Identification of evidence-based biospecimen quality-control tools

Control of biospecimen quality that is linked to processing is one of the goals of biospecimen science. Consensus is lacking, however, regarding optimal sample quality-control (QC) tools (ie, markers and assays). The aim of this review was to identify QC tools, both for fluid and solid-tissue samples, based on a comprehensive and critical literature review. The most readily applicable tools are those with a known threshold for the preanalytical variation and a known reference range for the QC analyte. Only a few meaningful markers were identified that meet these criteria, such as CD40L for assessing serum exposure at high temperatures and VEGF for assessing serum freeze-thawing. To fully assess biospecimen quality, multiple QC markers are needed. Here we present the most promising biospecimen QC tools that were identified.

Health service pathways for patients with chronic leg ulcers : identifying effective pathways for facilitation of evidence based wound care

Background: Chronic leg ulcers cause long term ill-health for older adults and the condition places a significant burden on health service resources. Although evidence on effective management of the condition is available, a significant evidence-practice gap is known to exist, with many suggested reasons e.g. multiple care providers, costs of care and treatments. This study aimed to identify effective health service pathways of care which facilitated evidence-based management of chronic leg ulcers. Methods: A sample of 70 patients presenting with a lower limb leg or foot ulcer at specialist wound clinics in Queensland, Australia were recruited for an observational study and survey. Retrospective data were collected on demographics, health, medical history, treatments, costs and health service pathways in the previous 12 months. Prospective data were collected on health service pathways, pain, functional ability, quality of life, treatments, wound healing and recurrence outcomes for 24 weeks from admission. Results: Retrospective data indicated that evidence based guidelines were poorly implemented prior to admission to the study, e.g. only 31% of participants with a lower limb ulcer had an ABPI or duplex assessment in the previous 12 months. On average, participants accessed care 2–3 times/week for 17 weeks from multiple health service providers in the twelve months before admission to the study clinics. Following admission to specialist wound clinics, participants accessed care on average once per week for 12 weeks from a smaller range of providers. The median ulcer duration on admission to the study was 22 weeks (range 2–728 weeks). Following admission to wound clinics, implementation of key indicators of evidence based care increased (p<0.001) and Kaplan-Meier survival analysis found the median time to healing was 12 weeks (95% CI 9.3–14.7). Implementation of evidence based care was significantly related to improved healing outcomes (p<0.001). Conclusions: This study highlights the complexities involved in accessing expertise and evidence based wound care for adults with chronic leg or foot ulcers. Results demonstrate that access to wound management expertise can promote streamlined health services and evidence based wound care, leading to efficient use of health resources and improved health.

Investigation of sensitivity based load ranking with composite load model in power system

Load modeling plays an important role in power system dynamic stability assessment. One of the widely used methods in assessing load model impact on system dynamic response is through parametric sensitivity analysis. Load ranking provides an effective measure of such impact. Traditionally, load ranking is based on either static or dynamic load model alone. In this paper, composite load model based load ranking framework is proposed. It enables comprehensive investigation into load modeling impacts on system stability considering the dynamic interactions between load and system dynamics. The impact of load composition on the overall sensitivity and therefore on ranking of the load is also investigated. Dynamic simulations are performed to further elucidate the results obtained through sensitivity based load ranking approach.

A taxonomy of model-based testing approaches

Model-based testing (MBT) relies on models of a system under test and/or its environment to derive test cases for the system. This paper discusses the process of MBT and defines a taxonomy that covers the key aspects of MBT approaches. It is intended to help with understanding the characteristics, similarities and differences of those approaches, and with classifying the approach used in a particular MBT tool. To illustrate the taxonomy, a description of how three different examples of MBT tools fit into the taxonomy is provided.

Feasibility of agent-based modelling of articular cartilage including a conceptual representation of its structure

Articular cartilage is a complex structure with an architecture in which fluid-swollen proteoglycans constrained within a 3D network of collagen fibrils. Because of the complexity of the cartilage structure, the relationship between its mechanical behaviours at the macroscale level and its components at the micro-scale level are not completely understood. The research objective in this thesis is to create a new model of articular cartilage that can be used to simulate and obtain insight into the micro-macro-interaction and mechanisms underlying its mechanical responses during physiological function. The new model of articular cartilage has two characteristics, namely: i) not use fibre-reinforced composite material idealization ii) Provide a framework for that it does probing the micro mechanism of the fluid-solid interaction underlying the deformation of articular cartilage using simple rules of repartition instead of constitutive / physical laws and intuitive curve-fitting. Even though there are various microstructural and mechanical behaviours that can be studied, the scope of this thesis is limited to osmotic pressure formation and distribution and their influence on cartilage fluid diffusion and percolation, which in turn governs the deformation of the compression-loaded tissue. The study can be divided into two stages. In the first stage, the distributions and concentrations of proteoglycans, collagen and water were investigated using histological protocols. Based on this, the structure of cartilage was conceptualised as microscopic osmotic units that consist of these constituents that were distributed according to histological results. These units were repeated three-dimensionally to form the structural model of articular cartilage. In the second stage, cellular automata were incorporated into the resulting matrix (lattice) to simulate the osmotic pressure of the fluid and the movement of water within and out of the matrix; following the osmotic pressure gradient in accordance with the chosen rule of repartition of the pressure. The outcome of this study is the new model of articular cartilage that can be used to simulate and study the micromechanical behaviours of cartilage under different conditions of health and loading. These behaviours are illuminated at the microscale level using the socalled neighbourhood rules developed in the thesis in accordance with the typical requirements of cellular automata modelling. Using these rules and relevant Boundary Conditions to simulate pressure distribution and related fluid motion produced significant results that provided the following insight into the relationships between osmotic pressure gradient and associated fluid micromovement, and the deformation of the matrix. For example, it could be concluded that: 1. It is possible to model articular cartilage with the agent-based model of cellular automata and the Margolus neighbourhood rule. 2. The concept of 3D inter connected osmotic units is a viable structural model for the extracellular matrix of articular cartilage. 3. Different rules of osmotic pressure advection lead to different patterns of deformation in the cartilage matrix, enabling an insight into how this micromechanism influences macromechanical deformation. 4. When features such as transition coefficient were changed, permeability (representing change) is altered due to the change in concentrations of collagen, proteoglycans (i.e. degenerative conditions), the deformation process is impacted. 5. The boundary conditions also influence the relationship between osmotic pressure gradient and fluid movement at the micro-scale level. The outcomes are important to cartilage research since we can use these to study the microscale damage in the cartilage matrix. From this, we are able to monitor related diseases and their progression leading to potential insight into drug-cartilage interaction for treatment. This innovative model is an incremental progress on attempts at creating further computational modelling approaches to cartilage research and other fluid-saturated tissues and material systems.

Assessment of applicability and transferability of evidence-based antenatal interventions to the Australian indigenous setting

There is a need for public health interventions to be based on the best available evidence. Unfortunately, well-conducted studies from settings similar to that in which an intervention is to be implemented are often not available. Therefore, health practitioners are forced to make judgements about proven effective interventions in one setting and their suitability to make a difference in their own setting. The framework of Wang et al. has been proposed to help with this process. This paper provides a case study on the application of the framework to a decision-making process regarding antenatal care in Aboriginal and Torres Strait Islander communities in Queensland. This method involved undertaking a systematic search of the current available evidence, then conducting a second literature search to determine factors that may affect the applicability and transferability of these interventions into these communities. Finally, in consideration of these factors, clinical judgement decisions on the applicability and transferability of these interventions were made. This method identified several interventions or strategies for which there was evidence of improving antenatal care or outcomes. By using the framework, we concluded that several of these effective interventions would be feasible in Aboriginal and Torres Strait Islander communities within Queensland.

Urban renewal, migration and memories : the affordances of place-based pedagogies for developing immigrant students’ literate repertoires

This paper reports on the new literacy demands in the middle years of schooling project in which the affordances of placed-based pedagogy are being explored through teacher inquiries and classroom-based design experiments. The school is located within a large-scale urban renewal project in which houses are being demolished and families relocated. The original school buildings have recently been demolished and replaced by a large ‘superschool’ which serves a bigger student population from a wider area. Drawing on both quantitative and qualitative data, the teachers reported that the language literacy learning of students (including a majority of students learning English as a second language) involved in the project exceeded their expectations. The project provided the motivation for them to develop their oral language repertoires, by involving them in processes such as conducting interviews with adults for their oral histories, through questioning the project manager in regular meetings, and through reporting to their peers and the wider community at school assemblies. At the same time students’ written and multimodal documentation of changes in the neighbourhood and the school grounds extended their literate and semiotic repertoires as they produced books, reports, films, powerpoints, visual designs and models of structures.

Usability and security of gaze-based graphical grid passwords

We present and analyze several gaze-based graphical password schemes based on recall and cued-recall of grid points; eye-trackers are used to record user's gazes, which can prevent shoulder-surfing and may be suitable for users with disabilities. Our 22-subject study observes that success rate and entry time for the grid-based schemes we consider are comparable to other gaze-based graphical password schemes. We propose the first password security metrics suitable for analysis of graphical grid passwords and provide an in-depth security analysis of user-generated passwords from our study, observing that, on several metrics, user-generated graphical grid passwords are substantially weaker than uniformly random passwords, despite our attempts at designing schemes to improve quality of user-generated passwords.

Prediction of IBD based on population history for fine gene mapping

A novel multiple regression method (RM) is developed to predict identity-by-descent probabilities at a locus L (IBDL), among individuals without pedigree, given information on surrounding markers and population history. These IBDL probabilities are a function of the increase in linkage disequilibrium (LD) generated by drift in a homogeneous population over generations. Three parameters are sufficient to describe population history: effective population size (Ne), number of generations since foundation (T), and marker allele frequencies among founders (p). IBD L are used in a simulation study to map a quantitative trait locus (QTL) via variance component estimation. RM is compared to a coalescent method (CM) in terms of power and robustness of QTL detection. Differences between RM and CM are small but significant. For example, RM is more powerful than CM in dioecious populations, but not in monoecious populations. Moreover, RM is more robust than CM when marker phases are unknown or when there is complete LD among founders or Ne is wrong, and less robust when p is wrong. CM utilises all marker haplotype information, whereas RM utilises information contained in each individual marker and all possible marker pairs but not in higher order interactions. RM consists of a family of models encompassing four different population structures, and two ways of using marker information, which contrasts with the single model that must cater for all possible evolutionary scenarios in CM.

The efficiency of corpus-based distributional models for literature-based discovery on large data sets

This paper evaluates the efficiency of a number of popular corpus-based distributional models in performing discovery on very large document sets, including online collections. Literature-based discovery is the process of identifying previously unknown connections from text, often published literature, that could lead to the development of new techniques or technologies. Literature-based discovery has attracted growing research interest ever since Swanson's serendipitous discovery of the therapeutic effects of fish oil on Raynaud's disease in 1986. The successful application of distributional models in automating the identification of indirect associations underpinning literature-based discovery has been heavily demonstrated in the medical domain. However, we wish to investigate the computational complexity of distributional models for literature-based discovery on much larger document collections, as they may provide computationally tractable solutions to tasks including, predicting future disruptive innovations. In this paper we perform a computational complexity analysis on four successful corpus-based distributional models to evaluate their fit for such tasks. Our results indicate that corpus-based distributional models that store their representations in fixed dimensions provide superior efficiency on literature-based discovery tasks.

Synthesis and evaluation of resveratrol-based nitroxides as potential treatments for hypertension

The synthesis and evaluation of novel resveratrol-based nitroxides have been explored for the potential treatment of hypertension. New methodology for the direct aryl iodination of isoindoline and isoindoline nitroxide using periodic acid and potassium iodide in concentrated sulphuric acid was developed. Diiodinated tetramethyl and tetraethyl isoindolines and a tetramethyl isoindoline nitroxide were prepared in excellent yields (70 – 82%). A diiodinated tetraethyl isoindoline nitroxide was generated from the corresponding nitroxide in modest yield (37%) alongside iodinated nitrones. The mono-iodinated species were also generated in modest yields (34 – 48%). Incorporation of the nitroxide unit into the structure of resveratrol was achieved using palladium-catalysed Heck coupling. Use of the previously prepared iodo products 5-iodo-1,1,3,3-tetramethylisoindolin-2-yloyl 18 and 5,6-diiodo-1,1,3,3-tetramethylisoindolin-2-yloyl 22 gave resveratrol nitroxides 12 and 13 in yields of 50% (optimized) and 1.6% respectively. Preliminary evaluation of the resveratrol analogue 12 as a treatment for hypertension was undertaken in the DOCA-salt rat model. A reduction in systolic blood pressure as well as alleviation of ventricular hypertrophy was observed. A larger study involving the DOCA salt rats is currently in progress.

Characterisation of Polycaprolatone-Based Scaffold Plus Recombinant Human Morphogenetic Protein - 2 (RHBMP-2) in an Ovine Thoracic Spine Model

This thesis represents a step forward in the development of a pre-clinical model investigating a suitable substitute for host bone for use in human spinal fusion. By way of an animal model, it examines the biological performance of a novel bone graft substitute comprised of a combination of a custom-designed biodegradable material and biologics.

Effect of Imidazolium-based Ionic Liquids on the nanoscale morphology of CuTCNQ (TCNQ= 7, 7, 8, 8-tetracyanoquinodimethane) metal-organic semiconductors

We demonstrate for the first time the ionic-liquid-mediated synthesis of nanostructured CuTCNQ by the simple immersion of copper in a solution of TCNQ where the viscosity of the medium significantly impacts the corrosion–crystallization process and the final morphology of the material.

Improved adhesion of active electrode materials to metal electrode substrates

A battery electrode for a lithium ion battery comprising an elec. conductive substrate having an electrode layer applied thereto, characterized in that the electrode layer includes an org. material having high alky., or an org. material which can be dissolved in org. solvents, or an org. material having an imide group(s) and aminoacetal group(s), or an org. material that chelates with or bonds with a metal substrate or that chelates with or bonds with an active material in the electrode layer. The org. material may be guanidine carbonate. [on SciFinder(R)]