| 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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| 2. |
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- 2019
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Tidskriftsartikel (refereegranskat)
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| 3. |
- Sato, T., et al.
(författare)
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Overview of particle and heavy ion transport code system PHITS
- 2015
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Ingår i: Annals of Nuclear Energy. - : Elsevier BV. - 0306-4549 .- 1873-2100. ; 82, s. 110-115
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Tidskriftsartikel (refereegranskat)abstract
- A general purpose Monte Carlo Particle and Heavy Ion Transport code System, PHITS, is being developed through the collaboration of several institutes in Japan and Europe. The Japan Atomic Energy Agency is responsible for managing the entire project. PHITS can deal with the transport of nearly all particles, including neutrons, protons, heavy ions, photons, and electrons, over wide energy ranges using various nuclear reaction models and data libraries. It is written in Fortran language and can be executed on almost all computers. All components of PHITS such as its source, executable and data-library files are assembled in one package and then distributed to many countries via the Research Organization for Information Science and Technology, the Data Bank of the Organization for Economic Co-operation and Development's Nuclear Energy Agency, and the Radiation Safety Information Computational Center. More than 1500 researchers have been registered as PHITS users, and they apply the code to various research and development fields such as nuclear technology, accelerator design, medical physics, and cosmic-ray research. This paper briefly summarizes the physics models implemented in PHITS, and introduces some important functions useful for specific applications, such as an event generator mode and beam transport functions. (C) 2014 Elsevier Ltd. All rights reserved.
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| 4. |
- Sato, T., et al.
(författare)
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Overview of Particle and Heavy Ion Transport Code System PHITS
- 2014
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Ingår i: Sna + Mc 2013 - Joint International Conference on Supercomputing in Nuclear Applications + Monte Carlo. - Les Ulis, France : EDP Sciences. ; , s. article no 06018-
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Konferensbidrag (refereegranskat)abstract
- A general purpose Monte Carlo Particle and Heavy Ion Transport code System, PHITS, is being developed through the collaboration of several institutes in Japan and Europe. The Japan Atomic Energy Agency is responsible for managing the entire project. PHITS can deal with the transport of nearly all particles, including neutrons, protons, heavy ions, photons, and electrons, over wide energy ranges using various nuclear reaction models and data libraries. It is written in Fortran language and can be executed on almost all computers. All components of PHITS such as its source, executable and data-library files are assembled in one package and then distributed to many countries via the Research organization for Information Science and Technology, the Data Bank of the Organization for Economic Co-operation and Development's Nuclear Energy Agency, and the Radiation Safety Information Computational Center. More than 1,000 researchers have been registered as PHITS users, and they apply the code to various research and development fields such as nuclear technology, accelerator design, medical physics, and cosmic-ray research. This paper briefly summarizes the physics models implemented in PHITS, and introduces some important functions useful for specific applications, such as an event generator mode and beam transport functions.
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| 5. |
- Sato, T., et al.
(författare)
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Particle and Heavy Ion Transport code System, PHITS, version 2.52
- 2013
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Ingår i: Journal of Nuclear Science and Technology. - : Informa UK Limited. - 0022-3131 .- 1881-1248. ; 50:9, s. 913-923
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Tidskriftsartikel (refereegranskat)abstract
- An upgraded version of the Particle and Heavy Ion Transport code System, PHITS2.52, was developed and released to the public. The new version has been greatly improved from the previously released version, PHITS2.24, in terms of not only the code itself but also the contents of its package, such as the attached data libraries. In the new version, a higher accuracy of simulation was achieved by implementing several latest nuclear reaction models. The reliability of the simulation was improved by modifying both the algorithms for the electron-, positron-, and photon-transport simulations and the procedure for calculating the statistical uncertainties of the tally results. Estimation of the time evolution of radioactivity became feasible by incorporating the activation calculation program DCHAIN-SP into the new package. The efficiency of the simulation was also improved as a result of the implementation of shared-memory parallelization and the optimization of several time-consuming algorithms. Furthermore, a number of new user-support tools and functions that help users to intuitively and effectively perform PHITS simulations were developed and incorporated. Due to these improvements, PHITS is now a more powerful tool for particle transport simulation applicable to various research and development fields, such as nuclear technology, accelerator design, medical physics, and cosmic-ray research.
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| 6. |
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| 7. |
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| 8. |
- Smith, RM, et al.
(författare)
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Rituximab as therapy to induce remission after relapse in ANCA-associated vasculitis
- 2020
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Ingår i: Annals of the rheumatic diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 79:9, s. 1243-1249
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Tidskriftsartikel (refereegranskat)abstract
- Evaluation of rituximab and glucocorticoids as therapy to induce remission after relapse in ANCA-associated vasculitis (AAV) in a prospective observational cohort of patients enrolled into the induction phase of the RITAZAREM trial.MethodsPatients relapsing with granulomatosis with polyangiitis or microscopic polyangiitis were prospectively enrolled and received remission-induction therapy with rituximab (4×375 mg/m2) and a higher or lower dose glucocorticoid regimen, depending on physician choice: reducing from either 1 mg/kg/day or 0.5 mg/kg/day to 10 mg/day by 4 months. Patients in this cohort achieving remission were subsequently randomised to receive one of two regimens to prevent relapse.Results188 patients were studied: 95/188 (51%) men, median age 59 years (range 19–89), prior disease duration 5.0 years (range 0.4–34.5). 149/188 (79%) had previously received cyclophosphamide and 67/188 (36%) rituximab. 119/188 (63%) of relapses had at least one major disease activity item, and 54/188 (29%) received the higher dose glucocorticoid regimen. 171/188 (90%) patients achieved remission by 4 months. Only six patients (3.2% of the study population) did not achieve disease control at month 4. Four patients died in the induction phase due to pneumonia (2), cerebrovascular accident (1), and active vasculitis (1). 41 severe adverse events occurred in 27 patients, including 13 severe infections.ConclusionsThis large prospective cohort of patients with relapsing AAV treated with rituximab in conjunction with glucocorticoids demonstrated a high level of efficacy for the reinduction of remission in patients with AAV who have relapsed, with a similar safety profile to previous studies.
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| 9. |
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| 10. |
- Smith, RM, et al.
(författare)
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Rituximab versus azathioprine for maintenance of remission for patients with ANCA-associated vasculitis and relapsing disease: an international randomised controlled trial
- 2023
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Ingår i: Annals of the rheumatic diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 82:7, s. 937-944
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Tidskriftsartikel (refereegranskat)abstract
- Following induction of remission with rituximab in anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) relapse rates are high, especially in patients with history of relapse. Relapses are associated with increased exposure to immunosuppressive medications, the accrual of damage and increased morbidity and mortality. The RITAZAREM trial compared the efficacy of repeat-dose rituximab to daily oral azathioprine for prevention of relapse in patients with relapsing AAV in whom remission was reinduced with rituximab.MethodsRITAZAREM was an international randomised controlled, open-label, superiority trial that recruited 188 patients at the time of an AAV relapse from 29 centres in seven countries between April 2013 and November 2016. All patients received rituximab and glucocorticoids to reinduce remission. Patients achieving remission by 4 months were randomised to receive rituximab intravenously (1000 mg every 4 months, through month 20) (85 patients) or azathioprine (2 mg/kg/day, tapered after month 24) (85 patients) and followed for a minimum of 36 months. The primary outcome was time to disease relapse (either major or minor relapse).ResultsRituximab was superior to azathioprine in preventing relapse: HR 0.41; 95% CI 0.27 to 0.61, p<0.001. 19/85 (22%) patients in the rituximab group and 31/85 (36%) in the azathioprine group experienced at least one serious adverse event during the treatment period. There were no differences in rates of hypogammaglobulinaemia or infection between groups.ConclusionsFollowing induction of remission with rituximab, fixed-interval, repeat-dose rituximab was superior to azathioprine for preventing disease relapse in patients with AAV with a prior history of relapse.Trial registration numberNCT01697267; ClinicalTrials.gov identifier
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