Discovery and replication of gene influences on brain structure using LASSO regression

We implemented least absolute shrinkage and selection operator (LASSO) regression to evaluate gene effects in genome-wide association studies (GWAS) of brain images, using an MRI-derived temporal lobe volume measure from 729 subjects scanned as part of the Alzheimer's Disease Neuroimaging Initiative (ADNI). Sparse groups of SNPs in individual genes were selected by LASSO, which identifies efficient sets of variants influencing the data. These SNPs were considered jointly when assessing their association with neuroimaging measures. We discovered 22 genes that passed genome-wide significance for influencing temporal lobe volume. This was a substantially greater number of significant genes compared to those found with standard, univariate GWAS. These top genes are all expressed in the brain and include genes previously related to brain function or neuropsychiatric disorders such as MACROD2, SORCS2, GRIN2B, MAGI2, NPAS3, CLSTN2, GABRG3, NRXN3, PRKAG2, GAS7, RBFOX1, ADARB2, CHD4, and CDH13. The top genes we identified with this method also displayed significant and widespread post hoc effects on voxelwise, tensor-based morphometry (TBM) maps of the temporal lobes. The most significantly associated gene was an autism susceptibility gene known as MACROD2.We were able to successfully replicate the effect of the MACROD2 gene in an independent cohort of 564 young, Australian healthy adult twins and siblings scanned with MRI (mean age: 23.8±2.2 SD years). Our approach powerfully complements univariate techniques in detecting influences of genes on the living brain.

A commonly carried genetic variant in the delta opioid receptor gene, OPRD1, is associated with smaller regional brain volumes: Replication in elderly and young populations

Delta opioid receptors are implicated in a variety of psychiatric and neurological disorders. These receptors play a key role in the reinforcing properties of drugs of abuse, and polymorphisms in OPRD1 (the gene encoding delta opioid receptors) are associated with drug addiction. Delta opioid receptors are also involved in protecting neurons against hypoxic and ischemic stress. Here, we first examined a large sample of 738 elderly participants with neuroimaging and genetic data from the Alzheimer's Disease Neuroimaging Initiative. We hypothesized that common variants in OPRD1 would be associated with differences in brain structure, particularly in regions relevant to addictive and neurodegenerative disorders. One very common variant (rs678849) predicted differences in regional brain volumes. We replicated the association of this single-nucleotide polymorphism with regional tissue volumes in a large sample of young participants in the Queensland Twin Imaging study. Although the same allele was associated with reduced volumes in both cohorts, the brain regions affected differed between the two samples. In healthy elderly, exploratory analyses suggested that the genotype associated with reduced brain volumes in both cohorts may also predict cerebrospinal fluid levels of neurodegenerative biomarkers, but this requires confirmation. If opiate receptor genetic variants are related to individual differences in brain structure, genotyping of these variants may be helpful when designing clinical trials targeting delta opioid receptors to treat neurological disorders.

Discovery and replication of dopamine-related gene effects on caudate volume in young and elderly populations (N1198) using genome-wide search

The caudate is a subcortical brain structure implicated in many common neurological and psychiatric disorders. To identify specific genes associated with variations in caudate volume, structural magnetic resonance imaging and genome-wide genotypes were acquired from two large cohorts, the Alzheimer's Disease NeuroImaging Initiative (ADNI; N=734) and the Brisbane Adolescent/Young Adult Longitudinal Twin Study (BLTS; N=464). In a preliminary analysis of heritability, around 90% of the variation in caudate volume was due to genetic factors. We then conducted genome-wide association to find common variants that contribute to this relatively high heritability. Replicated genetic association was found for the right caudate volume at single-nucleotide polymorphism rs163030 in the ADNI discovery sample (P=2.36 × 10 -6) and in the BLTS replication sample (P=0.012). This genetic variation accounted for 2.79 and 1.61% of the trait variance, respectively. The peak of association was found in and around two genes, WDR41 and PDE8B, involved in dopamine signaling and development. In addition, a previously identified mutation in PDE8B causes a rare autosomal-dominant type of striatal degeneration. Searching across both samples offers a rigorous way to screen for genes consistently influencing brain structure at different stages of life. Variants identified here may be relevant to common disorders affecting the caudate.

'Create a better online you': Designing online learning resources to develop undergraduate social media skills

‘Create a Better Online You’ (CBOY) is an emerging initiative from QUT Library. CBOY focusses on developing the social media skills of undergraduates at QUT. While many students will have encountered ‘cybersafety’ training in primary or secondary school, a comprehensive environmental scan revealed little in the way of social media resources targeted at undergraduates. In particular, there was little to no focus on the ways in which social media could be used strategically to develop a positive online reputation and enhance chances of employability post tertiary education. The resources created as part of CBOY are the result of a literature review, environmental scan, and discussions with staff and students at QUT. Following the comprehensive environmental scan, it appears that CBOY represents one of the first free, openly accessible, interactive resources targeting the social media skills of undergraduates.

Implementing a holistic process for embedding sustainability: A case study in first year engineering, Monash University, Australia

While there is clear recognition of the need to incorporate sustainable development into university curricula, there is limited research that examines how to achieve that integration or evaluates its impacts on student learning. This paper responds to these knowledge gaps through a case study of curriculum renewal that involved embedding sustainability into a first year engineering curriculum. The initiative was guided by a deliberative and dynamic model for curriculum renewal that brought together internal and external stakeholders through a structured sequence of facilitated workshops and meetings. That process identified sustainability-related knowledge and skills relevant for first year engineering, and faculty members teaching in the first year program were guided through a process of curriculum renewal to meet those needs. The process through which the whole of curriculum renewal was undertaken is innovative and provides a case study of precedent in the field of education for sustainability. The study demonstrates the contribution that can be made by a web-based sustainability portal in supporting curriculum renewal. Learning and teaching outcomes were evaluated through ‘before and after surveys’ of the first year engineering students. Statistically significant increases in student's self-reported knowledge of sustainability were measured as a result of exposure to the renewed first year curriculum and this confirmed the value of the initiative in terms of enhancing student learning. While applied in this case to engineering, the process to achieve integration of sustainability into the curriculum approach is likely to have value for other academic disciplines. Considering student performance on assignments and exam questions relating to sustainability would provide a stronger basis for future research to understand the impact of initiatives like this on student learning.

Global rules on conflict-of-laws matters in international insolvency law cases: An Australian perspective

The 2012 Report “Transnational Insolvency: Global Principles for Co-operation in International Insolvency Cases” – commissioned by The American Law Institute in conjunction with The International Insolvency Institute – annexed 23 “Global Rules on Conflict-of-Laws Matters in International Insolvency Cases”. These proposed “Global Rules” are intended to “serve as legislative recommendations” to (inter alia) promote uniformity and greater certainty in the unpredictable area of conflict of laws. This article provides a brief commentary upon the 23 proposed Global Rules from an Australian perspective (comparing the effect and intent of each rule with the current Australian conflict-of-laws position) and offers some conclusions as to the merits of the “Global Rules” initiative.

The sequence: Inside the race for the human genome

The human genome project was a grand scientific enterprise which attracted both hyperbole and ridicule alike. The project was lauded as “the moon shot of the life sciences”, the “holy grail of man”, “the code of codes”, and “the book of life”. Such rhetoric has also received scorn. President George Bush senior managed to deflate the pretensions of the project with the accidental slip that it was the “human gnome initiative”. In The Sequence, Kevin Davies seeks to go beyond such metaphors, and provide a candid and honest account of the race of the human genome project. The author is indebted to the authoritative book The Gene Wars, which considered the early struggles over the human genome project. Robert Cook-Deegan observes that there was initially much debate over whether there should be a Human Genome Project at all: The debate became one of “big” science versus “small” science. The reliance on systematic technology development and goal-directed gene-mapping efforts presaged a new style for biology, one that elicited excitement from those attracted to whiz-bang technologies but drew gasps of revulsion from those who aspired to cultivate biology on a more modest scale and with decentralized organisation. The battle was, among other things, over whose vision would control the budget and which scientific aesthetic would prevail.

The Sorcerer II expedition: Intellectual property and biodiscovery

This article considers the significance of a leading marine biodiscovery initiative. In March 2004, Dr. J. Craig Venter announced the official launch of the Sorcerer II Expedition, a scientific expedition of discovery, which would survey marine and terrestrial microbial populations. The Expedition has the potential to uncover tens of thousands of new microbial species and tens of millions of new genes. Venter has disavowed that the Sorcerer II Expedition has any commercial ambitions. However, some have viewed the Sorcerer II Expedition with suspicion. Various civil society groups have accused the Expedition of engaging in 'biopiracy'. This article investigates the Convention on Biological Diversity 1992 and other relevant international treaties, various national and regional regimes to govern access to genetic resources, and benefit-sharing agreements. It considers the intersection of intellectual property law, contract law, environmental law, and international law in this field. This article provides a blueprint for a nationally consistent scheme for access to genetic resources, and a model for future international developments.

The plain truth: Australia, tobacco control, and Southeast Asia

As of December 2012, Australia will be the first country in the world where tobacco products will be sold in olive plain packaging without branding. There has been much discussion as to whether this pioneering initiative will spark an ‘Olive Revolution’ around the world — with other countries adopting the plain packaging of tobacco products. Australia’s neighbours in Southeast Asia would particularly benefit from tobacco control measures such as the plain packaging.

Peer mentoring for radiotherapy planning skills development: A pilot study

Introduction: This study aimed to determine the potential role and guidelines for implementation of skill-based peer mentoring for radiotherapy planning education. Methods: After four weekly mentoring sessions, both Year 3 mentors (n=9) and Year 2 mentees (n=9) were invited to complete a short online questionnaire relating to the impact of the initiative. The tool contained a mixture of Likert-style questions concerning student enjoyment and perceived usefulness of the initiative as well as more qualitative open questions that gathered perceptions of the peer mentoring process, implementation methods and potential future scope. Results: Several key discussion themes related to benefits to each stakeholder group, challenges arising, improvements and potential future directions. There were high levels of enjoyment and perceived value of the mentoring from both sides with 100% of the 18 respondents enjoying the experience. The informal format encouraged further learning, while mentors reported acquisition of valuable skills and gains in knowledge. Conclusions: Peer mentoring has a valuable and enjoyable role to play in radiotherapy planning training and helps consolidate theoretical understanding for experienced students. An informal approach allows for students to adopt the most appropriate mentoring model for their needs while providing them with a free space to engender additional discussion.

Green procurement framework for the Malaysian construction industry

Construction projects have a negative impact on the environment. As Malaysia is planning more construction projects to cater for its current and future development needs, practitioners are urged to undertake greener approaches to construction. One of the efforts is the introduction of green procurement, which is promoted under the Malaysian Government’s MyHijau initiative. Construction procurement is recognised as a tool to shift the construction business into a greener industry. However, the implementation of green procurement in Malaysia is still in its infancy and faces a number of challenges, such as the lack of knowledge. A significant gap has been found between policy formulation and actual project delivery as there are no practical guidelines for stakeholders to procure environmental-friendly construction projects. To address this problem, the present research (as part of an ongoing PhD project) aims to develop a green procurement framework that guides stakeholders in procuring green projects in Malaysia. This article highlights the concept of green procurement in Malaysia, the work carried out to date to achieve the research objectives and the preliminary framework that has been established. It is hoped that this research will help academics and practitioners to further explore the potential of green procurement to improve sustainability in the current construction industry practices.

Research around practice partnerships: An example of building partnerships to address overweight and obesity in children

Prevention and management of childhood overweight and obesity is a health priority for governments and communities throughout the developed world. A conceptual model, Research around Practice in Childhood Obesity (RAPICO), has been developed to guide capacity building in a coordinated 'bench to fieldwork' initiative to address this public health problem. Translation of research findings into sustainable responses with optimal fit requires consideration of context-specific relevance, cost-effectiveness, feasibility and levels of available support. The RAPICO model uses program theory to describe a framework for progressing practitionercommunityresearch partnerships to address low, medium and high levels of risk for childhood overweight and obesity within community settings. A case study describing the development of a logic model to inform risk-linked responses to childhood overweight and obesity is presented for the Ipswich community in south-east Queensland.

Associated schools of construction of southern Africa infrastructure design and delivery workshop - Report. CIB task group 91 infrastructure

This workshop comprised a diverse group of African construction experts, ranging far wider than RSA. Each of the attendees had attended the annual ASOCSA conference and was additionally provided with a short workshop pre-brief. The aim was to develop a view of their 15-20 year vision of construction improvement in RSA and the steps necessary to get there. These included sociological, structural, technical and process changes. Whilst some suggestions are significantly challenging, none are impossible, given sufficient collaboration between government, industry, academia and NGOs. The highest priority projects (more properly, programmes) were identified and further explored. These are: 1. Information Hub (‘Open Africa’). Aim – to utilise emerging trends in Open Data to provide a force for African unity. 2. Workforce Development. Aim – to rebuild a competent, skilled construction industry for RSA projects and for export. 3. Modular DIY Building. Aim – to accelerate the development of sustainable, cost-efficient and desirable housing for African economic immigrants and others living in makeshift and slum dwellings. Open Data is a maturing theme in different cities and governments around the world and the workshop attendees were very keen to seize such a possibility to assist in developing an environment where Africans can share information and foster collaboration. It is likely that NGOs might be keen to follow up such an initiative. There are significant developments taking place around the world in the construction sector currently, with comparatively large savings being made for taxpayers (20% plus in the UK). Not all of these changes would be easy to transplant to RSA (even more so to much of the rest of Africa). Workforce development was a keen plea amongst the attendees, who seemed concerned that expertise has leaked away and is not being replaced with sufficient intensity. It is possible today to develop modular buildings in such a way that even unskilled residents can assist in their construction, and even their appropriate design. These buildings can be sited nearly autonomously from infrastructures, thus relieving the tensions on cities and townships, whilst providing humane accommodation for the economically disadvantaged. Development of suitable solutions could either be conducted with other similarly stressed countries or developed in-country and the expertise exported. Finally, it should be pointed out that this was very much a first step. Any opportunity to collaborate from an Australian, QUT or CIB perspective would be welcomed, whilst acknowledging that the leading roles belong to RSA, CSIR, NRF, ASOCSA and the University of KwaZulu-Natal.

Integration of Geospatial and Built Environment - National Data Policy

Digital technology offers enormous benefits (economic, quality of design and efficiency in use) if adopted to implement integrated ways of representing the physical world in a digital form. When applied across the full extent of the built and natural world, it is referred to as the Digital Built Environment (DBE) and encompasses a wide range of approaches and technology initiatives, all aimed at the same end goal: the development of a virtual world that sufficiently mirrors the real world to form the basis for the smart cities of the present and future, enable efficient infrastructure design and programmed maintenance, and create a new foundation for economic growth and social well-being through evidence-based analysis. The creation of a National Data Policy for the DBE will facilitate the creation of additional high technology industries in Australia; provide Governments, industries and citizens with greater knowledge of the environments they occupy and plan; and offer citizen-driven innovations for the future. Australia has slipped behind other nations in the adoption and execution of Building Information Modelling (BIM) and the principal concern is that the gap is widening. Data driven innovation added $67 billion to the Australian economy in 20131. Strong open data policy equates to $16 billion in new value2. Australian Government initiatives such as the Digital Earth inspired “National Map” offer a platform and pathway to embrace the concept of a “BIM Globe”, while also leveraging unprecedented growth in open source / open data collaboration. Australia must address the challenges by learning from international experiences—most notably the UK and NZ—and mandate the use of BIM across Government, extending the Framework for Spatial Data Foundation to include the Built Environment as a theme and engaging collaboration through a “BIM globe” metaphor. This proposed DBE strategy will modernise the Australian urban planning and the construction industry. It will change the way we develop our cities by fundamentally altering the dynamics and behaviours of the supply chains and unlocking new and more efficient ways of collaborating at all stages of the project life-cycle. There are currently two major modelling approaches that contribute to the challenge of delivering the DBE. Though these collectively encompass many (often competing) approaches or proprietary software systems, all can be categorised as either: a spatial modelling approach, where the focus is generally on representing the elements that make up the world within their geographic context; and a construction modelling approach, where the focus is on models that support the life cycle management of the built environment. These two approaches have tended to evolve independently, addressing two broad industry sectors: the one concerned with understanding and managing global and regional aspects of the world that we inhabit, including disciplines concerned with climate, earth sciences, land ownership, urban and regional planning and infrastructure management; the other is concerned with planning, design, construction and operation of built facilities and includes architectural and engineering design, product manufacturing, construction, facility management and related disciplines (a process/technology commonly known as Building Information Modelling, BIM). The spatial industries have a strong voice in the development of public policy in Australia, while the construction sector, which in 2014 accounted for around 8.5% of Australia’s GDP3, has no single voice and because of its diversity, is struggling to adapt to and take advantage of the opportunity presented by these digital technologies. The experience in the UK over the past few years has demonstrated that government leadership is very effective in stimulating industry adoption of digital technologies by, on the one hand, mandating the use of BIM on public procurement projects while at the same time, providing comparatively modest funding to address the common issues that confront the industry in adopting that way of working across the supply chain. The reported result has been savings of £840m in construction costs in 2013/14 according to UK Cabinet Office figures4. There is worldwide recognition of the value of bringing these two modelling technologies together. Australia has the expertise to exercise leadership in this work, but it requires a commitment by government to recognise the importance of BIM as a companion methodology to the spatial technologies so that these two disciplinary domains can cooperate in the development of data policies and information exchange standards to smooth out common workflows. buildingSMART Australasia, SIBA and their academic partners have initiated this dialogue in Australia and wish to work collaboratively, with government support and leadership, to explore the opportunities open to us as we develop an Australasian Digital Built Environment. As part of that programme, we must develop and implement a strategy to accelerate the adoption of BIM processes across the Australian construction sector while at the same time, developing an integrated approach in concert with the spatial sector that will position Australia at the forefront of international best practice in this area. Australia and New Zealand cannot afford to be on the back foot as we face the challenges of rapid urbanisation and change in the global environment. Although we can identify some exemplary initiatives in this area, particularly in New Zealand in response to the need for more resilient urban development in the face of earthquake threats, there is still much that needs to be done. We are well situated in the Asian region to take a lead in this challenge, but we are at imminent risk of losing the initiative if we do not take action now. Strategic collaboration between Governments, Industry and Academia will create new jobs and wealth, with the potential, for example, to save around 20% on the delivery costs of new built assets, based on recent UK estimates.

A comparative study of two design charrettes: Implications for codesign and participatory action research

The purpose of this paper is to explore how participatory prototyping, through the use of design charrettes, can advance participatory action research (PAR) approaches and contribute to codesign practices in organisational settings. This will be achieved through the comparison of two varying design charrette experiences from a PAR initiative to redesign spaces in the Auraria Library in Denver, Colorado. Each design charrette followed a three-stage sequence of information sharing, idea generation and prototyping, and prioritisation with each stage building upon the former, both in terms of design concepts and in building up elements of ‘making’. While both charrette structures were similar, leadership and execution varied considerably. Lessons learned from the two design charrette experiences are presented, including the value of participatory prototyping within PAR to support ‘research through design’ activities. In addition, it highlights the value of authentic design participation of ‘designing with’ rather than ‘designing for’ to encourage optimal design outcomes.