يعرض 1 - 10 نتائج من 23 نتيجة بحث عن '"White, Rhian"', وقت الاستعلام: 0.66s تنقيح النتائج
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    دورية أكاديمية

    المصدر: Morgan , R D , Clamp , A R , Barnes , B M , Timms , K , Schlecht , H , Yarram-Smith , L , Wallis , Y , Valganon-Petrizan , M , Macmahon , S , White , R , Morgan , S , Mckenna , S , Hudson , E , Tookman , L , George , A , Manchanda , R , Sundar , S S , Nicum , S , Brenton , J D , Kristeleit , R S , Banerjee , S , Mcneish , I A , Ledermann , J A ....

    الوصف: Objective Olaparib plus bevacizumab maintenance therapy improves survival outcomes in women with newly diagnosed, advanced, high-grade ovarian cancer with a deficiency in homologous recombination. We report data from the first year of routine homologous recombination deficiency testing in the National Health Service (NHS) in England, Wales, and Northern Ireland between April 2021 and April 2022. Methods The Myriad myChoice companion diagnostic was used to test DNA extracted from formalin-fixed, paraffin-embedded tumor tissue in women with newly diagnosed International Federation of Gynecology and Obstetrics (FIGO) stage III/IV high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer. Tumors with homologous recombination deficiency were those with a BRCA1/2 mutation and/or a Genomic Instability Score (GIS) ≥42. Testing was coordinated by the NHS Genomic Laboratory Hub network. Results The myChoice assay was performed on 2829 tumors. Of these, 2474 (87%) and 2178 (77%) successfully underwent BRCA1/2 and GIS testing, respectively. All complete and partial assay failures occurred due to low tumor cellularity and/or low tumor DNA yield. 385 tumors (16%) contained a BRCA1/2 mutation and 814 (37%) had a GIS ≥42. Tumors with a GIS ≥42 were more likely to be BRCA1/2 wild-type (n=510) than BRCA1/2 mutant (n=304). The distribution of GIS was bimodal, with BRCA1/2 mutant tumors having a higher mean score than BRCA1/2 wild-type tumors (61 vs 33, respectively, χ2 test p Conclusion This is the largest real-world evaluation of homologous recombination deficiency testing in newly diagnosed FIGO stage III/IV high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer. It is important to select tumor tissue with adequate tumor content and quality to reduce the risk of assay failure. The rapid uptake of testing across England, Wales, and Northern Ireland demonstrates the power of centralized NHS funding, center specialization, and the NHS Genomic Laboratory Hub network.

    وصف الملف: application/pdf

  2. 2
    دورية أكاديمية

    الوصف: Aims FOCUS4 was a phase II/III umbrella trial, recruiting patients with advanced or metastatic colorectal cancer, between 2014 and 2020. Molecular profiling of patients’ formalin-fixed, paraffin-embedded tumour blocks was undertaken at two centralised biomarker laboratories (Leeds and Cardiff), and the results fed directly to the Medical Research Council Clinical Trials Unit, and used for subsequent randomisation. Here the laboratories discuss their experiences. Methods Following successful tumour content assessment, blocks were sectioned for DNA extraction and immunohistochemistry (IHC). Pyrosequencing was initially used to determine tumour mutation status (KRAS, NRAS, BRAF and PIK3CA), then from 2018 onwards, next-generation sequencing was employed to allow the inclusion of TP53. Protein expression of MLH1, MSH2, MSH6, PMS2 and pTEN was determined by IHC. An interlaboratory comparison programme was initiated, allowing sample exchanges, to ensure continued assay robustness. Results 1291 tumour samples were successfully analysed. Assay failure rates were very low; 1.9%–3.3% for DNA sequencing and 0.9%–1.3% for IHC. Concordance rates of >98% were seen for the interlaboratory comparisons, where a result was obtained by both laboratories. Conclusions Practical and logistical problems were identified, including poor sample quality and difficulties with sample anonymisation. The often last-minute receipt of a sample for testing and a lack of integration with National Health Service mutation analysis services were challenging. The laboratories benefitted from both pretrial validations and interlaboratory comparisons, resulting in robust assay development and provided confidence during the implementation of new sequencing technologies. We conclude that our centralised approach to biomarker testing in FOCUS4 was effective and successful.

    وصف الملف: application/pdf

    العلاقة: https://orca.cardiff.ac.uk/id/eprint/148327/1/jclinpath-2022-208233.full%20FOCUS4%20.pdfTest; Richman, Susan D., Hemmings, Gemma, Roberts, Helen, Gallop, Niall, Dodds, Rachel, Wilkinson, Lyndsay, Davis, Jonathan, White, Rhian, Yates, Emma, Jasani, Bharat, Brown, Louise, Maughan, Tim S., Butler, Rachel, Quirke, Philip and Adams, Richard https://orca.cardiff.ac.uk/view/cardiffauthors/A104870D.htmlTest orcid:0000-0003-3915-7243 orcid:0000-0003-3915-7243 2023. FOCUS4 biomarker laboratories: from the benefits to the practical and logistical issues faced during 6 years of centralised testing. Journal of Clinical Pathology 76 (8) , pp. 548-554. 10.1136/jclinpath-2022-208233 https://doi.org/10.1136/jclinpath-2022-208233Test file https://orca.cardiff.ac.uk/id/eprint/148327/1/jclinpath-2022-208233.full%20FOCUS4%20.pdfTest

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    دورية أكاديمية

    المصدر: British Journal of Cancer ; volume 128, issue 2, page 161-164 ; ISSN 0007-0920 1532-1827

    مصطلحات موضوعية: Cancer Research, Oncology

    الوصف: Summary Genomic screening is routinely used to guide the treatment of cancer patients in many countries. However, several multi-layered factors make this effort difficult to deliver within a clinically relevant timeframe. Here we share the learnings from the CRUK-funded Stratified Medicine Programme for advanced NSCLC patients, which could be useful to better plan future studies.

  5. 5
    دورية أكاديمية

    المصدر: Journal of Clinical Pathology (2022) (In press).

    الوصف: AIMS: FOCUS4 was a phase II/III umbrella trial, recruiting patients with advanced or metastatic colorectal cancer, between 2014 and 2020. Molecular profiling of patients’ formalin-fixed, paraffin-embedded tumour blocks was undertaken at two centralised biomarker laboratories (Leeds and Cardiff), and the results fed directly to the Medical Research Council Clinical Trials Unit, and used for subsequent randomisation. Here the laboratories discuss their experiences. METHODS: Following successful tumour content assessment, blocks were sectioned for DNA extraction and immunohistochemistry (IHC). Pyrosequencing was initially used to determine tumour mutation status (KRAS, NRAS, BRAF and PIK3CA), then from 2018 onwards, next-generation sequencing was employed to allow the inclusion of TP53. Protein expression of MLH1, MSH2, MSH6, PMS2 and pTEN was determined by IHC. An interlaboratory comparison programme was initiated, allowing sample exchanges, to ensure continued assay robustness. RESULTS: 1291 tumour samples were successfully analysed. Assay failure rates were very low; 1.9%–3.3% for DNA sequencing and 0.9%–1.3% for IHC. Concordance rates of >98% were seen for the interlaboratory comparisons, where a result was obtained by both laboratories. CONCLUSIONS: Practical and logistical problems were identified, including poor sample quality and difficulties with sample anonymisation. The often last-minute receipt of a sample for testing and a lack of integration with National Health Service mutation analysis services were challenging. The laboratories benefitted from both pretrial validations and interlaboratory comparisons, resulting in robust assay development and provided confidence during the implementation of new sequencing technologies. We conclude that our centralised approach to biomarker testing in FOCUS4 was effective and successful.

    وصف الملف: application/pdf

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    دورية أكاديمية
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  8. 8
    دورية

    المصدر: Journal of Clinical Pathology; 2023, Vol. 76 Issue: 8 p548-554, 7p

    مستخلص: AimsFOCUS4 was a phase II/III umbrella trial, recruiting patients with advanced or metastatic colorectal cancer, between 2014 and 2020. Molecular profiling of patients’ formalin-fixed, paraffin-embedded tumour blocks was undertaken at two centralised biomarker laboratories (Leeds and Cardiff), and the results fed directly to the Medical Research Council Clinical Trials Unit, and used for subsequent randomisation. Here the laboratories discuss their experiences.MethodsFollowing successful tumour content assessment, blocks were sectioned for DNA extraction and immunohistochemistry (IHC). Pyrosequencing was initially used to determine tumour mutation status (KRAS, NRAS, BRAF and PIK3CA), then from 2018 onwards, next-generation sequencing was employed to allow the inclusion of TP53. Protein expression of MLH1, MSH2, MSH6, PMS2 and pTEN was determined by IHC. An interlaboratory comparison programme was initiated, allowing sample exchanges, to ensure continued assay robustness.Results1291 tumour samples were successfully analysed. Assay failure rates were very low; 1.9%–3.3% for DNA sequencing and 0.9%–1.3% for IHC. Concordance rates of >98% were seen for the interlaboratory comparisons, where a result was obtained by both laboratories.ConclusionsPractical and logistical problems were identified, including poor sample quality and difficulties with sample anonymisation. The often last-minute receipt of a sample for testing and a lack of integration with National Health Service mutation analysis services were challenging. The laboratories benefitted from both pretrial validations and interlaboratory comparisons, resulting in robust assay development and provided confidence during the implementation of new sequencing technologies. We conclude that our centralised approach to biomarker testing in FOCUS4 was effective and successful.

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    دورية أكاديمية

    المصدر: The FASEB Journal ; volume 25, issue 5, page 1729-1736 ; ISSN 0892-6638 1530-6860

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    دورية أكاديمية

    المساهمون: Lectoraat Move to be, Fontys@@@Fontys Sporthogeschool

    المصدر: Journal of Educational Psychology. 2023

    الوصف: The things teachers do in class have an important influence on their students’ motivation, engagement, and learning. This study uses an international expert panel to identify the teacher behaviors most likely to influence motivation—specifically, teacher behaviors that increase the more healthy, autonomous motivation that comes from within students. This list of behaviors, agreed upon by the experts, could be used by teachers trying to improve their practice, policymakers trying to scale interventions, and researchers trying to assess which behaviors best predict student outcomes.