| 1. |
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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. |
- Birney, Ewan, et al.
(författare)
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Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project
- 2007
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 447:7146, s. 799-816
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Tidskriftsartikel (refereegranskat)abstract
- We report the generation and analysis of functional data from multiple, diverse experiments performed on a targeted 1% of the human genome as part of the pilot phase of the ENCODE Project. These data have been further integrated and augmented by a number of evolutionary and computational analyses. Together, our results advance the collective knowledge about human genome function in several major areas. First, our studies provide convincing evidence that the genome is pervasively transcribed, such that the majority of its bases can be found in primary transcripts, including non-protein-coding transcripts, and those that extensively overlap one another. Second, systematic examination of transcriptional regulation has yielded new understanding about transcription start sites, including their relationship to specific regulatory sequences and features of chromatin accessibility and histone modification. Third, a more sophisticated view of chromatin structure has emerged, including its inter-relationship with DNA replication and transcriptional regulation. Finally, integration of these new sources of information, in particular with respect to mammalian evolution based on inter- and intra-species sequence comparisons, has yielded new mechanistic and evolutionary insights concerning the functional landscape of the human genome. Together, these studies are defining a path for pursuit of a more comprehensive characterization of human genome function.
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| 4. |
- Urban, Philip, et al.
(författare)
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Defining High Bleeding Risk in Patients Undergoing Percutaneous Coronary Intervention : A Consensus Document From the Academic Research Consortium for High Bleeding Risk
- 2019
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Ingår i: Circulation. - : LIPPINCOTT WILLIAMS & WILKINS. - 0009-7322 .- 1524-4539. ; 140:3, s. 240-261
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Tidskriftsartikel (refereegranskat)abstract
- Identification and management of patients at high bleeding risk undergoing percutaneous coronary intervention are of major importance, but a lack of standardization in defining this population limits trial design, data interpretation, and clinical decision-making. The Academic Research Consortium for High Bleeding Risk (ARC-HBR) is a collaboration among leading research organizations, regulatory authorities, and physician-scientists from the United States, Asia, and Europe focusing on percutaneous coronary intervention-related bleeding. Two meetings of the 31-member consortium were held in Washington, DC, in April 2018 and in Paris, France, in October 2018. These meetings were organized by the Cardiovascular European Research Center on behalf of the ARC-HBR group and included representatives of the US Food and Drug Administration and the Japanese Pharmaceuticals and Medical Devices Agency, as well as observers from the pharmaceutical and medical device industries. A consensus definition of patients at high bleeding risk was developed that was based on review of the available evidence. The definition is intended to provide consistency in defining this population for clinical trials and to complement clinical decision-making and regulatory review. The proposed ARC-HBR consensus document represents the first pragmatic approach to a consistent definition of high bleeding risk in clinical trials evaluating the safety and effectiveness of devices and drug regimens for patients undergoing percutaneous coronary intervention.
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| 5. |
- Urban, Philip, et al.
(författare)
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Defining high bleeding risk in patients undergoing percutaneous coronary intervention : a consensus document from the Academic Research Consortium for High Bleeding Risk
- 2019
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Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 40:31, s. 2632-2653
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Tidskriftsartikel (refereegranskat)abstract
- Identification and management of patients at high bleeding risk undergoing percutaneous coronary intervention are of major importance, but a lack of standardization in defining this population limits trial design, data interpretation, and clinical decision-making. The Academic Research Consortium for High Bleeding Risk (ARC-HBR) is a collaboration among leading research organizations, regulatory authorities, and physician-scientists from the United States, Asia, and Europe focusing on percutaneous coronary intervention-related bleeding. Two meetings of the 31-member consortium were held in Washington, DC, in April 2018 and in Paris, France, in October 2018. These meetings were organized by the Cardiovascular European Research Center on behalf of the ARC-HBR group and included representatives of the US Food and Drug Administration and the Japanese Pharmaceuticals and Medical Devices Agency, as well as observers from the pharmaceutical and medical device industries. A consensus definition of patients at high bleeding risk was developed that was based on review of the available evidence. The definition is intended to provide consistency in defining this population for clinical trials and to complement clinical decision-making and regulatory review. The proposed ARC-HBR consensus document represents the first pragmatic approach to a consistent definition of high bleeding risk in clinical trials evaluating the safety and effectiveness of devices and drug regimens for patients undergoing percutaneous coronary intervention.
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| 6. |
- Maksuti, Elira, et al.
(författare)
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ARTERIAL STIFFNESS ESTIMATION BY SHEAR WAVE ELASTOGRAPHY : VALIDATION IN PHANTOMS WITH MECHANICAL TESTING
- 2016
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Ingår i: Ultrasound in Medicine and Biology. - : Elsevier BV. - 0301-5629 .- 1879-291X. ; 42:1, s. 308-321
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Tidskriftsartikel (refereegranskat)abstract
- Arterial stiffness is an independent risk factor found to correlate with a wide range of cardiovascular diseases. It has been suggested that shear wave elastography (SWE) can be used to quantitatively measure local arterial shear modulus, but an accuracy assessment of the technique for arterial applications has not yet been performed. In this study, the influence of confined geometry on shear modulus estimation, by both group and phase velocity analysis, was assessed, and the accuracy of SWE in comparison with mechanical testing was measured in nine pressurized arterial phantoms. The results indicated that group velocity with an infinite medium assumption estimated shear modulus values incorrectly in comparison with mechanical testing in arterial phantoms (6.7 +/- 0.0 kPa from group velocity and 30.5 +/- 0.4 kPa from mechanical testing). To the contrary, SWE measurements based on phase velocity analysis (30.6 +/- 3.2 kPa) were in good agreement with mechanical testing, with a relative error between the two techniques of 8.8 +/- 6.0% in the shear modulus range evaluated (40-100 kPa). SWE by phase velocity analysis was validated to accurately measure stiffness in arterial phantoms.
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| 7. |
- Maksuti, Elira, et al.
(författare)
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Influence of wall thickness and diameter on arterial shear wave elastography : a phantom and finite element study.
- 2017
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Ingår i: Physics in Medicine and Biology. - : Institute of Physics (IOP). - 0031-9155 .- 1361-6560. ; 62:7, s. 2694-2718
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Tidskriftsartikel (refereegranskat)abstract
- Quantitative, non-invasive and local measurements of arterial mechanical properties could be highly beneficial for early diagnosis of cardiovascular disease and follow up of treatment. Arterial shear wave elastography (SWE) and wave velocity dispersion analysis have previously been applied to measure arterial stiffness. Arterial wall thickness (h) and inner diameter (D) vary with age and pathology and may influence the shear wave propagation. Nevertheless, the effect of arterial geometry in SWE has not yet been systematically investigated. In this study the influence of geometry on the estimated mechanical properties of plates (h = 0.5-3 mm) and hollow cylinders (h = 1, 2 and 3 mm, D = 6 mm) was assessed by experiments in phantoms and by finite element method simulations. In addition, simulations in hollow cylinders with wall thickness difficult to achieve in phantoms were performed (h = 0.5-1.3 mm, D = 5-8 mm). The phase velocity curves obtained from experiments and simulations were compared in the frequency range 200-1000 Hz and showed good agreement (R (2) = 0.80 ± 0.07 for plates and R (2) = 0.82 ± 0.04 for hollow cylinders). Wall thickness had a larger effect than diameter on the dispersion curves, which did not have major effects above 400 Hz. An underestimation of 0.1-0.2 mm in wall thickness introduces an error 4-9 kPa in hollow cylinders with shear modulus of 21-26 kPa. Therefore, wall thickness should correctly be measured in arterial SWE applications for accurate mechanical properties estimation.
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| 8. |
- Marlevi, David, et al.
(författare)
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Plaque characterization using shear wave elastography-evaluation of differentiability and accuracy using a combined ex vivo and in vitro setup
- 2018
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Ingår i: Physics in Medicine and Biology. - : IOP PUBLISHING LTD. - 0031-9155 .- 1361-6560. ; 63:23
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Tidskriftsartikel (refereegranskat)abstract
- Ultrasound elastography has shown potential for improved plaque risk stratification. However, no clear consensus exists on what output metric to use, or what imaging parameters would render optimal plaque differentiation. For this reason we developed a combined ex vivo and in vitro setup, in which the ability to differentiate phantom plaques of varying stiffness was evaluated as a function of plaque geometry, push location, imaging plane, and analysed wave speed metric. The results indicate that group velocity or phase velocity >= 1 kHz showed the highest ability to significantly differentiate plaques of different stiffness, successfully classifying a majority of the 24 analysed plaque geometries, respectively. The ability to differentiate plaques was also better in the longitudinal views than in the transverse view. Group velocity as well as phase velocities <1 kHz showed a systematic underestimation of plaque stiffness, stemming from the confined plaque geometries, however, despite this group velocity analysis showed lowest deviation in estimated plaque stiffness (0.1 m s(-1) compared to 0.2 m s(-1) for phase velocity analysis). SWE results were also invariant to SWE push location, albeit apparent differences in signal-to-noise ratio (SNR) and generated plaque particle velocity. With that, the study has reinforced the potential of SWE for successful plaque differentiation; however the results also highlight the importance of choosing optimal imaging settings and using an appropriate wave speed metric when attempting to differentiate different plaque groups.
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| 9. |
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| 10. |
- Nordenfur, Tim, 1990-, et al.
(författare)
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Safety of arterial shear wave elastography-ex-vivo assessment of induced strain and strain rates
- 2022
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Ingår i: Biomedical Engineering & Physics Express. - : IOP Publishing. - 2057-1976. ; 8:5
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Tidskriftsartikel (refereegranskat)abstract
- Shear wave elastography (SWE) is a promising technique for characterizing carotid plaques and assessing local arterial stiffness. The mechanical stress to which the tissue is subjected during SWE using acoustic radiation force (ARF), leading to strain at a certain strain rate, is still relatively unknown. Because SWEis increasingly used for arterial applications where the mechanical stress could potentially lead to significant consequences, it is important to understand the risks of SWE-induced strain and strain rate. The aim of this study was to investigate the safety of SWE in terms of induced arterial strain and strain rate ex-vivo and in a human carotid artery in-vivo. SWE was performed on six porcine aortae as a model of the human carotid artery using different combinations of ARF push parameters (push voltage: 60/90 V, aperture width: f/1.0/1.5, push length: 100/150/200 mu s) and distance to push position. The largest induced strain and strain rate were 1.46% and 54 s(-1) (90 V, f/ 1.0, 200 mu s), respectively. Moreover, the SWE-induced strains and strain rates increased with increasing push voltage, aperture, push length, and decreasing distance between the region of interest and the push. In the human carotid artery, the SWE-induced maximum strain was 0.06% and the maximum strain rate was 1.58 s(-1), compared with the maximum absolute strain and strain rate of 12.61% and 5.12 s(-1), respectively, induced by blood pressure variations in the cardiac cycle. Our results indicate that ex-vivo arterial SWE does not expose the artery to higher strain rate than normal blood pressure variations, and to strain one order of magnitude higher than normal blood pressure variations, at the push settings and distances from the region of interest used in this study.
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