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- Frisoni, G. B., et al.
(author)
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Strategic roadmap for an early diagnosis of Alzheimer's disease based on biomarkers
- 2017
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In: Lancet Neurology. - 1474-4422 .- 1474-4465. ; 16:8, s. 661-676
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Journal article (peer-reviewed)abstract
- The diagnosis of Alzheimer's disease can be improved by the use of biological measures. Biomarkers of functional impairment, neuronal loss, and protein deposition that can be assessed by neuroimaging (ie, MRI and PET) or CSF analysis are increasingly being used to diagnose Alzheimer's disease in research studies and specialist clinical settings. However, the validation of the clinical usefulness of these biomarkers is incomplete, and that is hampering reimbursement for these tests by health insurance providers, their widespread clinical implementation, and improvements in quality of health care. We have developed a strategic five-phase roadmap to foster the clinical validation of biomarkers in Alzheimer's disease, adapted from the approach for cancer biomarkers. Sufficient evidence of analytical validity (phase 1 of a structured framework adapted from oncology) is available for all biomarkers, but their clinical validity (phases 2 and 3) and clinical utility (phases 4 and 5) are incomplete. To complete these phases, research priorities include the standardisation of the readout of these assays and thresholds for normality, the evaluation of their performance in detecting early disease, the development of diagnostic algorithms comprising combinations of biomarkers, and the development of clinical guidelines for the use of biomarkers in qualified memory clinics.
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| 2. |
- Gupta, S, et al.
(author)
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Quantitative assessments and clinical outcomes in HER2 equivocal 2018 ASCO/CAP ISH group 4 breast cancer
- 2019
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In: NPJ breast cancer. - : Springer Science and Business Media LLC. - 2374-4677. ; 5, s. 28-
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Journal article (peer-reviewed)abstract
- We quantified human epidermal growth factor receptor 2 (HER2) RNA and protein expression in 2018 American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) in situ hybridization (ISH) group 4 (HER2/centromeric probe 17 (CEP17) ratio <2.0, average HER2 copy number ≥4.0 and <6.0, and 2013 ASCO/CAP ISH equivocal) breast cancers. Breast cancers in 2018 ASCO/CAP ISH group 4 between 2014 and 2017 were identified from the Yale archives. Sixty-three patients (34 with HER2 immunohistochemistry (IHC) 0/1+ and 29 with HER2 IHC 2+) were included. We compared patient characteristics, systemic treatments, and outcomes. We assessed HER2 by real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) and quantitative immunofluorescence (QIF). Among ISH group 4 cancers, higher HER2 mRNA (P < 0.0001) but similar HER2 protein levels were observed in IHC 2+ compared to IHC 0/1+ cancers. The distribution of RT-qPCR and QIF scores were independent of fluorescence in situ hybridization (FISH) ratio/copy number. Concordance between HER2 RT-qPCR and QIF was 69.8% (r = 0.52). Among 29 patients with IHC2+ results, 16 were HER2 positive by RT-qPCR and 12 were HER2 positive by QIF. Systemic treatment, recurrence, and survival outcomes were comparable among ISH group 4 cancers regardless of IHC 0/1+ or 2+ results. ISH group 4 cancers appear to form a distinct group with intermediate levels of RNA/protein expression, close to positive/negative cut points. Therefore, adjudication into positive or negative categories may not be meaningful. Our results support the 2018 ASCO/CAP recommendation to refrain from routine additional testing of these samples. Additional outcome information after trastuzumab treatment for patients in this special group might help to guide treatment decisions in these patients.
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- Laakso, S.V.A., et al.
(author)
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Dull punch line is not a joke – Worn cutting edge causes higher iron losses in electrical steel piercing
- 2018
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In: Robotics and Computer-Integrated Manufacturing. - : Elsevier BV. - 0736-5845.
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Journal article (peer-reviewed)abstract
- © 2018 Elsevier Ltd Electrical steel is used for the active parts in electrical machinery that form the magnetic circuits because the material experiences low iron loss, and thus, has superior magnetizing properties. A typical electrical sheet has a thickness of 0.5 mm and is punched into its final shape via a piercing process. Piercing causes large deformations and residual stresses in the narrow zone of the cut surface. The deformations and stresses weaken the magnetic properties of the electrical sheet and result in additional losses, as the iron loss increases after piercing [1]. This paper presents a simulation model of the piercing process to evaluate the deformations and stresses on the cut surface. The model is constructed using the commercial FEM solver Deform. There has been an attempt to simulate the magneto-mechanical state of the punched surfaces, but the piercing process itself was not simulated [2] . The electrical steel sheet investigated in this paper is isotropic electrical silicon steel M400-50A (EN 10106-96).
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