Genetic architecture of subcortical brain regions: Common and region-specific genetic contributions

Understanding the aetiology of patterns of variation within and covariation across brain regions is key to advancing our understanding of the functional, anatomical and developmental networks of the brain. Here we applied multivariate twin modelling and principal component analysis (PCA) to investigate the genetic architecture of the size of seven subcortical regions (caudate nucleus, thalamus, putamen, pallidum, hippocampus, amygdala and nucleus accumbens) in a genetically informative sample of adolescents and young adults (N=1038; mean age=21.6±3.2years; including 148 monozygotic and 202 dizygotic twin pairs) from the Queensland Twin IMaging (QTIM) study. Our multivariate twin modelling identified a common genetic factor that accounts for all the heritability of intracranial volume (0.88) and a substantial proportion of the heritability of all subcortical structures, particularly those of the thalamus (0.71 out of 0.88), pallidum (0.52 out of 0.75) and putamen (0.43 out of 0.89). In addition, we also found substantial region-specific genetic contributions to the heritability of the hippocampus (0.39 out of 0.79), caudate nucleus (0.46 out of 0.78), amygdala (0.25 out of 0.45) and nucleus accumbens (0.28 out of 0.52). This provides further insight into the extent and organization of subcortical genetic architecture, which includes developmental and general growth pathways, as well as the functional specialization and maturation trajectories that influence each subcortical region. This multivariate twin study identifies a common genetic factor that accounts for all the heritability of intracranial volume (0.88) and a substantial proportion of the heritability of all subcortical structures, particularly those of the thalamus (0.71 out of 0.88), pallidum (0.52 out of 0.75) and putamen (0.43 out of 0.89). In parallel, it also describes substantial region-specific genetic contributions to the heritability of the hippocampus (0.39 out of 0.79), caudate nucleus (0.46 out of 0.78), amygdala (0.25 out of 0.45) and nucleus accumbens (0.28 out of 0.52).

Brain network efficiency and topology depend on the fiber tracking method: 11 tractography algorithms compared in 536 subjects

As connectivity analyses become more popular, claims are often made about how the brain's anatomical networks depend on age, sex, or disease. It is unclear how results depend on tractography methods used to compute fiber networks. We applied 11 tractography methods to high angular resolution diffusion images of the brain (4-Tesla 105-gradient HARDI) from 536 healthy young adults. We parcellated 70 cortical regions, yielding 70×70 connectivity matrices, encoding fiber density. We computed popular graph theory metrics, including network efficiency, and characteristic path lengths. Both metrics were robust to the number of spherical harmonics used to model diffusion (4th-8th order). Age effects were detected only for networks computed with the probabilistic Hough transform method, which excludes smaller fibers. Sex and total brain volume affected networks measured with deterministic, tensor-based fiber tracking but not with the Hough method. Each tractography method includes different fibers, which affects inferences made about the reconstructed networks.

Patterned fen formation and development from the Great Sandy Region, south-east Queensland, Australia

The Great Sandy Region (incorporating Fraser Island and the Cooloola sand-mass), south-east Queensland, contains a significant area of Ramsar-listed coastal wetlands, including the globally important patterned fen complexes. These mires form an elaborate network of pools surrounded by vegetated peat ridges and are the only known subtropical, Southern Hemisphere examples, with wetlands of this type typically located in high northern latitudes. Sedimentological, palynological and charcoal analysis from the Wathumba and Moon Point complexes on Fraser Island indicate two periods of swamp formation (that may contain patterned fens), one commencing at 12 000 years ago (Moon Point) and the other ~4300 years ago (Wathumba). Wetland formation and development is thought to be related to a combination of biological and hydrological processes with the dominant peat-forming rush, Empodisma minus, being an important component of both patterned and non-patterned mires within the region. In contrast to Northern Hemisphere paludifying systems, the patterning appears to initiate at the start of wetland development or as part of an infilling process. The wetlands dominated by E. minus are highly resilient to disturbance, particularly burning and sea level alterations, and appear to form important refuge areas for amphibians, fish and birds (both non-migratory and migratory) over thousands of years.

Making connections within the Asia-Pacific region: Case study around the Mentoring for Effective Teaching (MET) program

University strategic plans emphasise the essential nature of partnerships at national and international levels. Along with establishing collaborative research partnerships, providing professional development to key stakeholders is considered a crucial activity for making and sustaining partnerships. Utilising knowledge from professional development in Australian contexts can be managed creatively for making connections internationally. Indeed, knowledge transfer is a cornerstone for the globalisation of education and needs to occur as a multiplex dialogue between participating countries. This paper presents a qualitative study around the Mentoring for Effective Teaching (MET) program, its growth and development nationally (e.g., scope and impact) along with insights into making connections within the Asia-Pacific region. At a national level, we outline how to facilitate a program though relationship building and face-to-face implementation of professional learning. Internationally, we highlight how to mould and shape Australian professional learning for the Asia-Pacific region, particularly with regard to facilitating fluid interactions within environments outside of Australia. The contexts for the study include a university in Hong Kong and another university in the Philippines. In this presentation, examples will be provided from the MET program to demonstrate contextual differences and similarities for implementation in Australian and Asian contexts. For instance, determining strategies for mentoring pedagogical knowledge can elicit viewpoints that align between cultures (e.g., use of specific teaching and questioning strategies) and also present alternative ideas as a result of cultural differences. We have learnt about having a structured program that draws on the research yet has sufficient flexibility to cater for cultures and contexts. With openmindedness, facilitating professional learning can become a two-way knowledge transfer, where learnings from other cultures and contexts can be refined for advancing programs in Australia.

Interim financial reporting in the Asia-Pacific region

This study examines Interim Financial Reporting disclosure compliance and associated factors for listed firms in Asia-Pacific countries: Australia, Hong Kong, Malaysia, Singapore, the Philippines, Thailand, and Vietnam. Employing disclosure theory (in the context of information economics), with the central premise being that manager' trade-off costs and benefits relating to disclosure, the factors influencing the variation in interim reporting disclosure compliance are examined. Using researcher-constructed disclosure indices and regression modelling, the results reveal significant cross-country variation in interim reporting disclosure compliance, with higher compliance associated with IFRS adoption, audit review, quarterly reporting (rather than six-monthly) and shorter reporting lags.

New graph-based algorithms to efficiently solve large scale open pit mining optimisation problems

In the mining optimisation literature, most researchers focused on two strategic-level and tactical-level open-pit mine optimisation problems, which are respectively termed ultimate pit limit (UPIT) or constrained pit limit (CPIT). However, many researchers indicate that the substantial numbers of variables and constraints in real-world instances (e.g., with 50-1000 thousand blocks) make the CPIT’s mixed integer programming (MIP) model intractable for use. Thus, it becomes a considerable challenge to solve the large scale CPIT instances without relying on exact MIP optimiser as well as the complicated MIP relaxation/decomposition methods. To take this challenge, two new graph-based algorithms based on network flow graph and conjunctive graph theory are developed by taking advantage of problem properties. The performance of our proposed algorithms is validated by testing recent large scale benchmark UPIT and CPIT instances’ datasets of MineLib in 2013. In comparison to best known results from MineLib, it is shown that the proposed algorithms outperform other CPIT solution approaches existing in the literature. The proposed graph-based algorithms leads to a more competent mine scheduling optimisation expert system because the third-party MIP optimiser is no longer indispensable and random neighbourhood search is not necessary.

Visual openness in urban environments: Measuring visual openness and visibility to natural landscapes in a changing urban landscape in Gold Coast, Australia

The visual characteristics of urban environments have been changing dramatically with the growth of cities around the world. Protection and enhancement of landscape character in urban environments have been one of the challenges for policy makers in addressing sustainable urban growth. Visual openness and enclosure in urban environments are important attributes in perception of visual space which affect the human interaction with physical space and which can be often modified by new developments. Measuring visual openness in urban areas results in more accurate, reliable, and systematic approach to manage and control visual qualities in growing cities. Recent advances in techniques in geographic information systems (GIS) and survey systems make it feasible to measure and quantify this attribute with a high degree of realism and precision. Previous studies in this field do not take full advantage of these improvements. This paper proposes a method to measure the visual openness and enclosure in a changing urban landscape in Australia, on the Gold Coast, by using the improved functionality in GIS. Using this method, visual openness is calculated and described for all publicly accessible areas in the selected study area. A final map is produced which shows the areas with highest visual openness and visibility to natural landscape resources. The output of this research can be used by planners and decision-makers in managing and controlling views in complex urban landscapes. Also, depending on the availability of GIS data, this method can be applied to any region including non-urban landscapes to help planners and policy-makers manage views and visual qualities.

Sequential MRI reveals individual level deformities in the growing scoliotic spine that are clinically masked by the Cobb angle

Introduction Clinically, the Cobb angle method measures the overall scoliotic curve in the coronal plane but does not measure individual vertebra and disc wedging. The contributions of the vertebrae and discs in the growing scoliotic spine were measured to investigate coronal plane deformity progression with growth. Methods A 0.49mm isotropic 3D MRI technique was developed to investigate the level-by-level changes that occur in the growing spine of a group of Adolescent Idiopathic Scoliosis (AIS) patients, who received two to four sequential scans (spaced 3-12 months apart). The coronal plane wedge angles of each vertebra and disc in the major curve were measured to capture any changes that occurred during their adolescent growth phase. Results Seventeen patients had at least two scans. Mean patient age was 12.9 years (SD 1.5 years). Sixteen were classified as right-sided major thoracic Lenke Type 1 (one left sided). Mean standing Cobb angle at initial presentation was 31° (SD 12°). Six received two scans, nine three scans and two four scans, with 65% showing a Cobb angle progression of 5° or more between scans. Overall, there was no clear pattern of deformity progression of individual vertebrae and discs, nor between patients who progressed and those who didn’t. There were measurable changes in the wedging of the vertebrae and discs in all patients. In sequential scans, change in direction of wedging was also seen. In several patients there was reverse wedging in the discs that counteracted increased wedging of the vertebrae such that no change in overall Cobb angle was seen. Conclusion Sequential MRI data showed complex patterns of deformity progression. Changes to the wedging of individual vertebrae and discs may occur in patients who have no increase in Cobb angle measure; the Cobb method alone may be insufficient to capture the complex mechanisms of deformity progression.

Sequential MRI of growing scoliotic spines reveals individual level deformities that are clinically masked by the cobb angle

INTRODUCTION. Clinically, the Cobb angle method measures the overall scoliotic curve in the coronal plane but does not measure individual vertebra and disc wedging. The contributions of the vertebrae and discs in the growing scoliotic spine were measured to investigate coronal plane deformity progression with growth. METHODS. A 0.49mm isotropic 3D MRI technique was developed to investigate the level-by-level changes that occur in the growing spine of a group of Adolescent Idiopathic Scoliosis (AIS) patients, who received two to four sequential scans (spaced 3-12 months apart). The coronal plane wedge angles of each vertebra and disc in the major curve were measured to capture any changes that occurred during their adolescent growth phase. RESULTS. Seventeen patients had at least two scans. Mean patient age was 12.9 years (SD 1.5 years). Sixteen were classified as right-sided major thoracic Lenke Type 1 (one left sided). Mean standing Cobb angle at initial presentation was 31° (SD 12°). Six received two scans, nine three scans and two four scans, with 65% showing a Cobb angle progression of 5° or more between scans. Overall, there was no clear pattern of deformity progression of individual vertebrae and discs, nor between patients who progressed and those who didn’t. There were measurable changes in the wedging of the vertebrae and discs in all patients. In sequential scans, change in direction of wedging was also seen. In several patients there was reverse wedging in the discs that counteracted increased wedging of the vertebrae such that no change in overall Cobb angle was seen. CONCLUSION. Sequential MRI data showed complex patterns of deformity progression. Changes to the wedging of individual vertebrae and discs may occur in patients who have no increase in Cobb angle measure; the Cobb method alone may be insufficient to capture the complex mechanisms of deformity progression.

Sequential MRI reveals individual level deformities in the growing scoliotic spine that are not seen clinically by the cobb angle

Clinically, the Cobb angle method measures the overall scoliotic curve in the coronal plane but does not measure individual vertebra and disc wedging. The contributions of the vertebrae and discs in the growing scoliotic spine were measured to investigate coronal plane deformity progression with growth. Sequential MRI data in this project showed complex patterns of deformity progression. Changes to the wedging of individual vertebrae and discs may occur in patients who have no increase in Cobb angle measure; the Cobb method alone may be insufficient to capture the complex mechanisms of deformity progression.

The chromosome 16q region associated with ankylosing spondylitis includes the candidate gene tumour necrosis factor receptor type 1-associated death domain (TRADD)

Objective: To replicate and refine the reported association of ankylosing spondylitis (AS) with two nonsynonymous single nucleotide polymorphisms (nsSNPs) on chromosome 16q22.1. Methods: Firstly, 730 independent UK patients with AS were genotyped for rs9939768 and rs6979 and allele frequencies were compared with 2879 previously typed historic disease controls. Secondly, the two data sets were combined in meta-analyses. Finally, 5 tagging SNPs, located between rs9939768 and rs6979, were analysed in 1604 cases and 1020 controls. Results: The association of rs6979 with AS was replicated, p=0.03, OR=1.14 (95% CI 1.01 to 1.28), and a trend for association with rs9939768 detected, p=0.06, OR=1.25 (95% CI 0.99 to 1.57). Meta-analyses revealed association of both SNPs with AS, p=0.0008, OR=1.31 (95% CI 1.12 to 1.54) and p=0.0009, OR=1.15 (95% CI 1.06 to 1.23) for rs9939768 and rs6979, respectively. New associations with rs9033 and rs868213 (p=0.00002, OR=1.23 (95% CI 1.12 to 1.36) and p=0.00002 OR=1.45 (95% CI 1.22 to 1.72), respectively, were identified. Conclusions: The region on chromosome 16 that has been replicated in the present work is interesting as the highly plausible candidate gene, tumour necrosis factor receptor type 1 (TNFR1)-associated death domain (TRADD), is located between rs9033 and rs868213. It will require additional work to identify the primary genetic association(s) with AS.

Association of sporadic chondrocalcinosis with a -4-basepair G-to-A transition in the 5′-untranslated region of ANKH that promotes enhanced expression of ANKH protein and excess generation of extracellular inorganic pyrophosphate

Objective Certain mutations in ANKH, which encodes a multiple-pass transmembrane protein that regulates inorganic pyrophosphate (PPi) transport, are linked to autosomal-dominant familial chondrocalcinosis. This study investigated the potential for ANKH sequence variants to promote sporadic chondrocalcinosis. Methods ANKH variants identified by genomic sequencing were screened for association with chondrocalcinosis in 128 patients with severe sporadic chondrocalcinosis or pseudogout and in ethnically matched healthy controls. The effects of specific variants on expression of common markers were evaluated by in vitro transcription/translation. The function of these variants was studied in transfected human immortalized CH-8 articular chondrocytes. Results Sporadic chondrocalcinosis was associated with a G-to-A transition in the ANKH 5′-untranslated region (5′-UTR) at 4 bp upstream of the start codon (in homozygotes of the minor allele, genotype relative risk 6.0, P = 0.0006; overall genotype association P = 0.02). This -4-bp transition, as well as 2 mutations previously linked with familial and sporadic chondrocalcinosis (+14 bp C-to-T and C-terminal GAG deletion, respectively), but not the French familial chondrocalcinosis kindred 143-bp T-to-C mutation, increased reticulocyte ANKH transcription/ANKH translation in vitro. Transfection of complementary DNA for both the wild-type ANKH and the -4-bp ANKH protein variant promoted increased extracellular PPi in CH-8 cells, but unexpectedly, these ANKH mutants had divergent effects on the expression of extracellular PPi and the chondrocyte hypertrophy marker, type X collagen. Conclusion A subset of sporadic chondrocalcinosis appears to be heritable via a -4-bp G-to-A ANKH 5′-UTR transition that up-regulates expression of ANKH and extracellular PPi in chondrocyte cells. Distinct ANKH mutations associated with heritable chondrocalcinosis may promote disease by divergent effects on extracellular PPi and chondrocyte hypertrophy, which is likely to mediate differences in the clinical phenotypes and severity of the disease.

New England Youth Speeding Project: A pilot study of young drivers and risky driving: Effective strategies for preventing speeding amongst young Australians aged 16-25 years in the New England Region

Young Australian drivers aged 17 – 25 years are overwhelmingly represented in road fatalities where speed is a factor. In the combined LGAs of Armidale Dumaresq, Guyra, Uralla and Walcha in the 5 years 1999-2003 inclusive, 43% of speeding related casualty crashes involved a young driver aged less than 25 years. This is despite the fact that the 17-25 age group account for only 25% of the driving population in this area. Young male drivers account for the majority of these crashes and also tend to have a higher number of driving offences and accrue more penalties for road traffic offences, especially speeding. By analysing data from questionnaires by male and female participants this research project has been able to evaluate road safety advertisements to determine which ones are most effective to young drivers, what features of these advertisements are effective, how males differ from females in their receptiveness and preferences for road safety advertisements and specifically how to target young people especially young men in conveying road safety messages. Finally this research project has identified factors that are important in the production of media road safety advertisements and has made recommendations for how best to convey effective road safety messages to young Australian drivers in rural areas.

Regional and seasonal variation in airborne grass pollen levels between cities of Australia and New Zealand

Although grass pollen is widely regarded as the major outdoor aeroallergen source in Australia and New Zealand (NZ), no assemblage of airborne pollen data for the region has been previously compiled. Grass pollen count data collected at 14 urban sites in Australia and NZ over periods ranging from 1 to 17 years were acquired, assembled and compared, revealing considerable spatiotemporal variability. Although direct comparison between these data is problematic due to methodological differences between monitoring sites, the following patterns are apparent. Grass pollen seasons tended to have more than one peak from tropics to latitudes of 37°S and single peaks at sites south of this latitude. A longer grass pollen season was therefore found at sites below 37°S, driven by later seasonal end dates for grass growth and flowering. Daily pollen counts increased with latitude; subtropical regions had seasons of both high intensity and long duration. At higher latitude sites, the single springtime grass pollen peak is potentially due to a cooler growing season and a predominance of pollen from C3 grasses. The multiple peaks at lower latitude sites may be due to a warmer season and the predominance of pollen from C4 grasses. Prevalence and duration of seasonal allergies may reflect the differing pollen seasons across Australia and NZ. It must be emphasized that these findings are tentative due to limitations in the available data, reinforcing the need to implement standardized pollen-monitoring methods across Australasia. Furthermore, spatiotemporal differences in grass pollen counts indicate that local, current, standardized pollen monitoring would assist with the management of pollen allergen exposure for patients at risk of allergic rhinitis and asthma. © 2015 Springer Science+Business Media Dordrecht