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Sökning: WFRF:(Metcalfe Julian D.)

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1.
  • Yang, Xin, et al. (författare)
  • Cancer risks associated with germline PALB2 pathogenic variants : An international study of 524 families
  • 2020
  • Ingår i: Journal of Clinical Oncology. - 0732-183X. ; 38:7, s. 674-685
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE To estimate age-specific relative and absolute cancer risks of breast cancer and to estimate risks of ovarian, pancreatic, male breast, prostate, and colorectal cancers associated with germline PALB2 pathogenic variants (PVs) because these risks have not been extensively characterized. METHODS We analyzed data from 524 families with PALB2 PVs from 21 countries. Complex segregation analysis was used to estimate relative risks (RRs; relative to country-specific population incidences) and absolute risks of cancers. The models allowed for residual familial aggregation of breast and ovarian cancer and were adjusted for the family-specific ascertainment schemes. RESULTS We found associations between PALB2 PVs and risk of female breast cancer (RR, 7.18; 95% CI, 5.82 to 8.85; P = 6.5 × 10-76), ovarian cancer (RR, 2.91; 95% CI, 1.40 to 6.04; P = 4.1 × 10-3), pancreatic cancer (RR, 2.37; 95% CI, 1.24 to 4.50; P = 8.7 × 10-3), and male breast cancer (RR, 7.34; 95% CI, 1.28 to 42.18; P = 2.6 3 1022). There was no evidence for increased risks of prostate or colorectal cancer. The breast cancer RRs declined with age (P for trend = 2.0 × 10-3). After adjusting for family ascertainment, breast cancer risk estimates on the basis of multiple case families were similar to the estimates from families ascertained through population-based studies (P for difference = .41). On the basis of the combined data, the estimated risks to age 80 years were 53% (95% CI, 44% to 63%) for female breast cancer, 5% (95% CI, 2% to 10%) for ovarian cancer, 2%-3% (95% CI females, 1% to 4%; 95% CI males, 2% to 5%) for pancreatic cancer, and 1% (95% CI, 0.2% to 5%) for male breast cancer. CONCLUSION These results confirm PALB2 as a major breast cancer susceptibility gene and establish substantial associations between germline PALB2 PVs and ovarian, pancreatic, and male breast cancers. These findings will facilitate incorporation of PALB2 into risk prediction models and optimize the clinical cancer risk management of PALB2 PV carriers.
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2.
  • Chapman, Jason W., et al. (författare)
  • Animal Orientation Strategies for Movement in Flows
  • 2011
  • Ingår i: Current Biology. - : Elsevier BV. - 1879-0445 .- 0960-9822. ; 21:20, s. 861-870
  • Forskningsöversikt (refereegranskat)abstract
    • For organisms that fly or swim, movement results from the combined effects of the moving medium - air or water - and the organism's own locomotion. For larger organisms, propulsion contributes significantly to progress but the flow usually still provides significant opposition or assistance, or produces lateral displacement ('drift'). Animals show a range of responses to flows, depending on the direction of the flow relative to their preferred direction, the speed of the flow relative to their own self-propelled speed, the incidence of flows in different directions and the proportion of the journey remaining. We here present a classification of responses based on the direction of the resulting movement relative to flow and preferred direction, which is applicable to a range of taxa and environments. The responses adopted in particular circumstances are related to the organisms' locomotory and sensory capacities and the environmental cues available. Advances in biologging technologies and particle tracking models are now providing a wealth of data, which often demonstrate a striking level of convergence in the strategies that very different animals living in very different environments employ when moving in a flow.
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