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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. |
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| 4. |
- Hatch, D. R., et al.
(författare)
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Microtearing modes as the source of magnetic fluctuations in the JET pedestal
- 2021
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Ingår i: Nuclear Fusion. - : IOP Publishing. - 0029-5515 .- 1741-4326. ; 61:3
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Tidskriftsartikel (refereegranskat)abstract
- We report on a detailed study of magnetic fluctuations in the JET pedestal, employing basic theoretical considerations, gyrokinetic simulations, and experimental fluctuation data to establish the physical basis for their origin, role, and distinctive characteristics. We demonstrate quantitative agreement between gyrokinetic simulations of microtearing modes (MTMs) and two magnetic frequency bands with corresponding toroidal mode numbers n = 4 and 8. Such disparate fluctuation scales, with substantial gaps between toroidal mode numbers, are commonly observed in pedestal fluctuations. Here we provide a clear explanation, namely the alignment of the relevant rational surfaces (and not others) with the peak in the omega(*) profile, which is localized in the steep gradient region of the pedestal. We demonstrate that a global treatment is required to capture this effect. Nonlinear simulations suggest that the MTM fluctuations produce experimentally-relevant transport levels and saturate by relaxing the background electron temperature gradient, slightly downshifting the fluctuation frequencies from the linear predictions. Scans in collisionality are compared with a simple MTM dispersion relation. At the experimental points considered, MTM growth rates can either increase or decrease with collision frequency depending on the parameters thus defying any simple characterization of collisionality dependence.
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| 5. |
- Frassinetti, Lorenzo, et al.
(författare)
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Role of the separatrix density in the pedestal performance in deuterium low triangularity JET-ILW plasmas and comparison with JET-C
- 2021
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Ingår i: Nuclear Fusion. - : IOP Publishing Ltd. - 0029-5515 .- 1741-4326. ; 61:12
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Tidskriftsartikel (refereegranskat)abstract
- A reduction of the pedestal pressure with increasing separatrix density over pedestal density (n (e) (sep)/n (e) (ped)) has been observed in JET. The physics behind this correlation is investigated. The correlation is due to two distinct mechanisms. The increase of n (e) (sep)/n (e) (ped) till approximate to 0.4 shifts the pedestal pressure radially outwards, decreasing the peeling-balloning stability and reducing the pressure height. The effect of the position saturates above n (e) (sep)/n (e) (ped) approximate to 0.4. For higher values, the reduction of the pedestal pressure is ascribed to increased turbulent transport and, likely, to resistive MHD effects. The increase of n (e) (sep)/n (e) (ped) above approximate to 0.4 reduces backward difference n (e) /n (e), increasing eta (e) and the pedestal turbulent transport. This reduces the pressure gradient and the pedestal temperature, producing an increase in the pedestal resistivity. The work suggests that the increase in resistivity might destabilize resistive balloning modes, further reducing the pedestal stability.
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| 6. |
- Field, A. R., et al.
(författare)
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The dependence of exhaust power components on edge gradients in JET-C and JET-ILW H-mode plasmas
- 2020
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Ingår i: Plasma Physics and Controlled Fusion. - : IOP PUBLISHING LTD. - 0741-3335 .- 1361-6587. ; 62:5
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Tidskriftsartikel (refereegranskat)abstract
- Exhaust power components due to ELMs, radiation and heat transport across the edge transport barrier (ETB) between ELMs are quantifed for H-mode plasmas in JET-C and JET-ILW for comparison with simulations of pedestal heat transport. In low-current, JET-ILW pulses with a low rate of gas fuelling, the pedestal heat transport is found not to be stiff, i.e. the effective, mean heat diffusivity ac n eff does not increase with the electron temperature gradient adTe dRnped across the pedestal and the parameter he = Lne LTe increases with the conducted loss power across the pedestal, with the latter saturating at mean values.h.. 2 e ped. This increase in pedestal temperature gradient is partly due to a relative reduction of the ion neo-classical heat transport (which is more significant at low plasma current) with decreasing collisionality at higher power. In JET-ILW pulses, significantly more power is required at a high gas puffing rate to achieve a similar pedestal pressure and normalised confinement to that in otherwise similar JET-C pulses without gas-puffing. The increased heat transport across the JET-ILW pedestals is caused by changes to the pedestal structure induced by the gas puffing, which is required to mitigate contamination by W impurities sputtered from the target plates. In high-power JET-ILW pulses, the radiated power is dominated by that from W, which exhibits a highly asymmetric poloidal distribution due to toroidal rotation. During the ELMy H-mode phase, the W is concentrated in the outer `mantle' region (0.7. r. 0.96 N) inside the pedestal top by a favourable alignment of profile gradients, where it can be effectively flushed by ELMs. Transport analysis reveals that the strong mantle radiation cools the outer region of the plasma, causing more of the heat to be lost through the electron channel. However, direct cooling by W radiation from the ETB region is shown to be insignificant compared to the power conducted through the pedestal.
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| 7. |
- Ham, C. J., et al.
(författare)
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Towards understanding reactor relevant tokamak pedestals
- 2021
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Ingår i: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 61:9
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Tidskriftsartikel (refereegranskat)abstract
- The physics of the tokamak pedestal is still not fully understood, for example there is no fully predictive model for the pedestal height and width. However, the pedestal is key in determining the fusion power for a given scenario. If we can improve our understanding of reactor relevant pedestals we will improve our confidence in designing potential fusion power plants. Work has been carried out as part of a collaboration on reactor relevant pedestal physics. We report some of the results in detail here and review some of the wider work which will be reported in full elsewhere. First, we attempt to use a gyrokinetic-based calculation to eliminate the pedestal top density as a model input for Europed/EPED pedestal predictions. We assume power balance at the top of the pedestal, that is, the heat flux crossing the separatrix must be equal to the heat source at the top of the pedestal and investigate the consequences of this assumption. Unfortunately, the transport assumptions of the EPED model mean that this method does not discriminate between different pairs of density and temperature profiles for a given pressure profile. Second, we investigate the effects of non flux surface density on the bootstrap current. Third, type I ELMs will not be tolerable for a reactor relevant regime due to the damage that they are expected to cause to plasma facing components. In recent years various methods of running tokamak plasmas without large ELMs have been developed. These include small and no ELM regimes, the use of resonant magnetic perturbations and the use of vertical kicks. We discuss the quiescent H-mode here. Finally we give a summary and directions for future work.
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| 8. |
- Wijewardene, A, et al.
(författare)
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Change in Practice of Radioactive Iodine Administration in Differentiated Thyroid Cancer: A Single-Centre Experience
- 2021
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Ingår i: European thyroid journal. - : Bioscientifica. - 2235-0640 .- 2235-0802. ; 10:5, s. 408-415
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Tidskriftsartikel (refereegranskat)abstract
- <b><i>Objective:</i></b> Our study aimed to analyse temporal trends in radioactive iodine (RAI) treatment for thyroid cancer over the past decade; to analyse key factors associated with clinical decisions in RAI dosing; and to confirm lower activities of RAI for low-risk patients were not associated with an increased risk of recurrence. <b><i>Methods:</i></b> Retrospective analysis of 1,323 patients who received RAI at a quaternary centre in Australia between 2008 and 2018 was performed. Prospectively collected data included age, gender, histology, and American Joint Committee on Cancer stage (7th ed). American Thyroid Association risk was calculated retrospectively. <b><i>Results:</i></b> The median activities of RAI administered to low-risk patients decreased from 3.85 GBq (104 mCi) in 2008–2016 to 2.0 GBq (54 mCi) in 2017–2018. The principal driver of this change was an increased use of 1 GBq (27 mCi) from 1.3% of prescriptions in 2008–2011 to 18.5% in 2017–2018. In patients assigned as low risk per ATA stratification, lower activities of 1 GBq or 2 GBq (27 mCi or 54 mCi) were not associated with an increased risk of recurrence. In patients assigned to intermediate- or high-risk categories who received RAI as adjuvant therapy, there was no difference in risk of recurrence between 4 GBq (108 mCi) and 6 GBq (162 mCi). <b><i>Conclusions:</i></b> Our data demonstrate an evolution of RAI activities consistent with translation of ATA guidelines into clinical practice. Use of lower RAI activities was not associated with an increase in recurrence in low-risk thyroid cancer patients. Our data also suggest lower RAI activities may be as efficacious for adjuvant therapy in intermediate- and high-risk patients.
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