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- Ambros, I. M., et al.
(författare)
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Age Dependency of the Prognostic Impact of Tumor Genomics in Localized Resectable MYCN-Nonamplified Neuroblastomas. Report From the SIOPEN Biology Group on the LNESG Trials and a COG Validation Group
- 2020
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Ingår i: Journal of Clinical Oncology. - : American Society of Clinical Oncology (ASCO). - 0732-183X .- 1527-7755. ; 38:31
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSEFor localized, resectable neuroblastoma without MYCN amplification, surgery only is recommended even if incomplete. However, it is not known whether the genomic background of these tumors may influence outcome.PATIENTS AND METHODSDiagnostic samples were obtained from 317 tumors, International Neuroblastoma Staging System stages 1/2A/2B, from 3 cohorts: Localized Neuroblastoma European Study Group I/II and Children's Oncology Group. Genomic data were analyzed using multi- and pangenomic techniques and fluorescence in-situ hybridization in 2 age groups (cutoff age, 18 months) and were quality controlled by the International Society of Pediatric Oncology European Neuroblastoma (SIOPEN) Biology Group.RESULTSPatients with stage 1 tumors had an excellent outcome (5-year event-free survival [EFS] standard deviation [SD], 95% +/- 2%; 5-year overall survival [OS], 99% +/- 1%). In contrast, patients with stage 2 tumors had a reduced EFS in both age groups (5-year EFS +/- SD, 84% +/- 3% in patients < 18 months of age and 75% 7% in patients >= 18 months of age). However, OS was significantly decreased only in the latter group (5-year OS +/- SD in < 18months and 18months, 96% +/- 2% and 81% +/- 7%, respectively; P = .001). In < 18months, relapses occurred independent of segmental chromosome aberrations (SCAs); only 1p loss decreased EFS (5-year EFS SD in patients 1p loss and no 1p loss, 62% +/- 13% and 87% +/- 3%, respectively; P = .019) but not OS (5-year OS +/- SD, 92% +/- 8% and 97% +/- 2%, respectively). In patients >= 18 months, only SCAs led to relapse and death, with 11q loss as the strongest marker (11q loss and no 11q loss: 5-year EFS +/- SD, 48% +/- 16% and 85% +/- 7%, P = .033; 5-year OS +/- SD, 46% +/- 22% and 92% +/- 6%, P = .038).CONCLUSIONGenomic aberrations of resectable non-MYCN-amplified stage 2 neuroblastomas have a distinct age-dependent prognostic impact. Chromosome 1p loss is a risk factor for relapse but not for diminished OS in patients < 18 months, SCAs (especially 11q loss) are risk factors for reduced EFS and OS in those > 18months. In older patients with SCA, a randomized trial of postoperative chemotherapy compared with observation alone may be indicated.
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| 6. |
- Benard, N., et al.
(författare)
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Shear Layer and Shedding Modes Excitations of a Backward-Facing Step Flow by Surface Plasma Discharge
- 2020
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Ingår i: Advances in Effective Flow Separation Control for Aircraft Drag Reduction. - Cham : Springer. ; , s. 55-74
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Bokkapitel (refereegranskat)abstract
- The present experimental study interests in determining the influence of a linear plasma actuator (dielectric barrier discharge) on the development of a separated turbulent shear layer. More specifically, the plasma actuator is used to impose periodic perturbations at the step corner of a backward-facing step. Two different modes of excitation are explored. One concerns the shear layer mode of instability, a mode whose amplification leads to a minimization of the recirculation bubble. The present investigation shows how a dielectric barrier discharge plasma actuator can impose periodic perturbations that excite the shear layer mode and result in a strong regularization of the vortex street. The case of excitation at the shedding mode is also experimentally investigated using a DBD actuator. The measurements show the increase in Reynolds stress caused by this excitation as well as the specific growing mechanism of the shear layer. Indeed, phase-averaged flow measurements highlights the difference in the mechanism of development of the shear layer regarding the type of excitation used, the shear layer mode promoting a growing mechanism by fluid entrainment while the shedding mode enhancing the pairing of successive vortical flow structures.
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| 7. |
- Pawar, Harvinder, et al.
(författare)
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Ghost admixture in eastern gorillas
- 2023
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Ingår i: Nature Ecology & Evolution. - 2397-334X. ; 7:9, s. 1503-1514
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Tidskriftsartikel (refereegranskat)
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| 8. |
- Pawar, Harvinder, et al.
(författare)
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Ghost admixture in eastern gorillas
- 2023
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Ingår i: Nature Ecology & Evolution. - : Springer Nature. - 2397-334X. ; 7:9, s. 1503-1514
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Tidskriftsartikel (refereegranskat)abstract
- Archaic admixture has had a significant impact on human evolution with multiple events across different clades, including from extinct hominins such as Neanderthals and Denisovans into modern humans. Within the great apes archaic admixture has been identified in chimpanzees and bonobos, but the possibility of such events has not been explored in other species. Here, we address this question using high-coverage whole genome sequences from all four extant gorilla subspecies, including six newly sequenced eastern gorillas from previously unsampled geographic regions. Using Approximate Bayesian Computation (ABC) with neural networks to model the demographic history of gorillas, we find a signature of admixture from an archaic 'ghost' lineage into the common ancestor of eastern gorillas, but not western gorillas. We infer that up to 3% of the genome of these individuals is introgressed from an archaic lineage that diverged more than 3 million years ago from the common ancestor of all extant gorillas. This introgression event took place before the split of mountain and eastern lowland gorillas, likely more than 40 thousand years ago, and may have influenced perception of bitter taste in eastern gorillas. When comparing the introgression landscapes of gorillas, humans and bonobos, we find a consistent depletion of introgressed fragments on the X chromosome across these species. However, depletion in protein-coding content is not detectable in eastern gorillas, possibly as a consequence of stronger genetic drift in this species.
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