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.

A Phenomic Scan of the Norfolk Island Genetic Isolate Identifies a Major Pleiotropic Effect Locus Associated with Metabolic and Renal Disorder Markers

Multiphenotype genome-wide association studies (GWAS) may reveal pleiotropic genes, which would remain undetected using single phenotype analyses. Analysis of large pedigrees offers the added advantage of more accurately assessing trait heritability, which can help prioritise genetically influenced phenotypes for GWAS analysis. In this study we performed a principal component analysis (PCA), heritability (h2) estimation and pedigree-based GWAS of 37 cardiovascular disease -related phenotypes in 330 related individuals forming a large pedigree from the Norfolk Island genetic isolate. PCA revealed 13 components explaining >75% of the total variance. Nine components yielded statistically significant h2 values ranging from 0.22 to 0.54 (P<0.05). The most heritable component was loaded with 7 phenotypic measures reflecting metabolic and renal dysfunction. A GWAS of this composite phenotype revealed statistically significant associations for 3 adjacent SNPs on chromosome 1p22.2 (P<1x10-8). These SNPs form a 42kb haplotype block and explain 11% of the genetic variance for this renal function phenotype. Replication analysis of the tagging SNP (rs1396315) in an independent US cohort supports the association (P = 0.000011). Blood transcript analysis showed 35 genes were associated with rs1396315 (P<0.05). Gene set enrichment analysis of these genes revealed the most enriched pathway was purine metabolism (P = 0.0015). Overall, our findings provide convincing evidence for a major pleiotropic effect locus on chromosome 1p22.2 influencing risk of renal dysfunction via purine metabolism pathways in the Norfolk Island population. Further studies are now warranted to interrogate the functional relevance of this locus in terms of renal pathology and cardiovascular disease risk.

A genome wide linkage scan for dizygotic twinning in 525 families of mothers of dizygotic twins

BACKGROUND: The tendency to conceive dizygotic (DZ) twins is a complex trait influenced by genetic and environmental factors. To search for new candidate loci for twinning, we conducted a genome-wide linkage scan in 525 families using microsatellite and single nucleotide polymorphism marker panels. METHODS AND RESULTS: Non-parametric linkage analyses, including 523 families containing a total of 1115 mothers of DZ twins (MODZT) from Australia and New Zealand (ANZ) and The Netherlands (NL), produced four linkage peaks above the threshold for suggestive linkage, including a highly suggestive peak at the extreme telomeric end of chromosome 6 with an exponential logarithm of odds \[(exp)LOD] score of 2.813 (P = 0.0002). Since the DZ twinning rate increases steeply with maternal age independent of genetic effects, we also investigated linkage including only families where at least one MODZT gave birth to her first set of twins before the age of 30. These analyses produced a maximum expLOD score of 2.718 (P = 0.0002), largely due to linkage signal from the ANZ cohort, however, ordered subset analyses indicated this result is most likely a chance finding in the combined dataset. Linkage analyses were also performed for two large DZ twinning families from the USA, one of which produced a peak on chromosome 2 in the region of two potential candidate genes. Sequencing of FSHR and FIGLA, along with INHBB in MODZTs from two large NL families with family specific linkage peaks directly over this gene, revealed a potentially functional variant in the 5' untranslated region of FSHR that segregated with the DZ twinning phenotype in the Utah family. CONCLUSION: Our data provide further evidence for complex inheritance of familial DZ twinning.

A genome-wide linkage scan provides evidence for both new and previously reported loci influencing common migraine

Latent class analysis was performed on migraine symptom data collected in a Dutch population sample (N = 12,210, 59% female) in order to obtain empirical groupings of individuals suffering from symptoms of migraine headache. Based on these heritable groupings (h(2) = 0.49, 95% CI: 0.41-0.57) individuals were classified as affected (migrainous headache) or unaffected. Genome-wide linkage analysis was performed using genotype data from 105 families with at least 2 affected siblings. In addition to this primary phenotype, linkage analyses were performed for the individual migraine symptoms. Significance levels, corrected for the analysis of multiple traits, were determined empirically via a novel simulation approach. Suggestive linkage for migrainous headache was found on chromosomes 1 (LOD = 1.63; pointwise P = 0.0031), 13 (LOD = 1.63; P = 0.0031), and 20 (LOD = 1.85; P = 0.0018). Interestingly, the chromosome 1 peak was located close to the ATP1A2 gene, associated with familial hemiplegic migraine type 2 (FHM2). Individual symptom analysis produced a LOD score of 1.97 (P = 0.0013) on chromosome 5 (photo/phonophobia), a LOD score of 2.13 (P = 0.0009) on chromosome 10 (moderate/severe pain intensity) and a near significant LOD score of 3.31 (P = 0.00005) on chromosome 13 (pulsating headache). These peaks were all located near regions previously reported in migraine linkage studies. Our results provide important replication and support for the presence of migraine susceptibility genes within these regions, and further support the utility of an LCA-based phenotyping approach and analysis of individual symptoms in migraine genetic research. Additionally, our novel "2-step" analysis and simulation approach provides a powerful means to investigate linkage to individual trait components.

The anatomical and biomechanical consequences of anterior vertebral stapling for the fusionless correction of scoliosis

Fusionless scoliosis surgery is an emerging treatment for idiopathic scoliosis as it offers theoretical advantages over current forms of treatment. Anterior vertebral stapling using a nitinol staple is one such treatment. Despite increasing interest in this technique, little is known about the effects on the spine following insertion, or the mechanism of action of the staple. The aims of this study were threefold; (1) to measure changes in the bending stiffness of a single motion segment following staple insertion, (2) to describe the forces that occur within the staple during spinal movement, and (3) to describe the anatomical changes that occur following staple insertion. Results suggest that staple insertion consistently decreased stiffness in all directions of motion. An explanation for the finding may be found in the outcomes of the strain gauge testing and micro-CT scan. The strain gauge testing showed that once inserted, the staple tips applied a baseline compressive force to the surrounding trabecular bone and vertebral end-plate. This finding would be consistent with the current belief that the clinical effect of the staples is via unilateral compression of the physis. Interestingly however, as each specimen progressed through the five cycles of each test, the baseline load on the staple tips gradually decreased, implying that the force at the staple tip-bone interface was decreasing. We believe that this was likely occurring as a result of structural damage to the trabecular bone and vertebral end-plate by the staple effectively causing ‘loosening’ of the staple. This hypothesis is further supported by the findings of the micro-CT scan. The pictures depict significant trabecular bone and physeal injury around the staple blades. These results suggest that the current hypothesis that stapling modulates growth through physeal compression may be incorrect, but rather the effect occurs through mechanical disruption of the vertebral growth plate.

Ethnic differences in the BMI-%BF relationships between young Japanese and Australian-Caucasian males living in Australia using dual-energy X-ray absorptiometry

The Body Mass Index (BMI) has been used worldwide as an indicator of fatness. However, the universal cut-off points by the World Health Organisation (WHO) classification may not be appropriate for every ethnic group when consider the relationship with their actual total body fatness(%BF). The application of population-specific classifications to assess BMI may be more relevant to public health. Ethnic differences in the BMI%BF relationship between 45 Japanese and 42 Australian-Caucasian males were assessed using whole body dual-energy X-ray absorptiometry (DXA) scan and anthropometry using a standard protocol. Japanese males had significantly (p<0.05) greater %BF at given BMI values than Australian males. When this is taken into account the newly proposed Asia-Pacific BMI classification of BMI 23 as overweight and 25 as obese may better assess the level of obesity that is associated increased health risks for this population. To clarify the current findings, further studies that compare the relationships across other Japanese populations are recommended.

Addressing Challenges for Internationalisation and Mobility in Engineering Through CDIO Standards

There is a growing need for international transparency of engineering qualifications, and mechanisms to support and facilitate student mobility. In response, there are a number of global initiatives attempting to address these needs, particularly in Europe, North America and Australia. The Conceive-Design-Implement-Operate (CDIO) Initiative has a set of standards, competencies, and proficiency levels developed through a global community of practice. It is a well-structured framework in which best-practice internationalisation and student mobility can be embedded. However, the current 12 CDIO Standards do not address international qualifications or student mobility. Based on an environmental scan of global activities, the underpinning principles of best practice are identified and form the basis of the proposed 13th CDIO Standard — “Internationalization and Mobility”.

Queensland government agency libraries review : literature review

Dr Gillian Hallam is project leader for the Queensland Government Agency Libraries Review. As an initial step in the project, a literature review was commissioned to guide the research activities and inform the development of options for potential future service delivery models for the Government agency libraries. The review presents an environmental scan and review of the professional and academic literature to consider a range of current perspectives on library and information services. Significant in this review is the focus on the specific issues and challenges impacting on contemporary government libraries and their staff. The review incorporates four key areas: current directions in government administration; trends in government library services; issues in contemporary special libraries; and the skills and competencies of special librarians. Rather than representing an exhaustive review, the research has primarily centred on recent journal articles, conference papers, reports and web resources. Commentary prepared by national and international library associations has also played a role informing this review, as does the relevant State and Federal government documentation and reporting.

Blackcloud

The work was derived from terrestrial laser scan data of a bio-diverse landscape on the SE coast of Western Australia. The digital three dimensional scan data has been converged and then a portion of that computer aided design (CAD) file has been captured via ‘screen capture’ to produce Blackcloud.---------- The primary intention behind the production of the work was to expand understanding on the means of representing and then designing for sites in ‘kwongan’ landscapes which are constituted by highly biodiverse, bushfire prone heath vegetation.

Before and after the fire

The work was derived from terrestrial laser scan data of a bio-diverse landscape on the SE coast of Western Australia. The scanning was conducted both before and after a significant bushfire event. The digital three dimensional scan data has been converged and then abstracted into a two dimensional vertical sections or slice which reveals the vegetal surface of heath vegetation and the surface of the landform.---------- This abstraction converts the complex data into spatial information so that it is meaningful in the context the architectural and landscape architectural design process. The primary intention behind the production of the work was to expand understanding on the means of representing and then designing for sites in ‘kwongan’ landscapes which are constituted by highly biodiverse, bushfire prone heath vegetation.

Heathsections

The work was derived from terrestrial laser scan data of a bio-diverse landscape on the SE coast of Western Australia. The three dimensional scan data has been abstracted into two dimensional side sections or slices – in a manner which converts the complex data into spatial information which is meaningful in the context of the act of architectural and landscape architectural design. The primary intention behind the production of the work was to expand understanding on the means of representation of ‘kwongan’ landscapes which are constituted by highly biodiverse - and thus difficult to measure - heath vegetation.

Horizonal

Horizonal was derived from terrestrial laser scan data of a bio-diverse landscape on the SE coast of Western Australia. The digital three dimensional scan data has been converged with geospatial survey of the landform captured through RTKGPS survey technology. Also incorporated into the image is a series of photographs taken using a photogrammetric technique wherein the position and view angle of each photograph is measured relative to a geographic datum point. The primary intention behind the production of the work was to expand understandings on the relationship between scenic photography and geospatial maps of remote, bio-diverse landscapes which are experiencing urban development for the first time.

Heathprint

The work was derived from terrestrial laser scan data of a bio-diverse landscape on the SE coast of Western Australia. The digital three dimensional scan data has been abstracted into two dimensional horizontal sections or slices. This abstraction converts the complex data into spatial information which is meaningful in the context of the act of architectural and landscape architectural design. The primary intention behind the production of the work was to expand understanding on the means of representing and then designing for sites in 'kwongan' landscapes which are constituted by highly biodiverse - and thus difficult to measure - heath vegetation. From Heathprint the author generated contour intervals of the landform upon which an associate (Daniela Simon architect) designed a work of architecture, which subsequently was awarded a commendation for residential architecture in the WA Chapter Australia Institute of Architects awards 2007.

3D lung and rib cage reconstruction using low dose CT scans of adolescent idiopathic scoliosis pre and post anterior thoracoscopic correction

Adolescent Idiopathic Scoliosis (AIS) has been associated with reduced pulmonary function believed to be due to a restriction of lung volume by the deformed thoracic cavity. A recent study by our group examined the changes in lung volume pre and post anterior thoracoscopic scoliosis correction using pulmonary function testing (1), however the anatomical changes in ribcage shape and left/right lung volume after thoracoscopic surgery which govern overall respiratory capacity are unknown. The aim of this study was to use 3D rendering from CT scan data to compare lung and ribcage anatomical changes from pre to two years post thoracoscopic anterior scoliosis correction. The study concluded that 3D volumetric reconstruction from CT scans is a powerful means of evaluating changes in pulmonary and thoracic anatomy following surgical AIS correction. Most likely, lung volume changes following thoracoscopic scoliosis correction are multifactorial and affected by changes in height (due to residual growth), ribcage shape, diaphragm positioning, Cobb angle correction in the thoracic spine. Further analysis of the 3D reconstructions will be performed to assess how each of these factors affect lung volume in this patient cohort.

Comprehensive evaluation of driver gaze pattern using fuzzy rules for driver training

The over representation of novice drivers in crashes is alarming. Research indicates that one in five drivers’ crashes within their first year of driving. Driver training is one of the interventions aimed at decreasing the number of crashes that involve young drivers. Currently, there is a need to develop comprehensive driver evaluation system that benefits from the advances in Driver Assistance Systems. Since driving is dependent on fuzzy inputs from the driver (i.e. approximate distance calculation from the other vehicles, approximate assumption of the other vehicle speed), it is necessary that the evaluation system is based on criteria and rules that handles uncertain and fuzzy characteristics of the drive. This paper presents a system that evaluates the data stream acquired from multiple in-vehicle sensors (acquired from Driver Vehicle Environment-DVE) using fuzzy rules and classifies the driving manoeuvres (i.e. overtake, lane change and turn) as low risk or high risk. The fuzzy rules use parameters such as following distance, frequency of mirror checks, gaze depth and scan area, distance with respect to lanes and excessive acceleration or braking during the manoeuvre to assess risk. The fuzzy rules to estimate risk are designed after analysing the selected driving manoeuvres performed by driver trainers. This paper focuses mainly on the difference in gaze pattern for experienced and novice drivers during the selected manoeuvres. Using this system, trainers of novice drivers would be able to empirically evaluate and give feedback to the novice drivers regarding their driving behaviour.