Mixture models of nucleotide sequence evolution that account for heterogeneity in the substitution process across sites and across lineages

Molecular phylogenetic studies of homologous sequences of nucleotides often assume that the underlying evolutionary process was globally stationary, reversible, and homogeneous (SRH), and that a model of evolution with one or more site-specific and time-reversible rate matrices (e.g., the GTR rate matrix) is enough to accurately model the evolution of data over the whole tree. However, an increasing body of data suggests that evolution under these conditions is an exception, rather than the norm. To address this issue, several non-SRH models of molecular evolution have been proposed, but they either ignore heterogeneity in the substitution process across sites (HAS) or assume it can be modeled accurately using the distribution. As an alternative to these models of evolution, we introduce a family of mixture models that approximate HAS without the assumption of an underlying predefined statistical distribution. This family of mixture models is combined with non-SRH models of evolution that account for heterogeneity in the substitution process across lineages (HAL). We also present two algorithms for searching model space and identifying an optimal model of evolution that is less likely to over- or underparameterize the data. The performance of the two new algorithms was evaluated using alignments of nucleotides with 10 000 sites simulated under complex non-SRH conditions on a 25-tipped tree. The algorithms were found to be very successful, identifying the correct HAL model with a 75% success rate (the average success rate for assigning rate matrices to the tree's 48 edges was 99.25%) and, for the correct HAL model, identifying the correct HAS model with a 98% success rate. Finally, parameter estimates obtained under the correct HAL-HAS model were found to be accurate and precise. The merits of our new algorithms were illustrated with an analysis of 42 337 second codon sites extracted from a concatenation of 106 alignments of orthologous genes encoded by the nuclear genomes of Saccharomyces cerevisiae, S. paradoxus, S. mikatae, S. kudriavzevii, S. castellii, S. kluyveri, S. bayanus, and Candida albicans. Our results show that second codon sites in the ancestral genome of these species contained 49.1% invariable sites, 39.6% variable sites belonging to one rate category (V1), and 11.3% variable sites belonging to a second rate category (V2). The ancestral nucleotide content was found to differ markedly across these three sets of sites, and the evolutionary processes operating at the variable sites were found to be non-SRH and best modeled by a combination of eight edge-specific rate matrices (four for V1 and four for V2). The number of substitutions per site at the variable sites also differed markedly, with sites belonging to V1 evolving slower than those belonging to V2 along the lineages separating the seven species of Saccharomyces. Finally, sites belonging to V1 appeared to have ceased evolving along the lineages separating S. cerevisiae, S. paradoxus, S. mikatae, S. kudriavzevii, and S. bayanus, implying that they might have become so selectively constrained that they could be considered invariable sites in these species.

A theory of process modelling affordances

This thesis studies how conceptual process models - that is, graphical documentations of an organisation's business processes - can enable and constrain the actions of their users. The results from case study and experiment indicate that model design decisions and people's characteristics influence how these opportunities for action are perceived and acted upon in practice.

The development of a component to improve the loading safety of bone-anchored prostheses

Use of socket prostheses Currently, for individuals with limb loss, the conventional method of attaching a prosthetic limb relies on a socket that fits over the residual limb. However, there are a number of issues concerning the use of a socket (e.g., blisters, irritation, and discomfort) that result in dissatisfaction with socket prostheses, and these lead ultimately a significant decrease in quality of life. Bone-anchored prosthesis Alternatively, the concept of attaching artificial limbs directly to the skeletal system has been developed (bone anchored prostheses), as it alleviates many of the issues surrounding the conventional socket interface.Bone anchored prostheses rely on two critical components: the implant, and the percutaneous abutment or adapter, which forms the connection for the external prosthetic system (Figure 1). To date, an implant that screws into the long bone of the residual limb has been the most common intervention. However, more recently, press-fit implants have been introduced and their use is increasing. Several other devices are currently at various stages of development, particularly in Europe and the United States. Benefits of bone-anchored prostheses Several key studies have demonstrated that bone-anchored prostheses have major clinical benefits when compared to socket prostheses (e.g., quality of life, prosthetic use, body image, hip range of motion, sitting comfort, ease of donning and doffing, osseoperception (proprioception), walking ability) and acceptable safety, in terms of implant stability and infection. Additionally, this method of attachment allows amputees to participate in a wide range of daily activities for a substantially longer duration. Overall, the system has demonstrated a significant enhancement to quality of life. Challenges of direct skeletal attachment However, due to the direct skeletal attachment, serious injury and damage can occur through excessive loading events such as during a fall (e.g., component damage, peri-prosthetic fracture, hip dislocation, and femoral head fracture). These incidents are costly (e.g., replacement of components) and could require further surgical interventions. Currently, these risks are limiting the acceptance of bone-anchored technology and the substantial improvement to quality of life that this treatment offers. An in-depth investigation into these risks highlighted a clear need to re-design and improve the componentry in the system (Figure 2), to improve the overall safety during excessive loading events. Aim and purposes The ultimate aim of this doctoral research is to improve the loading safety of bone-anchored prostheses, to reduce the incidence of injury and damage through the design of load restricting components, enabling individuals fitted with the system to partake in everyday activities, with increased security and self-assurance. The safety component will be designed to release or ‘fail’ external to the limb, in a way that protects the internal bone-implant interface, thus removing the need for restorative surgery and potential damage to the bone. This requires detailed knowledge of the loads typically experienced by the limb and an understanding of potential overload situations that might occur. Hence, a comprehensive review of the loading literature surrounding bone anchored prostheses will be conducted as part of this project, with the potential for additional experimental studies of the loads during normal activities to fill in gaps in the literature. This information will be pivotal in determining the specifications for the properties of the safety component, and the bone-implant system. The project will follow the Stanford Biodesign process for the development of the safety component.

Integrated lean six sigma approach for patient flow improvement in hospital emergency department

This research aims to develop an Integrated Lean Six Sigma approach to investigate and resolve the patient flow problems in hospital emergency departments. It was proposed that the voice of the customer and the voice of the process should be considered simultaneously to investigate the current process of patient flow. Statistical analysis, visual process mapping with A3 problem solving sheet, and cause and effect diagrams have been used to identify the major patient flow issues. This research found that engaged frontline workers, long-term leadership obligation, an understanding of patients' requirements and the implementation of a systematic integration of lean strategies could continuously improve patient flow, health care service and growth in the emergency departments.

Equilibrium studies of ammonium exchange with Australian natural zeolites

This paper is concerned with the study of the equilibrium exchange of ammonium ions with two natural zeolite samples sourced in Australia from Castle Mountain Zeolites and Zeolite Australia. A range of sorption models including Langmuir Vageler, Competitive Langmuir, Freundlich, Temkin, Dubinin Astakhov and Brouers–Sotolongo were applied in order to gain an insight as to the exchange process. In contrast to most previous studies, non-linear regression was used in all instances to determine the best fit of the experimental data. Castle Mountain natural zeolite was found to exhibit higher ammonium capacity than Zeolite Australia material when in the freshly received state, and this behavior was related to the greater amount of sodium ions present relative to calcium ions on the zeolite exchange sites. The zeolite capacity for ammonium ions was also found to be dependent on the solution normality, with 35–60% increase inuptake noted when increasing the ammonium concentration from 250 to 1000 mg/L. The optimal fit ofthe equilibrium data was achieved by the Freundlich expression as confirmed by use of Akaikes Information Criteria. It was emphasized that the bottle-point method chosen influenced the isotherm profile in several ways, and could lead to misleading interpretation of experiments, especially if the constant zeolite mass approach was followed. Pre-treatment of natural zeolite with acid and subsequently sodium hydroxide promoted the uptake of ammonium species by at least 90%. This paper highlighted the factors which should be taken into account when investigating ammonium ion exchange with natural zeolites.

Feedback and clinical practice improvement: A tool to assist workplace supervisors and students

In work integrated learning, students may report difficulties applying theory learned at university to clinical practice. One contributing factor may be students' inability to engage in meaningful reflection and self-correcting behaviours. This paper reports the evaluation of a tool, process and resources developed to assist students to reflect on feedback and engage in self-assessment. Students were assisted to develop self-assessment skills by reflecting on, and engaging with feedback from previous workplace experiences to develop goals, learning outcomes and strategies to improve performance with mostly positive results. A secondary aim was to identify common learning strategies or barriers that impacted on student outcomes. Four themes emerged from the qualitative data: 1) preparing for clinical learning; 2) relationships and engagement levels; 3) shared awareness, and; 4) developing clinical practice. Overall students felt the tool assisted them to narrow their attention on what needed to be improved. While supervisors believed the tool helped them to focus on specific needs of each student. Common barriers to clinical practice improvement related to a lack of opportunity in some settings, and lack of staff willingness to support students to achieve identified goals. Students and supervisors found the use of the tools beneficial and assisted students to demonstrate a greater understanding of how to apply feedback received to support their learning in the clinical environment.

Patients with physical debility undergoing subacute physical rehabilitation following an acute hospital admission demonstrated improvement in cognitive functional task independence

Background: Hospitalised older adults often experience a decline in physical functioning and mobility in the lead up to (or during) an acute hospital admission. During acute illness and hospitalisation, older adults may also experience a decline or fluctuation in their cognitive functioning. Previous studies have demonstrated that patients with or without reduced cognitive functioning on admission to subacute inpatient rehabilitation have considerable potential to improve their physical functioning and quality of life.

Editorial of "International Journal of Critical Indigenous Studies Volume 4, Number 2, 2011"

This special edition of the International Journal of Critical Indigenous Studies focuses upon the work scholars within the growing discipline of Aboriginal and Torres Strait Islander health studies. The lamentable state of Indigenous health in Australia is reflected in Indigenous populations elsewhere, especially where settler colonialism has left an indelible mark. This special edition therefore speaks to where Indigenous health outcomes and the efficacy of remedies are causing concern. Common to all is the demand that Indigenous people are placed front and centre of all attempts to improve health outcomes and that improvements are sought in culturally sensitive ways. Terry Dunbar presents findings from a research study that set out to investigate the Indigenous experiences of health and family services in the Northern Territory, Australia. The study asserts that cultural security is an integral and vital element of any policy that will impact upon Indigenous peoples. Dunbar concludes by arguing that in seeking positive change with regard to cultural security or otherwise, the most vociferous champions of that change are likely to be the Aboriginal communities affected. The article by Bronwyn Fredericks, Karen Adams, Sandra Angus and Melissa Walker also highlights the need to involve Aboriginal and Torres Strait Islander people, in this case women, in the design and development of strategies affecting their lives. Utilising routine communication methods such the ‘talking circle’ and the process referred to as ‘talkin’ up’, where women ‘talk back’ to one another about issues of personal importance, the article argues that the health strategy which emerged through these consultation approaches was more accurately informed by and responsive to women’s health need. Indeed, the resulting strategy reflected the women’s sense of themselves and the clear direction they felt their health services and polices should take.

Towards an understanding of the information dynamics of the handover process in aged care settings: A prerequisite for the safe and effective use of ICT

Background Poor clinical handover has been associated with inaccurate clinical assessment and diagnosis, delays in diagnosis and test ordering, medication errors and decreased patient satisfaction in the acute care setting. Research on the handover process in the residential aged care sector is very limited. Purpose The aims of this study were to: (i) Develop an in-depth understanding of the handover process in aged care by mapping all the key activities and their information dynamics, (ii) Identify gaps in information exchange in the handover process and analyze implications for resident safety, (iii) Develop practical recommendations on how information communication technology (ICT) can improve the process and resident safety. Methods The study was undertaken at a large metropolitan facility in NSW with more than 300 residents and a staff including 55 registered nurses (RNs) and 146 assistants in nursing (AINs). A total of 3 focus groups, 12 interviews and 3 observation sessions were conducted over a period from July to October 2010. Process mapping was undertaken by translating the qualitative data via a five-category code book that was developed prior to the analysis. Results Three major sub-processes were identified and mapped. The three major stages are Handover process (HOP) I “Information gathering by RN”, HOP II “Preparation of preliminary handover sheet” and HOP III “Execution of handover meeting”. Inefficient processes were identified in relation to the handover including duplication of information, utilization of multiple communication modes and information sources, and lack of standardization. Conclusion By providing a robust process model of handover this study has made two critical contributions to research in aged care: (i) a means to identify important, possibly suboptimal practices; and (ii) valuable evidence to plan and improve ICT implementation in residential aged care. The mapping of this process enabled analysis of gaps in information flow and potential impacts on resident safety. In addition it offers the basis for further studies into a process that, despite its importance for securing resident safety and continuity of care, lacks research.

Medication errors in residential aged care facilities: A distributed cognition analysis of the information exchange process

Background Medication safety is a pressing concern for residential aged care facilities (RACFs). Retrospective studies in RACF settings identify inadequate communication between RACFs, doctors, hospitals and community pharmacies as the major cause of medication errors. Existing literature offers limited insight about the gaps in the existing information exchange process that may lead to medication errors. The aim of this research was to explicate the cognitive distribution that underlies RACF medication ordering and delivery to identify gaps in medication-related information exchange which lead to medication errors in RACFs. Methods The study was undertaken in three RACFs in Sydney, Australia. Data were generated through ethnographic field work over a period of five months (May–September 2011). Triangulated analysis of data primarily focused on examining the transformation and exchange of information between different media across the process. Results The findings of this study highlight the extensive scope and intense nature of information exchange in RACF medication ordering and delivery. Rather than attributing error to individual care providers, the explication of distributed cognition processes enabled the identification of gaps in three information exchange dimensions which potentially contribute to the occurrence of medication errors namely: (1) design of medication charts which complicates order processing and record keeping (2) lack of coordination mechanisms between participants which results in misalignment of local practices (3) reliance on restricted communication bandwidth channels mainly telephone and fax which complicates the information processing requirements. The study demonstrates how the identification of these gaps enhances understanding of medication errors in RACFs. Conclusions Application of the theoretical lens of distributed cognition can assist in enhancing our understanding of medication errors in RACFs through identification of gaps in information exchange. Understanding the dynamics of the cognitive process can inform the design of interventions to manage errors and improve residents’ safety.

Experimental studies on web crippling strength of hollow flange channels under EOF and IOF load cases

LiteSteel beam (LSB) is a hollow flange channel made from cold-formed steel using a patented manufacturing process involving simultaneous cold-forming and dual electric resistance welding. LSBs are currently used as floor joists and bearers in buildings. However, there are no appropriate design standards available due to its unique hollow flange geometry, residual stress characteristics and initial geometric imperfections arising from manufacturing processes. Recent research studies have focused on investigating the structural behaviour of LSBs under pure bending, predominant shear and combined actions. However, web crippling behaviour and strengths of LSBs still need to be examined. Therefore, an experimental study was undertaken to investigate the web crippling behaviour and strengths of LSBs under EOF (End One Flange) and IOF (Interior One Flange) load cases. A total of 23 web crippling tests were performed and the results were compared with the current AS/NZS 4600 and AISI S100 design standards, which showed that the cold-formed steel design rules predicted the web crippling capacity of LSB sections very conservatively under EOF and IOF load cases. Therefore, suitably improved design equations were proposed to determine the web crippling capacity of LSBs based on experimental results. In addition, new design equations were also developed under the Direct Strength Method format. This paper presents the details of this experimental study on the web crippling behaviour and strengths of LiteSteel beams under EOF and IOF load cases and the results.

Experimental and numerical studies of hollow flange channel beams subject to web crippling under ETF and ITF load cases

This paper presents the details of experimental and numerical studies on the web crippling behaviour of hollow flange channel beams, known as LiteSteel beams (LSB). The LSB has a unique shape of a channel beam with two rectangular hollow flanges, made using a unique manufacturing process. Experimental and numerical studies have been carried out to evaluate the behaviour and design of LSBs subject to pure bending actions, predominant shear actions and combined actions. To date, however, no investigation has been conducted into the web crippling behaviour and strength of LSB sections under ETF and ITF load conditions. Hence experimental studies consisting of 28 tests were first conducted in this research to assess the web crippling behaviour and strengths of LSBs under two flange load cases (ETF and ITF). Experimental web crippling capacity results were then compared with the predictions from AS/NZS 4600 and AISI S100 design rules, which showed that AS/NZS 4600 and AISI S100 design equations are very unconservative for LSBs under ETF and ITF load cases. Hence improved equations were proposed to determine the web crippling capacities of LSBs. Finite element models of the tested LSBs were then developed, and used to determine the elastic buckling loads of LSBs under ETF and ITF load cases. New equations were proposed to determine the corresponding elastic buckling coefficients of LSBs. Finally suitable design rules were also developed under the Direct Strength Method format using the test results and buckling analysis results from finite element analyses.

Behaviour of natural zeolites used for the treatment of simulated and actual coal seam gas water

Coal seam gas operations produce significant quantities of associated water which often require demineralization. Ion exchange with natural zeolites has been proposed as a possible approach. The interaction of natural zeolites with solutions of sodium chloride and sodium bicarbonate in addition to coal seam gas water is not clear. Hence, we investigated ion exchange kinetics, equilibrium, and column behaviour of an Australian natural zeolite. Kinetic tests suggested that the pseudo first order equation best simulated the data. Intraparticle diffusion was part of the rate limiting step and more than one diffusion process controlled the overall rate of sodium ion uptake. Using a constant mass of zeolite and variable concentration of either sodium chloride or sodium bicarbonate resulted in a convex isotherm which was fitted by a Langmuir model. However, using a variable mass of zeolite and constant concentration of sodium ions revealed that the exchange of sodium ions with the zeolite surface sites was in fact unfavourable. Sodium ion exchange from bicarbonate solutions (10.3 g Na/kg zeolite) was preferred relative to exchange from sodium chloride solutions (6.4 g Na/kg zeolite). The formation of calcium carbonate species was proposed to explain the observed behaviour. Column studies of coal seam gas water showed that natural zeolite had limited ability to reduce the concentration of sodium ions (loading 2.1 g Na/kg zeolite) with rapid breakthrough observed. It was concluded that natural zeolites may not be suitable for the removal of cations from coal seam gas water without improvement of their physical properties.

Augmenting process elicitation with visual priming: An empirical exploration of user behaviour and modelling outcomes

Business process models have become an effective way of examining business practices to identify areas for improvement. While common information gathering approaches are generally efficacious, they can be quite time consuming and have the risk of developing inaccuracies when information is forgotten or incorrectly interpreted by analysts. In this study, the potential of a role-playing approach to process elicitation and specification has been examined. This method allows stakeholders to enter a virtual world and role-play actions similarly to how they would in reality. As actions are completed, a model is automatically developed, removing the need for stakeholders to learn and understand a modelling grammar. An empirical investigation comparing both the modelling outputs and participant behaviour of this virtual world role-play elicitor with an S-BPM process modelling tool found that while the modelling approaches of the two groups varied greatly, the virtual world elicitor may not only improve both the number of individual process task steps remembered and the correctness of task ordering, but also provide a reduction in the time required for stakeholders to model a process view.

Automated Discovery of Structured Process Models: Discover Structured vs. Discover and Structure

This paper addresses the problem of discovering business process models from event logs. Existing approaches to this problem strike various tradeoffs between accuracy and understandability of the discovered models. With respect to the second criterion, empirical studies have shown that block-structured process models are generally more understandable and less error-prone than unstructured ones. Accordingly, several automated process discovery methods generate block-structured models by construction. These approaches however intertwine the concern of producing accurate models with that of ensuring their structuredness, sometimes sacrificing the former to ensure the latter. In this paper we propose an alternative approach that separates these two concerns. Instead of directly discovering a structured process model, we first apply a well-known heuristic technique that discovers more accurate but sometimes unstructured (and even unsound) process models, and then transform the resulting model into a structured one. An experimental evaluation shows that our “discover and structure” approach outperforms traditional “discover structured” approaches with respect to a range of accuracy and complexity measures.