Biological performance of a polycaprolactone-based scaffold plus recombinant human morphogenetic protein-2 (rhBMP-2) in an ovine thoracic interbody fusion model

Introduction. We develop a sheep thoracic spine interbody fusion model to study the suitability of polycaprolactone-based scaffold and recombinant human bone morphogenetic protein-2 (rhBMP-2) as a bone graft substitute within the thoracic spine. The surgical approach is a mini- open thoracotomy with relevance to minimally invasive deformity correction surgery for adolescent idiopathic scoliosis. To date there are no studies examining the use of this biodegradable implant in combination with biologics in a sheep thoracic spine model. Methods. In the present study, six sheep underwent a 3-level (T6/7, T8/9 and T10/11) discectomy with randomly allocated implantation of a different graft substitute at each of the three levels; (i) calcium phosphate (CaP) coated polycaprolactone based scaffold plus 0.54µg rhBMP-2, (ii) CaP coated PCL- based scaffold alone or (iii) autograft (mulched rib head). Fusion was assessed at six months post-surgery. Results. Computed Tomographic scanning demonstrated higher fusion grades in the rhBMP-2 plus PCL- based scaffold group in comparison to either PCL-based scaffold alone or autograft. These results were supported by histological evaluations of the respective groups. Biomechanical testing revealed significantly higher stiffness for the rhBMP-2 plus PCL- based scaffold group in all loading directions in comparison to the other two groups. Conclusions. The results of this study demonstrate that rhBMP-2 plus PCL-based scaffold is a viable bone graft substitute, providing an optimal environment for thoracic interbody spinal fusion in a large animal model.

Data warehousing model for integrating fragmented electronic health records from disparate and heterogeneous clinical data stores

This research was a step forward in developing a data integration framework for Electronic Health Records. The outcome of the research is a conceptual and logical Data Warehousing model for integrating Cardiac Surgery electronic data records. This thesis investigated the main obstacles for the healthcare data integration and proposes a data warehousing model suitable for integrating fragmented data in a Cardiac Surgery Unit.

A comprehensive dual-scale wood torrefaction model : application to the analysis of thermal run-away in industrial heat treatment processes

A dual-scale model of the torrefaction of wood was developed and used to study industrial configurations. At the local scale, the computational code solves the coupled heat and mass transfer and the thermal degradation mechanisms of the wood components. At the global scale, the two-way coupling between the boards and the stack channels is treated as an integral component of the process. This model is used to investigate the effect of the stack configuration on the heat treatment of the boards. The simulations highlight that the exothermic reactions occurring in each single board can be accumulated along the stack. This phenomenon may result in a dramatic eterogeneity of the process and poses a serious risk of thermal runaway, which is often observed in industrial plants. The model is used to explain how thermal runaway can be lowered by increasing the airflow velocity, the sticker thickness or by gas flow reversal.

Natural articular joints : model of lamellar-rollerbearing lubrication and the nature of the cartilage surface

The influence of pH on interfacial energy and wettability distributed over the phospholipid bilayer surface were studied, and the importance of cartilage hydrophobicity (wettability) on the coefficient of friction (f) was established. It is argued that the wettability of cartilage signifi antly depends on the number of phospholipid bilayers acting as solid lubricant; the hypothesis was proven by conducting friction tests with normal and lipid- depleted cartilage samples. A lamellar-roller-bearing lubrication model was devised involving two mechanisms: (i) lamellar frictionless movement of bilayers, and (ii) roller-bearing lubrication mode through structured synovial fluid, which operates when lamellar spheres, liposomes and macromolecules act like a roller-bearing situated between two cartilage surfaces in effective biological lubrication.

A general model for host plant selection in phytophagous insects

We develop a general theoretical framework for exploring the host plant selection behaviour of herbivorous insects. This model can be used to address a number of questions, including the evolution of specialists, generalists, preference hierarchies, and learning. We use our model to: (i) demonstrate the consequences of the extent to which the reproductive success of a foraging female is limited by the rate at which they find host plants (host limitation) or the number of eggs they carry (egg limitation); (ii) emphasize the different consequences of variation in behaviour before and after landing on (locating) a host (termed pre- and post-alighting, respectively); (iii) show that, in contrast to previous predictions, learning can be favoured in post-alighting behaviour--in particular, individuals can be selected to concentrate oviposition on an abundant low-quality host, whilst ignoring a rare higher-quality host; (iv) emphasize the importance of interactions between mechanisms in favouring specialization or learning.

How host plant variability influences the advantages to learning : a theoretical model for oviposition behaviour in Lepidoptera

Learning can allow individuals to increase their fitness in particular environments. The advantage to learning depends on the predictability of the environment and the extent to which animals can adjust their behaviour. Earlier general models have investigated when environmental predictability might favour the evolution of learning in foraging animals. Here, we construct a theoretical model that predicts the advantages to learning using a specific biological example: oviposition in the Lepidoptera. Our model includes environmental and behavioural complexities relevant to host selection in these insects and tests whether the predictions of the general models still hold. Our results demonstrate how the advantage of learning is maximised when within-generation variability is minimised (the local environment consists mainly of a single host plant species) and between-generation variability is maximised (different host plant species are the most common in different generations). We discuss how our results: (a) can be applied to recent empirical work in different lepidopteran species and (b) predict an important role of learning in lepidopteran agricultural pests.

Investigating epidermogenesis in a human skin equivalent model

Skin is the largest, and arguably, the most important organ of the body. It is a complex and multi-dimensional tissue, thus making it essentially impossible to fully model in vitro in conventional 2-dimensional culture systems. In view of this, rodents or pigs are utilised to study wound healing therapeutics or to investigate the biological effects of treatments on skin. However, there are many differences between the wound healing processes in rodents compared to humans (contraction vs. re-epithelialisation) and there are also ethical issues associated with animal testing for scientific research. Therefore, the development of skin equivalent (HSE) models from surgical discard human skin has become an important area of research. The studies in this thesis compare, for the first time, native human skin and the epidermogenesis process in a HSE model. The HSE was reported to be a comparable model for human skin in terms of expression and localisation of key epidermal cell markers. This validated HSE model was utilised to study the potential wound healing therapeutic, hyperbaric oxygen (HBO) therapy. There is a significant body of evidence suggesting that lack of cutaneous oxygen results in and potentiates the chronic, non-healing wound environment. Although the evidence is anecdotal, HBO therapy has displayed positive effects on re-oxygenation of chronic wounds and the clinical outcomes suggest that HBO treatment may be beneficial. Therefore, the HSE was subjected to a daily clinical HBO regime and assessed in terms of keratinocyte migration, proliferation, differentiation and epidermal thickening. HBO treatment was observed to increase epidermal thickness, in particular stratum corneum thickening, but it did not alter the expression or localisation of standard epidermal cell markers. In order to elucidate the mechanistic changes occurring in response to HBO treatment in the HSE model, gene microarrays were performed, followed by qRT-PCR of select genes which were differentially regulated in response to HBO treatment. The biological diversity of the HSEs created from individual skin donors, however, overrode the differences in gene expression between treatment groups. Network analysis of functional changes in the HSE model revealed general trends consistent with normal skin growth and maturation. As a more robust and longer term study of these molecular changes, protein localisation and expression was investigated in sections from the HSEs undergoing epidermogenesis in response to HBO treatment. These proteins were CDCP1, Metallothionein, Kallikrein (KLK) 1 and KLK7 and early growth response 1. While the protein expression within the HSE models exposed to HBO treatment were not consistent in all HSEs derived from all skin donors, this is the first study to detect and compare both KLK1 and CDCP1 protein expression in both a HSE model and native human skin. Furthermore, this is the first study to provide such an in depth analysis of the effect of HBO treatment on a HSE model. The data presented in this thesis, demonstrates high levels of variation between individuals and their response to HBO treatment, consistent with the clinical variation that is currently observed.

A conversation approach to business model innovation

Sense making through conversation plays a key role in channelling and furthering participatory business model innovation. The designer as facilitator, with conversation as a core tool, is an emerging area of interest within the design research literature. This paper will discuss preliminary findings of a case study of Second Road, a strategy and innovation consultancy that employed a design thinking approach and conversational methods to redesign a client’s business development model. Through this study conversation based co-creation emerged as the primary method for participatory innovation.

Quantitative and qualitative assessment of the regenerative potential of osteoblasts versus bone marrow derived mesenchymal stem cells in the reconstruction of critical sized segmental tibial bone defects in a large animal model

This thesis is about the use of different cells for bone tissue engineering. The cells were used in combination with a novel biomaterial in a large tibial bone defects in a sheep model. Furthermore this study developed a novel cell delivery procedure for bone tissue engineering. This novel procedure of cell delivery could overcome the current problems of cell-based tissue engineering and serve as a baseline for the translation of novel concepts into clinical application.

Business model experimentation : what is the role of deign-led prototyping in developing novel business models?

This book presents readers with the opportunity to fundamentally re-evaluate the processes of innovation and entrepreneurship, and to rethink how they might best be stimulated and fostered within our organizations and communities. The fundamental thesis of the book is that the entrepreneurial process is not a linear progression from novel idea to successful innovation, but is an iterative series of experiments, where progress depends on the persistence and resilience of the individuals involved, and their ability and to learn from failure as well as success. From this premise, the authors argue that the ideal environment for new venture creation is a form of “experimental laboratory,” a community of innovators where ideas are generated, shared, and refined; experiments are encouraged; and which in itself serves as a test environment for those ideas and experiments. This environment is quite different from the traditional “incubator,” which may impose the disciplines of the established firm too early in the development of the new venture.

A critical success factors model for ERP implementation

An effective IT infrastructure can support a business vision and strategy; a poor, decentralized one can break a company. More and more companies are turning to off-the-shelf ERP (enterprise resource planning) solutions for IT planning and legacy systems management. The authors have developed a framework to help managers successfully plan and implement an ERP project

The development of a naturalistic car following model for assessing managed motorway systems' safety effects

This thesis highlights the limitations of the existing car following models to emulate driver behaviour for safety study purposes. It also compares the capabilities of the mainstream car following models emulating driver behaviour precise parameters such as headways and Time to Collisions. The comparison evaluates the robustness of each car following model for safety metric reproductions. A new car following model, based on the personal space concept and fish school model is proposed to simulate more precise traffic metrics. This new model is capable of reflecting changes in the headway distribution after imposing the speed limit form VSL systems. This research facilitates assessing Intelligent Transportation Systems on motorways, using microscopic simulation.

Hydrogeological framework, conceptual and numerical groundwater flow model of Laidley Creek catchment, Queensland, Australia

This thesis studies the water resources of Laidley Creek catchment within the Lockyer Valley where groundwater is used for intensive irrigation of crops. A holistic approach was used to consider groundwater within the total water cycle. The project mapped the geology, measured stream flows and groundwater levels, and analysed the chemistry of the waters. These data were integrated within a catchment-wide conceptual model, including historic and rainfall records. From this a numerical simulation was produced to test data validity and develop predictions of behaviour, which can support management decisions, particularly in times of variable climate.

Determining process model precision and generalization with weighted artificial negative events

Process mining encompasses the research area which is concerned with knowledge discovery from event logs. One common process mining task focuses on conformance checking, comparing discovered or designed process models with actual real-life behavior as captured in event logs in order to assess the “goodness” of the process model. This paper introduces a novel conformance checking method to measure how well a process model performs in terms of precision and generalization with respect to the actual executions of a process as recorded in an event log. Our approach differs from related work in the sense that we apply the concept of so-called weighted artificial negative events towards conformance checking, leading to more robust results, especially when dealing with less complete event logs that only contain a subset of all possible process execution behavior. In addition, our technique offers a novel way to estimate a process model’s ability to generalize. Existing literature has focused mainly on the fitness (recall) and precision (appropriateness) of process models, whereas generalization has been much more difficult to estimate. The described algorithms are implemented in a number of ProM plugins, and a Petri net conformance checking tool was developed to inspect process model conformance in a visual manner.

Measuring IS-support : a conceptual model

This paper reports on a conceptual model of a larger research effort proceeding from a central interest in the importance of assessing the IS-Support provided to key-user groups. This study conceptualised a new multidimensional IS-Support construct with four dimensions: training, documentation, assistance and authorisation, which form the overarching construct – IS-Support. We argue that a holistic measure for assessing IS-Support should consist of dimensions, and measures, that together assess the variety of the support provided to IS key-user groups. The proposed IS-Support construct is defined as the support the IS key-user groups receive to increase their capabilities in utilising information systems within the organisation. With two interrelated phases, conceptualisation phase and validation phase, to rigorously hypothesise and validate a measurement model, the IS-Support model, proposed in this study, is intended to include the characteristics of analytic theory.