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Cousins C.,Addenbrookes Hospital NHS Trust
Annals of the ICRP | Year: 2015

The International Commission on Radiological Protection (ICRP) has been in existence for 87 y, since its establishment in 1928. It remains a leading authority in radiological protection, and its role is to provide recommendations and guidance on all aspects of protection against ionising radiation. The published recommendations of ICRP form the basis of radiation safety standards worldwide. Modernisation of the organisation in recent years has led to new initiatives and changes. These have included writing a strategic plan and code of ethics for the first time. Elections for committee membership have been through open nominations, a process which will shortly be repeated for the membership in the next term, commencing on 1 July 2017. Biennial symposia started in 2011, and the success of the first two symposia has secured this venture as a regular part of the ICRP calendar. ICRP has also revised its method of working with other organisations by establishing ‘special liaison organisation’ status. This has improved collaboration with the ever-expanding number of organisations working in radiological protection, with whom it is important that ICRP has essential links. ICRP is also looking to review its legal basis and governing documents in the future, in order to ensure that best practices are being followed as ICRP evolves. In addition, the strategic plan will be reviewed and updated regularly. Other ways of working with organisations will be considered to further strengthen engagement with the wider radiological protection community. ICRP aims to make its publications available at low or no cost, and to produce both a plain language overview of the system of radiological protection and a summary of the recommendations. These activities will require additional financial resources, and ICRP has embarked on a fundraising campaign to support such efforts. ICRP can be proud of its history of maintaining its independence and preserving the wide respect earned over many years. Despite long traditions, ICRP has evolved and will continue to do so to perform as a more modern organisation as it heads towards a centenary and beyond. © 2015, © The International Society for Prosthetics and Orthotics.

Mavaddat N.,University of Cambridge | Pharoah P.D.,University of Cambridge | Blows F.,University of Cambridge | Driver K.E.,University of Cambridge | And 7 more authors.
Breast Cancer Research | Year: 2010

Introduction: The risk of breast cancer to first degree relatives of breast cancer patients is approximately twice that of the general population. Breast cancer, however, is a heterogeneous disease and it is plausible that the familial relative risk (FRR) for breast cancer may differ by the pathological subtype of the tumour. The contribution of genetic variants associated with breast cancer susceptibility to the subtype-specific FRR is still unclear.Methods: We computed breast cancer FRR for subtypes of breast cancer by comparing breast cancer incidence in relatives of breast cancer cases from a population-based series with known estrogen receptor (ER), progesterone receptor (PR) or human epidermal growth factor receptor 2 (HER2) status with that expected from the general population. We estimated the contribution to the FRR of genetic variants associated with breast cancer susceptibility using subtype-specific genotypic relative risks and allele frequencies for each variant.Results: At least one marker was measured for 4,590 breast cancer cases, who reported 9,014 affected and unaffected first-degree female relatives. There was no difference between the breast cancer FRR for relatives of patients with ER-negative (FRR = 1.78, 95% confidence intervals (CI): 1.44 to 2.11) and ER-positive disease (1.82, 95% CI: 1.67 to 1.98), P = 0.99. There was some suggestion that the breast cancer FRR for relatives of patients with ER-negative disease was higher than that for ER-positive disease for ages of the relative less than 50 years old (FRR = 2.96, 95% CI: 2.04 to 3.87; and 2.05, 95% CI: 1.70 to 2.40 respectively; P = 0.07), and that the breast cancer FRR for relatives of patients with ER-positive disease was higher than for ER-negative disease when the age of the relative was greater than 50 years (FRR = 1.76, 95% CI: 1.59 to 1.93; and 1.41, 95% CI: 1.08 to 1.74 respectively, P = 0.06). We estimated that mutations in BRCA1 and BRCA2 explain 32% of breast cancer FRR for relatives of patients with ER-negative and 9.4% of the breast cancer FRR for relatives of patients with ER-positive disease. Twelve recently identified common breast cancer susceptibility variants were estimated to explain 1.9% and 9.6% of the FRR to relatives of patients with ER-negative and ER-positive disease respectively.Conclusions: FRR for breast cancer was significantly increased for both ER-negative and ER-positive disease. Including receptor status in conjunction with genetic status may aid risk prediction in women with a family history. © 2010 Mavaddat et al.; licensee BioMed Central Ltd.

Fernandez-Rebollo E.,Harvard University | Perez De Nanclares G.,Research Unit | Lecumberri B.,Hospital Universitario La Paz | Turan S.,Harvard University | And 6 more authors.
Journal of Bone and Mineral Research | Year: 2011

Most patients with autosomal dominant pseudohypoparathyroidism type Ib (AD-PHP-Ib) carry maternally inherited microdeletions upstream of GNAS that are associated with loss of methylation restricted to GNAS exon A/B. Only few AD-PHP-Ib patients carry microdeletions within GNAS that are associated with loss of all maternal methylation imprints. These epigenetic changes are often indistinguishable from those observed in patients affected by an apparently sporadic PHP-Ib form that has not yet been defined genetically. We have now investigated six female patients affected by PHP-Ib (four unrelated and two sisters) with complete or almost complete loss of GNAS methylation, whose healthy children (11 in total) showed no epigenetic changes at this locus. Analysis of several microsatellite markers throughout the 20q13 region made it unlikely that PHP-Ib is caused in these patients by large deletions involving GNAS or by paternal uniparental isodisomy or heterodisomy of chromosome 20 (patUPD20). Microsatellite and single-nucleotide variation (SNV) data revealed that the two affected sisters share their maternally inherited GNAS alleles with unaffected relatives that lack evidence for abnormal GNAS methylation, thus excluding linkage to this locus. Consistent with these findings, healthy children of two unrelated sporadic PHP-Ib patients had inherited different maternal GNAS alleles, also arguing against linkage to this locus. Based on our data, it appears plausible that some forms of PHP-Ib are caused by homozygous or compound heterozygous mutation(s) in an unknown gene involved in establishing or maintaining GNAS methylation. Copyright © 2011 American Society for Bone and Mineral Research.

Cousins C.,Addenbrookes Hospital NHS Trust
Annals of the ICRP | Year: 2015

The International Commission on Radiological Protection (ICRP) is a premier international organisation for the protection of workers, patients, and the public against ionising radiation. It was established in 1928 to advance, for the public benefit, the science of radiological protection, with its work in the early years focusing mainly on occupational exposure in medicine. The name ‘International Commission on Radiological Protection’ was adopted in 1950 to reflect the wider and more diverse areas of work that were being undertaken. ICRP has published 13 sets of general recommendations and these form the basis of radiation safety standards worldwide. ICRP consists of the Main Commission and five standing committees. There are 84 official members of the Main Commission and Committees 1–5, but more than 200 members who work with ICRP through its task groups. ICRP has developed a strategic plan for 2011–2017 and has made progress with some of its initiatives. These include establishing close liaison with other radiological protection organisations, responding to the needs and concerns of the radiological protection community, and identifying areas of work that require scrutiny of science and practice to produce relevant recommendations. This strategy means that ICRP will continue to be a leader in radiological protection for many years to come. © The International Society for Prosthetics and Orthotics Reprints and permissions: sagepub.co.uk/journalsPermissions.nav

Lu S.-J.,Foundation Medicine | Lu S.-J.,National University Hospital Singapore | Gnanasegaran G.,Foundation Medicine | Buscombe J.,Addenbrookes Hospital NHS Trust | Navalkissoor S.,Royal Free Hospital NHS Trust
Nuclear Medicine Communications | Year: 2013

The scintigraphic investigation of neuroendocrine tumours such as carcinoids has depended on standard techniques such as 123I- metaiodobenzylguanidine and 111In-pentetreotide imaging. More recently, the use of PET techniques such as 68Ga-DOTATATE has been advocated. An alternative improved modality is high-quality single photon emission computed tomography/computed tomography (SPECT/CT), which has the advantages of better sensitivity and specificity and has shown improved localization in up to 60% of cases. These advantages are especially true for pancreatic and lymph node lesions. Overall, SPECT/CT can result in a change in clinical management in 25% of patients. Although it is possible to combine SPECT and CT performed at different time points, there is better anatomical localization and improved reporter confidence when SPECT and CT are performed simultaneously. © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins.

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