Zoledronic acid preserves bone structure and increases survival but does not limit tumour incidence in a prostate cancer bone metastasis model

Background The bisphosphonate, zoledronic acid (ZOL), can inhibit osteoclasts leading to decreased osteoclastogenesis and osteoclast activity in bone. Here, we used a mixed osteolytic/osteoblastic murine model of bone-metastatic prostate cancer, RM1(BM), to determine how inhibiting osteolysis with ZOL affects the ability of these cells to establish metastases in bone, the integrity of the tumour-bearing bones and the survival of the tumour-bearing mice. Methods The model involves intracardiac injection for arterial dissemination of the RM1(BM) cells in C57BL/6 mice. ZOL treatment was given via subcutaneous injections on days 0, 4, 8 and 12, at 20 and 100 µg/kg doses. Bone integrity was assessed by micro-computed tomography and histology with comparison to untreated mice. The osteoclast and osteoblast activity was determined by measuring serum tartrate-resistant acid phosphatase 5b (TRAP 5b) and osteocalcin, respectively. Mice were euthanased according to predetermined criteria and survival was assessed using Kaplan Meier plots. Findings Micro-CT and histological analysis showed that treatment of mice with ZOL from the day of intracardiac injection of RM1(BM) cells inhibited tumour-induced bone lysis, maintained bone volume and reduced the calcification of tumour-induced endochondral osteoid material. ZOL treatment also led to a decreased serum osteocalcin and TRAP 5b levels. Additionally, treated mice showed increased survival compared to vehicle treated controls. However, ZOL treatment did not inhibit the cells ability to metastasise to bone as the number of bone-metastases was similar in both treated and untreated mice. Conclusions ZOL treatment provided significant benefits for maintaining the integrity of tumour-bearing bones and increased the survival of tumour bearing mice, though it did not prevent establishment of bone-metastases in this model. From the mechanistic view, these observations confirm that tumour-induced bone lysis is not a requirement for establishment of these bone tumours.

Verifying a Student Engagement, Success and Retention Maturity Model (SESR-MM): A reality check of the model using data derived from three universities

Australian higher education institutions (HEIs) have entered a new phase of regulation and accreditation which includes performance-based funding relating to the participation and retention of students from social and cultural groups previously underrepresented in higher education. However, in addressing these priorities, it is critical that HEIs do not further disadvantage students from certain groups by identifying them for attention because of their social or cultural backgrounds, circumstances which are largely beyond the control of students. In response, many HEIs are focusing effort on university-wide approaches to enhancing the student experience because such approaches will enhance the engagement, success and retention of all students, and in doing so, particularly benefit those students who come from underrepresented groups. Measuring and benchmarking student experiences and engagement that arise from these efforts is well supported by extensive collections of student experience survey data. However no comparable instrument exists that measures the capability of institutions to influence and/or enhance student experiences where capability is an indication of how well an organisational process does what it is designed to do (Rosemann & de Bruin, 2005). We have proposed that the concept of a maturity model (Marshall, 2010; Paulk, 1999) may be useful as a way of assessing the capability of HEIs to provide and implement student engagement, success and retention activities and we are currently articulating a Student Engagement, Success and Retention Maturity Model (SESR-MM), (Clarke, Nelson & Stoodley, 2012; Nelson, Clarke & Stoodley, 2012). Our research aims to address the current gap by facilitating the development of an SESR-MM instrument that aims (i) to enable institutions to assess the capability of their current student engagement and retention programs and strategies to influence and respond to student experiences within the institution; and (ii) to provide institutions with the opportunity to understand various practices across the sector with a view to further improving programs and practices relevant to their context. Our research extends the generational approach which has been useful in considering the evolutionary nature of the first year experience (FYE) (Wilson, 2009). Three generations have been identified and explored: First generation approaches that focus on co-curricular strategies (e.g. orientation and peer programs); Second generation approaches that focus on curriculum (e.g. pedagogy, curriculum design, and learning and teaching practice); and third generation approaches—also referred to as transition pedagogy—that focus on the production of an institution-wide integrated holistic intentional blend of curricular and co-curricular activities (Kift, Nelson & Clarke, 2010). Our research also moves beyond assessments of students’ experiences to focus on assessing institutional processes and their capability to influence student engagement. In essence, we propose to develop and use the maturity model concept to produce an instrument that will indicate the capability of HEIs to manage and improve student engagement, success and retention programs and strategies. The issues explored in this workshop are (i) whether the maturity model concept can be usefully applied to provide a measure of institutional capability for SESR; (ii) whether the SESR-MM can be used to assess the maturity of a particular set of institutional practices; and (iii) whether a collective assessment of an institution’s SESR capabilities can provide an indication of the maturity of the institution’s SESR activities. The workshop will be approached in three stages. Firstly, participants will be introduced to the key characteristics of maturity models, followed by a discussion of the SESR-MM and the processes involved in its development. Secondly, participants will be provided with resources to facilitate the development of a maturity model and an assessment instrument for a range of institutional processes and related practices. In the final stage of the workshop, participants will “assess” the capability of these practices to provide a collective assessment of the maturity of these processes. References Australian Council for Educational Research. (n.d.). Australasian Survey of Student Engagement. Retrieved from http://www.acer.edu.au/research/ausse/background Clarke, J., Nelson, K., & Stoodley, I. (2012, July). The Maturity Model concept as framework for assessing the capability of higher education institutions to address student engagement, success and retention: New horizon or false dawn? A Nuts & Bolts presentation at the 15th International Conference on the First Year in Higher Education, “New Horizons,” Brisbane, Australia. Department of Education, Employment and Workplace Relations. (n.d.). The University Experience Survey. Advancing quality in higher education information sheet. Retrieved from http://www.deewr.gov.au/HigherEducation/Policy/Documents/University_Experience_Survey.pdf Kift, S., Nelson, K., & Clarke, J. (2010) Transition pedagogy - a third generation approach to FYE: A case study of policy and practice for the higher education sector. The International Journal of the First Year in Higher Education, 1(1), pp. 1-20. Marshall, S. (2010). A quality framework for continuous improvement of e-Learning: The e-Learning Maturity Model. Journal of Distance Education, 24(1), 143-166. Nelson, K., Clarke, J., & Stoodley, I. (2012). An exploration of the Maturity Model concept as a vehicle for higher education institutions to assess their capability to address student engagement. A work in progress. Submitted for publication. Paulk, M. (1999). Using the Software CMM with good judgment, ASQ Software Quality Professional, 1(3), 19-29. Wilson, K. (2009, June–July). The impact of institutional, programmatic and personal interventions on an effective and sustainable first-year student experience. Keynote address presented at the 12th Pacific Rim First Year in Higher Education Conference, “Preparing for Tomorrow Today: The First Year as Foundation,” Townsville, Australia. Retrieved from http://www.fyhe.com.au/past_papers/papers09/ppts/Keithia_Wilson_paper.pdf

An in-vitro 3-D cell culture model for studying pathomechanisms in AMD

Purpose To develop a novel 3-D cell culture model with the view to studying the pathomechanisms underlying the development of age-related macular degeneration (AMD). Our central hypothesis is that the silk structural protein fibroin used in conjunction with cultured human cells can be used to mimic the structural relationships between the RPE and choriocapillaris in health and disease. Methods Co-cultures of human RPE cells (ARPE-19 cells grown in Miller’s medium) and microvascular endothelial cells (HMEC-1 cells grown in endothelial culture medium) were established on opposing sides of a synthetic Bruch’s membrane (3 microns thick) constructed from B mori silk fibroin. Cell attachment was facilitated by pre-coating the fibroin membrane with vitronectin (for ARPE-19 cells) and gelatin (for HMEC-1 cells) respectively. The effects of tropoelastin on attachment of ARPE-19 cells was also examined. Barrier function was examined by measurement of trans-epithelial resistance (TER) using a voltohmmeter (EVOM-2). The phagocytic activity of the synthetic RPE was tested using vitronectin-coated microspheres (2 micron diameter FluoSpheres). In some cultures, membrane defects were created by puncturing within a 24 G needle. The architecture of the synthetic tissue before and after wounding was examined by confocal microscopy after staining for ZO-1 and F-actin. Results The RPE layer of the 3D model developed a cobblestoned morphology (validated by staining for ZO-1 and F-actin), displayed barrier function (validated by measurement of TER) and demonstrated cytoplasmic uptake of vitronectin-coated microspheres. Attachment of ARPE-19 cells to fibroin was unaffected by tropoelastin. Microvascular endothelial cells attached well to the gelatin-coated surface of the fibroin membrane and remained physically separated from the overlaying RPE layer. The fibroin membranes were amenable to puncturing without collapse thus providing the opportunity to study transmembrane migration of the endothelial cells. Conclusions Synthetic Bruch’s membranes constructed from silk fibroin, vitronectin and gelatin, support the co-cultivation of RPE cells and microvascular endothelial cells. The resulting RPE layer displays functions similar to that of native RPE and the entire tri-layered structure displays potential to be used as an in vitro model of choroidal neovascularization.

Numerical solution of an optimal control model of dendritic cell treatment of a growing tumour

A new optimal control model of the interactions between a growing tumour and the host immune system along with an immunotherapy treatment strategy is presented. The model is based on an ordinary differential equation model of interactions between the growing tu- mour and the natural killer, cytotoxic T lymphocyte and dendritic cells of the host immune system, extended through the addition of a control function representing the application of a dendritic cell treat- ment to the system. The numerical solution of this model, obtained from a multi species Runge–Kutta forward-backward sweep scheme, is described. We investigate the effects of varying the maximum al- lowed amount of dendritic cell vaccine administered to the system and find that control of the tumour cell population is best effected via a high initial vaccine level, followed by reduced treatment and finally cessation of treatment. We also found that increasing the strength of the dendritic cell vaccine causes an increase in the number of natural killer cells and lymphocytes, which in turn reduces the growth of the tumour.

Analysing the Sri Lankan conflict using Michael Mann's four-dimensional model of social power

This thesis provides an overview of the Sri Lankan civil war with a view to identifying some of the factors that contributed to the dispute between the Sri Lankan government and the Liberation Tigers of Tamil Eelam. It adopts a multi-causal explanation of the conflict by reference to the theories of social power developed by Michael Mann. The conflict has been variously described as an ethnic or political conflict, or has been characterised as a determined by a number of interacting factors (including colonialism, ethnicity, religion, economy, politics and globalisation). Mann’s four-dimensional model of social power is deployed to analyse the causal relationships, together with their inter-connections, which clarify the origins of the dispute. It argues that Mann’s theoretical framework helps to highlight some of the interconnected elements that contributed to the conflict.

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 systemic view of innovation adoption in the Australian beef industry

Significant investments in developing technological innovations have been made in the Australian beef industry but with low adoption rates. By modelling the key variables and their interactions in the innovation adoption process, this research seeks to demonstrate the complexity and dynamics of the process. This research uses causal loop modelling and develops a holistic model of the current innovation adoption system in the Australian beef industry to show the complexity of dynamic interactions among multiple variables. It is suggested that innovation adoption is such an extremely complex issue, and we need to shift our views on this issue from a paradigm of linear thinking to systems thinking. Innovation adoption is more likely to be enhanced based on a full understanding of the complexity and dynamics of the system as a whole. The paper demonstrates to practitioners and developers of innovation the multiple variables and interactions impacting innovation adoption.

A geometric construction of travelling wave solutions to the Keller–Segel model

We study a version of the Keller–Segel model for bacterial chemotaxis, for which exact travelling wave solutions are explicitly known in the zero attractant diffusion limit. Using geometric singular perturbation theory, we construct travelling wave solutions in the small diffusion case that converge to these exact solutions in the singular limit.

University Students Depression Inventory : measurement model and psychometric properties

Depression is a serious condition that impacts the academic success and emotional well-being of the university students globally. Keeping in view the debilitating nature of this condition, the present study examined the stability of the factor structure and psychometric properties of the University Student Depression Inventory (USDI; Khawaja and Bryden, 2006). There is a need to translate and validate the scale for Persian speaking students, who live in Iran, its neighboring countries and in many other Western countries. The scale was translated into the Persian language and was used as part of a battery consisting of the scales measuring suicide, depression, stress, happiness and academic achievement. The battery was administered to 359 undergraduate students, and an additional 150 students who had been referred to the mental health center of the University of Tehran as clinical sample. Confirmatory factor analysis upheld the original three-factor structure. The results exhibited internal consistency, test-retest reliability, convergent, and divergent validity, and discriminant validity. There were gender differences and male had higher mean scores on Lethargy, Cognitive\emotion, and Academic motivation subscales than female students. Findings supported the Persian version of the USDI for cross-cultural use as a valid and reliable measure in the diagnosis of depression.

A spatial-indexing model for measuring neighbourhood-level land-use and transport integration

Significant attention has been given in urban policy literature to the integration of land-use and transport planning and policies—with a view to curbing sprawling urban form and diminishing externalities associated with car-dependent travel patterns. By taking land-use and transport interaction into account, this debate mainly focuses on how a successful integration can contribute to societal well-being, providing efficient and balanced economic growth while accomplishing the goal of developing sustainable urban environments and communities. The integration is also a focal theme of contemporary urban development models, such as smart growth, liveable neighbourhoods, and new urbanism. Even though available planning policy options for ameliorating urban form and transport-related externalities have matured—owing to growing research and practice worldwide—there remains a lack of suitable evaluation models to reflect on the current status of urban form and travel problems or on the success of implemented integration policies. In this study we explore the applicability of indicator-based spatial indexing to assess land-use and transport integration at the neighbourhood level. For this, a spatial index is developed by a number of indicators compiled from international studies and trialled in Gold Coast, Queensland, Australia. The results of this modelling study reveal that it is possible to propose an effective metric to determine the success level of city plans considering their sustainability performance via composite indicator methodology. The model proved useful in demarcating areas where planning intervention is applicable, and in identifying the most suitable locations for future urban development and plan amendments. Lastly, we integrate variance-based sensitivity analysis with the spatial indexing method, and discuss the applicability of the model in other urban contexts.

A model of workplace safety incorporating worker interactions and simple interventions

Although there was substantial research into the occupational health and safety sector over the past forty years, this generally focused on statistical analyses of data related to costs and/or fatalities and injuries. There is a lack of mathematical modelling of the interactions between workers and the resulting safety dynamics of the workplace. There is also little work investigating the potential impact of different safety intervention programs prior to their implementation. In this article, we present a fundamental, differential equation-based model of workplace safety that treats worker safety habits similarly to an infectious disease in an epidemic model. Analytical results for the model, derived via phase plane and stability analysis, are discussed. The model is coupled with a model of a generic safety strategy aimed at minimising unsafe work habits, to produce an optimal control problem. The optimal control model is solved using the forward-backward sweep numerical scheme implemented in Matlab.

A meshfree model for plant tissue deformations during drying

Plant tissue has a complex cellular structure which is an aggregate of individual cells bonded by middle lamella. During drying processes, plant tissue undergoes extreme deformations which are mainly driven by moisture removal and turgor loss. Numerical modelling of this problem becomes challenging when conventional grid-based modelling techniques such as Finite Element Methods (FEM) and Finite Difference Methods (FDM) have grid-based limitations. This work presents a meshfree approach to model and simulate the deformations of plant tissues during drying. This method demonstrates the fundamental capabilities of meshfree methods in handling extreme deformations of multiphase systems. A simplified 2D tissue model is developed by aggregating individual cells while accounting for the stiffness of the middle lamella. Each individual cell is simply treated as consisting of two main components: cell fluid and cell wall. The cell fluid is modelled using Smoothed Particle Hydrodynamics (SPH) and the cell wall is modelled using a Discrete Element Method (DEM). During drying, moisture removal is accounted for by reduction of cell fluid and wall mass, which causes local shrinkage of cells eventually leading to tissue scale shrinkage. The cellular deformations are quantified using several cellular geometrical parameters and a favourably good agreement is observed when compared to experiments on apple tissue. The model is also capable of visually replicating dry tissue structures. The proposed model can be used as a step in developing complex tissue models to simulate extreme deformations during drying.

An object-oriented design of a World Model for autonomous city vehicles

This paper presents an object-oriented world model for the road traffic environment of autonomous (driver-less) city vehicles. The developed World Model is a software component of the autonomous vehicle's control system, which represents the vehicle's view of its road environment. Regardless whether the information is a priori known, obtained through on-board sensors, or through communication, the World Model stores and updates information in real-time, notifies the decision making subsystem about relevant events, and provides access to its stored information. The design is based on software design patterns, and its application programming interface provides both asynchronous and synchronous access to its information. Experimental results of both a 3D simulation and real-world experiments show that the approach is applicable and real-time capable.

Unbalance identification in large steam turbo-generator unit using a model-based method

Fault identification in industrial machine is a topic of major importance under engineering point of view. In fact, the possibility to identify not only the type, but also the severity and the position of a fault occurred along a shaft-line allows quick maintenance and shorten the downtime. This is really important in the power generation industry where the units are often of several tenths of meters long and where the rotors are enclosed by heavy and pressure-sealed casings. In this paper, an industrial experimental case is presented related to the identification of the unbalance on a large size steam turbine of about 1.3 GW, belonging to a nuclear power plant. The case history is analyzed by considering the vibrations measured by the condition monitoring system of the unit. A model-based method in the frequency domain, developed by the authors, is introduced in detail and it is then used to identify the position of the fault and its severity along the shaft-line. The complete model of the unit (rotor – modeled by means of finite elements, bearings – modeled by linearized damping and stiffness coefficients and foundation – modeled by means of pedestals) is analyzed and discussed before being used for the fault identification. The assessment of the actual fault was done by inspection during a scheduled maintenance and excellent correspondence was found with the identified one by means of authors’ proposed method. Finally a complete discussion is presented about the effectiveness of the method, even in presence of a not fine tuned machine model and considering only few measuring planes for the machine vibration.