Resequencing and fine-mapping of the chromosome 12q13-14 locus associated with multiple sclerosis refines the number of implicated genes

Multiple sclerosis (MS) is a common chronic inflammatory disease of the central nervous system. Susceptibility to the disease is affected by both environmental and genetic factors. Genetic factors include haplotypes in the histocompatibility complex (MHC) and over 50 non-MHC loci reported by genome-wide association studies. Amongst these, we previously reported polymorphisms in chromosome 12q13-14 with a protective effect in individuals of European descent. This locus spans 288 kb and contains 17 genes, including several candidate genes which have potentially significant pathogenic and therapeutic implications. In this study, we aimed to fine-map this locus. We have implemented a two-phase study: a variant discovery phase where we have used next-generation sequencing and two target-enrichment strategies [long-range polymerase chain reaction (PCR) and Nimblegen's solution phase hybridization capture] in pools of 25 samples; and a genotyping phase where we genotyped 712 variants in 3577 healthy controls and 3269 MS patients. This study confirmed the association (rs2069502, P = 9.9 × 10−11, OR = 0.787) and narrowed down the locus of association to an 86.5 kb region. Although the study was unable to pinpoint the key-associated variant, we have identified a 42 (genotyped and imputed) single-nucleotide polymorphism haplotype block likely to harbour the causal variant. No evidence of association at previously reported low-frequency variants in CYP27B1 was observed. As part of the study we compared variant discovery performance using two target-enrichment strategies. We concluded that our pools enriched with Nimblegen's solution phase hybridization capture had better sensitivity to detect true variants than the pools enriched with long-range PCR, whilst specificity was better in the long-range PCR-enriched pools compared with solution phase hybridization capture enriched pools; this result has important implications for the design of future fine-mapping studies.

Linkage mapping of CVD risk traits in the isolated Norfolk Island population

To understand the underlying genetic architecture of cardiovascular disease (CVD) risk traits, we undertook a genome-wide linkage scan to identify CVD quantitative trait loci (QTLs) in 377 individuals from the Norfolk Island population. The central aim of this research focused on the utilization of a genetically and geographically isolated population of individuals from Norfolk Island for the purposes of variance component linkage analysis to identify QTLs involved in CVD risk traits. Substantial evidence supports the involvement of traits such as systolic and diastolic blood pressures, high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol, body mass index and triglycerides as important risk factors for CVD pathogenesis. In addition to the environmental inXuences of poor diet, reduced physical activity, increasing age, cigarette smoking and alcohol consumption, many studies have illustrated a strong involvement of genetic components in the CVD phenotype through family and twin studies. We undertook a genome scan using 400 markers spaced approximately 10 cM in 600 individuals from Norfolk Island. Genotype data was analyzed using the variance components methods of SOLAR. Our results gave a peak LOD score of 2.01 localizing to chromosome 1p36 for systolic blood pressure and replicated previously implicated loci for other CVD relevant QTLs.

Outcomes of the Chemistry Discipline Network Mapping Exercises: Are the Threshold Learning Outcomes met?

The Chemistry Discipline Network has recently completed two distinct mapping exercises. The first is a snapshot of chemistry taught at 12 institutions around Australia in 2011. There were many similarities but also important differences in the content taught and assessed at different institutions. There were also significant differences in delivery, particularly laboratory contact hours, as well as forms and weightings of assessment. The second mapping exercise mapped the chemistry degrees at three institutions to the Threshold Learning Outcomes for chemistry. Importantly, some of the TLOs were addressed by multiple units at all institutions, while others were not met, or were met at an introductory level only. The exercise also exposed some challenges in using the TLOs as currently written.

Survey and Mapping Infrastructure Regulation 2004- Comments Relating to a 10-Year Review

Democratic governments raise taxes and charges and spend revenue on delivering peace, order and good government. The delivery process begins with a legislature as that can provide a framework of legally enforceable rules enacted according to the government’s constitution. These rules confer rights and obligations that allow particular people to carry on particular functions at particular places and times. Metadata standards as applied to public records contain information about the functioning of government as distinct from the non-government sector of society. Metadata standards apply to database construction. Data entry, storage, maintenance, interrogation and retrieval depend on a controlled vocabulary needed to enable accurate retrieval of suitably catalogued records in a global information environment. Queensland’s socioeconomic progress now depends in part on technical efficiency in database construction to address queries about who does what, where and when; under what legally enforceable authority; and how the evidence of those facts is recorded. The Survey and Mapping Infrastructure Act 2003 (Qld) addresses technical aspects of where questions – typically the officially recognised name of a place and a description of its boundaries. The current 10-year review of the Survey and Mapping Regulation 2004 provides a valuable opportunity to consider whether the Regulation makes sense in the context of a number of later laws concerned with management of Public Sector Information (PSI) as well as policies for ICT hardware and software procurement. Removing ambiguities about how official place names are to be regarded on a whole-of-government basis can achieve some short term goals. Longer-term goals depend on a more holistic approach to information management – and current aspirations for more open government and community engagement are unlikely to occur without such a longer-term vision.

Prospects for whole genome linkage disequilibrium mapping in domestic dog breeds

Linkage disequilibrium (LD) mapping is commonly used as a fine mapping tool in human genome mapping and has been used with some success for initial disease gene isolation in certain isolated in-bred human populations. An understanding of the population history of domestic dog breeds suggests that LD mapping could be routinely utilized in this species for initial genome-wide scans. Such an approach offers significant advantages over traditional linkage analysis. Here, we demonstrate, using canine copper toxicosis in the Bedlington terrier as the model, that LD mapping could be reasonably expected to be a useful strategy in low-resolution, genome-wide scans in pure-bred dogs. Significant LD was demonstrated over distances up to 33.3 cM. It is very unlikely, for a number of reasons discussed, that this result could be extrapolated to the rest of the genome. It is, however, consistent with the expectation given the population structure of canine breeds and, in this breed at least, with the hypothesis that it may be possible to utilize LD in a genome-wide scan. In this study, LD mapping confirmed the location of the copper toxicosis in Bedlington terrier gene (CT-BT) and was able to do so in a population that was refractory to traditional linkage analysis.

The embodied hybrid space : designing social and digital interventions to facilitate connected learning in coworking spaces

This thesis developed and evaluated strategies for social and ubiquitous computing designs that can enhance connected learning and networking opportunities for users in coworking spaces. Based on a social and a technical design intervention deployed at the State Library of Queensland, the research findings illustrate the potential of combining social, spatial and digital affordances in order to nourish peer-to-peer learning, creativity, inspiration, and innovation. The study proposes a hybrid notion of placemaking as a new way of thinking about the design of coworking and interactive learning spaces.

Regional chromosomal assignment of human renin gene to 1q12→qter and use in linkage studies in Charcot-Marie-Tooth disease

The gene for renin, previously mapped to human chromosome 1, was further localized to 1q12 → qter using human-mouse somatic cell hybrid DNAs. The renin DNA probe used (λ HR5) could detect a HindIII restriction fragment length polymorphism. When used in studies of 12 informative families, no linkage could be found between the renin and Charcot-Marie-Tooth disease. Furthermore, an association of any renin allele with hypertension was not apparent.

Isolation and use of chromosome 1 probes for linkage studies on Charcot-Marie-Tooth disease

Nine probes were isolated from a human chromosome 1 enriched library and mapped to regions of chromosome 1 using somatic cell hybrid lines. One clone, LR67, which mapped 1q12→q23 detected a BglI RFLP. This probe, as well as 4 other known chromosome 1 markers, α-spectrin, Factor XIIIB, DR10 and DR78, were used for linkage studies in 15 Charcot-Marie-Tooth disease (CMT1) families. Close linking of CMT1 to any of the 5 markers was not indicated. Total lod scores excluded linkage of CMT1 to LR67 and to DR10 at 5 cM or less, to DR78 and 10 cM or less, α-spectrin at 15 cM or less and Factor XIIIB at 20 cM or less. Possible linkage, however, was shown between LR67 and CMT1 at a distance of 30 cM. Also linkage at a distance of 5 cM was detected between this probe and α-spectrin.

Development and implementation of the Australian universities radiation therapy student clinical assessment form

Purpose: Prior to 2009, one of the problems faced by radiation therapists who supervised and assessed students on placement in Australian clinical centres, was that each of the six Australian universities where Radiation Therapy (RT) programmes were conducted used different clinical assessment and reporting criteria. This paper describes the development of a unified national clinical assessment and reporting form that was implemented nationally by all six universities in 2009. Methods: A four phase methodology was used to develop the new assessment form and user guide. Phase 1 included university consensus around domains of student practice and assessment, and alignment with national competency standards; Phase 2 was a national consensus workshop attended by radiation therapists involved in student supervision and assessment; Phase 3 was an action research re-iterative Delphi technique involving two rounds of a mail-out to gain further expert consensus; and stage 4 was national piloting of the developed assessment form. Results: The new assessment form includes five main domains of practice and 19 sub-domain criteria which students are assessed against during placement. Feedback from the pilot centre participants was positive, with the new form being assessed to be comprehensive and complemented by the accompanying user guide. Conclusion: The new assessment form has improved both the formative and summative assessment of students on placement, as well as enhancing the quality of feedback to students and the universities. The new national form has high acceptance from the Australian universities and has been subject to wide review by the profession.

Person centred nursing care in radiation oncology : a case study

Purpose The aim of this case study is to describe clinical staff perceptions of implementing a person-centred model of nursing in an outpatient radiotherapy treatment department, using a Primary Nursing/Collaborative Practice framework. The questions are: 1) what are the nursing and radiotherapy staff perspectives of the changed model of care, 2) what factors impacted on aspects of the evolving model?, and 3) how was interdisciplinary collaboration influenced by the new model? Methods An instrumental case study addressed the multiple perspectives of several radiotherapy health professionals, within a qualitative approach, to assess the new model of nursing care. Interview data were obtained from thirteen clinical staff over a six month period approximately one year after the model was implemented. Results The new model supports nurses to work more closely with the individual patient, with some perceived positive patient outcomes. Nurses reported increased satisfaction with their work, more autonomy and responsibility, and improved working relationships with medical staff. They also became more aware of the holistic approach to support positive patient outcomes. However, this study acknowledged that education was required for nurses to provide holistic care, especially in the context of complex interdisciplinary relationships. Conclusions A person-centred nursing approach in radiotherapy represents a radical change to the functional approach, providing some benefits for patients. However, the challenges of providing holistic care in the context of complex interdisciplinary relationships are evident, and this study acknowledges the importance of a team approach to addressing changes in practice in the future.

Mapping local solutions to entrenched transport problems: Key lessons regarding the use of geographical information technologies in community mapping with disadvantaged communities

There is an increasing interest in the use of information technology as a participatory planning tool, particularly the use of geographical information technologies to support collaborative activities such as community mapping. However, despite their promise, the introduction of such technologies does not necessarily promote better participation nor improve collaboration. In part this can be attributed to a tendency for planners to focus on the technical considerations associated with these technologies at the expense of broader participation considerations. In this paper we draw on the experiences of a community mapping project with disadvantaged communities in suburban Australia to highlight the importance of selecting tools and techniques which support and enhance participatory planning. This community mapping project, designed to identify and document community-generated transport issues and solutions, had originally intended to use cadastral maps extracted from the government’s digital cadastral database as the foundation for its community mapping approach. It was quickly discovered that the local residents found the cadastral maps confusing as the maps lacked sufficient detail to orient them to their suburb (the study area). In response to these concerns and consistent with the project’s participatory framework, a conceptual base map based on resident’s views of landmarks of local importance was developed to support the community mapping process. Based on this community mapping experience we outline four key lessons learned regarding the process of community mapping and the place of geographical information technologies within this process.

Dynamic simulation of a light-weight, low-drag, hybrid-electric sports coupe

The University of Queensland UltraCommuter concept is an ultra- light, low-drag, hybrid-electric sports coupe designed to minimize energy consumption and environmental impact while enhancing the performance, styling, features and convenience that motorists enjoy. This paper presents a detailed simulation study of the vehicle's performance and fuel economy using ADVISOR, including a detailed description of the component models and parameters assumed. Results from the study include predictions of a 0-100 kph acceleration time of ≺9s, and top speed of 170 kph, an electrical energy consumption of ≺67 Wh/km in ZEV mode and a petrol-equivalent fuel consumption of ≺2.5 L/100 km in charge-sustaining HEV mode. Overall, the results of the ADVISOR modelling confirm the UltraCommuter's potential to achieve high performance with high efficiency, and the authors look forward to a confirmation of these estimates following completion of the vehicle.

A parametric analysis technique for design of fuel cell and hybrid-electric vehicles

This paper presents a new simplified parametric analysis technique for the design of fuel cell and hybrid-electric vehicles. The technique utilizes a comprehensive set of ∼30 parameters to fully characterize the vehicle platform, powertrain components, vehicle performance requirements and driving conditions. It is best applied to the sizing of powertrain components and prediction of energy consumption in a vehicle. This new parametric technique makes a good complement to existing vehicle simulation software packages and therefore represents a potentially valuable tool for the hybrid vehicle designer.

Brake system performance requirements of a lightweight electric/hybrid rear wheel drive vehicle

Investigates the braking performance requirements of the UltraCommuter, a lightweight series hybrid electric vehicle currently under development at the University of Queensland. With a predicted vehicle mass of 600 kg and two in-wheel motors each capable of 500 Nm of peak torque, decelerations up to 0.46 g are theoretically possible using purely regenerative braking. With 99% of braking demands less than 0.35 g, essentially all braking can be regenerative. The wheel motors have sufficient peak torque capability to lock the rear wheels in combination with front axle braking, eliminating the need for friction braking at the rear. Emergency braking levels approaching 1 g are achieved by supplementation with front disk brakes. This paper presents equations describing the peak front and rear axle braking forces which occur under straight line braking, including gradients. Conventionally, to guarantee stability, mechanical front/rear proportioning of braking effort ensures that the front axle locks first. In this application, all braking is initially regenerative at the rear, and an adaptive ''by-wire'' proportioning system presented ensures this stability requirement is still satisfied. Front wheel drive and all wheel drive systems are also discussed. Finally, peak and continuous performance measures, not commonly provided for friction brakes, are derived for the UltraCommuter's motor capability and range of operation.

More naturalness, less control: The effect of natural mapping on the co-located player experience

In the past years, there has been a surge in game controllers that allow players to play in a more physical, more natural way. In this paper we present an experimental study of the effect of gaming using these naturally mapped controllers on the player experience in a social setting. Results support the hypothesis that more naturally mapped controllers augment spatial presence. Furthermore, the results suggest that gaming with more naturally mapped controllers augment social presence for female players, but not for male players. However, gaming via naturally mapped controllers decreases perceived control and actual performance. Hence, users with high performance expectations might not benefit from gaming via naturally mapped controllers.