for the attribution of observed changes in natural, human, and managed systems to climate change, rising CH4 and CO2 concentrations, and sea level rise according to the definition of the Working Group II contribution to the IPCC AR6.
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| 10. |
- Heinz, Amadeus T., et al.
(författare)
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Significance of fusion status, Oberlin risk factors, local and maintenance treatment in pediatric and adolescent patients with metastatic rhabdomyosarcoma : Data of the European Soft Tissue Sarcoma Registry SoTiSaR
- 2024
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Ingår i: Pediatric Blood & Cancer. - : John Wiley & Sons. - 1545-5009 .- 1545-5017. ; 71:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Outcome of primary metastatic rhabdomyosarcoma (RMS) is poor. Certain risk factors as fusion status, Oberlin score, and local treatment of primary tumor are known to influence prognosis.Procedure: Patients with metastatic RMS were treated according to Cooperative Weichteilsarkom Studiengruppe (CWS) guidance with chemotherapy (CHT), radiotherapy (RT) excluding total lung irradiation (TLI), complete resection of the primary tumor, and metastasectomy if possible. Kaplan-Meier estimators and Cox proportional hazard models were used to examine event-free survival (EFS) and overall survival (OS) involving also landmark analyses.Results: In the European Soft Tissue Sarcoma Registry SoTiSaR (2009-2018), 211 patients were analyzed. Many patients had fusion-positive alveolar RMS (n = 83; 39%). Median age was 9.4 years [0.1-19.7 years]. Treatment primarily consisted of CHT with CEVAIE (carboplatin, epirubicine, vincristine, actinomycin-D, ifosfamide, etoposide: 86%, other regimens: 14%), RT (71%), resection of primary tumor (37%), metastasectomy (19%), and lymph node sampling/dissection (21%). Maintenance treatment (MT) (oral trofosfamide, idarubicin, etoposide) was added in 74% of patients. Oberlin factors, fusion status, and MT were predictive for EFS and OS. MT with O-TIE was not improving outcome when adjusting for the immortal time bias. Local treatment of the primary tumor and radical irradiation (except TLI) improved EFS, not OS, when adjusting for the Oberlin score. Patients with fusion-negative alveolar RMS (n = 9) had an excellent outcome with a 5-year EFS and OS of 100%, compared to patients with embryonal RMS (49%/62%), PAX7- (22%/47%) and PAX3/FOXO1-positive ARMS (10/13%), respectively (p < .001).Conclusions: Prognosis of metastatic RMS primarily depends on fusion status and Oberlin score. Fusion status needs to be considered in future trials to optimize treatment outcome. The role of radical irradiation needs further investigation.
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