Second Set of Spaces

This document describes the Gloss infrastructure supporting implementation of location-aware services. The document is in two parts. The first part describes software architecture for the smart space. As described in D8, a local architecture provides a framework for constructing Gloss applications, termed assemblies, that run on individual physical nodes, whereas a global architecture defines an overlay network for linking individual assemblies. The second part outlines the hardware installation for local sensing. This describes the first phase of the installation in Strathclyde University

Genome-wide association study of germline variants and breast cancer-specific mortality

AbstractBackground: We examined the associations between germline variants and breast cancer mortality using a large meta-analysis of women of European ancestry.Methods: Meta-analyses included summary estimates based on Cox models of twelve datasets using ~10.4 million variants for 96,661 women with breast cancer and 7697 events (breast cancer-specific deaths). Oestrogen receptor (ER)-specific analyses were based on 64,171 ER-positive (4116) and 16,172 ER-negative (2125) patients. We evaluated the probability of a signal to be a true positive using the Bayesian false discovery probability (BFDP).Results: We did not find any variant associated with breast cancer-specific mortality at P −8. For ER-positive disease, the most significantly associated variant was chr7:rs4717568 (BFDP = 7%, P = 1.28 × 10−7, hazard ratio [HR] = 0.88, 95% confidence interval [CI] = 0.84–0.92); the closest gene is AUTS2. For ER-negative disease, the most significant variant was chr7:rs67918676 (BFDP = 11%, P = 1.38 × 10−7, HR = 1.27, 95% CI = 1.16–1.39); located within a long intergenic non-coding RNA gene (AC004009.3), close to the HOXA gene cluster.Conclusions: We uncovered germline variants on chromosome 7 at BFDP Abstract Background: We examined the associations between germline variants and breast cancer mortality using a large meta-analysis of women of European ancestry. Methods: Meta-analyses included summary estimates based on Cox models of twelve datasets using ~10.4 million variants for 96,661 women with breast cancer and 7697 events (breast cancer-specific deaths). Oestrogen receptor (ER)-specific analyses were based on 64,171 ER-positive (4116) and 16,172 ER-negative (2125) patients. We evaluated the probability of a signal to be a true positive using the Bayesian false discovery probability (BFDP). Results: We did not find any variant associated with breast cancer-specific mortality at P < 5 × 10−8. For ER-positive disease, the most significantly associated variant was chr7:rs4717568 (BFDP = 7%, P = 1.28 × 10−7, hazard ratio [HR] = 0.88, 95% confidence interval [CI] = 0.84–0.92); the closest gene is AUTS2. For ER-negative disease, the most significant variant was chr7:rs67918676 (BFDP = 11%, P = 1.38 × 10−7, HR = 1.27, 95% CI = 1.16–1.39); located within a long intergenic non-coding RNA gene (AC004009.3), close to the HOXA gene cluster. Conclusions: We uncovered germline variants on chromosome 7 at BFDP < 15% close to genes for which there is biological evidence related to breast cancer outcome. However, the paucity of variants associated with mortality at genome-wide significance underpins the challenge in providing genetic-based individualised prognostic information for breast cancer patients

Polygenic Risk Scores for Prediction of Breast Cancer and Breast Cancer Subtypes

Stratification of women according to their risk of breast cancer based on polygenic risk scores (PRSs) could improve screening and prevention strategies. Our aim was to develop PRSs, optimized for prediction of estrogen receptor (ER)-specific disease, from the largest available genome-wide association dataset and to empirically validate the PRSs in prospective studies. The development dataset comprised 94,075 case subjects and 75,017 control subjects of European ancestry from 69 studies, divided into training and validation sets. Samples were genotyped using genome-wide arrays, and single-nucleotide polymorphisms (SNPs) were selected by stepwise regression or lasso penalized regression. The best performing PRSs were validated in an independent test set comprising 11,428 case subjects and 18,323 control subjects from 10 prospective studies and 190,040 women from UK Biobank (3,215 incident breast cancers). For the best PRSs (313 SNPs), the odds ratio for overall disease per 1 standard deviation in ten prospective studies was 1.61 (95%CI: 1.57-1.65) with area under receiver-operator curve (AUC) = 0.630 (95%CI: 0.628-0.651). The lifetime risk of overall breast cancer in the top centile of the PRSs was 32.6%. Compared with women in the middle quintile, those in the highest 1% of risk had 4.37- and 2.78-fold risks, and those in the lowest 1% of risk had 0.16- and 0.27-fold risks, of developing ER-positive and ER-negative disease, respectively. Goodness-of-fit tests indicated that this PRS was well calibrated and predicts disease risk accurately in the tails of the distribution. This PRS is a powerful and reliable predictor of breast cancer risk that may improve breast cancer prevention programs.NovartisEli Lilly and CompanyAstraZenecaAbbViePfizer UKCelgeneEisaiGenentechMerck Sharp and DohmeRocheCancer Research UKGovernment of CanadaArray BioPharmaGenome CanadaNational Institutes of HealthEuropean CommissionMinistère de l'Économie, de l’Innovation et des Exportations du QuébecSeventh Framework ProgrammeCanadian Institutes of Health Researc

Genome-wide association study identifies 32 novel breast cancer susceptibility loci from overall and subtype-specific analyses.

Breast cancer susceptibility variants frequently show heterogeneity in associations by tumor subtype1-3. To identify novel loci, we performed a genome-wide association study including 133,384 breast cancer cases and 113,789 controls, plus 18,908 BRCA1 mutation carriers (9,414 with breast cancer) of European ancestry, using both standard and novel methodologies that account for underlying tumor heterogeneity by estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 status and tumor grade. We identified 32 novel susceptibility loci (P < 5.0 × 10-8), 15 of which showed evidence for associations with at least one tumor feature (false discovery rate < 0.05). Five loci showed associations (P < 0.05) in opposite directions between luminal and non-luminal subtypes. In silico analyses showed that these five loci contained cell-specific enhancers that differed between normal luminal and basal mammary cells. The genetic correlations between five intrinsic-like subtypes ranged from 0.35 to 0.80. The proportion of genome-wide chip heritability explained by all known susceptibility loci was 54.2% for luminal A-like disease and 37.6% for triple-negative disease. The odds ratios of polygenic risk scores, which included 330 variants, for the highest 1% of quantiles compared with middle quantiles were 5.63 and 3.02 for luminal A-like and triple-negative disease, respectively. These findings provide an improved understanding of genetic predisposition to breast cancer subtypes and will inform the development of subtype-specific polygenic risk scores

A mechanised environment for Frege’s Begriffsschrift notation

Abstract. Frege’s Begriffschrift [3] introduced new levels of sophistication and complexity in logical syntax and its representation; its twodimensional nature has proved a stumbling block for those seeking to understand Frege’s ideas and his system. It is, however, merely a form of abstract syntax for a higher-order predicate logic, with proofs represented linearly and formulae two-dimensionally. Our work concerns the development of a Java and XML-based GUI for the interactive construction of formulae (and, in due course, of proofs) of this system, with output in concrete form such as L ATEX. It is intended to make Frege’s notation more easily used and understood, and to illustrate XML techniques on a seriously challenging and unusual problem. End users will be Frege scholars; we plan to make the system available in due course as a web-based application either publicly or in association with a publisher.

Second set of spaces

This document describes the Gloss infrastructure supporting implementation of location-aware services. The document is in two parts. The first part describes software architecture for the smart space. As described in D8, a local architecture provides a framework for constructing Gloss applications, termed assemblies, that run on individual physical nodes, whereas a global architecture defines an overlay network for linking individual assemblies. The second part outlines the hardware installation for local sensing. This describes the first phase of the installation in Strathclyde University

Second set of spaces

This document describes the Gloss infrastructure supporting implementation of location-aware services. The document is in two parts. The first part describes software architecture for the smart space. As described in D8, a local architecture provides a framework for constructing Gloss applications, termed assemblies, that run on individual physical nodes, whereas a global architecture defines an overlay network for linking individual assemblies. The second part outlines the hardware installation for local sensing. This describes the first phase of the installation in Strathclyde University

Quasi-trial experiences through sensory information on destination websites

Tourism Web sites have unique interactive and multimedia qualities with the potential to create experiences similar to product trial. The purpose of the study is to investigate whether destination Web sites with sounds and sensory descriptions can have a positive impact on consumers’ mental imagery processing, which in turn should enhance quasi-trial experiences. A Web-based experiment is conducted for a fictitious island destination Web site. Empirical results show that sensory descriptions, but not sound, have a positive influence on the extent to which participants experience mental imagery and that the experience of extensive mental imagery leads to greater feelings of virtual presence and, as a result, to stronger attitudes about the destination. Implications for destination Web site design and future research are discussed