Assessing the usefulness of a novel MRI-based breast density estimation algorithm in a cohort of women at high genetic risk of breast cancer: the UK MARIBS study

Introduction Mammographic breast density is one of the strongest known risk factors for breast cancer. We present a novel technique for estimating breast density based on 3D T1-weighted Magnetic Resonance Imaging (MRI) and evaluate its performance, including for breast cancer risk prediction, relative to two standard mammographic density-estimation methods.Methods The analyses were based on MRI (n = 655) and mammography (n = 607) images obtained in the course of the UK multicentre magnetic resonance imaging breast screening (MARIBS) study of asymptomatic women aged 31 to 49 years who were at high genetic risk of breast cancer. The MRI percent and absolute dense volumes were estimated using our novel algorithm (MRIBview) while mammographic percent and absolute dense area were estimated using the Cumulus thresholding algorithm and also using a 21-point Visual Assessment scale for one medio-lateral oblique image per woman. We assessed the relationships of the MRI and mammographic measures to one another, to standard anthropometric and hormonal factors, to BRCA1/2 genetic status, and to breast cancer risk (60 cases) using linear and Poisson regression.Results MRI percent dense volume is well correlated with mammographic percent dense area (R = 0.76) but overall gives estimates 8.1 percentage points lower (P < 0.0001). Both show strong associations with established anthropometric and hormonal factors. Mammographic percent dense area, and to a lesser extent MRI percent dense volume were lower in BRCA1 carriers (P = 0.001, P = 0.010 respectively) but there was no association with BRCA2 carrier status. The study was underpowered to detect expected associations between percent density and breast cancer, but women with absolute MRI dense volume in the upper half of the distribution had double the risk of those in the lower half (P = 0.009).Conclusions The MRIBview estimates of volumetric breast density are highly correlated with mammographic dense area but are not equivalent measures; the MRI absolute dense volume shows potential as a predictor of breast cancer risk that merits further investigation

A grounded theory of Internet and social media use by young people who use augmentative and alternative communication (AAC).

PURPOSE: This paper presents a conceptual grounded theory for how young people with a diagnosis of cerebral palsy who use augmentative and alternative communication (AAC), perceive using the Internet and social media. The aims of the research were to understand and contextualise their perceptions of access and use and explore implications for self-representation and social participation; to date literature on this topic is limited. METHOD: A constructivist grounded theory research approach concurrently collected and analysed interview data from 25 participants (aged 14-24 years) who use AAC and additional sources. RESULTS: A conceptual grounded theory was developed around an emergent core category that showed young people who use AAC have a clear desire to use the Internet and social media. This was underpinned by eight supporting categories: reported use, described support, online challenges, access technology, speech generating device (SGD) issues, self-determination, self-representation and online social ties. CONCLUSION: The conceptual grounded theory supports understanding of facilitators and challenges to use of the Internet and social media by young people with a diagnosis of cerebral palsy who use AAC. The grounded theory illustrates how the desire to use the Internet and social media is based upon perceived benefits for enriching social relationships and enhancing opportunities for self-representation and self-determination that are synonymous with identified antecedents for community-based social inclusion. Some of the participants are engaging with the Internet and social media through collaborative practice and the implications for how this phenomenon may impact on orthographic literacy and the personal care workforce are raised

Using GWAS top hits to inform priors in Bayesian fine-mapping association studies

The default causal single‐nucleotide polymorphism (SNP) effect size prior in Bayesian fine‐mapping studies is usually the Normal distribution. This choice is often based on computational convenience, rather than evidence that it is the most suitable prior distribution. The choice of prior is important because previous studies have shown considerable sensitivity of causal SNP Bayes factors to the form of the prior. In some well‐studied diseases there are now considerable numbers of genome‐wide association study (GWAS) top hits along with estimates of the number of yet‐to‐be‐discovered causal SNPs. We show how the effect sizes of the top hits and estimates of the number of yet‐to‐be‐discovered causal SNPs can be used to choose between the Laplace and Normal priors, to estimate the prior parameters and to quantify the uncertainty in this estimation. The methodology can readily be applied to other priors. We show that the top hits available from breast cancer GWAS provide overwhelming support for the Laplace over the Normal prior, which has important consequences for variant prioritisation. This work in this paper enables practitioners to derive more objective priors than are currently being used and could lead to prioritisation of different variants

At the coalface and the cutting edge: general practitioners’ accounts of the rewards of engaging with HIV medicine

The interviews we conducted with GPs suggest that an engagement with HIV medicine enables clinicians to develop strong and long-term relationships with and expertise about the care needs of people living with HIV ‘at the coalface’, while also feeling connected with a broader network of medical practitioners and other professionals concerned with and contributing to the ever-changing world of science: ‘the cutting edge’. The general practice HIV prescriber is being modelled here as the interface between these two worlds, offering a rewarding opportunity for general practitioners to feel intimately connected to both community needs and scientific change

Financial Accounting 1: AFA 321

Financial Accounting 1: AFA 321, examination November 2010