Evidence for CRHR1 in multiple sclerosis using supervised machine learning and meta-analysis in 12 566 individuals

The primary genetic risk factor in multiple sclerosis (MS) is the HLA-DRB1*1501 allele; however, much of the remaining genetic contribution to MS has yet to be elucidated. Several lines of evidence support a role for neuroendocrine system involvement in autoimmunity which may, in part, be genetically determined. Here, we comprehensively investigated variation within eight candidate hypothalamic-pituitary-adrenal (HPA) axis genes and susceptibility to MS. A total of 326 SNPs were investigated in a discovery dataset of 1343 MS cases and 1379 healthy controls of European ancestry using a multi-analytical strategy. Random Forests, a supervised machine-learning algorithm, identified eight intronic SNPs within the corticotrophin-releasing hormone receptor 1 or CRHR1 locus on 17q21.31 as important predictors of MS. On the basis of univariate analyses, six CRHR1 variants were associated with decreased risk for disease following a conservative correction for multiple tests. Independent replication was observed for CRHR1 in a large meta-analysis comprising 2624 MS cases and 7220 healthy controls of European ancestry. Results from a combined meta-analysis of all 3967 MS cases and 8599 controls provide strong evidence for the involvement of CRHR1 in MS. The strongest association was observed for rs242936 (OR = 0.82, 95% CI = 0.74-0.90, P = 9.7 × 10-5). Replicated CRHR1 variants appear to exist on a single associated haplotype. Further investigation of mechanisms involved in HPA axis regulation and response to stress in MS pathogenesis is warranted. © The Author 2010. Published by Oxford University Press. All rights reserved.

Investigating the performance of automatic new topic identification across multiple datasets 1

Recent studies on automatic new topic identification in Web search engine user sessions demonstrated that neural networks are successful in automatic new topic identification. However most of this work applied their new topic identification algorithms on data logs from a single search engine. In this study, we investigate whether the application of neural networks for automatic new topic identification are more successful on some search engines than others. Sample data logs from the Norwegian search engine FAST (currently owned by Overture) and Excite are used in this study. Findings of this study suggest that query logs with more topic shifts tend to provide more successful results on shift-based performance measures, whereas logs with more topic continuations tend to provide better results on continuation-based performance measures.

Towards automatic object segmentation with sequential multiple views

Object segmentation is one of the fundamental steps for a number of robotic applications such as manipulation, object detection, and obstacle avoidance. This paper proposes a visual method for incorporating colour and depth information from sequential multiview stereo images to segment objects of interest from complex and cluttered environments. Rather than segmenting objects using information from a single frame in the sequence, we incorporate information from neighbouring views to increase the reliability of the information and improve the overall segmentation result. Specifically, dense depth information of a scene is computed using multiple view stereo. Depths from neighbouring views are reprojected into the reference frame to be segmented compensating for imperfect depth computations for individual frames. The multiple depth layers are then combined with color information from the reference frame to create a Markov random field to model the segmentation problem. Finally, graphcut optimisation is employed to infer pixels belonging to the object to be segmented. The segmentation accuracy is evaluated over images from an outdoor video sequence demonstrating the viability for automatic object segmentation for mobile robots using monocular cameras as a primary sensor.

Analysis of multiple shared channel cooperative routing in OFDM based wireless networks

Diversity techniques have long been used to combat the channel fading in wireless communications systems. Recently cooperative communications has attracted lot of attention due to many benefits it offers. Thus cooperative routing protocols with diversity transmission can be developed to exploit the random nature of the wireless channels to improve the network efficiency by selecting multiple cooperative nodes to forward data. In this paper we analyze and evaluate the performance of a novel routing protocol with multiple cooperative nodes which share multiple channels. Multiple shared channels cooperative (MSCC) routing protocol achieves diversity advantage by using cooperative transmission. It unites clustering hierarchy with a bandwidth reuse scheme to mitigate the co-channel interference. Theoretical analysis of average packet reception rate and network throughput of the MSCC protocol are presented and compared with simulated results.

Evaluation of novel Streptococcus pyogenes vaccine candidates incorporating multiple conserved sequences from the C-repeat region of the M-protein

A major challenge for Streptococcus pyogenes vaccine development is the identification of epitopes that confer protection from infection by multiple S. pyogenes M-types. Here we have identified and characterised the distribution of common variant sequences from individual repeat units of the C-repeat region (CRR) of M-proteins representing 77 different M-types. Three polyvalent fusion vaccine candidates (SV1, SV2 and SV3) incorporating the most common variants were subsequently expressed and purified, and demonstrated to be alpha-helical by Circular Dichroism (CD), a secondary conformational characteristic of the CRR in the M-protein. Antibodies raised against each of these constructs recognise M-proteins that vary in their CRR, and bind to the surface of multiple S. pyogenes isolates. Antibodies raised against SV1, containing five variant sequences, also kill heterologous S. pyogenes isolates in in vitro bactericidal assays. Further structural characterisation of this construct demonstrated the conformation of SV1 was stable at different pHs, and thermal unfolding of SV1 a reversible process. Our findings demonstrate that linkage of multiple variant sequences into a single recombinant construct overcomes the need to embed the variant sequences in foreign helix promoting flanking sequences for conformational stability, and demonstrates the viability of the polyvalent candidates as global S. pyogenes vaccine candidates.

Multiple perspectives of design thinking in business education

Business education leaders have expressed interest in learning more about design and design thinking and their contributions to better problem framing, problem solving and to generating new solutions. Many business schools have engaged in educational programs with students from multiple disciplines, applying design thinking to business problems around workplace issues. This paper investigates a range of educational programs that teach design thinking to students in business education, at undergraduate and postgraduate levels around the world. We identify four patterns of program delivery that are emerging: human-centered design, integrative thinking, design management and design as strategy and discuss contributions from each. We expect that these four patterns of program delivery will continue and predict an increasing focus on programs around design as strategy in the near future.

Reduced variance in monozygous twins for multiple MR parameters : implications for disease studies and the genetic basis of brain structure

Twin studies offer the opportunity to determine the relative contribution of genes versus environment in traits of interest. Here, we investigate the extent to which variance in brain structure is reduced in monozygous twins with identical genetic make-up. We investigate whether using twins as compared to a control population reduces variability in a number of common magnetic resonance (MR) structural measures, and we investigate the location of areas under major genetic influences. This is fundamental to understanding the benefit of using twins in studies where structure is the phenotype of interest. Twenty-three pairs of healthy MZ twins were compared to matched control pairs. Volume, T2 and diffusion MR imaging were performed as well as spectroscopy (MRS). Images were compared using (i) global measures of standard deviation and effect size, (ii) voxel-based analysis of similarity and (iii) intra-pair correlation. Global measures indicated a consistent increase in structural similarity in twins. The voxel-based and correlation analyses indicated a widespread pattern of increased similarity in twin pairs, particularly in frontal and temporal regions. The areas of increased similarity were most widespread for the diffusion trace and least widespread for T2. MRS showed consistent reduction in metabolite variation that was significant in the temporal lobe N-acetylaspartate (NAA). This study has shown the distribution and magnitude of reduced variability in brain volume, diffusion, T2 and metabolites in twins. The data suggest that evaluation of twins discordant for disease is indeed a valid way to attribute genetic or environmental influences to observed abnormalities in patients since evidence is provided for the underlying assumption of decreased variability in twins.

The role of the multiple banded antigen of ureaplasma parvum in intra-amniotic infection : major virulence factor or decoy?

The multiple banded antigen (MBA) is a predicted virulence factor of Ureaplasma species. Antigenic variation of the MBA is a potential mechanism by which ureaplasmas avoid immune recognition and cause chronic infections of the upper genital tract of pregnant women. We tested whether the MBA is involved in the pathogenesis of intra-amniotic infection and chorioamnionitis by injecting virulent or avirulent-derived ureaplasma clones (expressing single MBA variants) into the amniotic fluid of pregnant sheep. At 55 days of gestation pregnant ewes (n = 20) received intra-amniotic injections of virulent-derived or avirulent-derived U. parvum serovar 6 strains (2×104 CFU), or 10B medium (n = 5). Amniotic fluid was collected every two weeks post-infection and fetal tissues were collected at the time of surgical delivery of the fetus (140 days of gestation). Whilst chronic colonisation was established in the amniotic fluid of animals infected with avirulent-derived and virulent-derived ureaplasmas, the severity of chorioamnionitis and fetal inflammation was not different between these groups (p>0.05). MBA size variants (32–170 kDa) were generated in vivo in amniotic fluid samples from both the avirulent and virulent groups, whereas in vitro antibody selection experiments led to the emergence of MBA-negative escape variants in both strains. Anti-ureaplasma IgG antibodies were detected in the maternal serum of animals from the avirulent (40%) and virulent (55%) groups, and these antibodies correlated with increased IL-1β, IL-6 and IL-8 expression in chorioamnion tissue (p<0.05). We demonstrate that ureaplasmas are capable of MBA phase variation in vitro; however, ureaplasmas undergo MBA size variation in vivo, to potentially prevent eradication by the immune response. Size variation of the MBA did not correlate with the severity of chorioamnionitis. Nonetheless, the correlation between a maternal humoral response and the expression of chorioamnion cytokines is a novel finding. This host response may be important in the pathogenesis of inflammation-mediated adverse pregnancy outcomes.

Extensible software for research data capture

Projects funded by the Australian National Data Service(ANDS). The specific projects that were funded included: a) Greenhouse Gas Emissions Project (N2O) with Prof. Peter Grace from QUT’s Institute of Sustainable Resources. b) Q150 Project for the management of multimedia data collected at Festival events with Prof. Phil Graham from QUT’s Institute of Creative Industries. c) Bio-diversity environmental sensing with Prof. Paul Roe from the QUT Microsoft eResearch Centre. For the purposes of these projects the Eclipse Rich Client Platform (Eclipse RCP) was chosen as an appropriate software development framework within which to develop the respective software. This poster will present a brief overview of the requirements of the projects, an overview of the experiences of the project team in using Eclipse RCP, report on the advantages and disadvantages of using Eclipse and it’s perspective on Eclipse as an integrated tool for supporting future data management requirements.

Delegation framework for federated systems

It is not uncommon for enterprises today to be faced with the demand to integrate and incor- porate many different and possibly heterogeneous systems which are generally independently designed and developed, to allow seamless access. In effect, the integration of these systems results in one large whole system that must be able, at the same time, to maintain the local autonomy and to continue working as an independent entity. This problem has introduced a new distributed architecture called federated systems. The most challenging issue in federated systems is to find answers for the question of how to efficiently cooperate while preserving their autonomous characteristic, especially the security autonomy. This thesis intends to address this issue. The thesis reviews the evolution of the concept of federated systems and discusses the organisational characteristics as well as remaining security issues with the existing approaches. The thesis examines how delegation can be used as means to achieve better security, especially authorisation while maintaining autonomy for the participating member of the federation. A delegation taxonomy is proposed as one of the main contributions. The major contribution of this thesis is to study and design a mechanism to support dele- gation within and between multiple security domains with constraint management capability. A novel delegation framework is proposed including two modules: Delegation Constraint Man- agement module and Policy Management module. The first module is designed to effectively create, track and manage delegation constraints, especially for delegation processes which require re-delegation (indirect delegation). The first module employs two algorithms to trace the root authority of a delegation constraint chain and to prevent the potential conflict when creating a delegation constraint chain if necessary. The first module is designed for conflict prevention not conflict resolution. The second module is designed to support the first module via the policy comparison capability. The major function of this module is to provide the delegation framework the capability to compare policies and constraints (written under the format of a policy). The module is an extension of Lin et al.'s work on policy filtering and policy analysis. Throughout the thesis, some case studies are used as examples to illustrate the discussed concepts. These two modules are designed to capture one of the most important aspects of the delegation process: the relationships between the delegation transactions and the involved constraints, which are not very well addressed by the existing approaches. This contribution is significant because the relationships provide information to keep track and en- force the involved delegation constraints and, therefore, play a vital role in maintaining and enforcing security for transactions across multiple security domains.

Next generation low-cost motion capture systems can provide comparable spatial accuracy to high-end systems

The objective quantification of three-dimensional kinematics during different functional and occupational tasks is now more in demand than ever. The introduction of new generation of low-cost passive motion capture systems from a number of manufacturers has made this technology accessible for teaching, clinical practice and in small/medium industry. Despite the attractive nature of these systems, their accuracy remains unproved in independent tests. We assessed static linear accuracy, dynamic linear accuracy and compared gait kinematics from a Vicon MX20 system to a Natural Point OptiTrack system. In all experiments data were sampled simultaneously. We identified both systems perform excellently in linear accuracy tests with absolute errors not exceeding 1%. In gait data there was again strong agreement between the two systems in sagittal and coronal plane kinematics. Transverse plane kinematics differed by up to 3 at the knee and hip, which we attributed to the impact of soft tissue artifact accelerations on the data. We suggest that low-cost systems are comparably accurate to their high-end competitors and offer a platform with accuracy acceptable in research for laboratories with a limited budget.

A radiological method to determine the accuracy of motion capture marker placement on palpable anatomical landmarks through a shoe

The accuracy of marker placement on palpable surface anatomical landmarks is an important consideration in biomechanics. Although marker placement reliability has been studied in some depth, it remains unclear whether or not the markers are accurately positioned over the intended landmark in order to define the static position and orientation of the segment. A novel method using commonly available X-ray imaging was developed to identify the accuracy of markers placed on the shoe surface by palpating landmarks through the shoe. An anterior–posterior and lateral–medial X-ray was taken on 24 participants with a newly developed marker set applied to both the skin and shoe. The vector magnitude of both skin- and shoe-mounted markers from the anatomical landmark was calculated, as well as the mean marker offset between skin- and shoe-mounted markers. The accuracy of placing markers on the shoe relative to the skin-mounted markers, accounting for shoe thickness, was less than 5mm for all markers studied. Further, when using the developed guidelines provided in this study, the method was deemed reliable (Intra-rater ICCs¼0.50–0.92). In conclusion, the method proposed here can reliably assess marker placement accuracy on the shoe surface relative to chosen anatomical landmarks beneath the skin.

A comparison of two commercially available motion capture systems for gait analysis : high end vs low-cost

In 1999 Richards compared the accuracy of commercially available motion capture systems commonly used in biomechanics. Richards identified that in static tests the optical motion capture systems generally produced RMS errors of less than 1.0 mm. During dynamic tests, the RMS error increased to up to 4.2 mm in some systems. In the last 12 years motion capture systems have continued to evolve and now include high-resolution CCD or CMOS image sensors, wireless communication, and high full frame sampling frequencies. In addition to hardware advances, there have also been a number of advances in software, which includes improved calibration and tracking algorithms, real time data streaming, and the introduction of the c3d standard. These advances have allowed the system manufactures to maintain a high retail price in the name of advancement. In areas such as gait analysis and ergonomics many of the advanced features such as high resolution image sensors and high sampling frequencies are not required due to the nature of the task often investigated. Recently Natural Point introduced low cost cameras, which on face value appear to be suitable as at very least a high quality teaching tool in biomechanics and possibly even a research tool when coupled with the correct calibration and tracking software. The aim of the study was therefore to compare both the linear accuracy and quality of angular kinematics from a typical high end motion capture system and a low cost system during a simple task.

Handling incomplete data in survival analysis with multiple covariates

This paper studies the missing covariate problem which is often encountered in survival analysis. Three covariate imputation methods are employed in the study, and the effectiveness of each method is evaluated within the hazard prediction framework. Data from a typical engineering asset is used in the case study. Covariate values in some time steps are deliberately discarded to generate an incomplete covariate set. It is found that although the mean imputation method is simpler than others for solving missing covariate problems, the results calculated by it can differ largely from the real values of the missing covariates. This study also shows that in general, results obtained from the regression method are more accurate than those of the mean imputation method but at the cost of a higher computational expensive. Gaussian Mixture Model (GMM) method is found to be the most effective method within these three in terms of both computation efficiency and predication accuracy.