No evidence that protein truncating variants in BRIP1 are associated with breast cancer risk: implications for gene panel testing.

BACKGROUND: BRCA1 interacting protein C-terminal helicase 1 (BRIP1) is one of the Fanconi Anaemia Complementation (FANC) group family of DNA repair proteins. Biallelic mutations in BRIP1 are responsible for FANC group J, and previous studies have also suggested that rare protein truncating variants in BRIP1 are associated with an increased risk of breast cancer. These studies have led to inclusion of BRIP1 on targeted sequencing panels for breast cancer risk prediction. METHODS: We evaluated a truncating variant, p.Arg798Ter (rs137852986), and 10 missense variants of BRIP1, in 48 144 cases and 43 607 controls of European origin, drawn from 41 studies participating in the Breast Cancer Association Consortium (BCAC). Additionally, we sequenced the coding regions of BRIP1 in 13 213 cases and 5242 controls from the UK, 1313 cases and 1123 controls from three population-based studies as part of the Breast Cancer Family Registry, and 1853 familial cases and 2001 controls from Australia. RESULTS: The rare truncating allele of rs137852986 was observed in 23 cases and 18 controls in Europeans in BCAC (OR 1.09, 95% CI 0.58 to 2.03, p=0.79). Truncating variants were found in the sequencing studies in 34 cases (0.21%) and 19 controls (0.23%) (combined OR 0.90, 95% CI 0.48 to 1.70, p=0.75). CONCLUSIONS: These results suggest that truncating variants in BRIP1, and in particular p.Arg798Ter, are not associated with a substantial increase in breast cancer risk. Such observations have important implications for the reporting of results from breast cancer screening panels.The COGS project is funded through a European Commission's Seventh Framework Programme grant (agreement number 223175 - HEALTH-F2-2009-223175). BCAC is funded by Cancer Research UK [C1287/A10118, C1287/A12014] and by the European Community´s Seventh Framework Programme under grant agreement number 223175 (grant number HEALTH-F2-2009-223175) (COGS). Funding for the iCOGS infrastructure came from: the European Community's Seventh Framework Programme under grant agreement n° 223175 (HEALTH-F2-2009-223175) (COGS), Cancer Research UK (C1287/A10118, C1287/A 10710, C12292/A11174, C1281/A12014, C5047/A8384, C5047/A15007, C5047/A10692, C8197/A16565), the National Institutes of Health (CA128978) and Post-Cancer GWAS initiative (1U19 CA148537, 1U19 16 CA148065 and 1U19 CA148112 - the GAME-ON initiative), the Department of Defense (W81XWH-10-1- 0341), the Canadian Institutes of Health Research (CIHR) for the CIHR Team in Familial Risks of Breast Cancer, Komen Foundation for the Cure, the Breast Cancer Research Foundation, and the Ovarian Cancer Research Fund. This study made use of data generated by the Wellcome Trust Case Control consortium. Funding for the project was provided by the Wellcome Trust under award 076113. The results published here are in part based upon data generated by The Cancer Genome Atlas Project established by the National Cancer Institute and National Human Genome Research Institute.This is the author accepted manuscript. The final version is available from BMJ Group at http://dx.doi.org/10.1136/jmedgenet-2015-103529

Design and Operation of Very Slow-Speed Generators for a Bristol Cylinder Sea Wave Generating Device

This paper describes the operation of a direct-drive brushless generator for a Bristol cylinder ocean wave device. This is a very low speed device so the pole number and diameter is very large. While the machine may be large the pole pitch and axial length is low. The application is described and simulated using analytical and finite element analysis techniques. A 248 pole design with surface rotor magnets is developed with both surface and slotted windings. An analysis of the control is put forward

Utilisation of website logo for phishing detection

Phishing is a security threat which combines social engineering and website spoofing techniques to deceive users into revealing confidential information. In this paper, we propose a phishing detection method to protect Internet users from the phishing attacks. In particular, given a website, our proposed method will be able to detect if it is a phishing website. We use a logo image to determine the identity consistency between the real and the portrayed identity of a website. Consistent identity indicates a legitimate website and inconsistent identity indicates a phishing website. The proposed method consists of two processes, namely logo extraction and identity verification. The first process will detect and extract the logo image from all the downloaded image resources of a webpage. In order to detect the right logo image, we utilise a machine learning technique. Based on the extracted logo image, the second process will employ the Google image search to retrieve the portrayed identity. Since the relationship between the logo and domain name is exclusive, it is reasonable to treat the domain name as the identity. Hence, a comparison between the domain name returned by Google with the one from the query website will enable us to differentiate a phishing from a legitimate website. The conducted experiments show reliable and promising results. This proves the effectiveness and feasibility of using a graphical element such as a logo to detect a phishing website

Numerical Solution of the Gardner Equation

The Gardner equation is commonly used to describe wave propagation in weakly nonlinear dispersive medium. The Gardner equation has a higher order nonlinear term, which could make the numerical calculation inaccurate. In this paper, the Gardner equation is solved using two numerical methods, i.e., the method of lines and pseudospectral method. The efficiency and accuracy of both methods were studied. Our results show that both methods are accurate and efficient methods to solve the Gardner equation. By comparing the accuracy of both the methods, the method of lines performs better than pseudospectral method most of the time

Implementation of Safety Management System for Improving Construction Safety Performance: A Structural Equation Modelling Approach

The construction industry contributes to a large proportion of industrial injury and mortality. It is of high importance to evaluate the effectiveness of the Safety Management System (SMS). In particular, it is necessary to compare the quality and level of achievement of SMS and safety performance of a construction project. However, a sizeable sample of construction accidents is often not available. Therefore, possible proxies to indicate the safety performance were established. Moreover, the motivation factors which characterize the quality and level of achievement should be identified. In this study, a structural model has been established to examine the relationship between the SMS implementation and operational & safety performance of the construction projects. Results of the structural model illustrated the relationship between (i) SMS implementation and project safety outcome, (ii) SMS implementation and five motivation factors, and (iii) project safety outcome and six proxies. Results of this study have unfolded the motivation factors in SMS implementation and their subsequent effects on project performance, throwing light on the need to enhance the safety management practice in order to reduce accidents and injuries in the construction industry in the long run