Exploring the parameter space of a rabbit ventricular action potential model to investigate the effect of variation on action potential and calcium transients

Computational models for cardiomyocyte action potentials (AP) often make use of a large parameter set. This parameter set can contain some elements that are fitted to experimental data independently of any other element, some elements that are derived concurrently with other elements to match experimental data, and some elements that are derived purely from phenomenological fitting to produce the desired AP output. Furthermore, models can make use of several different data sets, not always derived for the same conditions or even the same species. It is consequently uncertain whether the parameter set for a given model is physiologically accurate. Furthermore, it is only recently that the possibility of degeneracy in parameter values in producing a given simulation output has started to be addressed. In this study, we examine the effects of varying two parameters (the L-type calcium current (I(CaL)) and the delayed rectifier potassium current (I(Ks))) in a computational model of a rabbit ventricular cardiomyocyte AP on both the membrane potential (V(m)) and calcium (Ca(2+)) transient. It will subsequently be determined if there is degeneracy in this model to these parameter values, which will have important implications on the stability of these models to cell-to-cell parameter variation, and also whether the current methodology for generating parameter values is flawed. The accuracy of AP duration (APD) as an indicator of AP shape will also be assessed.

Stochastic simulation for spatial modelling of dynamic process in a living cell

One of the fundamental motivations underlying computational cell biology is to gain insight into the complicated dynamical processes taking place, for example, on the plasma membrane or in the cytosol of a cell. These processes are often so complicated that purely temporal mathematical models cannot adequately capture the complex chemical kinetics and transport processes of, for example, proteins or vesicles. On the other hand, spatial models such as Monte Carlo approaches can have very large computational overheads. This chapter gives an overview of the state of the art in the development of stochastic simulation techniques for the spatial modelling of dynamic processes in a living cell.

Sequential release of BMP-7 and VEGF from the PLGA/AK-Gelatin Composite Scaffolds

Vascular endothelial growth factor (VEGF) and bone morphogenetic proteins (BMP-7) are key regulators of angiogenesis and osteogenesis during bone regeneration. The aim of this study was to investigate the possibility of realizing sequential release of the two growth factors using a novel composite scaffold. Poly(lactic-co-glycolic acid) (PLGA)-Akermanite (AK) microspheres were used to make the composite scaffold, which was then loaded with BMP-7, followed by embedding in a gelatin hydrogel matrix loaded with VEGF. The release profiles of the growth factors were studied and selected osteogenic related markers of bone marrow stromal cells (BMSCs) were analysed. It was shown that the composite scaffolds exhibited a fast initial burst release of VEGF within the first 3 days and a sustained slow release of BMP-7 over the full period of 20 days. The in vitro proliferation and differentiation of the BMSCs cultured in the osteogenic medium were enhanced by 1 to 2 times, resulting from the additionally and sequentially release of growth factors from the PLGA-AK/gelatin composite scaffolds.

Stochastic chemical kinetics and the quasi-steady-state assumption : application to the stochastic simulation algorithm and chemical master equation

Recently the application of the quasi-steady-state approximation (QSSA) to the stochastic simulation algorithm (SSA) was suggested for the purpose of speeding up stochastic simulations of chemical systems that involve both relatively fast and slow chemical reactions [Rao and Arkin, J. Chem. Phys. 118, 4999 (2003)] and further work has led to the nested and slow-scale SSA. Improved numerical efficiency is obtained by respecting the vastly different time scales characterizing the system and then by advancing only the slow reactions exactly, based on a suitable approximation to the fast reactions. We considerably extend these works by applying the QSSA to numerical methods for the direct solution of the chemical master equation (CME) and, in particular, to the finite state projection algorithm [Munsky and Khammash, J. Chem. Phys. 124, 044104 (2006)], in conjunction with Krylov methods. In addition, we point out some important connections to the literature on the (deterministic) total QSSA (tQSSA) and place the stochastic analogue of the QSSA within the more general framework of aggregation of Markov processes. We demonstrate the new methods on four examples: Michaelis–Menten enzyme kinetics, double phosphorylation, the Goldbeter–Koshland switch, and the mitogen activated protein kinase cascade. Overall, we report dramatic improvements by applying the tQSSA to the CME solver.

Non-redundant sequential association rule mining based on closed sequential patterns

In many applications, e.g., bioinformatics, web access traces, system utilisation logs, etc., the data is naturally in the form of sequences. People have taken great interest in analysing the sequential data and finding the inherent characteristics or relationships within the data. Sequential association rule mining is one of the possible methods used to analyse this data. As conventional sequential association rule mining very often generates a huge number of association rules, of which many are redundant, it is desirable to find a solution to get rid of those unnecessary association rules. Because of the complexity and temporal ordered characteristics of sequential data, current research on sequential association rule mining is limited. Although several sequential association rule prediction models using either sequence constraints or temporal constraints have been proposed, none of them considered the redundancy problem in rule mining. The main contribution of this research is to propose a non-redundant association rule mining method based on closed frequent sequences and minimal sequential generators. We also give a definition for the non-redundant sequential rules, which are sequential rules with minimal antecedents but maximal consequents. A new algorithm called CSGM (closed sequential and generator mining) for generating closed sequences and minimal sequential generators is also introduced. A further experiment has been done to compare the performance of generating non-redundant sequential rules and full sequential rules, meanwhile, performance evaluation of our CSGM and other closed sequential pattern mining or generator mining algorithms has also been conducted. We also use generated non-redundant sequential rules for query expansion in order to improve recommendations for infrequently purchased products.

Parallel implementation of stochastic simulation for large scale cellular processes

Experimental and theoretical studies have shown the importance of stochastic processes in genetic regulatory networks and cellular processes. Cellular networks and genetic circuits often involve small numbers of key proteins such as transcriptional factors and signaling proteins. In recent years stochastic models have been used successfully for studying noise in biological pathways, and stochastic modelling of biological systems has become a very important research field in computational biology. One of the challenge problems in this field is the reduction of the huge computing time in stochastic simulations. Based on the system of the mitogen-activated protein kinase cascade that is activated by epidermal growth factor, this work give a parallel implementation by using OpenMP and parallelism across the simulation. Special attention is paid to the independence of the generated random numbers in parallel computing, that is a key criterion for the success of stochastic simulations. Numerical results indicate that parallel computers can be used as an efficient tool for simulating the dynamics of large-scale genetic regulatory networks and cellular processes

Investigation of methods for increasing the energy efficiency on unmanned aerial vehicles (UAVS)

In recent years, development of Unmanned Aerial Vehicles (UAV) has become a significant growing segment of the global aviation industry. These vehicles are developed with the intention of operating in regions where the presence of onboard human pilots is either too risky or unnecessary. Their popularity with both the military and civilian sectors have seen the use of UAVs in a diverse range of applications, from reconnaissance and surveillance tasks for the military, to civilian uses such as aid relief and monitoring tasks. Efficient energy utilisation on an UAV is essential to its functioning, often to achieve the operational goals of range, endurance and other specific mission requirements. Due to the limitations of the space available and the mass budget on the UAV, it is often a delicate balance between the onboard energy available (i.e. fuel) and achieving the operational goals. This thesis presents an investigation of methods for increasing the energy efficiency on UAVs. One method is via the development of a Mission Waypoint Optimisation (MWO) procedure for a small fixed-wing UAV, focusing on improving the onboard fuel economy. MWO deals with a pre-specified set of waypoints by modifying the given waypoints within certain limits to achieve its optimisation objectives of minimising/maximising specific parameters. A simulation model of a UAV was developed in the MATLAB Simulink environment, utilising the AeroSim Blockset and the in-built Aerosonde UAV block and its parameters. This simulation model was separately integrated with a multi-objective Evolutionary Algorithm (MOEA) optimiser and a Sequential Quadratic Programming (SQP) solver to perform single-objective and multi-objective optimisation procedures of a set of real-world waypoints in order to minimise the onboard fuel consumption. The results of both procedures show potential in reducing fuel consumption on a UAV in a ight mission. Additionally, a parallel Hybrid-Electric Propulsion System (HEPS) on a small fixedwing UAV incorporating an Ideal Operating Line (IOL) control strategy was developed. An IOL analysis of an Aerosonde engine was performed, and the most efficient (i.e. provides greatest torque output at the least fuel consumption) points of operation for this engine was determined. Simulation models of the components in a HEPS were designed and constructed in the MATLAB Simulink environment. It was demonstrated through simulation that an UAV with the current HEPS configuration was capable of achieving a fuel saving of 6.5%, compared to the ICE-only configuration. These components form the basis for the development of a complete simulation model of a Hybrid-Electric UAV (HEUAV).

A traffic simulation standard based on data marts

Traffic Simulation models tend to have their own data input and output formats. In an effort to standardise the input for traffic simulations, we introduce in this paper a set of data marts that aim to serve as a common interface between the necessaary data, stored in dedicated databases, and the swoftware packages, that require the input in a certain format. The data marts are developed based on real world objects (e.g. roads, traffic lights, controllers) rather than abstract models and hence contain all necessary information that can be transformed by the importing software package to their needs. The paper contains a full description of the data marts for network coding, simulation results, and scenario management, which have been discussed with industry partners to ensure sustainability.

A sequential Monte Carlo approach to design for population pharmacokinetics studies

Here we present a sequential Monte Carlo approach that can be used to find optimal designs. Our focus is on the design of phase III clinical trials where the derivation of sampling windows is required, along with the optimal sampling schedule. The search is conducted via a particle filter which traverses a sequence of target distributions artificially constructed via an annealed utility. The algorithm derives a catalogue of highly efficient designs which, not only contain the optimal, but can also be used to derive sampling windows. We demonstrate our approach by designing a hypothetical phase III clinical trial.

Development and validation of novel methods for microbial source tracking based on Escherichia coli as an indicator of water quality

Microbial pollution in water periodically affects human health in Australia, particularly in times of drought and flood. There is an increasing need for the control of waterborn microbial pathogens. Methods, allowing the determination of the origin of faecal contamination in water, are generally referred to as Microbial Source Tracking (MST). Various approaches have been evaluated as indicatorsof microbial pathogens in water samples, including detection of different microorganisms and various host-specific markers. However, until today there have been no universal MST methods that could reliably determine the source (human or animal) of faecal contamination. Therefore, the use of multiple approaches is frequently advised. MST is currently recognised as a research tool, rather than something to be included in routine practices. The main focus of this research was to develop novel and universally applicable methods to meet the demands for MST methods in routine testing of water samples. Escherichia coli was chosen initially as the object organism for our studies as, historically and globally, it is the standard indicator of microbial contamination in water. In this thesis, three approaches are described: single nucleotide polymorphism (SNP) genotyping, clustered regularly interspaced short palindromic repeats (CRISPR) screening using high resolution melt analysis (HRMA) methods and phage detection development based on CRISPR types. The advantage of the combination SNP genotyping and CRISPR genes has been discussed in this study. For the first time, a highly discriminatory single nucleotide polymorphism interrogation of E. coli population was applied to identify the host-specific cluster. Six human and one animal-specific SNP profile were revealed. SNP genotyping was successfully applied in the field investigations of the Coomera watershed, South-East Queensland, Australia. Four human profiles [11], [29], [32] and [45] and animal specific SNP profile [7] were detected in water. Two human-specific profiles [29] and [11] were found to be prevalent in the samples over a time period of years. The rainfall (24 and 72 hours), tide height and time, general land use (rural, suburban), seasons, distance from the river mouth and salinity show a lack of relashionship with the diversity of SNP profiles present in the Coomera watershed (p values > 0.05). Nevertheless, SNP genotyping method is able to identify and distinquish between human- and non-human specific E. coli isolates in water sources within one day. In some samples, only mixed profiles were detected. To further investigate host-specificity in these mixed profiles CRISPR screening protocol was developed, to be used on the set of E. coli, previously analysed for SNP profiles. CRISPR loci, which are the pattern of previous DNA coliphages attacks, were considered to be a promising tool for detecting host-specific markers in E. coli. Spacers in CRISPR loci could also reveal the dynamics of virulence in E. coli as well in other pathogens in water. Despite the fact that host-specificity was not observed in the set of E. coli analysed, CRISPR alleles were shown to be useful in detection of the geographical site of sources. HRMA allows determination of ‘different’ and ‘same’ CRISPR alleles and can be introduced in water monitoring as a cost-effective and rapid method. Overall, we show that the identified human specific SNP profiles [11], [29], [32] and [45] can be useful as marker genotypes globally for identification of human faecal contamination in water. Developed in the current study, the SNP typing approach can be used in water monitoring laboratories as an inexpensive, high-throughput and easy adapted protocol. The unique approach based on E. coli spacers for the search for unknown phage was developed to examine the host-specifity in phage sequences. Preliminary experiments on the recombinant plasmids showed the possibility of using this method for recovering phage sequences. Future studies will determine the host-specificity of DNA phage genotyping as soon as first reliable sequences can be acquired. No doubt, only implication of multiple approaches in MST will allow identification of the character of microbial contamination with higher confidence and readability.

A study of abrasive water jet characteristics by CFD simulation

Computational fluid dynamics (CFD) models for ultrahigh velocity waterjets and abrasive waterjets (AWJs) are established using the Fluent 6 flow solver. Jet dynamic characteristics for the flow downstream from a very fine nozzle are then simulated under steady state, turbulent, two-phase and three-phase flow conditions. Water and particle velocities in a jet are obtained under different input and boundary conditions to provide an insight into the jet characteristics and a fundamental understanding of the kerf formation process in AWJ cutting. For the range of downstream distances considered, the results indicate that a jet is characterised by an initial rapid decay of the axial velocity at the jet centre while the cross-sectional flow evolves towards a top-hat profile downstream.

High fidelity simulation; challenges encountered in developing and implementing student learning experiences, staff education and researching approaches to learning

High fidelity simulation as a teaching and learning approach is being embraced by many schools of nursing. Our school embarked on integrating high fidelity (HF) simulation into the undergraduate clinical education program in 2011. Low and medium fidelity simulation has been used for many years, but this did not simplify the integration of HF simulation. Alongside considerations of how and where HF simulation would be integrated, issues arose with: student consent and participation for observed activities; data management of video files; staff development, and conceptualising how methods for student learning could be researched. Simulation for undergraduate student nurses commenced as a formative learning activity, undertaken in groups of eight, where four students undertake the ‘doing’ role and four are structured observers, who then take a formal role in the simulation debrief. Challenges for integrating simulation into student learning included conceptualising and developing scenarios to trigger students’ decision making and application of skills, knowledge and attitudes explicit to solving clinical ‘problems’. Developing and planning scenarios for students to ‘try out’ skills and make decisions for problem solving lay beyond choosing pre-existing scenarios inbuilt with the software. The supplied scenarios were not concept based but rather knowledge, skills and technology (of the manikin) focussed. Challenges lay in using the technology for the purpose of building conceptual mastery rather than using technology simply because it was available. As we integrated use of HF simulation into the final year of the program, focus was on building skills, knowledge and attitudes that went beyond technical skill, and provided an opportunity to bridge the gap with theory-based knowledge that students often found difficult to link to clinical reality. We wished to provide opportunities to develop experiential knowledge based on application and clinical reasoning processes in team environments where problems are encountered, and to solve them, the nurse must show leadership and direction. Other challenges included students consenting for simulations to be videotaped and ethical considerations of this. For example if one student in a group of eight did not consent, did this mean they missed the opportunity to undertake simulation, or that others in the group may be disadvantaged by being unable to review their performance. This has implications for freely given consent but also for equity of access to learning opportunities for students who wished to be taped and those who did not. Alongside this issue were the details behind data management, storage and access. Developing staff with varying levels of computer skills to use software and undertake a different approach to being the ‘teacher’ required innovation where we took an experiential approach. Considering explicit learning approaches to be trialled for learning was not a difficult proposition, but considering how to enact this as research with issues of blinding, timetabling of blinded groups, and reducing bias for testing results of different learning approaches along with gaining ethical approval was problematic. This presentation presents examples of these challenges and how we overcame them.

Using ‘think aloud’ as a strategy for learning clinical reasoning in high fidelity case-based simulation for undergraduate nursing students

AIMS This paper reports on the implementation of a research project that trials an educational strategy implemented over six months of an undergraduate third year nursing curriculum. This project aims to explore the effectiveness of ‘think aloud’ as a strategy for learning clinical reasoning for students in simulated clinical settings. BACKGROUND Nurses are required to apply and utilise critical thinking skills to enable clinical reasoning and problem solving in the clinical setting [1]. Nursing students are expected to develop and display clinical reasoning skills in practice, but may struggle articulating reasons behind decisions about patient care. For students learning to manage complex clinical situations, teaching approaches are required that make these instinctive cognitive processes explicit and clear [2-5]. In line with professional expectations, nursing students in third year at Queensland University of Technology (QUT) are expected to display clinical reasoning skills in practice. This can be a complex proposition for students in practice situations, particularly as the degree of uncertainty or decision complexity increases [6-7]. The ‘think aloud’ approach is an innovative learning/teaching method which can create an environment suitable for developing clinical reasoning skills in students [4, 8]. This project aims to use the ‘think aloud’ strategy within a simulation context to provide a safe learning environment in which third year students are assisted to uncover cognitive approaches that best assist them to make effective patient care decisions, and improve their confidence, clinical reasoning and active critical reflection on their practice. MEHODS In semester 2 2011 at QUT, third year nursing students will undertake high fidelity simulation, some for the first time commencing in September of 2011. There will be two cohorts for strategy implementation (group 1= use think aloud as a strategy within the simulation, group 2= not given a specific strategy outside of nursing assessment frameworks) in relation to problem solving patient needs. Students will be briefed about the scenario, given a nursing handover, placed into a simulation group and an observer group, and the facilitator/teacher will run the simulation from a control room, and not have contact (as a ‘teacher’) with students during the simulation. Then debriefing will occur as a whole group outside of the simulation room where the session can be reviewed on screen. The think aloud strategy will be described to students in their pre-simulation briefing and allow for clarification of this strategy at this time. All other aspects of the simulations remain the same, (resources, suggested nursing assessment frameworks, simulation session duration, size of simulation teams, preparatory materials). RESULTS Methodology of the project and the challenges of implementation will be the focus of this presentation. This will include ethical considerations in designing the project, recruitment of students and implementation of a voluntary research project within a busy educational curriculum which in third year targets 669 students over two campuses. CONCLUSIONS In an environment of increasingly constrained clinical placement opportunities, exploration of alternate strategies to improve critical thinking skills and develop clinical reasoning and problem solving for nursing students is imperative in preparing nurses to respond to changing patient needs. References 1. Lasater, K., High-fidelity simulation and the development of clinical judgement: students' experiences. Journal of Nursing Education, 2007. 46(6): p. 269-276. 2. Lapkin, S., et al., Effectiveness of patient simulation manikins in teaching clinical reasoning skills to undergraduate nursing students: a systematic review. Clinical Simulation in Nursing, 2010. 6(6): p. e207-22. 3. Kaddoura, M.P.C.M.S.N.R.N., New Graduate Nurses' Perceptions of the Effects of Clinical Simulation on Their Critical Thinking, Learning, and Confidence. The Journal of Continuing Education in Nursing, 2010. 41(11): p. 506. 4. Banning, M., The think aloud approach as an educational tool to develop and assess clinical reasoning in undergraduate students. Nurse Education Today, 2008. 28: p. 8-14. 5. Porter-O'Grady, T., Profound change:21st century nursing. Nursing Outlook, 2001. 49(4): p. 182-186. 6. Andersson, A.K., M. Omberg, and M. Svedlund, Triage in the emergency department-a qualitative study of the factors which nurses consider when making decisions. Nursing in Critical Care, 2006. 11(3): p. 136-145. 7. O'Neill, E.S., N.M. Dluhy, and C. Chin, Modelling novice clinical reasoning for a computerized decision support system. Journal of Advanced Nursing, 2005. 49(1): p. 68-77. 8. Lee, J.E. and N. Ryan-Wenger, The "Think Aloud" seminar for teaching clinical reasoning: a case study of a child with pharyngitis. J Pediatr Health Care, 1997. 11(3): p. 101-10.

Sky high and back again : the evolution of simulation-based design from aerospace to construction

Emerging from the challenge to reduce energy consumption in buildings is a need for research and development into the more effective use of simulation as a decision-support tool. Despite significant research, persistent limitations in process and software inhibit the integration of energy simulation in early architectural design. This paper presents a green star case study to highlight the obstacles commonly encountered with current integration strategies. It then examines simulation-based design in the aerospace industry, which has overcome similar limitations. Finally, it proposes a design system based on this contrasting approach, coupling parametric modelling and energy simulation software for rapid and iterative performance assessment of early design options.

Using cooperative vehicle systems to collect near collision incidents events : a simulation study

On the road, near collision events (also close calls or near-miss incidents) largely outnumber actual crashes, yet most of them can never be recorded by current traffic data collection technologies or crashes analysis tools. The analysis of near collisions data is an important step in the process of reducing the crash rate. There have been several studies that have investigated near collisions; to our knowledge, this is the first study that uses the functionalities provided by cooperative vehicles to collect near misses information. We use the VISSIM traffic simulator and a custom C++ engine to simulate cooperative vehicles and their ability to detect near collision events. Our results showed that, within a simple simulated environment, adequate information on near collision events can be collected using the functionalities of cooperative perception systems. The relationship between the ratio of detected events and the ratio of equipped vehicle was shown to closely follow a squared law, and the largest source of nondetection was packet loss instead of packet delays and GPS imprecision.