24 results on '"DOROTHY BYRNE"'
Search Results
2. British Society for Rheumatology guideline on diagnosis and treatment of giant cell arteritis: executive summary
- Author
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Wolfgang A. Schmidt, Sarah L. Mackie, Marco A. Cimmino, Lorna Neill, Tanaz A. Kermani, Peter A. Merkel, Peter Lanyon, Alexandre Wagner Silva de Souza, Susan P Mollan, Dorothy Byrne, Asad Khan, Chetan Mukhtyar, Christina Duftner, Madeline Whitlock, Dario Camellino, Simone Appenzeller, Elaine Yacyshyn, Eric L. Matteson, Maria C. Cid, Alfred Mahr, Marwan Bukhari, Haner Direskeneli, Christian D Mallen, Eoin O' Sullivan, Justin C Mason, Richard A. Watts, Christian Dejaco, Maria Sandovici, Raashid Luqmani, Frank Buttgereit, Elisabeth Brouwer, Gary Reynolds, Bhaskar Dasgupta, Steven R. Ytterberg, Kate Gilbert, Solange Gonzalez-Chiappe, Mackie, Sarah L., Dejaco, Christian, Appenzeller, Simone, Camellino, Dario, Duftner, Christina, Gonzalez-Chiappe, Solange, Mahr, Alfred, Mukhtyar, Chetan, Reynolds, Gary, de Souza, Alexandre Wagner S., Brouwer, Elisabeth, Bukhari, Marwan, Buttgereit, Frank, Byrne, Dorothy, Cid, Maria C., Cimmino, Marco, Direskeneli, Haner, Gilbert, Kate, Kermani, Tanaz A., Khan, Asad, Lanyon, Peter, Luqmani, Raashid, Mallen, Christian, Mason, Justin C., Matteson, Eric L., Merkel, Peter A., Mollan, Susan, Neill, Lorna, O' Sullivan, Eoin, Sandovici, Maria, Schmidt, Wolfgang A., Watts, Richard, Whitlock, Madeline, Yacyshyn, Elaine, Ytterberg, Steven, Dasgupta, Bhaskar, Translational Immunology Groningen (TRIGR), and Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI)
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medicine.medical_specialty ,diagnosis ,POLYMYALGIA-RHEUMATICA ,large-vessel vasculitis ,RECOMMENDATIONS ,Polymyalgia rheumatica ,chemistry.chemical_compound ,DOUBLE-BLIND ,Tocilizumab ,Rheumatology ,Internal medicine ,Large vessel vasculitis ,medicine ,MANAGEMENT ,Humans ,Pharmacology (medical) ,guidelines ,BSR ,Glucocorticoids ,TOCILIZUMAB ,Ultrasonography ,Executive summary ,treatment ,business.industry ,giant cell arteritis ,BHPR GUIDELINES ,Guideline ,medicine.disease ,Dermatology ,investigations ,Giant cell arteritis ,chemistry ,temporal arteritis ,TRIAL ,COLLEGE ,Vasculitis ,business - Published
- 2020
3. British Society for Rheumatology guideline on diagnosis and treatment of giant cell arteritis
- Author
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Alfred Mahr, Eric L. Matteson, Maria Sandovici, Elisabeth Brouwer, Justin C Mason, Tanaz A. Kermani, Gary Reynolds, Madeline Whitlock, Lorna Neill, Alexandre Wagner Silva de Souza, Wolfgang A. Schmidt, Dario Camellino, Marco A. Cimmino, Chetan Mukhtyar, Susan P Mollan, Bhaskar Dasgupta, Christian D Mallen, Christian Dejaco, Steven R. Ytterberg, Raashid Luqmani, Elaine Yacyshyn, Frank Buttgereit, Richard A. Watts, Sarah L. Mackie, Eoin O' Sullivan, Marwan Bukhari, Dorothy Byrne, Haner Direskeneli, Kate Gilbert, Asad Khan, Peter A. Merkel, Peter Lanyon, Solange Gonzalez-Chiappe, Christina Duftner, Simone Appenzeller, Maria C. Cid, Mackie, Sarah L., Dejaco, Christian, Appenzeller, Simone, Camellino, Dario, Duftner, Christina, Gonzalez-Chiappe, Solange, Mahr, Alfred, Mukhtyar, Chetan, Reynolds, Gary, de Souza, Alexandre Wagner S., Brouwer, Elisabeth, Bukhari, Marwan, Buttgereit, Frank, Byrne, Dorothy, Cid, Maria C., Cimmino, Marco, Direskeneli, Haner, Gilbert, Kate, Kermani, Tanaz A., Khan, Asad, Lanyon, Peter, Luqmani, Raashid, Mallen, Christian, Mason, Justin C., Matteson, Eric L., Merkel, Peter A., Mollan, Susan, Neill, Lorna, O' Sullivan, Eoin, Sandovici, Maria, Schmidt, Wolfgang A., Watts, Richard, Whitlock, Madeline, Yacyshyn, Elaine, Ytterberg, Steven, Dasgupta, Bhaskar, Imperial College Healthcare NHS Trust- BRC Funding, Translational Immunology Groningen (TRIGR), and Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI)
- Subjects
medicine.medical_specialty ,COLOR DUPLEX ULTRASONOGRAPHY ,diagnosis ,POPULATION-BASED COHORT ,MEDLINE ,Placebo-controlled study ,POLYMYALGIA-RHEUMATICA ,TEMPORAL ARTERITIS ,large-vessel vasculitis ,PLACEBO-CONTROLLED TRIAL ,AORTIC-ANEURYSM ,1117 Public Health and Health Services ,Polymyalgia rheumatica ,Aortic aneurysm ,LARGE-VESSEL INVOLVEMENT ,DOUBLE-BLIND ,Rheumatology ,Internal medicine ,Large vessel vasculitis ,medicine ,Humans ,Pharmacology (medical) ,guidelines ,Science & Technology ,treatment ,business.industry ,giant cell arteritis ,1103 Clinical Sciences ,Guideline ,PERMANENT VISUAL-LOSS ,medicine.disease ,Arthritis & Rheumatology ,investigations ,Giant cell arteritis ,1107 Immunology ,RISK-FACTORS ,Radiology ,business ,Life Sciences & Biomedicine - Published
- 2020
4. On Digital Trust: Analysis and ideas on trust and security in a digital age
- Author
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Mark Elliot, Barbara Ribiero, Emma Barret, Nicholas Lord, Rachel Gibson, David Buil-Gil, Dorothy Byrne, Niels Peek, John Ainsworth, Margarita Panayiotou, Gerard P. Hodgkinson, and Daniel Dresner
- Published
- 2019
5. TRUST ME, I'M NOT A POLITICIAN : A Simple Guide to Saving Democracy
- Author
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Dorothy Byrne and Dorothy Byrne
- Abstract
In an age where more British people believe in aliens than trust our politicians, Dorothy Byrne asks the question: what went wrong and how can our trust in democracy and public life be regained? In this scintillating essay, nothing and no one escapes Byrne's razor-sharp wit as she takes on the politicians avoiding rigorous journalistic scrutiny, explores the pitfalls of impartiality, imagines what Plato might say to Trump – and calls out plenty of sexist bastards along the way. This is a ferocious, frank, and often wildly funny attempt to separate the truth from the lies at a time of national crisis.
- Published
- 2019
6. Characterization of AGN from the XMM-Newton Slew Survey
- Author
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European Commission, Science and Technology Facilities Council (UK), Ministerio de Economía y Competitividad (España), UK Space Agency, Jack and Dorothy Byrne Foundation, Starling, R.L.C., Wildy, C., Wiersema, Klass, Mateos, Silvia, Saxton, R. D., Read, A. M., Mingo, B., European Commission, Science and Technology Facilities Council (UK), Ministerio de Economía y Competitividad (España), UK Space Agency, Jack and Dorothy Byrne Foundation, Starling, R.L.C., Wildy, C., Wiersema, Klass, Mateos, Silvia, Saxton, R. D., Read, A. M., and Mingo, B.
- Abstract
We present optical spectroscopy of candidate active galactic nuclei (AGN) pinpointed by a Swift follow-up campaign on unidentified transients in the XMM-Newton Slew Survey, increasing the completeness of the identifications of AGN in the Survey. Our Swift follow-up campaign identified 17 X-ray Telescope-detected candidate AGN, of which 9 were selected for optical follow-up and a further two were confirmed as AGN elsewhere. Using data obtained at the William Herschel Telescope, Very Large Telescope and New Technology Telescope, we find AGN features in seven of the candidates. We classify six as Seyfert types 1.0-1.5, with broad-line region velocities spanning 2000-12000 km s-1, and identify one as a possible type II AGN, consistent with the lack of a soft band X-ray detection in the Slew Survey. The virial black hole mass estimates for the sample lie between 1× 108 and 3× 109 M⊙, with one source likely emitting close to its Eddington rate, LBol/LEdd ~ 0.9. We find a wide redshift range 0.08 < z < 0.9 for the nine now confirmed AGN drawn from the unidentified Slew Survey sample. One source remaining unclassified shows outbursts rarely seen before in AGN. We conclude that AGN discovered in this way are consistent with the largely non-varying, Slew-selected, known AGN population. We also find parallels with XMM-Newton Bright Serendipitous Survey AGN selected from pointed observations, and postulate that shallow X-ray surveys select AGN drawn from the same populations that have been characterized in deeper X-ray-selected samples.
- Published
- 2017
7. Association between BRAF V600E mutation and recurrence of papillary thyroid cancer
- Author
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Comunidad de Madrid, National Institutes of Health (US), National Science Centre (Poland), Instituto de Salud Carlos III, Jack and Dorothy Byrne Foundation, Fondazione Cassa di Risparmio di Perugia, Associazione Italiana per la Ricerca sul Cancro, Beadle Family Foundation, Ministry of Health of the Czech Republic, Ministero dell'Istruzione, dell'Università e della Ricerca, Ministero della Salute, Xing, Mingzhao, Riesco-Eizaguirre, Garcilaso, Santisteban, Pilar, Comunidad de Madrid, National Institutes of Health (US), National Science Centre (Poland), Instituto de Salud Carlos III, Jack and Dorothy Byrne Foundation, Fondazione Cassa di Risparmio di Perugia, Associazione Italiana per la Ricerca sul Cancro, Beadle Family Foundation, Ministry of Health of the Czech Republic, Ministero dell'Istruzione, dell'Università e della Ricerca, Ministero della Salute, Xing, Mingzhao, Riesco-Eizaguirre, Garcilaso, and Santisteban, Pilar
- Abstract
[Purpose]: To investigate the prognostic value of BRAF V600E mutation for the recurrence of papillary thyroid cancer (PTC). [Patients and Methods]: This was a retrospective multicenter study of the relationship between BRAF V600E mutation and recurrence of PTC in 2,099 patients (1,615 women and 484 men), with a median age of 45 years (interquartile range [IQR], 34 to 58 years) and a median follow-up time of 36 months (IQR, 14 to 75 months). [Results]: The overall BRAF V600E mutation prevalence was 48.5% (1,017 of 2,099). PTC recurrence occurred in 20.9% (213 of 1,017) of BRAF V600E mutation–positive and 11.6% (125 of 1,082) of BRAF V600E mutation–negative patients. Recurrence rates were 47.71 (95% CI, 41.72 to 54.57) versus 26.03 (95% CI, 21.85 to 31.02) per 1,000 person-years in BRAF mutation–positive versus –negative patients (P < .001), with a hazard ratio (HR) of 1.82 (95% CI, 1.46 to 2.28), which remained significant in a multivariable model adjusting for patient sex and age at diagnosis, medical center, and various conventional pathologic factors. Significant association between BRAF mutation and PTC recurrence was also found in patients with conventionally low-risk disease stage I or II and micro-PTC and within various subtypes of PTC. For example, in BRAF mutation–positive versus –negative follicular-variant PTC, recurrence occurred in 21.3% (19 of 89) and 7.0% (24 of 342) of patients, respectively, with recurrence rates of 53.84 (95% CI, 34.34 to 84.40) versus 19.47 (95% CI, 13.05 to 29.04) per 1,000 person-years (P < .001) and an HR of 3.20 (95% CI, 1.46 to 7.02) after adjustment for clinicopathologic factors. BRAF mutation was associated with poorer recurrence-free probability in Kaplan-Meier survival analyses in various clinicopathologic categories. [Conclusion]: This large multicenter study demonstrates an independent prognostic value of BRAF V600E mutation for PTC recurrence in various clinicopathologic categories.
- Published
- 2015
8. Why has NHS stopped inviting me for cancer screening now I'm 71?
- Author
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DOROTHY BYRNE
- Abstract
THE admirable decision by King Charles to reveal he has cancer sparked a huge rise in the number of people seeking information about the disease. In the 24 hours following the news, Cancer Research UK saw a 33 per cent increase in visits to its information pages. [ABSTRACT FROM PUBLISHER]
- Published
- 2024
9. Association between BRAF V600E mutation and mortality in patients with papillary thyroid cancer
- Author
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Comunidad de Madrid, National Institutes of Health (US), Instituto de Salud Carlos III, Jack and Dorothy Byrne Foundation, Fondazione Cassa di Risparmio di Perugia, Associazione Italiana per la Ricerca sul Cancro, Beadle Family Foundation, Cancer Institute NSW (Australia), Cancer Council NSW (Australia), Ministry of Science and Higher Education (Poland), Xing, Mingzhao, Riesco-Eizaguirre, Garcilaso, Santisteban, Pilar, Comunidad de Madrid, National Institutes of Health (US), Instituto de Salud Carlos III, Jack and Dorothy Byrne Foundation, Fondazione Cassa di Risparmio di Perugia, Associazione Italiana per la Ricerca sul Cancro, Beadle Family Foundation, Cancer Institute NSW (Australia), Cancer Council NSW (Australia), Ministry of Science and Higher Education (Poland), Xing, Mingzhao, Riesco-Eizaguirre, Garcilaso, and Santisteban, Pilar
- Abstract
[Importance]: BRAF V600E is a prominent oncogene in papillary thyroid cancer (PTC), but its role in PTC-related patient mortality has not been established. [Objective]: To investigate the relationship between BRAF V600E mutation and PTC-related mortality. [Design, Setting, and Participants]: Retrospective study of 1849 patients (1411 women and 438 men) with amedian age of 46 years (interquartile range, 34-58 years) and an overall median follow-up time of 33 months (interquartile range, 13-67 months) after initial treatment at 13 centers in 7 countries between 1978 and 2011. [Main Outcomes and Measures]: Patient deaths specifically caused by PTC. [Results]: Overall, mortality was 5.3% (45/845; 95% CI, 3.9%-7.1%) vs 1.1% (11/1004; 95% CI, 0.5%-2.0%) ( P < .001) in BRAF V600E-positive vs mutationnegative patients. Deaths per 1000 person-years in the analysis of all PTC were 12.87 (95% CI, 9.61-17.24) vs 2.52 (95% CI, 1.40-4.55) in BRAF V600E-positive vs mutation-negative patients; the hazard ratio (HR) was 2.66 (95% CI, 1.30-5.43) after adjustment for age at diagnosis, sex, and medical center. Deaths per 1000 person-years in the analysis of the conventional variant of PTC were 11.80 (95% CI, 8.39-16.60) vs 2.25 (95% CI, 1.01-5.00) in BRAF V600E-positive vs mutation-negative patients; the adjusted HR was 3.53 (95% CI, 1.25-9.98). When lymph node metastasis, extrathyroidal invasion, and distant metastasis were also included in the model, the association of BRAF V600E with mortality for all PTC was no longer significant (HR, 1.21; 95% CI, 0.53-2.76). A higher BRAF V600E-associated patient mortality was also observed in several clinicopathological subcategories, but statistical significance was lost with adjustment for patient age, sex, and medical center. For example, in patients with lymph node metastasis, the deaths per 1000 person-years were 26.26 (95% CI, 19.18-35.94) vs 5.93 (95% CI, 2.96-11.86) in BRAF V600E-positive vs mutation-negative patients (unadjusted HR, 4.4
- Published
- 2013
10. How I got myself in shape to work full-time in my 70s.
- Author
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DOROTHY BYRNE
- Abstract
WHAT'S it like going back to work when you are 55, 60 or even 65 ? or if, like me, you are 70? [ABSTRACT FROM PUBLISHER]
- Published
- 2023
11. Some Attendance Patterns Exhibited by Members of Parliament during the 28th Parliament
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Dorothy Byrne
- Subjects
Government ,Sociology and Political Science ,Work (electrical) ,Parliament ,media_common.quotation_subject ,Political science ,Law ,Attendance ,Active listening ,Public administration ,media_common - Abstract
It can be said that in the Liberal back bench there are 20 members, or 16.4 per cent of the total doing 36.8 per cent of the committee work. Similarly, 27.1 per cent of the members are doing 52.8 per cent of the committee work. One of the major complaints of government members is the extremely heavy work load which has been aggravated by the recent changes in the rules and procedures of the House. Indeed, if one is listening to the complaints of a member who is in this 27.1 per cent group, his complaints are justified and real. One must conclude that the remaining 53.2 per cent who are responsible for only 25.4 per cent of the committee work must be the victims of work from another source.
- Published
- 1972
12. And here is the news: Having a sperm donor baby is the hardest and best thing I've done.
- Author
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Dorothy Byrne
- Abstract
WHEN I was a journalist in my late 20s in the North East of England, I noticed how older women had this knack of steering the conversation in a certain direction: 'You're a nice girl,' they'd say. 'Are you courting?' I thought this question was really sweet and old-fashioned, but looking back, I think those old ladies were trying to tell me something. They knew something I didn't. [ABSTRACT FROM PUBLISHER]
- Published
- 2020
13. How can it be TABOo to advise girls to plan to be MOTHERS?
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Dorothy Byrne
- Published
- 2021
14. My fertility warning caused a stir but I have no regrets. I wish I'd been told to try for a baby earlier.
- Author
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Dorothy Byrne
- Abstract
I [ABSTRACT FROM PUBLISHER]
- Published
- 2021
15. Failures reveal utter contempt for a grieving mum and police.
- Author
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DOROTHY BYRNE
- Published
- 2021
16. Why I'm going back to the office, even though I'm 68 and 'vulnerable'.
- Author
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DOROTHY BYRNE
- Published
- 2020
17. I've gained a whole new social life in lockdown.
- Author
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Dorothy Byrne
- Abstract
AS we begin to return to work and start resuming our social lives, we are in danger of losing the wonderful things which happened during our months isolated in our communities. I want to urge people to make sure we don't. [ABSTRACT FROM PUBLISHER]
- Published
- 2020
18. Unable to get out of bed, this TV boss blamed it on overdoing it at the gym. In fact she had a crippling disease that can make you blind in days.
- Author
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DOROTHY BYRNE
- Abstract
SEVERAL weeks ago I was struck by a medical condition so dramatic that within days I went from being a vibrant television executive in her mid-50s to a shuffling wreck with the physical capacity of a woman in her 80s. [ABSTRACT FROM PUBLISHER]
- Published
- 2010
19. When a stiff jaw means you're losing your sight.
- Author
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DOROTHY BYRNE
- Abstract
KEN BOLTON'S problems began when he sat down to eat his lunch one day and found he couldn't open his mouth. 'My jaws were just stuck,' says Ken, 78. [ABSTRACT FROM PUBLISHER]
- Published
- 2012
20. Steroids save lives but we have to face up to their side-effects.
- Author
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DOROTHY BYRNE
- Abstract
A WOMAN I barely know leans across the dinner table and strokes my cheek. 'No wrinkles at all!' she says enviously. 'How do you do it?' [ABSTRACT FROM PUBLISHER]
- Published
- 2011
21. Wendy thought her muscle aches were signs of ageing - in fact she was days from going blind.
- Author
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DOROTHY BYRNE
- Abstract
AFORTNIGHT ago, Wendy, Lady Levene experienced one of the most important days in her life. After years leading a fund-raising campaign for The Jewish Musueum, she watched proudly as a host of celebrities, including Nigella Lawson, attended the final opening. [ABSTRACT FROM PUBLISHER]
- Published
- 2010
22. Characterisation of AGN from the XMM-Newton Slew Survey
- Author
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R. D. Saxton, R. L. C. Starling, Conor Wildy, Silvia Mateos, A. M. Read, Beatriz Mingo, K. Wiersema, European Commission, Science and Technology Facilities Council (UK), Ministerio de Economía y Competitividad (España), UK Space Agency, and Jack and Dorothy Byrne Foundation
- Subjects
Swift ,Seyfert [Galaxies] ,Galaxies: Seyfert ,active [Galaxies] ,Astrophysics::High Energy Astrophysical Phenomena ,Library science ,FOS: Physical sciences ,Astrophysics::Cosmology and Extragalactic Astrophysics ,01 natural sciences ,Max planck institute ,Observatory ,0103 physical sciences ,Astronomy observatory ,010303 astronomy & astrophysics ,Astrophysics::Galaxy Astrophysics ,computer.programming_language ,Physics ,High Energy Astrophysical Phenomena (astro-ph.HE) ,010308 nuclear & particles physics ,Astronomy and Astrophysics ,Galaxies: active ,Undergraduate research ,Space and Planetary Science ,Christian ministry ,National laboratory ,Astrophysics - High Energy Astrophysical Phenomena ,computer - Abstract
We present optical spectroscopy of candidate active galactic nuclei (AGN) pinpointed by a Swift follow-up campaign on unidentified transients in the XMM-Newton Slew Survey, increasing the completeness of the identifications of AGN in the Survey. Our Swift follow-up campaign identified 17 X-ray Telescope-detected candidate AGN, of which 9 were selected for optical follow-up and a further two were confirmed as AGN elsewhere. Using data obtained at the William Herschel Telescope, Very Large Telescope and New Technology Telescope, we find AGN features in seven of the candidates. We classify six as Seyfert types 1.0-1.5, with broad-line region velocities spanning 2000-12000 km s-1, and identify one as a possible type II AGN, consistent with the lack of a soft band X-ray detection in the Slew Survey. The virial black hole mass estimates for the sample lie between 1× 108 and 3× 109 M⊙, with one source likely emitting close to its Eddington rate, LBol/LEdd ~ 0.9. We find a wide redshift range 0.08 < z < 0.9 for the nine now confirmed AGN drawn from the unidentified Slew Survey sample. One source remaining unclassified shows outbursts rarely seen before in AGN. We conclude that AGN discovered in this way are consistent with the largely non-varying, Slew-selected, known AGN population. We also find parallels with XMM-Newton Bright Serendipitous Survey AGN selected from pointed observations, and postulate that shallow X-ray surveys select AGN drawn from the same populations that have been characterized in deeper X-ray-selected samples., RLCS was supported by a Royal Society Dorothy Hodgkin Fellowship during the proposal and observation phases of this work; CW and KW acknowledge funding from the Science and Technology Facilities Council. SM acknowledges financial support by the Spanish Ministry of Economy and Competitiveness through grant AYA2016-76730-P, which is partly funded by the FEDER programme. BM acknowledges funding from the UK Space Agency.
- Published
- 2017
- Full Text
- View/download PDF
23. Association between BRAF V600E mutation and recurrence of papillary thyroid cancer
- Author
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Eyal Robenshtok, Tae Yong Kim, Rossella Elisei, Elizabeth H. Holt, Federica Vianello, Mark Sywak, Bela Bendlova, Ali S. Alzahrani, Garcilaso Riesco-Eizaguirre, Linwah Yip, R. Michael Tuttle, Caterina Mian, Pilar Santisteban, Barbara Jarzab, Hirotaka Nakayama, Laura Fugazzola, Mingzhao Xing, Kathryn A. Carson, Young Kee Shong, James A. Fagin, Alfred King-Yin Lam, Vlasta Sýkorová, Efisio Puxeddu, Christine J. O'Neill, Agnieszka Czarniecka, Roderick J. Clifton-Bligh, David Viola, Giovanni Tallini, Comunidad de Madrid, National Institutes of Health (US), National Science Centre (Poland), Instituto de Salud Carlos III, Jack and Dorothy Byrne Foundation, Fondazione Cassa di Risparmio di Perugia, Associazione Italiana per la Ricerca sul Cancro, Beadle Family Foundation, Ministry of Health of the Czech Republic, Ministero dell'Istruzione, dell'Università e della Ricerca, Ministero della Salute, Xing, Mingzhao, Alzahrani, Ali S., Carson, Kathryn A., Shong, Young Kee, Kim, Tae Yong, Viola, David, Elisei, Rossella, Bendlová, Bela, Yip, Linwah, Mian, Caterina, Vianello, Federica, Tuttle, R. Michael, Robenshtok, Eyal, Fagin, James A., Puxeddu, Efisio, Fugazzola, Laura, Czarniecka, Agnieszka, Jarzab, Barbara, O'Neill, Christine J., Sywak, Mark S., Lam, Alfred K., Riesco-Eizaguirre, Garcilaso, Santisteban, Pilar, Nakayama, Hirotaka, Clifton-Bligh, Roderick, Tallini, Giovanni, Holt, Elizabeth H., and Sýkorová, Vlasta
- Subjects
Oncology ,Male ,Pathology ,Cancer Research ,endocrine system diseases ,Papillary ,Kaplan-Meier Estimate ,Papillary thyroid cancer ,Retrospective Studie ,Risk Factors ,Missense mutation ,Adult ,Carcinoma, Papillary ,Female ,Follow-Up Studies ,Humans ,Middle Aged ,Neoplasm Recurrence, Local ,Prognosis ,Proto-Oncogene Proteins B-raf ,Retrospective Studies ,Risk Assessment ,Thyroid Neoplasms ,Mutation, Missense ,skin and connective tissue diseases ,Thyroid Neoplasm ,Follow up studies ,Local ,Mutation (genetic algorithm) ,Human ,medicine.medical_specialty ,endocrine system ,Prognosi ,Follow-Up Studie ,Internal medicine ,Carcinoma ,medicine ,neoplasms ,business.industry ,Risk Factor ,Retrospective cohort study ,medicine.disease ,digestive system diseases ,BRAF V600E ,Neoplasm Recurrence ,Multicenter study ,Mutation ,Missense ,business - Abstract
et al., [Purpose]: To investigate the prognostic value of BRAF V600E mutation for the recurrence of papillary thyroid cancer (PTC). [Patients and Methods]: This was a retrospective multicenter study of the relationship between BRAF V600E mutation and recurrence of PTC in 2,099 patients (1,615 women and 484 men), with a median age of 45 years (interquartile range [IQR], 34 to 58 years) and a median follow-up time of 36 months (IQR, 14 to 75 months). [Results]: The overall BRAF V600E mutation prevalence was 48.5% (1,017 of 2,099). PTC recurrence occurred in 20.9% (213 of 1,017) of BRAF V600E mutation–positive and 11.6% (125 of 1,082) of BRAF V600E mutation–negative patients. Recurrence rates were 47.71 (95% CI, 41.72 to 54.57) versus 26.03 (95% CI, 21.85 to 31.02) per 1,000 person-years in BRAF mutation–positive versus –negative patients (P < .001), with a hazard ratio (HR) of 1.82 (95% CI, 1.46 to 2.28), which remained significant in a multivariable model adjusting for patient sex and age at diagnosis, medical center, and various conventional pathologic factors. Significant association between BRAF mutation and PTC recurrence was also found in patients with conventionally low-risk disease stage I or II and micro-PTC and within various subtypes of PTC. For example, in BRAF mutation–positive versus –negative follicular-variant PTC, recurrence occurred in 21.3% (19 of 89) and 7.0% (24 of 342) of patients, respectively, with recurrence rates of 53.84 (95% CI, 34.34 to 84.40) versus 19.47 (95% CI, 13.05 to 29.04) per 1,000 person-years (P < .001) and an HR of 3.20 (95% CI, 1.46 to 7.02) after adjustment for clinicopathologic factors. BRAF mutation was associated with poorer recurrence-free probability in Kaplan-Meier survival analyses in various clinicopathologic categories. [Conclusion]: This large multicenter study demonstrates an independent prognostic value of BRAF V600E mutation for PTC recurrence in various clinicopathologic categories., Supported by National Institutes of Health (NIH) Grants No. R01CA134225 and RO1CA113507 (M.X.); by Grant No. UL1 RR 025005 from the National Center for Advancing Translational Sciences of NIH and NIH Roadmap for Medical Research (K.A.C.); and by the following funding to individual study centers: National Science Centre Poland Grants No. N N403 194340 (A.C.) and N N401 612440 (B.J.); grants from Griffith Health Institute (Australia; A.K.L.); Grants No. BFU2010-16025, RD06/0020/0060-RD12/0036/0030 FIS, ISCIII, and S2011/BMD-2328 TIRONET (Spain; P.S.); NIH Grant No. RO1-CA50706 and the Byrne Foundation (J.A.F.); Grant No. IG 9338 from the Fondazione Cassa di Risparmio di Perugia and Associazione Italiana per la Ricerca sul Cancro (Italy) and the Beadle Family Foundation (San Antonio, TX; E.P.); Grant No. IGA MH CR NT 13901- 4 (Czech Republic; B.B., V.S.); grants from the New South Wales Cancer Institute (C.J.O.) and Cancer Council of New South Wales (Australia; R.C.- B.); Grant No. MIUR 20074zw8la from the Ministero della Istruzione Universitaria e Ricerca Scientifica and the Associazione Italiana per la Ricerca sul Cancro (Italy; G.T.); NIH/National Institute on Aging Grant No. 5R03AG042334-02 (L.Y.); grants from the Ministero della Istruzione Universitaria e Ricerca Scientifica, the Associazione Italiana per la Ricerca sul Cancro, the Istituto Toscano Tumori, and the Ministero della Salute (Italy; D.V., R.E.); and Grant No. CB-2011-03-02 from the Korean Foundation for Cancer Research (South Korea; Y.K.S., T.Y.K.).
- Published
- 2015
24. Association between BRAF V600E mutation and mortality in patients with papillary thyroid cancer
- Author
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Federica Vianello, Ali S. Alzahrani, Linwah Yip, Efisio Puxeddu, Sara I. Pai, Pilar Santisteban, Bela Bendlova, Christine J. O'Neill, Agnieszka Czarniecka, William H. Westra, Laura Fugazzola, Roderick J. Clifton-Bligh, Hirotaka Nakayama, Douglas P. Clark, Garcilaso Riesco-Eizaguirre, Vlasta Sykorova, Paul W. Ladenson, Ralph P. Tufano, David Viola, Michael Mingzhao Xing, Martha A. Zeiger, David Sidransky, Alfred King-Yin Lam, Eyal Robenshtok, Mark Sywak, Barbara Jarzab, R. Michael Tuttle, James A. Fagin, Caterina Mian, Rossella Elisei, Kathryn A. Carson, Comunidad de Madrid, National Institutes of Health (US), Instituto de Salud Carlos III, Jack and Dorothy Byrne Foundation, Fondazione Cassa di Risparmio di Perugia, Associazione Italiana per la Ricerca sul Cancro, Beadle Family Foundation, Cancer Institute NSW (Australia), Cancer Council NSW (Australia), and Ministry of Science and Higher Education (Poland)
- Subjects
Oncology ,Pathology ,medicine.medical_specialty ,endocrine system diseases ,business.industry ,Cancer ,Retrospective cohort study ,General Medicine ,BRAFV600E mutation ,Papillary Thyroid Carcinoma ,Cancer Mortality ,Cancer Prognosis ,medicine.disease ,Article ,Papillary thyroid cancer ,BRAF V600E ,Interquartile range ,Internal medicine ,Mutation (genetic algorithm) ,Carcinoma ,Medicine ,business ,Thyroid cancer - Abstract
PMID:23571588.-- et al., [Importance]: BRAF V600E is a prominent oncogene in papillary thyroid cancer (PTC), but its role in PTC-related patient mortality has not been established. [Objective]: To investigate the relationship between BRAF V600E mutation and PTC-related mortality. [Design, Setting, and Participants]: Retrospective study of 1849 patients (1411 women and 438 men) with amedian age of 46 years (interquartile range, 34-58 years) and an overall median follow-up time of 33 months (interquartile range, 13-67 months) after initial treatment at 13 centers in 7 countries between 1978 and 2011. [Main Outcomes and Measures]: Patient deaths specifically caused by PTC. [Results]: Overall, mortality was 5.3% (45/845; 95% CI, 3.9%-7.1%) vs 1.1% (11/1004; 95% CI, 0.5%-2.0%) ( P < .001) in BRAF V600E-positive vs mutationnegative patients. Deaths per 1000 person-years in the analysis of all PTC were 12.87 (95% CI, 9.61-17.24) vs 2.52 (95% CI, 1.40-4.55) in BRAF V600E-positive vs mutation-negative patients; the hazard ratio (HR) was 2.66 (95% CI, 1.30-5.43) after adjustment for age at diagnosis, sex, and medical center. Deaths per 1000 person-years in the analysis of the conventional variant of PTC were 11.80 (95% CI, 8.39-16.60) vs 2.25 (95% CI, 1.01-5.00) in BRAF V600E-positive vs mutation-negative patients; the adjusted HR was 3.53 (95% CI, 1.25-9.98). When lymph node metastasis, extrathyroidal invasion, and distant metastasis were also included in the model, the association of BRAF V600E with mortality for all PTC was no longer significant (HR, 1.21; 95% CI, 0.53-2.76). A higher BRAF V600E-associated patient mortality was also observed in several clinicopathological subcategories, but statistical significance was lost with adjustment for patient age, sex, and medical center. For example, in patients with lymph node metastasis, the deaths per 1000 person-years were 26.26 (95% CI, 19.18-35.94) vs 5.93 (95% CI, 2.96-11.86) in BRAF V600E-positive vs mutation-negative patients (unadjusted HR, 4.43 [95% CI, 2.06-9.51]; adjusted HR, 1.46 [95% CI, 0.62-3.47]). In patients with distant tumor metastasis, deaths per 1000 person-years were 87.72 (95% CI, 62.68-122.77) vs 32.28 (95% CI, 16.14-64.55) in BRAF V600E-positive vs mutation-negative patients (unadjusted HR, 2.63 [95% CI, 1.21-5.72]; adjusted HR, 0.84 [95% CI, 0.27-2.62]). Conclusions and Relevance: In this retrospective multicenter study, the presence of the BRAF V600E mutation was significantly associated with increased cancer-related mortality among patients with PTC. Because overall mortality in PTC is low and the association was not independent of tumor features, how to use BRAF V600E to manage mortality risk in patients with PTC is unclear. These findings support further investigation of the prognostic and therapeutic implications of BRAF V600E status in PTC. ©2013 American Medical Association. All rights reserved., Funding/Support: This project was supported by National Institutes of Health (NIH) grants R01CA134225 and R01CA113507 to Dr Xing. The statistical effort of Ms Carson for this project was supported by grant UL1RR025005 from the National Center for Advancing Translational Sciences and the NIH Roadmap for Medical Research. In addition, the studies at individual centers were supported as follows: the Ministry of Science and Higher Education Research grants N N403 194340 and N N401 612440 to Drs Czarniecka and Jarzab, respectively(Poland); grant NIDCR/NCI SPORE P50DE019032 to Dr Sindransky (United States); grants BFU2010–16025, RD06/0020/0060-RD12/0036/0030 FIS, ISCIII, and S2011/BMD-2328TIRONET to Dr Santisteban (Spain); grant NIH-R01-CA50706 and Byrne Foundation funding to Dr Fagin (United States); grants from Fondazione Cassa di Risparmio di Perugia and Associazione Italiana per la Ricerca sul Cancro (IG 9338) (Italy) and the Beadle Family Foundation (San Antonio, Texas) to Dr Puxeddu; grant IGA MHCRNT13901–4 to Drs Sykorova and Bendlova (Czech Republic); and grants from the New South Wales Cancer Institute to Dr O’Neill and from the Cancer Council of New South Wales to Dr Clifton-Bligh (Australia).
- Published
- 2013
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