Achieving high reliability for ambiguity resolutions with multiple GNSS constellations

Global Navigation Satellite Systems (GNSS)-based observation systems can provide high precision positioning and navigation solutions in real time, in the order of subcentimetre if we make use of carrier phase measurements in the differential mode and deal with all the bias and noise terms well. However, these carrier phase measurements are ambiguous due to unknown, integer numbers of cycles. One key challenge in the differential carrier phase mode is to fix the integer ambiguities correctly. On the other hand, in the safety of life or liability-critical applications, such as for vehicle safety positioning and aviation, not only is high accuracy required, but also the reliability requirement is important. This PhD research studies to achieve high reliability for ambiguity resolution (AR) in a multi-GNSS environment. GNSS ambiguity estimation and validation problems are the focus of the research effort. Particularly, we study the case of multiple constellations that include initial to full operations of foreseeable Galileo, GLONASS and Compass and QZSS navigation systems from next few years to the end of the decade. Since real observation data is only available from GPS and GLONASS systems, the simulation method named Virtual Galileo Constellation (VGC) is applied to generate observational data from another constellation in the data analysis. In addition, both full ambiguity resolution (FAR) and partial ambiguity resolution (PAR) algorithms are used in processing single and dual constellation data. Firstly, a brief overview of related work on AR methods and reliability theory is given. Next, a modified inverse integer Cholesky decorrelation method and its performance on AR are presented. Subsequently, a new measure of decorrelation performance called orthogonality defect is introduced and compared with other measures. Furthermore, a new AR scheme considering the ambiguity validation requirement in the control of the search space size is proposed to improve the search efficiency. With respect to the reliability of AR, we also discuss the computation of the ambiguity success rate (ASR) and confirm that the success rate computed with the integer bootstrapping method is quite a sharp approximation to the actual integer least-squares (ILS) method success rate. The advantages of multi-GNSS constellations are examined in terms of the PAR technique involving the predefined ASR. Finally, a novel satellite selection algorithm for reliable ambiguity resolution called SARA is developed. In summary, the study demonstrats that when the ASR is close to one, the reliability of AR can be guaranteed and the ambiguity validation is effective. The work then focuses on new strategies to improve the ASR, including a partial ambiguity resolution procedure with a predefined success rate and a novel satellite selection strategy with a high success rate. The proposed strategies bring significant benefits of multi-GNSS signals to real-time high precision and high reliability positioning services.

Pseudo-marginal algorithms with multiple CPUs

The emergence of pseudo-marginal algorithms has led to improved computational efficiency for dealing with complex Bayesian models with latent variables. Here an unbiased estimator of the likelihood replaces the true likelihood in order to produce a Bayesian algorithm that remains on the marginal space of the model parameter (with latent variables integrated out), with a target distribution that is still the correct posterior distribution. Very efficient proposal distributions can be developed on the marginal space relative to the joint space of model parameter and latent variables. Thus psuedo-marginal algorithms tend to have substantially better mixing properties. However, for pseudo-marginal approaches to perform well, the likelihood has to be estimated rather precisely. This can be difficult to achieve in complex applications. In this paper we propose to take advantage of multiple central processing units (CPUs), that are readily available on most standard desktop computers. Here the likelihood is estimated independently on the multiple CPUs, with the ultimate estimate of the likelihood being the average of the estimates obtained from the multiple CPUs. The estimate remains unbiased, but the variability is reduced. We compare and contrast two different technologies that allow the implementation of this idea, both of which require a negligible amount of extra programming effort. The superior performance of this idea over the standard approach is demonstrated on simulated data from a stochastic volatility model.

Social support promotes psychological well-being following a natural disaster

Receiving emotional support has consistently been demonstrated as an important factor associated with mental health but sparse research has investigated giving support in addition to receiving it or the types of support that predict well-being. In this paper the relationship between giving and receiving instrumental and emotional social support and psychological well-being during and following a natural disaster is investigated. A survey administered between four and six months after fatal floods was conducted with 200 community members consisting of men (n = 68) and women (n = 132) aged between 17 and 87 years. Social support experiences were assessed using the 2-Way Social Support Scale (2-Way SSS; Shakespeare-Finch & Obst, 2011) and eudemonic well-being was measured using the Psychological Well-Being Scale (PWBS; Ryff & Keyes, 1995). Hierarchical multiple regression analyses were used to examine expected relationships and to explore the differential effects of the four factors of the 2-Way SSS. Results indicated that social support shared significant positive associations with domains of psychological well-being, especially with regards to interpersonal relationships. Receiving and giving emotional support were respectively the strongest unique predictors of psychological well-being. However, receiving instrumental support predicted less autonomy. Results highlight the importance of measuring social support as a multidimensional construct and affirm that disaster response policy and practice should focus on emotional as well as instrumental needs in order to promote individual and community psychosocial health following a flooding crisis.

Multiple sclerosis susceptibility-associated SNPs do not influence disease severity measures in a cohort of Australian MS patients

Recent association studies in multiple sclerosis (MS) have identified and replicated several single nucleotide polymorphism (SNP) susceptibility loci including CLEC16A, IL2RA, IL7R, RPL5, CD58, CD40 and chromosome 12q13–14 in addition to the well established allele HLA-DR15. There is potential that these genetic susceptibility factors could also modulate MS disease severity, as demonstrated previously for the MS risk allele HLA-DR15. We investigated this hypothesis in a cohort of 1006 well characterised MS patients from South-Eastern Australia. We tested the MS-associated SNPs for association with five measures of disease severity incorporating disability, age of onset, cognition and brain atrophy. We observed trends towards association between the RPL5 risk SNP and time between first demyelinating event and relapse, and between the CD40 risk SNP and symbol digit test score. No associations were significant after correction for multiple testing. We found no evidence for the hypothesis that these new MS disease risk-associated SNPs influence disease severity.

Results of a phase IIa clinical trial of an anti-inflammatory molecule, chaperonin 10, in multiple sclerosis

Background Chaperonin 10 (Cpn10) is a mitochondrial molecule involved in protein folding. The aim of this study was to determine the safety profile of Cpn10 in patients with multiple sclerosis (MS). Methods A total of 50 patients with relapse-remitting or secondary progressive MS were intravenously administered 5 mg or 10 mg of Cpn10 weekly for 12 weeks in a double-blind, randomized, placebo controlled, phase II trial. Clinical reviews, including Expanded Disability Status Scale and magnetic resonance imaging (MRI) with Gadolinium, were undertaken every 4 weeks. Stimulation of patient peripheral blood mononuclear cells with lipopolysaccharide ex vivo was used to measure the in vivo activity of Cpn10. Results No significant differences in the frequency of adverse events were seen between treatment and placebo arms. Leukocytes from both groups of Cpn10-treated patients produced significantly lower levels of critical proinflammatory cytokines. A trend toward improvement in new Gadolinium enhancing lesions on MRI was observed, but this difference was not statistically significant. No differences in clinical outcome measures were seen. Conclusions Cpn10 is safe and well tolerated when administered to patients with MS for 3 months, however, a further extended phase II study primarily focused on efficacy is warranted.

Gene expression studies in multiple sclerosis

Multiple sclerosis (MS) is a serious neurological disorder affecting young Caucasian individuals, usually with an age of onset at 18 to 40 years old. Females account for approximately 60x of MS cases and the manifestation and course of the disease is highly variable from patient to patient. The disorder is characterised by the development of plaques within the central nervous system (CNS). Many gene expression studies have been undertaken to look at the specific patterns of gene transcript levels in MS. Human tissues and experimental mice were used in these gene-profiling studies and a very valuable and interesting set of data has resulted from these various expression studies. In general, genes showing variable expression include mainly immunological and inflammatory genes, stress and antioxidant genes, as well as metabolic and central nervous system markers. Of particular interest are a number of genes localised to susceptible loci previously shown to be in linkage with MS. However due to the clinical complexity of the disease, the heterogeneity of the tissues used in expression studies, as well as the variable DNA chips/membranes used for the gene profiling, it is difficult to interpret the available information. Although this information is essential for the understanding of the pathogenesis of MS, it is difficult to decipher and define the gene pathways involved in the disorder. Experiments in gene expression profiling in MS have been numerous and lists of candidates are now available for analysis. Researchers have investigated gene expression in peripheral mononuclear white blood cells (PBMCs), in MS animal models Experimental Allergic Encephalomyelitis (EAE) and post mortem MS brain tissues. This review will focus on the results of these studies.

An examination of MS candidate genes identified as differentially regulated in multiple sclerosis plaque tissue, using absolute and comparative real-time Q-PCR analysis

In our laboratory, we have developed methods in real-time detection and quantitative-polymerase chain reaction (Q-PCR) to analyse the relative levels of gene expression in post mortem brain tissues. We have then applied this method to examine differences in gene activity between normal white matter (NWM) and plaque tissue from multiple sclerosis (MS) patients. Genes were selected based on their association with pathology and through identification by previously conducted global gene expression analysis. Plaque tissue was obtained from secondary progressive (SP) patients displaying chronic active, as well as acute pathologies; while NWM from the same location was obtained from age- and sex-matched controls (normal patients). In this study, we used both SYBR Green I supplementation and commercially available mixes to assess both comparative and absolute levels of gene activity. The results of both methods compared favourably for four of the five genes examined (P < 0.05, Pearsons), while differences in gene expression between chronic active and acute pathologies were also identified. For example, a >50-fold increase in osteopontin (Spp1) and inositol 1-4-5 phosphate 3 kinase B (Itpkb) levels in acute plaques contrasted with the 5-fold or less increase in chronic active plaques (P < 0.05, unpaired t test). By contrast, there was no significant difference in the levels of the MS marker and calcium-dependent protease (Calpain, Capns1) in MS plaque tissue. In summary, Q-PCR analysis using SYBR Green I has allowed us to economically obtain what may be clinically significant information from small amounts of the CNS, providing an opportunity for further clinical investigations.

A transcription factor map as revealed by a genome-wide gene expression analysis of whole-blood mRNA transcriptome in multiple sclerosis

Background Several lines of evidence suggests that transcription factors are involved in the pathogenesis of Multiple Sclerosis (MS) but a complete mapping the whole network has been elusive. One of the reasons is that there are several clinical subtypes of MS and transcription factors which may be involved in one subtype may not be in others. We investigated the possibility that this network could be mapped using microarray technologies and modern bioinformatics methods on a dataset from whole blood in 99 untreated MS patients (36 Relapse Remitting MS, 43 Primary Progressive MS, and 20 Secondary Progressive MS) and 45 age-matched healthy controls, Methodology/Principal Findings We have used two different analytical methodologies: a differential expression analysis and a differential co-expression analysis, which have converged on a significant number of regulatory motifs that seem to be statistically overrepresented in genes which are either differentially expressed (or differentially co-expressed) in cases and controls (e.g. V$KROX_Q6, p-value < 3.31E-6; V$CREBP1_Q2, p-value < 9.93E-6, V$YY1_02, p-value < 1.65E-5). Conclusions/significance: Our analysis uncovered a network of transcription factors that potentially dysregulate several genes in MS or one or more of its disease subtypes. Analysing the published literature we have found that these transcription factors are involved in the early T-lymphocyte specification and commitment as well as in oligodendrocytes dedifferentiation and development. The most significant transcription factors motifs were for the Early Growth response EGR/KROX family, ATF2, YY1 (Yin and Yang 1), E2F-1/DP-1 and E2F-4/DP-2 heterodimers, SOX5, and CREB and ATF families.

Saliva-derived DNA performs well in large-scale, high-density single-nucleotide polymorphism microarray studies

As of June 2009, 361 genome-wide association studies (GWAS) had been referenced by the HuGE database. GWAS require DNA from many thousands of individuals, relying on suitable DNA collections. We recently performed a multiple sclerosis (MS) GWAS where a substantial component of the cases (24%) had DNA derived from saliva. Genotyping was done on the Illumina genotyping platform using the Infinium Hap370CNV DUO microarray. Additionally, we genotyped 10 individuals in duplicate using both saliva- and blood-derived DNA. The performance of blood- versus saliva-derived DNA was compared using genotyping call rate, which reflects both the quantity and quality of genotyping per sample and the “GCScore,” an Illumina genotyping quality score, which is a measure of DNA quality. We also compared genotype calls and GCScores for the 10 sample pairs. Call rates were assessed for each sample individually. For the GWAS samples, we compared data according to source of DNA and center of origin. We observed high concordance in genotyping quality and quantity between the paired samples and minimal loss of quality and quantity of DNA in the saliva samples in the large GWAS sample, with the blood samples showing greater variation between centers of origin. This large data set highlights the usefulness of saliva DNA for genotyping, especially in high-density single-nucleotide polymorphism microarray studies such as GWAS.

Well-being, satisfaction and commitment : the substitutable nature of resources for maternity hospital nurses

Abstract Aims. To investigate the relationship between three types of organizational resources (job control, social support and organizational justice) and the impact of job demands on nurse’s well-being and attitudes towards their work. Background. The negative impact of work-related stress on nurse’s health and attitudes towards their work has been established. Increasingly, research is focusing on the role of organizational resources in reducing the impact of work related stress. Design. Cross-sectional survey. Method. Data collected in November 2008 from 226 Australian nurses and midwives were analysed using the full Job Strain Model with the addition of organizational justice variables. Multiple regression analyses explored the relationships among job control, job demands, three sources of social support and four types of organizational justice on well-being and work attitudes. Results. The overall regression models explained a significant amount of variance in well-being, job satisfaction and organizational commitment. Significant main effects were evident for support variables and organizational justice variables on well-being and job satisfaction. Interactions between job control and supervisor support and between job demands and supervisor support were evident for job satisfaction. Conclusions. Supervisor support and organizational justice have significant relationships with nurses’ well-being and job satisfaction. More broadly, the findings suggest that, in the triple-matching approach from a work-stressor to a resource to a work outcome, personal, supervisory and organizational resources may be substitutable. These findings provide nurse management with empirical endorsement for the development and delivery of the organization’s resources for nursing staff.

A metastatic neuroendocrine anaplastic small cell tumor in a patient with multiple endocrine neoplasia type 1 syndrome : assessment of disease status and response to doxorubicin, cyclophosphamide, etoposide chemotherapy through scintigraphic imaging with 111In-pentetreotide

Extrapulmonary small cell and small cell neuroendocrine tumors of unknown primary site are, in general, aggressive neoplasms with a short median survival. Like small cell lung cancer (SCLC), they often are responsive to chemotherapy and radiotherapy. Small cell lung cancer and well differentiated neuroendocrine carcinomas of the gastrointestinal tract and pancreas tend to express somatostatin receptors. These tumors may be localized in patients by scintigraphic imaging using radiolabeled somatostatin analogues. A patient with an anaplastic neuroendocrine small cell tumor arising on a background of multiple endocrine neoplasia type 1 syndrome is reported. The patient had a known large pancreatic gastrinoma and previously treated parathyroid adenopathy. At presentation, there was small cell cancer throughout the liver and skeleton. Imaging with a radiolabeled somatostatin analogue, 111In- pentetreotide (Mallinckrodt Medical B. V., Petten, Holland), revealed all sites of disease detected by routine biochemical and radiologic methods. After six cycles of chemotherapy with doxorubicin, cyclophosphamide, and etoposide, there was almost complete clearance of the metastatic disease. 111In-pentetreotide scintigraphy revealed uptake consistent with small areas of residual disease in the liver, the abdomen (in mesenteric lymph nodes), and posterior thorax (in a rib). The primary gastrinoma present before the onset of the anaplastic small cell cancer showed no evidence of response to the treatment. The patient remained well for 1 year and then relapsed with brain, lung, liver, and skeletal metastases. Despite an initial response to salvage radiotherapy and chemotherapy with carboplatin and dacarbazine, the patient died 6 months later.

Design, implementation and multisite evaluation of a system suitability protocol for the quantitative assessment of instrument performance in liquid chromatography-multiple reaction monitoring-MS (LC-MRM-MS)

Multiple reaction monitoring (MRM) mass spectrometry coupled with stable isotope dilution (SID) and liquid chromatography (LC) is increasingly used in biological and clinical studies for precise and reproducible quantification of peptides and proteins in complex sample matrices. Robust LC-SID-MRM-MS-based assays that can be replicated across laboratories and ultimately in clinical laboratory settings require standardized protocols to demonstrate that the analysis platforms are performing adequately. We developed a system suitability protocol (SSP), which employs a predigested mixture of six proteins, to facilitate performance evaluation of LC-SID-MRM-MS instrument platforms, configured with nanoflow-LC systems interfaced to triple quadrupole mass spectrometers. The SSP was designed for use with low multiplex analyses as well as high multiplex approaches when software-driven scheduling of data acquisition is required. Performance was assessed by monitoring of a range of chromatographic and mass spectrometric metrics including peak width, chromatographic resolution, peak capacity, and the variability in peak area and analyte retention time (RT) stability. The SSP, which was evaluated in 11 laboratories on a total of 15 different instruments, enabled early diagnoses of LC and MS anomalies that indicated suboptimal LC-MRM-MS performance. The observed range in variation of each of the metrics scrutinized serves to define the criteria for optimized LC-SID-MRM-MS platforms for routine use, with pass/fail criteria for system suitability performance measures defined as peak area coefficient of variation <0.15, peak width coefficient of variation <0.15, standard deviation of RT <0.15 min (9 s), and the RT drift <0.5min (30 s). The deleterious effect of a marginally performing LC-SID-MRM-MS system on the limit of quantification (LOQ) in targeted quantitative assays illustrates the use and need for a SSP to establish robust and reliable system performance. Use of a SSP helps to ensure that analyte quantification measurements can be replicated with good precision within and across multiple laboratories and should facilitate more widespread use of MRM-MS technology by the basic biomedical and clinical laboratory research communities.

Investigating well-being and mental health in Queensland fire-fighters

This thesis used survey and interview methods to examine how organisational and interpersonal factors impact on the mental health of fire and rescue workers. It was the first published research to assess and predict multiple indicators of mental health; psychological distress, well-being, posttraumatic growth and posttraumatic stress disorder symptoms. The results provide valuable information for supporting fire and rescue workers through psychoeducation and proactive intervention programs.

Volcanic architecture and chemostratigraphy within the Kalkarindji Continental Flood Basalt Province, Northern Territory : implications for eruption style from multiple fissure eruptions

This thesis was the first to define individual lava flow chemical variation and a detailed definition of the Kalkarindji Continental Flood Basalt Province, a lesser known province of the Phanerozoic eon. This thesis conducted an intensive field study that yielded numerous samples for petrography and chemical analyses as well as the generation of a detailed map of a portion of the Kalkarindji province.

Autonomous operation of multiple interconnected microgrids with self-healing capacity

This paper shows how multiple interconnected microgrids can operate in autonomous mode in a self–healing medium voltage network. This is possible if based on network self– healing capability, the neighbour microgrids are interconnected and a surplus generation capacity is available in some of the Distributed Energy Resources (DERs) of the interconnected microgrids. This will reduce or prevent load shedding within the microgrids with less generation capacity. Therefore, DERs in a microgrid are controlled such that they share the local load within that microgrid as well as the loads in other interconnected microgrids. Different control algorithms are proposed to manage the DERs at different operating conditions. On the other hand, a Distribution Static Compensator (DSTATCOM) is employed to regulate the voltage. The efficacy of the proposed power control, sharing and management among DERs in multiple interconnected microgrids is validated through extensive simulation studies using PSCAD/EMTDC.