Genome-wide association study identifies eight loci associated with blood pressure

Elevated blood pressure is a common, heritable cause of cardiovascular disease worldwide. To date, identification of common genetic variants influencing blood pressure has proven challenging. We tested 2.5 million genotyped and imputed SNPs for association with systolic and diastolic blood pressure in 34,433 subjects of European ancestry from the Global BPgen consortium and followed up findings with direct genotyping (N 71,225 European ancestry, N 12,889 Indian Asian ancestry) and in silico comparison (CHARGE consortium, N = 29,136). We identified association between systolic or diastolic blood pressure and common variants in eight regions near the CYP17A1 (P = 7 × 10 24), CYP1A2 (P = 1 × 10 23), FGF5 (P = 1 × 10 21), SH2B3 (P = 3 × 10 18), MTHFR (P = 2 × 10 13), c10orf107 (P = 1 × 10 9), ZNF652 (P = 5 × 10 9) and PLCD3 (P = 1 × 10 8) genes. All variants associated with continuous blood pressure were associated with dichotomous hypertension. These associations between common variants and blood pressure and hypertension offer mechanistic insights into the regulation of blood pressure and may point to novel targets for interventions to prevent cardiovascular disease.

Association scan of 14,500 nonsynonymous SNPs in four diseases identifies autoimmunity variants

We have genotyped 14,436 nonsynonymous SNPs (nsSNPs) and 897 major histocompatibility complex (MHC) tag SNPs from 1,000 independent cases of ankylosing spondylitis (AS), autoimmune thyroid disease (AITD), multiple sclerosis (MS) and breast cancer (BC). Comparing these data against a common control dataset derived from 1,500 randomly selected healthy British individuals, we report initial association and independent replication in a North American sample of two new loci related to ankylosing spondylitis, ARTS1 and IL23R, and confirmation of the previously reported association of AITD with TSHR and FCRL3. These findings, enabled in part by increased statistical power resulting from the expansion of the control reference group to include individuals from the other disease groups, highlight notable new possibilities for autoimmune regulation and suggest that IL23R may be a common susceptibility factor for the major 'seronegative' diseases.

Localization of type 1 diabetes susceptibility to the MHC class I genes HLA-B and HLA-A

The major histocompatibility complex (MHC) on chromosome 6 is associated with susceptibility to more common diseases than any other region of the human genome, including almost all disorders classified as autoimmune. In type 1 diabetes the major genetic susceptibility determinants have been mapped to the MHC class II genes HLA-DQB1 and HLA-DRB1 (refs 1–3), but these genes cannot completely explain the association between type 1 diabetes and the MHC region4, 5, 6, 7, 8, 9, 10, 11. Owing to the region's extreme gene density, the multiplicity of disease-associated alleles, strong associations between alleles, limited genotyping capability, and inadequate statistical approaches and sample sizes, which, and how many, loci within the MHC determine susceptibility remains unclear. Here, in several large type 1 diabetes data sets, we analyse a combined total of 1,729 polymorphisms, and apply statistical methods—recursive partitioning and regression...

John Frazer

John Frazer, Professor, trained at the Architectural Association, taught first at Cambridge University and then the AA in the 1970s and again in the '90s. He was Head of School of Design Research History and Criticism at the University of Ulster in the 1980s, he also ran a systems and design consultancy with his wife Julia (including projects for Cedric Price and Walter Segal) and was founder and chairman of Autographics software. He is currently Swire Chair Professor and Head of School of Design in Hong Kong.----- This is a very personal perspective on a concept of universal and future significance. It is personal, both is the sense that it is an unashamedly biased view of both the significance of the project, and the nature of that significance and because the author was personally involved as one of the consultants on GENERATOR and subsequently involved Cedric Price in its educational application at the Architectural Association. GENERATOR is still very much alive and was still developing whilst this chapter was being written.

Concerning the house museum and the picturesque landscape in the work of Sir John Soane : with raw hints for post-heritage museum space

The picturesque aesthetic in the work of Sir John Soane, architect and collector, resonates in the major work of his very personal practice – the development of his house museum, now the Soane Museum in Lincoln’s Inn Fields in London. Soane was actively involved with the debates, practices and proponents of picturesque and classical practices in architecture and landscape and his lectures reveal these influences in the making of The Soane, which was built to contain and present diverse collections of classical and contemporary art and architecture alongside scavenged curiosities. The Soane Museum has been described as a picturesque landscape, where a pictorial style, together with a carefully defined itinerary, has resulted in the ‘apotheosis of the Picturesque interior’. Soane also experimented with making mock ruinscapes within gardens, which led him to construct faux architectures alluding to archaeological practices based upon the ruin and the fragment. These ideas framed the making of interior landscapes expressed through spatial juxtapositions of room and corridor furnished with the collected object that characterise The Soane Museum. This paper is a personal journey through the Museum which describes and then reviews aspects of Soane’s work in the context of contemporary theories on ‘new’ museology. It describes the underpinning picturesque practices that Soane employed to exceed the boundaries between interior and exterior landscapes and the collection. It then applies particular picturesque principles drawn from visiting The Soane to a speculative project for a house/landscape museum for the Oratunga historic property in outback South Australia, where the often, normalising effects of conservation practices are reviewed using minimal architectural intervention through a celebration of ruinous states.

"Over The Hill" is not so far away : crossing teaching contexts to create benefits for all through rural teaching experiences.

Attracting and retaining quality teachers to rural and remote areas has been a challenge over the last decade. Many preservice teachers are reluctant to experience a rural and remote practicum and may not consider applying to teach in such areas when they graduate. Education departments and universities need to explore innovative ways that will encourage graduates to consider undertaking a teaching position in the bush. As a way forward, preservice teachers from a regional campus of a Queensland University were invited to participate in a six-day rural experience entitled ‘Over the Hill’ that included being billeted with local families, participating in community activities and observing and teaching in classrooms. Fifteen preservice teachers were accompanied by two university academics who returned to work in a classroom as teacher for their own rural and remote professional experience. The aim of this qualitative study was to explore and describe the perceptions of a rural and remote teaching experience from the perspectives of the preservice teachers, the accompanying academics and the school staff hosting the program. Data were collected from the preservice teachers and accompanying academics in the form of written reflections while fourteen school staff completed a related questionnaire. The results indicated that a six-day rural and remote teaching program can provide professional benefits for all involved, preservice teachers, accompanying academics and the school staff hosting the program. Indeed, this study indicates that short experiences such as “Over the Hill” not only assist preservice teachers to make informed decisions about teaching in rural and remote areas but can provide professional benefits for accompanying academics and the schools.

QoS-Based Web Service Scheduling Accommodating Inter-Service Dependencies Using Minimal-Conflict Hill-Climbing Repair Genetic Algorithm

In the filed of semantic grid, QoS-based Web service scheduling for workflow optimization is an important problem.However, in semantic and service rich environment like semantic grid, the emergence of context constraints on Web services is very common making the scheduling consider not only quality properties of Web services, but also inter service dependencies which are formed due to the context constraints imposed on Web services. In this paper, we present a repair genetic algorithm, namely minimal-conflict hill-climbing repair genetic algorithm, to address scheduling optimization problems in workflow applications in the presence of domain constraints and inter service dependencies. Experimental results demonstrate the scalability and effectiveness of the genetic algorithm.

Art, popular culture and cultural policy: variations on a theme of John Carey

The article presents a criticism of the accounts of John Carey in his book entitled "The Intellectuals and the Masses." The author focuses on Carey's argument that the art is not an eternal category but an invention of the late eighteenth century and it no longer has any intellectual legitimacy other than that of provoking feelings which are no more and no less valuable than those provoked by any other form of entertainment or physical activity

Does the summative assessment of real world learning using criterion-referenced assessment need to be discipline specific?

This paper synthesises the existing literature on the contemporary conception of ‘real world’ and compares it with similar notions such as ‘authentic’ and ‘work integrated learning’. While the term ‘real world’ may be partly dependent on the discipline, it does not necessarily follow that the criterion-referenced assessment of ‘real world’ assessment must involve criteria and performance descriptors that are discipline specific. Two examples of summative assessment (court report and trial process exercise) from a final year core subject at the Queensland University of Technology, LWB432 Evidence, emphasise real world learning, are authentic, innovative and better prepare students for the transition into the workplace than more generic forms of assessment such as tutorial participation or oral presentations. The court report requires students to attend a criminal trial in a Queensland Court and complete a two page report on what they saw in practice compared with what they learned in the classroom. The trial process exercise is a 50 minute written closed book activity conducted in tutorials, where students plan questions that they would ask their witness in examination-in-chief, plan questions that they would ask their opponent’s witness in cross-examination, plan questions that they would ask in reexamination given what their opponent asked in cross-examination, and prepare written objections to their opponent’s questions. The trial process exercise simulates the real world, whereas the court report involves observing the real world, and both assessment items are important to the role of counsel. The design of the criterion-referenced assessment rubrics for the court report and trial process exercise is justified by the literature. Notably, the criteria and performance descriptors are not necessarily law specific and this paper highlights the parts that may be easily transferred to other disciplines.