Atomic resolution of dielectric with low temperature coefficient

Ba(6-3x)Nd(8+2x)Ti(18)O(54) (BNTl14) is a high permittivity dielectric with low temperature coefficient (Tcf). Low coefficient of change of dielectric permittivity with temperature (Tcf) is an unusual materials property. The research is aimed at discovering how atomic structure relates to temperature coefficient. Sub-Ångström scanning transmission electron microscopy (STEM) is used to measure mixed occupancy of Nd and Ba in atomic columns. It was expected that phase separation would occur to accommodate mixing of dissimilar ions. However no evidence of phase separation was found. There is a good image match between experiment and high angle annular dark field (HAADF) simulation. Vacancies and excess Ba ions appear to be randomly arranged on the available sites which would result in distortion of TiO6 octahedra. The low Tcf may arise from TiO6 distortion.

A holistic, institution-wide approach to building sessional staff capacity

Sessional Academics enhance students’ learning experience by bringing a diverse range of perspectives and expertise into the classroom. As industry specialists, research students, and recent graduates who have excelled in their courses, they complement the discipline expertise of career academics. With increasing casualization of the academic workforce, Sessional Academics now deliver the majority of face-to-face undergraduate teaching in Australian Universities. To enable them to realize their full potential as effective contributors to student learning and course quality, universities need to offer effective training and access to advice and support and facilitate engagement in university life. However, in the face of complex and diverse contexts, overwhelming numbers, and the transitory nature of sessional cohorts, few universities have developed a comprehensive, systematic approach. During the past three years at QUT, we have set out to develop a multifaceted approach to Sessional Academic support and development. In this paper I will explain why and how we have done so, and describe the range of strategies and programs we have developed. They include a central academic development program, which is structured and scaffolded with learning objectives and outcomes, and aligned with a graduate certificate in Academic Practice; a Sessional Academic Success program, which deploys experienced, school-based sessional academic success advisors to provide local support, build a sense of community, and offer discipline focused academic development; an online, dialogic communication strategy; and opportunities to present and be acknowledged for good learning and teaching practices. Together, these strategies have impacted on sessional academics’ confidence, learning and teaching capacity, reflection and engagement.

Genome-wide association study for sight-threatening diabetic retinopathy reveals association with genetic variation near the GRB2 gene

Aims/hypothesis Diabetic retinopathy is a serious complication of diabetes mellitus and can lead to blindness. A genetic component, in addition to traditional risk factors, has been well described although strong genetic factors have not yet been identified. Here, we aimed to identify novel genetic risk factors for sight-threatening diabetic retinopathy using a genome-wide association study. Methods Retinopathy was assessed in white Australians with type 2 diabetes mellitus. Genome-wide association analysis was conducted for comparison of cases of sight-threatening diabetic retinopathy (n = 336) with diabetic controls with no retinopathy (n = 508). Top ranking single nucleotide polymorphisms were typed in a type 2 diabetes replication cohort, a type 1 diabetes cohort and an Indian type 2 cohort. A mouse model of proliferative retinopathy was used to assess differential expression of the nearby candidate gene GRB2 by immunohistochemistry and quantitative western blot. Results The top ranked variant was rs3805931 with p = 2.66 × 10−7, but no association was found in the replication cohort. Only rs9896052 (p = 6.55 × 10−5) was associated with sight-threatening diabetic retinopathy in both the type 2 (p = 0.035) and the type 1 (p = 0.041) replication cohorts, as well as in the Indian cohort (p = 0.016). The study-wide meta-analysis reached genome-wide significance (p = 4.15 × 10−8). The GRB2 gene is located downstream of this variant and a mouse model of retinopathy showed increased GRB2 expression in the retina. Conclusions/interpretation Genetic variation near GRB2 on chromosome 17q25.1 is associated with sight-threatening diabetic retinopathy. Several genes in this region are promising candidates and in particular GRB2 is upregulated during retinal stress and neovascularisation.

Genetic determinants of heel bone properties: Genome-wide association meta-analysis and replication in the GEFOS/GENOMOS consortium

Quantitative ultrasound of the heel captures heel bone properties that independently predict fracture risk and, with bone mineral density (BMD) assessed by X-ray (DXA), may be convenient alternatives for evaluating osteoporosis and fracture risk. We performed a meta-analysis of genome-wide association (GWA) studies to assess the genetic determinants of heel broadband ultrasound attenuation (BUA; n 5 14 260), velocity of sound (VOS; n 5 15 514) and BMD (n 5 4566) in 13 discovery cohorts. Independent replication involved seven cohorts with GWA data (in silico n 5 11 452) and new genotyping in 15 cohorts (de novo n 5 24 902). In combined random effects, meta-analysis of the discovery and replication cohorts, nine single nucleotide polymorphisms (SNPs) had genome-wide significant (P < 5 3 108) associations with heel bone properties. Alongside SNPs within or near previously identified osteoporosis susceptibility genes including ESR1 (6q25.1: rs4869739, rs3020331, rs2982552), SPTBN1 (2p16.2: rs11898505), RSPO3 (6q22.33: rs7741021), WNT16 (7q31.31: rs2908007), DKK1 (10q21.1: rs7902708) and GPATCH1 (19q13.11: rs10416265), we identified a new locus on chromosome 11q14.2 (rs597319 close to TMEM135, a gene recently linked to osteoblastogenesis and longevity) significantly associated with both BUA and VOS (P < 8.23 3 1014). In meta-analyses involving 25 cohorts with up to 14 985 fracture cases, six of 10 SNPs associated with heel bone properties at P < 5 3 106 also had the expected direction of association with any fracture (P < 0.05), including threeSNPswithP < 0.005: 6q22.33 (rs7741021), 7q31.31 (rs2908007) and 10q21.1 (rs7902708). In conclusion, thisGWAstudy reveals the effect of several genescommon to central DXA-derivedBMDand heel ultrasound/DXAmeasures and points to anewgenetic locus with potential implications for better understanding of osteoporosis pathophysiology.

Utility of temporal artery biopsy samples for genome-wide analysis of giant cell arteritis

Giant Cell Arteritis (GCA) is the most common vasculitis affecting the elderly. Archived formalin-fixed paraffin-embedded (FFPE) temporal artery biopsy (TAB) specimens potentially represent a valuable resource for large-scale genetic analysis of this disease. FFPE TAB samples were obtained from 12 patients with GCA. Extracted TAB DNA was assessed by real time PCR before restoration using the Illumina HD FFPE Restore Kit. Paired FFPE-blood samples were genotyped on the Illumina OmniExpress FFPE microarray. The FFPE samples that passed stringent quality control measures had a mean genotyping success of >97%. When compared with their matching peripheral blood DNA, the mean discordant heterozygote and homozygote single nucleotide polymorphisms calls were 0.0028 and 0.0003, respectively, which is within the accepted tolerance of reproducibility. This work demonstrates that it is possible to successfully obtain high-quality microarray-based genotypes FFPE TAB samples and that this data is similar to that obtained from peripheral blood.

Community uses of co-creative media digital storytelling and co-creative Media: The role of community arts and media in propagating and coordinating population-wide creative practice

How is creative expression and communication extended among whole populations? What is the social and cultural value of this activity? What roles do formal agencies, community-based organisations and content producer networks play? Specifically, how do participatory media and arts projects and networks contribute to building this capacity in the contemporary communications environment? The latest issue of CSJ article in a special issue on “Broadening Digital Storytelling Horizons” edited by Burcu Simsek.

Making an IMPACT: Campus-wide collaboration for course and learning space transformation

At Purdue University, the Libraries participate in a provost-initiated, campus-wide course redesign program called Instruction Matters: Purdue Academic Course Transformation (IMPACT). This initiative aims to bring active-learning to foundational courses traditionally taught through lectures. Purdue librarians recognized the IMPACT initiative as one way to enter the conversations blooming on our campus about the nature of learning, curriculum design, and how space design impacts potential learning. This article presents three perspectives: 1) the information literacy coordinator, 2) a libraries’ administrator with a gift for space planning, and; 3) an in-the-trenches liaison to course redesign projects. Each discusses the IMPACT initiative from his or her unique perspective and view of its impact on librarian roles. Collectively, the article explains why we think it is essential that this kind of campus effort is supported by libraries.

Genome-wide association analysis identifies 11 risk variants associated with the asthma with hay fever phenotype

Background To date, no genome-wide association study (GWAS) has considered the combined phenotype of asthma with hay fever. Previous analyses of family data from the Tasmanian Longitudinal Health Study provide evidence that this phenotype has a stronger genetic cause than asthma without hay fever. Objective We sought to perform a GWAS of asthma with hay fever to identify variants associated with having both diseases. Methods We performed a meta-analysis of GWASs comparing persons with both physician-diagnosed asthma and hay fever (n = 6,685) with persons with neither disease (n = 14,091). Results At genome-wide significance, we identified 11 independent variants associated with the risk of having asthma with hay fever, including 2 associations reaching this level of significance with allergic disease for the first time: ZBTB10 (rs7009110; odds ratio [OR], 1.14; P = 4 × 10−9) and CLEC16A (rs62026376; OR, 1.17; P = 1 × 10−8). The rs62026376:C allele associated with increased asthma with hay fever risk has been found to be associated also with decreased expression of the nearby DEXI gene in monocytes. The 11 variants were associated with the risk of asthma and hay fever separately, but the estimated associations with the individual phenotypes were weaker than with the combined asthma with hay fever phenotype. A variant near LRRC32 was a stronger risk factor for hay fever than for asthma, whereas the reverse was observed for variants in/near GSDMA and TSLP. Single nucleotide polymorphisms with suggestive evidence for association with asthma with hay fever risk included rs41295115 near IL2RA (OR, 1.28; P = 5 × 10−7) and rs76043829 in TNS1 (OR, 1.23; P = 2 × 10−6). Conclusion By focusing on the combined phenotype of asthma with hay fever, variants associated with the risk of allergic disease can be identified with greater efficiency.

Meta-analysis of genome-wide studies identifies MEF2C SNPs associated with bone mineral density at forearm

Background Forearm fractures affect 1.7 million individuals worldwide each year and most occur earlier in life than hip fractures. While the heritability of forearm bone mineral density (BMD) and fracture is high, their genetic determinants are largely unknown. Aim To identify genetic variants associated with forearm BMD and forearm fractures. Methods BMD at distal radius, measured by dualenergy x-ray absorptiometry, was tested for association with common genetic variants. We conducted a metaanalysis of genome-wide association studies for BMD in 5866 subjects of European descent and then selected the variants for replication in 715 Mexican American samples. Gene-based association was carried out to supplement the single-nucleotide polymorphism (SNP) association test. We then tested the BMD-associated SNPs for association with forearm fracture in 2023 cases and 3740 controls. Results We found that five SNPs in the introns of MEF2C were associated with forearm BMD at a genome-wide significance level (p<5×10-8) in meta-analysis (lead SNP, rs11951031[T] -0.20 SDs per allele, p=9.01×10-9). The gene-based association test suggested an association between MEF2C and forearm BMD ( p=0.003). The association between MEF2C variants and risk of fracture did not achieve statistical significance (SNP rs12521522[A]: OR=1.14 (95% CI 0.92 to 1.35), p=0.14). Meta-analysis also revealed two genome-wide suggestive loci at CTNNA2 and 6q23.2. Conclusions These findings demonstrate that variants at MEF2C were associated with forearm BMD, implicating this gene in the determination of BMD at forearm.

Genome-wide association analysis identifies 13 new risk loci for schizophrenia

Schizophrenia is an idiopathic mental disorder with a heritable component and a substantial public health impact. We conducted a multi-stage genome-wide association study (GWAS) for schizophrenia beginning with a Swedish national sample (5,001 cases and 6,243 controls) followed by meta-Analysis with previous schizophrenia GWAS (8,832 cases and 12,067 controls) and finally by replication of SNPs in 168 genomic regions in independent samples (7,413 cases, 19,762 controls and 581 parent-offspring trios). We identified 22 loci associated at genome-wide significance; 13 of these are new, and 1 was previously implicated in bipolar disorder. Examination of candidate genes at these loci suggests the involvement of neuronal calcium signaling. We estimate that 8,300 independent, mostly common SNPs (95% credible interval of 6,300-10,200 SNPs) contribute to risk for schizophrenia and that these collectively account for at least 32% of the variance in liability. Common genetic variation has an important role in the etiology of schizophrenia, and larger studies will allow more detailed understanding of this disorder.

Genetic insights into common pathways and complex relationships among iImmune-mediated diseases

Shared aetiopathogenic factors among immune-mediated diseases have long been suggested by their co-familiality and co-occurrence, and molecular support has been provided by analysis of human leukocyte antigen (HLA) haplotypes and genome-wide association studies. The interrelationships can now be better appreciated following the genotyping of large immune disease sample sets on a shared SNP array: the 'Immunochip'. Here, we systematically analyse loci shared among major immune-mediated diseases. This reveals that several diseases share multiple susceptibility loci, but there are many nuances. The most associated variant at a given locus frequently differs and, even when shared, the same allele often has opposite associations. Interestingly, risk alleles conferring the largest effect sizes are usually disease-specific. These factors help to explain why early evidence of extensive 'sharing' is not always reflected in epidemiological overlap. © 2013 Macmillan Publishers Limited. All rights reserved.

Comparison of the performance of two commercial genome-wide association study genotyping platforms in Han Chinese samples

Most genome-wide association studies to date have been performed in populations of European descent, but there is increasing interest in expanding these studies to other populations. The performance of genotyping chips in Asian populations is not well established. Therefore, we sought to test the performance of widely used fixed-marker, genome-wide association studies chips in the Han Chinese population. Non-HapMap Chinese samples (n = 396) were genotyped using the Illumina OmniExpress and Affymetrix 6.0 platforms, whereas a subset also were genotyped using the Immunochip. Genotyped markers from the Affymetrix 6.0 and Illumina OmniExpress were used for full genome imputation based on the HapMap 2 JPT+CHB (Japanese from Tokyo, Japan and Chinese from Beijing, China) reference panel. The concordance between markers genotypes for the three platforms was very high whether directly genotyped or genotyped and imputed single nucleotide polymorphisms (SNPs; .99.8% for directly genotyped and .99.5% for genotyped and imputed SNPs, respectively) were compared. The OmniExpress chip data enabled more SNPs to be imputed, particularly SNPs with minor allele frequency .5%. The OmniExpress chip achieved better coverage of HapMap SNPs than the Affymetrix 6.0 chip (73.6% vs. 65.9%, respectively, for minor allele frequency .5%). The Affymetrix 6.0 and Illumina OmniExpress chip have similar genotyping accuracy and provide similar accuracy of imputed SNPs. The OmniExpress chip however provides better coverage of Asian HapMap SNPs, although its coverage of HapMap SNPs is moderate. © 2013 Jiang et al.

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.

Genome-wide association studies

Genome-wide association studies (GWAS) are a powerful hypothesis-free tool for the dissection of susceptibility to common heritable human diseases, including osteoporosis. To date, more than 2000 loci for common human diseases have been identified by GWAS. Success using the GWAS model depends on genetic risk being determined by shared stretches of DNA carried with different frequencies in cases and controls, inherited from ancient ancestors, termed the “common disease–common variant” hypothesis. Not all disease risk is caused by common variants, however, and thus GWAS will not detect all variants involved. Successful GWAS performance requires careful quality control, especially as the effect sizes under study are modest, and there are multiple potential sources of error. Conservative interpretation, use of stringent significance thresholds, and replication in independent cohorts are required to ensure results are robust. Despite these challenging parameters, much has been learnt from GWAS and, as the approach matures and is modified to identify a wider range of variants, significantly more will be learnt about the etiopathogenesis of common diseases such as osteoporosis.

Genome-wide association study to identify genetic determinants of severe asthma

Background: The genetic basis for developing asthma has been extensively studied. However, association studies to date have mostly focused on mild to moderate disease and genetic risk factors for severe asthma remain unclear. Objective: To identify common genetic variants affecting susceptibility to severe asthma. Methods: A genome-wide association study was undertaken in 933 European ancestry individuals with severe asthma based on Global Initiative for Asthma (GINA) criteria 3 or above and 3346 clean controls. After standard quality control measures, the association of 480 889 genotyped single nucleotide polymorphisms (SNPs) was tested. To improve the resolution of the association signals identified, non-genotyped SNPs were imputed in these regions using a dense reference panel of SNP genotypes from the 1000 Genomes Project. Then replication of SNPs of interest was undertaken in a further 231 cases and 1345 controls and a meta-analysis was performed to combine the results across studies. Results: An association was confirmed in subjects with severe asthma of loci previously identified for association with mild to moderate asthma. The strongest evidence was seen for the ORMDL3/GSDMB locus on chromosome 17q12-21 (rs4794820, p=1.03×10 (-8)following meta-analysis) meeting genome-wide significance. Strong evidence was also found for the IL1RL1/IL18R1 locus on 2q12 (rs9807989, p=5.59×10 (-8) following meta-analysis) just below this threshold. No novel loci for susceptibility to severe asthma met strict criteria for genome-wide significance. Conclusions: The largest genome-wide association study of severe asthma to date was carried out and strong evidence found for the association of two previously identified asthma susceptibility loci in patients with severe disease. A number of novel regions with suggestive evidence were also identified warranting further study.