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Sökning: WFRF:(Preston MA)

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  • Heestermans, M, et al. (författare)
  • Identification of the factor XII contact activation site enables sensitive coagulation diagnostics
  • 2021
  • Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1, s. 5596-
  • Tidskriftsartikel (refereegranskat)abstract
    • Contact activation refers to the process of surface-induced activation of factor XII (FXII), which initiates blood coagulation and is captured by the activated partial thromboplastin time (aPTT) assay. Here, we show the mechanism and diagnostic implications of FXII contact activation. Screening of recombinant FXII mutants identified a continuous stretch of residues Gln317–Ser339 that was essential for FXII surface binding and activation, thrombin generation and coagulation. Peptides spanning these 23 residues competed with surface-induced FXII activation. Although FXII mutants lacking residues Gln317–Ser339 were susceptible to activation by plasmin and plasma kallikrein, they were ineffective in supporting arterial and venous thrombus formation in mice. Antibodies raised against the Gln317–Ser339 region induced FXII activation and triggered controllable contact activation in solution leading to thrombin generation by the intrinsic pathway of coagulation. The antibody-activated aPTT allows for standardization of particulate aPTT reagents and for sensitive monitoring of coagulation factors VIII, IX, XI.
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  • Ma, C. R., et al. (författare)
  • Addition of a Genetic Risk Score for Identification of Men with a Low Prostate-specific Antigen Level in Midlife at Risk of Developing Lethal Prostate Cancer
  • 2023
  • Ingår i: European Urology Open Science. - : Elsevier BV. - 2666-1691 .- 2666-1683. ; 50, s. 27-30
  • Tidskriftsartikel (refereegranskat)abstract
    • Men with a low prostate-specific antigen (PSA) level (<1 ng/ml) in midlife may extend the rescreening interval (if aged 40-59 yr) or forgo future PSA screening (if aged >60 yr) owing to their low risk of aggressive prostate cancer (PCa). However, there is a subset of men who develop lethal PCa despite low baseline PSA. We investigated how a PCa polygenic risk score (PRS) in addition to baseline PSA impacts the prediction of lethal PCa among 483 men aged 40-70 yr from the Physicians' Health Study followed over a median of 33 yr. We examined the association of the PRS with the risk of lethal PCa (lethal cases vs controls) using logistic regression adjusted for baseline PSA. The PCa PRS was associated with risk of lethal PCa (odds ratio per 1 standard deviation in PRS [OR] 1.79, 95% confidence interval [CI] 1.28-2.49). The association between the PRS and lethal PCa was stronger for those with PSA <1 ng/ml (OR 2.23, 95% CI 1.19-4.21) than for men with PSA >= 1 ng/ml (OR 1.61, 95% CI 1.07-2.42). Our PCa PRS improved the identification of men with PSA <1 ng/ml at greater risk of future lethal PCa who should consider ongoing PSA testing. Patient summary: A subset of men develop fatal prostate cancer despite having low prostate-specific antigen (PSA) levels in middle age. A risk score based on multiple genes can help in predicting men who may be at risk of developing lethal prostate cancer and who should be advised to have regular PSA measurements. (c) 2023 The Authors.
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  • Pascual, Unai, et al. (författare)
  • Valuing nature's contributions to people : the IPBES approach
  • 2017
  • Ingår i: Current Opinion in Environmental Sustainability. - : Elsevier BV. - 1877-3435. ; 26-27, s. 7-16
  • Forskningsöversikt (refereegranskat)abstract
    • Nature is perceived and valued in starkly different and often conflicting ways. This paper presents the rationale for the inclusive valuation of nature's contributions to people (NCP) in decision making, as well as broad methodological steps for doing so. While developed within the context of the Intergovernmental Platform on Biodiversity and Ecosystem Services (IPBES), this approach is more widely applicable to initiatives at the knowledge–policy interface, which require a pluralistic approach to recognizing the diversity of values. We argue that transformative practices aiming at sustainable futures would benefit from embracing such diversity, which require recognizing and addressing power relationships across stakeholder groups that hold different values on human nature-relations and NCP.
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  • Preston, MA, et al. (författare)
  • Metformin use and prostate cancer risk
  • 2014
  • Ingår i: European urology. - : Elsevier BV. - 1873-7560 .- 0302-2838. ; 66:6, s. 1012-1020
  • Tidskriftsartikel (refereegranskat)
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  • Resultat 11-20 av 29

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