Oral-contraceptive use may reduce the risk of ovarian cancer in women with pathogenic mutations in the BRCA1 or BRCA2 gene.

A weighted scoring system (Dental Panoramic Radiograph Score) taking into consideration the nature, extent, and site of osseous and dental changes on dental panoramic radiographs in familial adenomatous polyposis is described. The weighting takes into consideration the incidence of the anomaly in the general population. The reliability of the system was tested by application to 85 people known to be affected by clinical or mutation analysis, 30 people lacking mutation in the adenomatous polyposis gene, and 19 people shown to be at low risk (<1%) by linkage analysis. Using the highest thresholds, a specificity of 100% and sensitivity of -68% was obtained. Ifall positive findings were considered as significant, sensitivity was increased to -82% but the specificity was reduced to -88%. Significant DPRS findings were observed at a significantly higher frequency in patients aged over 20 compared to the patients aged 20 and under. Overall, 68% ofthe affected subjects had significant changes, and -18% had normal appearance on DPR, with the remainder having changes classified as minimal or equivocal.(J Med Genet 1995;32:458-464)

This article describes a flexible track system model (FTSM) that represents the track structure for a typical ballasted track, taking into account the flexibility of the rails, the sleeper mass and the resilience of the pad/fastening elements, as well as the ballast support stiffness condition. The detailed track model is integrated into a commercial railway vehicle dynamics software, thus allowing for any vehicle to be simulated onto the flexible track while at the same time taking into account the detailed calculation of the non-linear wheel-rail contact interaction. As an example, the application of the FTSM to the study of hanging sleepers, with respect to the UK Railway Group Standard limits, is presented. This example shows the impact of forces because of hanging sleepers on the vehicle and on the track, and attempts at quantifying the damage made to the track components for the specific conditions simulated.

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How far did the unanimous agreement on the responsibility to protect at the 2005 UN World Summit really mark the international community's acceptance of a new norm supporting collective action -including ultimately military action -when governments through either incapacity or ill-will fail to protect their own people from genocide, war crimes, ethnic cleansing and crimes against humanity? This article describes the rapid initial emergence and acceptance of the concept, but also the subsequent denial and evasion by a number of governments of the commitments they signed up to in 2005. It addresses the fi ve main conceptual misunderstandings and misapprehensions evident in the public debate that need to be overcome if the argument in support of the responsibility to protect is to be won.

Purpose:To evaluate acute toxicity induced by chemotherapy for breast cancer in a retrospective study of 62 BRCA1/2 mutation carriers matched 1:1with women who had treatment for sporadic disease in the United Kingdom between 1983 and 2003. Experimental Design: All participants were interviewed by one of two researchers using standardized questionnaires, and their medical records were reviewed by one research nurse.The two main regimens received were cyclophosphamide, methotrexate, and fluorouracil and fluorouracil, epirubicin, and cyclophosphamide. The proportion of cases and controls receiving anthracyclinebased treatment was equivalent, but fewer BRCA1 cases received this treatment than did BRCA2 mutation carriers. Toxicity was documented using the Eastern Cooperative Oncology Group Common Toxicity Criteria for hematologic, infective, and gastrointestinal toxicities. No increase in toxicity was seen in BRCA1/2 mutation carriers. Results: The only significant difference was that neutropenia was less evident in BRCA2 mutation carriers than in either BRCA1 mutation carriers or controls. As a result, there was no requirement for dose reduction among BRCA2 mutation carriers, in contrast to 10 of 39 BRCA1 carriers and 16 of 62 controls (P = 0.02). Conclusions:This result has implications for therapy and indicates that women with mutations in BRCA1 and BRCA2 may be given the same doses of chemotherapy as noncarriers.BRCA1 and BRCA2 mutation carriers face a high risk of both breast and ovarian cancer due to mutations in these DNA double-strand break repair genes. Adjuvant breast cancer treatments of chemotherapy and radiotherapy rely on killing cells by mechanisms which include inducing DNA damage, affecting cell cycle checkpoints, or cell division, as reviewed by Kennedy et al. (1). The BRCA1 and BRCA2 genes have been shown to be integrally involved in these pathways, particularly in the repair of DNA double-strand breaks by homologous recombination. It is important to examine the effects of radiation and chemotherapeutic agents in BRCA1 and BRCA2 carriers as one would expect that they could have a greater incidence of normal tissue toxicity from both modalities compared with women with sporadic disease. The accompanying report evaluates the late effects of radiation in a case-control study of BRCA1/2 mutation carriers and sporadic controls in the United Kingdom (17). In conjunction with that study, the toxicity of chemotherapy was also examined to address the following questions: are BRCA1/2 mutation carriers more at risk of acute toxicity from chemotherapy? Do such individuals experience more severe decreases in blood counts and chemotherapy cycle delays, and would this result in a requirement for

Introduction Uptake of preventive therapies for breast cancer is low. We examined whether women at increased risk of breast cancer can be categorized into groups with similar medication beliefs, and whether belief group membership was prospectively associated with uptake of preventive therapy. Patients and Methods Women (n = 732) attending an appointment to discuss breast cancer risk were approached; 408 (55.7%) completed the Beliefs About Medicines and the Perceived Sensitivity to Medicines questionnaires. Uptake of tamoxifen at 3 months was reported in 258 (63.2%). The optimal number of belief groups were identified using latent profile analysis. Results Uptake of tamoxifen was 14.7% (38/258). One in 5 women (19.4%; 78/402) reported a strong need for tamoxifen. The model fit statistics supported a 2-group model. Both groups held weak beliefs about their need for tamoxifen for current and future health. Group 2 (38%; 154/406 of the sample) reported stronger concerns about tamoxifen and medicines in general, and stronger perceived sensitivity to the negative effects of medicines compared with group 1 (62%; 252/406). Women with low necessity and lower concerns (group 1) were more likely to initiate tamoxifen (18.3%; 33/180) than those with low necessity and higher concerns (group 2) (6.4%; 5/78). After adjusting for demographic and clinical factors, the odds ratio was 3.37 (95% confidence interval, 1.08-10.51; P = .036). Conclusion Uptake of breast cancer preventive therapy was low. A subgroup of women reported low need for preventive therapy and strong medication concerns. These women were less likely to initiate tamoxifen. Medication beliefs are targets for supporting informed decision-making.

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