Genome-wide association study for radiographic vertebral fractures: A potential role for the 16q24 BMD locus

Vertebral fracture risk is a heritable complex trait. The aim of this study was to identify genetic susceptibility factors for osteoporotic vertebral fractures applying a genome-wide association study (GWAS) approach. The GWAS discovery was based on the Rotterdam Study, a population-based study of elderly Dutch individuals aged >55years; and comprising 329 cases and 2666 controls with radiographic scoring (McCloskey-Kanis) and genetic data. Replication of one top-associated SNP was pursued by de-novo genotyping of 15 independent studies across Europe, the United States, and Australia and one Asian study. Radiographic vertebral fracture assessment was performed using McCloskey-Kanis or Genant semi-quantitative definitions. SNPs were analyzed in relation to vertebral fracture using logistic regression models corrected for age and sex. Fixed effects inverse variance and Han-Eskin alternative random effects meta-analyses were applied. Genome-wide significance was set at p<5×10-8. In the discovery, a SNP (rs11645938) on chromosome 16q24 was associated with the risk for vertebral fractures at p=4.6×10-8. However, the association was not significant across 5720 cases and 21,791 controls from 14 studies. Fixed-effects meta-analysis summary estimate was 1.06 (95% CI: 0.98-1.14; p=0.17), displaying high degree of heterogeneity (I2=57%; Qhet p=0.0006). Under Han-Eskin alternative random effects model the summary effect was significant (p=0.0005). The SNP maps to a region previously found associated with lumbar spine bone mineral density (LS-BMD) in two large meta-analyses from the GEFOS consortium. A false positive association in the GWAS discovery cannot be excluded, yet, the low-powered setting of the discovery and replication settings (appropriate to identify risk effect size >1.25) may still be consistent with an effect size <1.10, more of the type expected in complex traits. Larger effort in studies with standardized phenotype definitions is needed to confirm or reject the involvement of this locus on the risk for vertebral fractures.

Common variants in the HLA-DRB1-HLA-DQA1 HLA class II region are associated with susceptibility to visceral leishmaniasis

To identify susceptibility loci for visceral leishmaniasis, we undertook genome-wide association studies in two populations: 989 cases and 1,089 controls from India and 357 cases in 308 Brazilian families (1,970 individuals). The HLA-DRB1-HLA-DQA1 locus was the only region to show strong evidence of association in both populations. Replication at this region was undertaken in a second Indian population comprising 941 cases and 990 controls, and combined analysis across the three cohorts for rs9271858 at this locus showed P combined = 2.76 × 10 -17 and odds ratio (OR) = 1.41, 95% confidence interval (CI) = 1.30-1.52. A conditional analysis provided evidence for multiple associations within the HLA-DRB1-HLA-DQA1 region, and a model in which risk differed between three groups of haplotypes better explained the signal and was significant in the Indian discovery and replication cohorts. In conclusion, the HLA-DRB1-HLA-DQA1 HLA class II region contributes to visceral leishmaniasis susceptibility in India and Brazil, suggesting shared genetic risk factors for visceral leishmaniasis that cross the epidemiological divides of geography and parasite species. © 2013 Nature America, Inc. All rights reserved.

High-resolution SNP microarray investigation of copy number variations on chromosome 18 in a control cohort

Copy number variations (CNVs) as described in the healthy population are purported to contribute significantly to genetic heterogeneity. Recent studies have described CNVs using lymphoblastoid cell lines or by application of specifically developed algorithms to interrogate previously described data. However, the full extent of CNVs remains unclear. Using high-density SNP array, we have undertaken a comprehensive investigation of chromosome 18 for CNV discovery and characterisation of distribution and association with chromosome architecture. We identified 399 CNVs, of which loss represents 98%, 58% are less than 2.5 kb in size and 71% are intergenic. Intronic deletions account for the majority of copy number changes with gene involvement. Furthermore, one-third of CNVs do not have putative breakpoints within repetitive sequences. We conclude that replicative processes, mediated either by repetitive elements or microhomology, account for the majority of CNVs in the healthy population. Genomic instability involving the formation of a non-B structure is demonstrated in one region.

Constructing a traditional Chinese medicine data warehouse application

The explosive growth in the development of Traditional Chinese Medicine (TCM) has resulted in the continued increase in clinical and research data. The lack of standardised terminology, flaws in data quality planning and management of TCM informatics are preventing clinical decision-making, drug discovery and education. This paper argues that the introduction of data warehousing technologies to enhance the effectiveness and durability in TCM is paramount. To showcase the role of data warehousing in the improvement of TCM, this paper presents a practical model for data warehousing with detailed explanation, which is based on the structured electronic records, for TCM clinical researches and medical knowledge discovery.

Terra Incognita: A symbolic mythical journey

This practice-led project is implemented in the context of rites of passage based on significant events in formative transitions of Self. It employs an intuitive methodology to examine and explore the 'Child archetype', mythos, symbolic imagination and self-narrative, through the manifestation of a visual symbolic language. The contexts, methods and processes enable empowerment, heightened awareness of personal and collective relationships, meaningful discovery and development of innovative ideas and forms. The implications for this project highlight the importance of intuition in creativity and innovation. Creative practice is a vehicle for personal and collective interconnectedness. I have discovered self-empowerment, meaningful learning and innovative forms of personal and collective communication as a way of enabling transition of a significant life event.

The Role of the Law in Communicating Patient Safety

This chapter considers the role of the law in communicating patient safety. Downie, Lahey, Ford, et al’s (2006) preventing, knowing and responding theoretical framework is adopted to classify the different elements of patient safety law. Rather than setting out all relevant patient safety laws in detail, this chapter highlights key legal strategies which are employed to: prevent the occurrence of patient safety incidents (preventing); support the discovery and open discussion of patient safety incidents when they do occur (knowing),; and guide responses after they occur (responding) (Downie, Lahey, Ford, et al 2006). The law is increasingly being invoked to facilitate open discussion of and communication surrounding patient safety. After highlighting some legal strategies used to communicate patient safety, two practice examples are presented. The practice examples highlight different aspects of patient safety law and are indicative of communication issues commonly faced in practice. The first practice example focuses on the role of the Ccoroner in communicating patient safety. This example highlights the investigative role of the law in relation to patient safety (knowing). It also showcases the preventing responding and preventing elements in respect of the significant number of communication errors that can occur in a multi-disciplinary, networked health system. The main focus of the second practice example is responding example illustrates how the law responds to health service providers’ and professionals’ miscommunication (and subsequent incidents) during treatment, however it also touches upon knowing and preventing.

Designing innovative business models with a framework that promotes experimentation

Purpose – Business models to date have remained the creation of management, however, it is the belief of the authors that designers should be critically approaching, challenging and creating new business models as part of their practice. This belief portrays a new era where business model constructs become the new design brief of the future and fuel design and innovation to work together at the strategic level of an organisation. Design/methodology/approach – The purpose of this paper is to explore and investigate business model design. The research followed a deductive structured qualitative content analysis approach utilizing a predetermined categorization matrix. The analysis of forty business cases uncovered commonalities of key strategic drivers behind these innovative business models. Findings – Five business model typologies were derived from this content analysis, from which quick prototypes of new business models can be created. Research limitations/implications – Implications from this research suggest there is no “one right” model, but rather through experimentation, the generation of many unique and diverse concepts can result in greater possibilities for future innovation and sustained competitive advantage. Originality/value – This paper builds upon the emerging research and exploration into the importance and relevance of dynamic, design-driven approaches to the creation of innovative business models. These models aim to synthesize knowledge gained from real world examples into a tangible, accessible and provoking framework that provide new prototyping templates to aid the process of business model experimentation.

Distributed Robotic Vision as a service

The vision sense of standalone robots is limited by line of sight and onboard camera capabilities, but processing video from remote cameras puts a high computational burden on robots. This paper describes the Distributed Robotic Vision Service, DRVS, which implements an on-demand distributed visual object detection service. Robots specify visual information requirements in terms of regions of interest and object detection algorithms. DRVS dynamically distributes the object detection computation to remote vision systems with processing capabilities, and the robots receive high-level object detection information. DRVS relieves robots of managing sensor discovery and reduces data transmission compared to image sharing models of distributed vision. Navigating a sensorless robot from remote vision systems is demonstrated in simulation as a proof of concept.

Developing an evolutionary/ecological approach in enterprise education

This paper presents an ecological/evolutionary approach to enterprise education. Ecological approaches are used at the University of Tasmania to heighten the awareness of students to a raft of difficult to observe environmental factors associated with developing enterprising ideas. At Sheffield University, the discovery and exploitation of entrepreneurial opportunities is viewed as a co-evolving system of emerging business ideas, and routines/heuristics respectively. It is argued that using both approaches enables students to develop a greater awareness of their situated environment, and ultimately the degree of fit between their learning process and a changing external world. The authors argue that in order to improve the chances of longer-term survival what is needed is a new level of organisation where the individual is capable of developing a representation of the external world that he or she can use to sense the appropriateness of local decisions. This reinterpretation of events allows individuals to step back and examine the broader consequences of their actions through the interpretation and anticipation of feedback from the environment. These approaches thus seek to develop practice-based heuristics which individuals can use to make sense of their lived experiences, as they learn to evolve in an increasingly complex world.

The student business plan: Useful or not?

This article offers a critical discussion of the role of the business plan in current enterprise educational practice. In addition to reviewing recent work that considers the ‘for’ and ‘against’ arguments about the use of business plans in higher education, the authors suggest that the context of student learning is largely omitted from these discussions. As such, they contextualize the debate so that the purpose of the business plan can be better appreciated. They build on recent work that offers alternatives to the business plan – approaches directly focused on customer discovery and explicit testing of assumptions. In doing so, recent concerns about the value of business plans and, conversely, the views of those who argue in favour of the role of business plans in enterprise education, are noted. The article provides insights into emerging alternative practices in the field of enterprise education, practices based on students’ use of such education as a vehicle for skills and knowledge development and/or wealth creation. It is acknowledged that various biases are present in the current debate, including those of the present authors: whilst it is accepted that these biases are unlikely to disappear, the article contextualizes their origins.