Australian data do not support current pharmaceutical benefits scheme criteria for use of tumour necrosis factor-α inhibitors in ankylosing spondylitis

On the basis of local data, we write in support of the conclusions of Smith and Ahern that current Pharmaceu- tical Benefits Scheme (PBS) criteria for tumour necrosis factor (TNF)-a inhibitors in ankylosing spondylitis (AS) are not evidence-based. 1 As a prerequisite to the appropriate use of biological therapy in AS, three aspects of the disease need to be defined: (i) diagnosis, (ii) activity and (iii) therapeutic failure (Table 1)....

The effect of transforming growth factor β1 gene polymorphisms in ankylosing spondylitis

Objectives. To determine whether genetic polymorphisms in or near the transforming growth factor β1 (TGFB1) locus were associated d with susceptibility to or severity of ankylosing spondylitis (AS). Methods. Five intragenic single-nucleotide polymorphisms (SNP) and three microsatellite markers flanking the TGFB1 locus were genotyped. Seven hundred and sixty-two individuals from 184 multiplex families were genotyped for the microsatellite markers and two of the promoter SNPs. One thousand and two individuals from 212 English and 170 Finnish families with AS were genotyped for all five intragenic SNPs. A structured questionnaire was used to assess the age of symptom onset, disease duration and disease severity scores, including the BASDAI (Bath Ankylosing Spondylitis Disease Activity Index) and BASFI (Bath Ankylosing Spondylitis Functional Index). Results. A weak association was noted between the rare TGFB1 + 1632 T allele and AS in the Finnish population (P = 0.04) and in the combined data set (P = 0.03). No association was noted between any other SNPs or SNP haplotype and AS, even among those families with positive non-parametric linkage scores. The TGFB1 +1632 polymorphism was also associated with a younger age of symptom onset (English population, allele 2 associated with age of onset greater by 4.2 yr, P = 0.05; combined data set, allele 2 associated with age of onset greater by 3.2 yr, P = 0.02). A haplotype of coding region SNPs (TGFB1 +869/ +915+1632 alleles 2/1/2) was associated with age of symptom onset in both the English parent-case trios and the combined data set (English data set, haplotype 2/1/2 associated with age of onset greater by 4.9 yr, P = 0.03; combined data set, haplotype 2/1/2 associated with greater age of onset by 4.2 yr, P = 0.006). Weak linkage with AS susceptibility was noted and the peak LOD score was 1.3 at distance 2 cM centromeric to the TGFB1 gene. No other linkage or association was found between quantitative traits and the markers. Conclusion. This study suggests that the polymorphisms within the TGFB1 gene play at most a small role in AS and that other genes encoded on chromosome 19 are involved in susceptibility to the disease.

Understanding the use of a bug tracking system in a global software development setup

Bug fixing is a highly cooperative work activity where developers, testers, product managers and other stake-holders collaborate using a bug tracking system. In the context of Global Software Development (GSD), where software development is distributed across different geographical locations, we focus on understanding the role of bug trackers in supporting software bug fixing activities. We carried out a small-scale ethnographic fieldwork in a software product team distributed between Finland and India at a multinational engineering company. Using semi-structured interviews and in-situ observations of 16 bug cases, we show that the bug tracker 1) supported information needs of different stake holder, 2) established common-ground, and 3) reinforced issues related to ownership, performance and power. Consequently, we provide implications for design around these findings.

Measurement of stenotic carotid arterial compliance with MRI

Arterial compliance has been shown to correlate well with overall cardiovascular outcome and it may also be a potential risk factor for the development of atheromatous disease. This study assesses the utility of 2-D phase contrast Magnetic Resonance (MR) imaging with intra-sequence blood pressure measurement to determine carotid compliance and distensibility. 20 patients underwent 2-D phase contrast MR imaging and also ultrasound-based wall tracking measurements. Values for carotid compliance and distensibility were derived from the two different modalities and compared. Linear regression analysis was utilised to determine the extent of correlation between MR and ultrasound derived parameters. In those variables that could be directly compared, an agreement analysis was undertaken. MR measures of compliance showed a good correlation with measures based on ultrasound wall-tracking (r=0.61, 95% CI 0.34 to 0.81 p=0.0003). Vessels that had undergone carotid endarterectomy previously were significantly less compliant than either diseased or normal contralateral vessels (p=0.04). Agreement studies showed a relatively poor intra-class correlation coefficient (ICC) between diameter-based measures of compliance through either MR or ultrasound (ICC=0.14). MRI based assessment of local carotid compliance appears to be both robust and technically feasible in most subjects. Measures of compliance correlate well with ultrasound-based values and correlate best when cross-sectional area change is used rather than derived diameter changes. If validated by further larger studies, 2-D phase contrast imaging with intra-sequence blood pressure monitoring and off-line radial artery tonometry may provide a useful tool in further assessment of patients with carotid atheroma.

Passivity-based Trajectory-tracking for Marine Craft with Disturbance Rejection

This paper presents a Hamiltonian model of marine vehicle dynamics in six degrees of freedom in both body-fixed and inertial momentum coordinates. The model in body-fixed coordinates presents a particular structure of the mass matrix that allows the adaptation and application of passivity-based control interconnection and damping assignment design methodologies developed for robust stabilisation of mechanical systems in terms of generalised coordinates. As an example of application, we follow this methodology to design a passivity-based tracking controller with integral action for fully actuated vehicles in six degrees of freedom. We also describe a momentum transformation that allows an alternative model representation that resembles general port-Hamiltonian mechanical systems with a coordinate dependent mass matrix. This can be seen as an enabling step towards the adaptation of the theory of control of port-Hamiltonian systems developed in robotic manipulators and multi-body mechanical systems to the case of marine craft dynamics.

Comparative proteomics of uropathogenic Escherichia coli during growth in human urine identify UCA-like (UCL) fimbriae as an adherence factor involved in biofilm formation and binding to uroepithelial cells

Uropathogenic Escherichia coli (UPEC) are the primary cause of urinary tract infection (UTI) in humans. For the successful colonisation of the human urinary tract, UPEC employ a diverse collection of secreted or surface-exposed virulence factors including toxins, iron acquisition systems and adhesins. In this study, a comparative proteomic approach was utilised to define the UPEC pan and core surface proteome following growth in pooled human urine. Identified proteins were investigated for subcellular origin, prevalence and homology to characterised virulence factors. Fourteen core surface proteins were identified, as well as eleven iron uptake receptor proteins and four distinct fimbrial types, including type 1, P, F1C/S and a previously uncharacterised fimbrial type, designated UCA-like (UCL) fimbriae in this study. These pathogenicity island (PAI)-associated fimbriae are related to UCA fimbriae of Proteus mirabilis, associated with UPEC and exclusively found in members of the E. coli B2 and D phylogroup. We further demonstrated that UCL fimbriae promote significant biofilm formation on abiotic surfaces and mediate specific attachment to exfoliated human uroepithelial cells. Combined, this study has defined the surface proteomic profiles and core surface proteome of UPEC during growth in human urine and identified a new type of fimbriae that may contribute to UTI.

Groucho homologue Grg5 interacts with the transcription factor Runx2-Cbfa1 and modulates its activity during postnatal growth in mice

Runx2-Cbfal, a Runt transcription factor, plays important roles during skeletal development. It is required for differentiation and function of osteoblasts. In its absence, chondrocyte hypertrophy is severely impaired and there is no vascularization of cartilage templates during skeletal development. These tissue-specific functions of Runx2 are likely to be dependent on its interaction with other proteins. We have therefore searched for proteins that may modulate the activity of Runx2. The yeast two-hybrid system was used to identify a groucho homologue, Grg5, as a Runx2-interacting protein. Grg5 enhances Runx2 activity in a cell culture-based assay and by analyses of postnatal growth in mice we demonstrate that Grg5 and Runx2 interact genetically. We also show that Runx2 haploinsufficiency in the absence of Grg5 results in a more severe delay in ossification of cranial sutures and fontanels than occurs with Runx2 haploinsufficiency on a wild-type background. Finally, we find shortening of the proliferative and hypertrophic zones, and expansion of the resting zone in the growth plates of Runx2(+/-)Grg5(-/-) mice that are associated with reduced Ihh expression and Indian hedgehog (Ihh) signaling. We therefore conclude that Grg5 enhances Runx2 activity in vivo.

Assessment of transit quality of service with occupancy load factor and passenger travel time measures

This paper investigates quality of service (QoS) and resource productivity implications of transit route passenger loading and travel time. It highlights the value of occupancy load factor as a direct passenger comfort QoS measure. Automatic Fare Collection data for a premium radial bus route in Brisbane, Australia, is used to investigate time series correlation between occupancy load factor and passenger average travel time. Correlation is strong across the entire span of service in both directions. Passengers tend to be making longer, peak direction commuter trips under significantly less comfortable conditions than off-peak. The Transit Capacity and Quality of Service Manual uses segment based load factor as a measure of onboard loading comfort QoS. This paper provides additional insight into QoS by relating the two route based dimensions of occupancy load factor and passenger average travel time together in a two dimensional format, both from the passenger’s and operator’s perspectives. Future research will apply Value of Time to QoS measurement, reflecting perceived passenger comfort through crowding and average time spent onboard. This would also assist in transit service quality econometric modeling. The methodology can be readily applied in a practical setting where AFC data for fixed scheduled routes is available. The study outcomes also provide valuable research and development directions.

Multi-Hypotheses Tracking using the Dempster–Shafer Theory, application to ambiguous road context

This paper presents a Multi-Hypotheses Tracking (MHT) approach that allows solving ambiguities that arise with previous methods of associating targets and tracks within a highly volatile vehicular environment. The previous approach based on the Dempster–Shafer Theory assumes that associations between tracks and targets are unique; this was shown to allow the formation of ghost tracks when there was too much ambiguity or conflict for the system to take a meaningful decision. The MHT algorithm described in this paper removes this uniqueness condition, allowing the system to include ambiguity and even to prevent making any decision if available data are poor. We provide a general introduction to the Dempster–Shafer Theory and present the previously used approach. Then, we explain our MHT mechanism and provide evidence of its increased performance in reducing the amount of ghost tracks and false positive processed by the tracking system.

A novel approach to 6-DOF adaptive trajectory tracking control of an AUV in the presence of parameter uncertainties

In this paper, the trajectory tracking control of an autonomous underwater vehicle (AUVs) in six-degrees-of-freedom (6-DOFs) is addressed. It is assumed that the system parameters are unknown and the vehicle is underactuated. An adaptive controller is proposed, based on Lyapunov׳s direct method and the back-stepping technique, which interestingly guarantees robustness against parameter uncertainties. The desired trajectory can be any sufficiently smooth bounded curve parameterized by time even if consist of straight line. In contrast with the majority of research in this field, the likelihood of actuators׳ saturation is considered and another adaptive controller is designed to overcome this problem, in which control signals are bounded using saturation functions. The nonlinear adaptive control scheme yields asymptotic convergence of the vehicle to the reference trajectory, in the presence of parametric uncertainties. The stability of the presented control laws is proved in the sense of Lyapunov theory and Barbalat׳s lemma. Efficiency of presented controller using saturation functions is verified through comparing numerical simulations of both controllers.

Polymorphisms in the vascular endothelial growth factor gene and the risk of familial endometriosis

Vascular endothelial growth factor (VEGF) is an endothelial cell-specific angiogenic protein suspected to be involved in the pathogenesis of endometriosis by establishing a new blood supply to the human exfoliated endometrium. Several transcription factor-binding sites are found in the VEGF 5'-untranslated region and variation within the region increases the transcriptional activity. Six previous studies which tested between one and three single nucleotide polymorphisms (SNPs) in samples comprising 105-215 cases and 100-219 controls have produced conflicting evidence for association between the SNPs in the VEGF region and endometriosis. To further investigate the reported association between VEGF variants and endometriosis, we tested the four VEGF polymorphisms (-2578 A/C, rs699947; -460 T/C, rs833061; +405 G/C, rs2010963 and +936 C/T, rs3025039) in a large Australian sample of 958 familial endometriosis cases and 959 controls. We also conducted a literature-based review of all relevant association studies of these VEGF SNPs in endometriosis and performed a meta-analysis. There was no evidence for association between endometriosis and the VEGF polymorphisms genotyped in our study. Combined association results from a meta-analysis did not provide any evidence for either genotypic or allelic association with endometriosis. Our detailed review and meta-analysis of the VEGF polymorphisms suggests that genotyping assay problems may underlie the previously reported associations between VEGF variants and endometriosis.

Genetic variation in tumour necrosis factor and lymphotoxin is not associated with endometriosis in an Australian sample

BACKGROUND Tumour necrosis factor (TNF) is a pleiotropic cytokine with a wide range of immunoregulatory effects. Variation in the promoter region of TNF and the neighbouring lymphotoxin alpha (LTA) gene might be associated with endometriosis. METHODS We examined the association between endometriosis and common single-nucleotide polymorphisms (SNPs) or haplotypes in the TNF/LTA region in an Australian sample by analysing 26 SNPs in 958 endometriosis cases and 959 unrelated controls. We selected functional SNPs in the coding and the promoter region of the TNF gene and HapMap tagging SNPs and typed them on a Sequenom MassARRAY platform. A key SNP (rs1800630) in the promoter region typed in previous studies did not give reliable results. Therefore, we also examined a statistically identical (r(2) = 1) SNP (siSNP) (rs2844482), identified using the web based program ssSNPer. RESULTS Genotype completion rate was 99.5% for SNPs spanning a region of 15.5 kb across the TNF/LTA locus. There was no evidence for association between endometriosis and TNF/LTA SNPs or SNP haplotypes in our case-control study. CONCLUSIONS Our data suggest both TNF and LTA genes are not major susceptibility genes for endometriosis.

Design and flight testing of a bio-inspired plume tracking algorithm for unmanned serial vehicles

There is an increased interest on the use of UAVs for environmental research such as tracking bush fires, volcanic eruptions, chemical accidents or pollution sources. The aim of this paper is to describe the theory and results of a bio-inspired plume tracking algorithm. A method for generating sparse plumes in a virtual environment was also developed. Results indicated the ability of the algorithms to track plumes in 2D and 3D. The system has been tested with hardware in the loop (HIL) simulations and in flight using a CO2 gas sensor mounted to a multi-rotor UAV. The UAV is controlled by the plume tracking algorithm running on the ground control station (GCS).

In bed with technology: Challenges and opportunities for sleep tracking

In recent years a variety of mobile apps, wearable technologies and embedded systems have emerged that allow individuals to track the amount and the quality of their sleep in their own beds. Despite the widespread adoption of these technologies, little is known about the challenges that current users face in tracking and analysing their sleep. Hence we conducted a qualitative study to examine the practices of current users of sleep tracking technologies and to identify challenges in current practice. Based on data collected from 5 online forums for users of sleep-tracking technologies, we identified 22 different challenges under the following 4 themes: tracking continuity, trust, data manipulation, and data interpretation. Based on these results, we propose 6 design opportunities to assist researchers and practitioners in designing sleep-tracking technologies.

On the integration of self-tracking data amongst quantified self members

Self-tracking, the process of recording one's own behaviours, thoughts and feelings, is a popular approach to enhance one's self-knowledge. While dedicated self-tracking apps and devices support data collection, previous research highlights that the integration of data constitutes a barrier for users. In this study we investigated how members of the Quantified Self movement---early adopters of self-tracking tools---overcome these barriers. We conducted a qualitative analysis of 51 videos of Quantified Self presentations to explore intentions for collecting data, methods for integrating and representing data, and how intentions and methods shaped reflection. The findings highlight two different intentions---striving for self-improvement and curiosity in personal data---which shaped how these users integrated data, i.e. the effort required. Furthermore, we identified three methods for representing data---binary, structured and abstract---which influenced reflection. Binary representations supported reflection-in-action, whereas structured and abstract representations supported iterative processes of data collection, integration and reflection. For people tracking out of curiosity, this iterative engagement with personal data often became an end in itself, rather than a means to achieve a goal. We discuss how these findings contribute to our current understanding of self-tracking amongst Quantified Self members and beyond, and we conclude with directions for future work to support self-trackers with their aspirations.