Neuropsychological development in children with early and continuously treated phenylketonuria : association with biochemical markers

PKU is a genetically inherited inborn error of metabolism caused by a deficiency of the enzyme phenylalanine hydroxylase. The failure of this enzyme causes incomplete metabolism of protein ingested in the diet, specifically the conversion of one amino acid, phenylalanine, to tyrosine, which is a precursor to the neurotransmitter dopamine. Rising levels of phenylalanine is toxic to the developing brain, disrupting the formation of white matter tracts. The impact of tyrosine deficiency is not as well understood, but is hypothesized to lead to a low dopamine environment for the developing brain. Detection in the newborn period and continuous treatment (a low protein phe-restricted diet supplemented with phenylalanine-free protein formulas) has resulted in children with early and continuously treated PKU now developing normal I.Q. However, deficits in executive function (EF) are common, leading to a rate of Attention Deficit Hyperactivity Disorder (ADHD) up to five times the norm. EF worsens with exposure to higher phenylalanine levels, however recent research has demonstrated that a high phenylalanine to tyrosine ratio (phenylalanine:tyrosine ratio), which is hypothesised to lead to poorer dopamine function, has a more negative impact on EF than phenylalanine levels alone. Research and treatment of PKU is currently phenylalanine-focused, with little investigation of the impact of tyrosine on neuropsychological development. There is no current consensus as to the veracity of tyrosine monitoring or treatment in this population. Further, the research agenda in this population has demonstrated a primary focus on EF impairment alone, even though there may be additional neuropsychological skills compromised (e.g., mood, visuospatial deficits). The aim of this PhD research was to identify residual neuropsychological deficits in a cohort of children with early and continuously treated phenylketonuria, at two time points in development (early childhood and early adolescence), separated by eight years. In addition, this research sought to determine which biochemical markers were associated with neuropsychological impairments. A clinical practice survey was also undertaken to ascertain the current level of monitoring/treatment of tyrosine in this population. Thirteen children with early and continuously treated PKU were tested at mean age 5.9 years and again at mean age 13.95 years on several neuropsychological measures. Four children with hyperphenylalaninemia (a milder version of PKU) were also tested at both time points and provide a comparison group in analyses. Associations between neuropsychological function and biochemical markers were analysed. A between groups analysis in adolescence was also conducted (children with PKU compared to their siblings) on parent report measures of EF and mood. Minor EF impairments were evident in the PKU group by age 6 years and these persisted into adolescence. Life-long exposure to high phenylalanine:tyrosine ratio and/or low tyrosine independent of phenylalanine were significantly associated with EF impairments at both time points. Over half the children with PKU showed severe impairment on a visuospatial task, and this was associated only with concurrent levels of tyrosine in adolescence. Children with PKU also showed a statistically significant decline in a language comprehension task from 6 years to adolescence (going from normal to subnormal), this deficit was associated with lifetime levels of phenylalanine. In comparison, the four children with hyperphenylalaninemia demonstrated normal function at both time points, across all measures. No statistically significant differences were detected between children with PKU and their siblings on the parent report of EF and mood. However, depressive symptoms were significantly correlated with: EF; long term high phe:tyr exposure; and low tyrosine levels independent of phenylalanine. The practice survey of metabolic clinics from 12 countries indicated a high level of variability in terms of monitoring/treatment of tyrosine in this population. Whilst over 80% of clinics surveyed routinely monitored tyrosine levels in their child patients, 25% reported treatment strategies to increase tyrosine (and thereby lower the phenylalanine:tyrosine ratio) under a variety of patient presentation conditions. Overall, these studies have shown that EF impairments associated with PKU provide support for the dopamine-deficiency model. A language comprehension task showed a different trajectory, serving a timely reminder that non-EF functions also remain vulnerable in this population; and that normal function in childhood does not guarantee normal function by adolescence. Mood impairments were associated with EF impairments as well as long term measures of phenylalanine:tyrosine and/or tyrosine. The implications of this research for enhanced clinical guidelines are discussed given varied current practice.

Understanding the phenomenon of IS success in China through the lens of the IS-Impact model

This study is conducted within the IS-Impact Research Track at Queensland University of Technology (QUT). The goal of the IS-Impact Track is, “to develop the most widely employed model for benchmarking information systems in organizations for the joint benefit of both research and practice” (Gable et al, 2006). IS-Impact is defined as “a measure at a point in time, of the stream of net benefits from the IS, to date and anticipated, as perceived by all key-user-groups” (Gable Sedera and Chan, 2008). Track efforts have yielded the bicameral IS-Impact measurement model; the “impact” half includes Organizational-Impact and Individual-Impact dimensions; the “quality” half includes System-Quality and Information-Quality dimensions. The IS-Impact model, by design, is intended to be robust, simple and generalizable, to yield results that are comparable across time, stakeholders, different systems and system contexts. The model and measurement approach employ perceptual measures and an instrument that is relevant to key stakeholder groups, thereby enabling the combination or comparison of stakeholder perspectives. Such a validated and widely accepted IS-Impact measurement model has both academic and practical value. It facilitates systematic operationalization of a main dependent variable in research (IS-Impact), which can also serve as an important independent variable. For IS management practice it provides a means to benchmark and track the performance of information systems in use. The objective of this study is to develop a Mandarin version IS-Impact model, encompassing a list of China-specific IS-Impact measures, aiding in a better understanding of the IS-Impact phenomenon in a Chinese organizational context. The IS-Impact model provides a much needed theoretical guidance for this investigation of ES and ES impacts in a Chinese context. The appropriateness and soundness of employing the IS-Impact model as a theoretical foundation are evident: the model originated from a sound theory of IS Success (1992), developed through rigorous validation, and also derived in the context of Enterprise Systems. Based on the IS-Impact model, this study investigates a number of research questions (RQs). Firstly, the research investigated what essential impacts have been derived from ES by Chinese users and organizations [RQ1]. Secondly, we investigate which salient quality features of ES are perceived by Chinese users [RQ2]. Thirdly, we seek to answer whether the quality and impacts measures are sufficient to assess ES-success in general [RQ3]. Lastly, the study attempts to address whether the IS-Impact measurement model is appropriate for Chinese organizations in terms of evaluating their ES [RQ4]. An open-ended, qualitative identification survey was employed in the study. A large body of short text data was gathered from 144 Chinese users and 633 valid IS-Impact statements were generated from the data set. A generally inductive approach was applied in the qualitative data analysis. Rigorous qualitative data coding resulted in 50 first-order categories with 6 second-order categories that were grounded from the context of Chinese organization. The six second-order categories are: 1) System Quality; 2) Information Quality; 3) Individual Impacts;4) Organizational Impacts; 5) User Quality and 6) IS Support Quality. The final research finding of the study is the contextualized Mandarin version IS-Impact measurement model that includes 38 measures organized into 4 dimensions: System Quality, information Quality, Individual Impacts and Organizational Impacts. The study also proposed two conceptual models to harmonize the IS-Impact model and the two emergent constructs – User Quality and IS Support Quality by drawing on previous IS effectiveness literatures and the Work System theory proposed by Alter (1999) respectively. The study is significant as it is the first effort that empirically and comprehensively investigates IS-Impact in China. Specifically, the research contributions can be classified into theoretical contributions and practical contributions. From the theoretical perspective, through qualitative evidence, the study test and consolidate IS-Impact measurement model in terms of the quality of robustness, completeness and generalizability. The unconventional research design exhibits creativity of the study. The theoretical model does not work as a top-down a priori seeking for evidence demonstrating its credibility; rather, the study allows a competitive model to emerge from the bottom-up and open-coding analysis. Besides, the study is an example extending and localizing pre-existing theory developed in Western context when the theory is introduced to a different context. On the other hand, from the practical perspective, It is first time to introduce prominent research findings in field of IS Success to Chinese academia and practitioner. This study provides a guideline for Chinese organizations to assess their Enterprise System, and leveraging IT investment in the future. As a research effort in ITPS track, this study contributes the research team with an alternative operationalization of the dependent variable. The future research can take on the contextualized Mandarin version IS-Impact framework as a theoretical a priori model, further quantitative and empirical testing its validity.

Improving patient privacy and confidentiality in one regional Emergency Department – a quality project

Background: Patient privacy and confidentiality (PPaC) is an important consideration for nurses and other members of the health care team. Can a patient expect to have confidentiality and in particular privacy in the current climate of emergency health care? Do staff who work in the Emergency Department (ED) see confidentiality as an important factor when providing emergency care? These questions are important to consider. Methods: This is a two phased quality improvement project, developed and implemented over a six month period in a busy regional, tertiary referral ED. Results: Issues identified for this department included department design and layout, overcrowding due to patient flow and access block, staff practices and department policies which were also impacted upon by culture of the team, and use of space. Conclusions: Changes successful in improving this issue include increased staff awareness about PPaC, intercom paging prior to nursing handover to remove visitors during handover, one visitor per patient policy, designated places for handover, allocated bed space for patient reviews/assessment and a strategy to temporarily move the patient if procedures would have been undertaken in shared bed space. These are important issues when considering policy, practice and department design in the ED.

The development and evaluation of a culturally affirmative counselling model for deaf clients in Australia

In Australia, there is only one, newly established, dedicated mental health service catering specifically for the signing *Deaf community. It is staffed by four part-time hearing professionals and based in Brisbane. There are currently no Deaf psychologists or psychiatrists and there is no valid or reliable empirical evidence on outcomes for Deaf people accessing specialised or mainstream mental health services. Further compounding these issues, is the fact that there are no sign language versions of the most common standardised mental health or psychological instruments available to clinicians in Australia. Contemporary counselling literature is acknowledging the role of the therapeutic alliance and the impact of 'common factors' on therapeutic outcomes. However, these issues are complicated by the relationship between the Deaf client and the hearing therapist being a cross-cultural exchange. The disability model of deafness is contentious and few professionals in Australia have the requisite knowledge and understanding of deafness from a cultural perspective to attend to the therapeutic relationship with this in mind. Consequently, Deaf people are severely disadvantaged by the current lack of services, resources and skilled professionals in the field of deafness and psychology in this country. The primary aim of the following program of research has been to propose a model for culturally affirmative service delivery and to provide clinicians with tools to evaluate the effect of their therapeutic work with Deaf people seeking mental health treatment. The research document is presented as a thesis by publication and comprises four specific objectives formulated in response to the lack of existing services and resources. The first objective was to explore the use of social constructionist counselling techniques and a reflecting team with Deaf clients, hearing therapists and an interpreter. Following the establishment of a pilot counselling clinic, indepth semi-structured interviews were conducted with two long-term clients following the one year pilot of this service. These interviews generated recommendations for the development of a new 'enriched' model of counselling to be implemented and evaluated in later stages of the research program. The second objective was to identify appropriate psychometric measures that could be translated into Australian Sign Language (Auslan) for research into efficacy, effectiveness and counselling outcomes. Two instruments were identified as potentially suitable; the Outcome Rating Scale (ORS), a measure of global functioning, and the Session Rating Scale (SRS), a measure of therapeutic alliance. A specialised team of bi-lingual and bi-cultural interpreters, native signers and the primary researcher for this thesis, produced the ORS-Auslan and the SRS-Auslan in DVD format, using the translation and back-translation process. The third objective was to establish the validity and reliability of these new Auslan measures based on normative data from the Deaf community. Data from the ORS-Auslan was collected from one clinical and one non-clinical sample of Deaf people. Statistical analyses revealed that the ORS-Auslan is reliable, valid and adequately distinguishes between clinical and non-clinical presentations. Furthermore, construct validity has been established using a yet to be validated sign language version of the Depression, Anxiety and Stress Scale-21 items (DASS-21), providing a platform for further research using the DASS-21 with Deaf people. The fourth objective was to evaluate counselling outcomes following the implementation of an enriched counselling service, based on the findings generated by the first objective, and using the newly translated Auslan measures. A second university counselling clinic was established and implemented over the course of one year. Practice-based evidence guided the research and the ORS-Auslan and the SRS-Auslan were administered at every session and provided outcome data on Deaf clients' global functioning. Data from six clients over the course of ten months indicated that this culturally affirmative model was an effective approach for these six clients. This is the first time that outcome data have been collected in Australia using valid and reliable Auslan measures to establish preliminary evidence for the effectiveness of any therapeutic intervention for clinical work with adult, signing Deaf clients. The research generated by this thesis contributes theoretical knowledge, professional development and practical resources that can be used by a variety of mental health clinicians in the context of mental health service delivery to Deaf clients in Australia.

Improving self-report measures of speeding

There is continuing debate regarding the psychometric properties of self-report measures of behaviour, particularly in road safety research. Practical considerations often preclude the use of objective assessments, leading to reliance on self-report measures. Acknowledging that such measures are likely to remain commonly used, this pilot project sought not to argue whether self-report measures should continue to be used, but to explore factors associated with how individuals respond to self-reported speeding measures. This paper reports preliminary findings from a qualitative study (focus groups and in-depth interviews) conducted with licensed drivers to explore the operational utility of self-reported speeding behaviour measures. Drawing upon concepts from the Theory of Planned Behaviour (TPB; Ajzen, 1991) and Agency Theory (Bandura, 2001), we identified four dimensions of self-reported speeding: including timeframe, speed zone, degree over the speed limit and, overall frequency of the behaviour, and examined participants’ perceptions of the operational utility of these factors. Issues related to comprehensibility, perceived accuracy, response format and layout were also explored. Results indicated that: heterogeneity in the timeframe of behavioural reflections suggests a need to provide a set timeframe for participants to consider when thinking about their previous speeding behaviour; response categories and formats should be carefully considered to ensure the most accurate representations of the frequency and degree of speeding are captured; the need to clearly articulate “low-level” speeding on self-report measures; and, that self-reports of speeding behaviour are typically context-irrelevant unless stipulated in the question. Limitations and directions for further research are discussed.

Impact of urban traffic and climate change on water quality from road runoff

Urban traffic and climate change are two phenomena that have the potential to degrade urban water quality by influencing the build-up and wash-off of pollutants, respectively. However, limited knowledge has made it difficult to establish any link between pollutant buildup and wash-off under such dynamic conditions. In order to safeguard urban water quality, adaptive water quality mitigation measures are required. In this research, pollutant build-up and wash-off have been investigated from a dynamic point of view which incorporated the impacts of changed urban traffic as well as changes in the rainfall characteristics induced by climate change. The study has developed a dynamic object classification system and thereby, conceptualised the study of pollutant build-up and wash-off under future changes in urban traffic and rainfall characteristics. This study has also characterised the buildup and wash-off processes of traffic generated heavy metals, volatile, semi-volatile and non-volatile hydrocarbons under dynamic conditions which enables the development of adaptive mitigation measures for water quality. Additionally, predictive frameworks for the build-up and wash-off of some pollutants have also been developed.

Thresholds for error probability measures of business process models

The quality of conceptual business process models is highly relevant for the design of corresponding information systems. In particular, a precise measurement of model characteristics can be beneficial from a business perspective, helping to save costs thanks to early error detection. This is just as true from a software engineering point of view. In this latter case, models facilitate stakeholder communication and software system design. Research has investigated several proposals as regards measures for business process models, from a rather correlational perspective. This is helpful for understanding, for example size and complexity as general driving forces of error probability. Yet, design decisions usually have to build on thresholds, which can reliably indicate that a certain counter-action has to be taken. This cannot be achieved only by providing measures; it requires a systematic identification of effective and meaningful thresholds. In this paper, we derive thresholds for a set of structural measures for predicting errors in conceptual process models. To this end, we use a collection of 2,000 business process models from practice as a means of determining thresholds, applying an adaptation of the ROC curves method. Furthermore, an extensive validation of the derived thresholds was conducted by using 429 EPC models from an Australian financial institution. Finally, significant thresholds were adapted to refine existing modeling guidelines in a quantitative way.

Responsiveness of the Effective Consumer Scale (EC-17)

Objective. The Effective Consumer Scale (EC-17) comprises 17 items measuring the main skills and behaviors people need to effectively manage their healthcare. We tested the responsiveness of the EC-17. Methods. Participants, in 2 waves of a 6-week Arthritis Self-Management Program (ASMP) from Arthritis Ireland, received a questionnaire at the first and last week of the weekly ASMP. The questionnaire included the EC-17 and 10 other measures for arthritis. Deficits, mean change, and standard deviations were calculated at baseline and Week 6. The EC-17 scores were compared to the Arthritis Self-Efficacy (ASE) and Patient Activation Measure (PAM) scales. Results were presented at OMERACT 9. Results. There is some overlap between the EC-17 and the ASE and PAM; however, most items of greatest deficit in the EC-17 are not covered by those scales. In 327 participants representing both intervention waves (2006 and 2007), the EC-17 was more efficient than the ASE but less efficient than the PAM for detecting improvements after the ASMP, and was moderately correlated with the PAM. Conclusion. The EC-17 appears to measure different skills and attributes than the ASE and PAM. Discussions with participants at OMERACT 9 agreed that it is worthwhile to measure the skills and attributes of an effective consumer, and supported the development of an intervention (such as proposed online decision aids) that would include education in the categories in the EC-17.

Patient-Specific Modeling of Scoliosis

Current complication rates for adolescent spinal deformity surgery are unacceptably high and in order to improve patient outcomes, the development of a simulation tool which enables the surgical strategy for an individual patient to be optimized is necessary. In this chapter we will present our work to date in developing and validating patient-specific modeling techniques to simulate and predict patient outcomes for surgery to correct adolescent scoliosis deformity. While these simulation tools are currently being developed to simulate adolescent idiopathic scoliosis patients, they will have broader applications in simulating spinal disorders and optimizing surgical planning for other types of spine surgery. Our studies to date have highlighted the need for not only patient-specific anatomical data, but also patient-specific tissue parameters and biomechanical loading data, in order to accurately predict the physiological behaviour of the spine. Even so, patient-specific computational models are the state-of-the art in computational biomechanics and offer much potential as a pre-operative surgical planning tool.

Regulations and policy measures related to the reduction of ambient particulate matter

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Smart Measures for Sustainable Outcomes: Integrated Considerations for Sustainable Refurbishment of Office Buildings

The increasing stock of aging office buildings will see a significant growth in retrofitting projects in Australian capital cities. Stakeholders of refitting works will also need to take on the sustainability challenge and realize tangible outcomes through project delivery. Traditionally, decision making for aged buildings, when facing the alternatives, is typically economically driven and on ad hoc basis. This leads to the tendency to either delay refitting for as long as possible thus causing building conditions to deteriorate, or simply demolish and rebuild with unjust financial burden. The technologies involved are often limited to typical strip-clean and repartition with dry walls and office cubicles. Changing business operational patterns, the efficiency of office space, and the demand on improved workplace environment, will need more innovative and intelligent approaches to refurbishing office buildings. For example, such projects may need to respond to political, social, environmental and financial implications. There is a need for the total consideration of buildings structural assessment, modeling of operating and maintenance costs, new architectural and engineering designs that maximise the utility of the existing structure and resulting productivity improvement, specific construction management procedures including procurement methods, work flow and scheduling and occupational health and safety. Recycling potential and conformance to codes may be other major issues. This paper introduces examples of Australian research projects which provided a more holistic approach to the decision making of refurbishing office space, using appropriate building technologies and products, assessment of residual service life, floor space optimisation and project procurement in order to bring about sustainable outcomes. The paper also discusses a specific case study on critical factors that influence key building components for these projects and issues for integrated decision support when dealing with the refurbishment, and indeed the “re-life”, of office buildings.

Special Measures in Indigenous Welfare Reform: Examining the Cape York Trial

The Cape York Welfare Reform (‘CYWR’) trial was due to expire at the end of 2011. In October 2011, the Queensland Government voted to extend the trial until the end of 2013. In November 2011, the Federal Minister for Indigenous Affairs announced changes to the Social Security (Administration) Act 1999 (Cth) that will extend another similar welfare reform, the School Enrolment and Attendance through Welfare Reform Measure (‘SEAM’), throughout other parts of Australia. This article examines the CYWR with reference to the Racial Discrimination Act 1975 (Cth) (‘RDA’), using the data available in the publications from the Family Responsibilities Commission (‘FRC’).It finds no clear evidence that the reforms have been effective in improving social conditions thus far and, as such, serious concerns as to whether the CYWR breaches the RDA.

Using operations research methodologies to improve operating theatre scheduling

A hospital consists of a number of wards, units and departments that provide a variety of medical services and interact on a day-to-day basis. Nearly every department within a hospital schedules patients for the operating theatre (OT) and most wards receive patients from the OT following post-operative recovery. Because of the interrelationships between units, disruptions and cancellations within the OT can have a flow-on effect to the rest of the hospital. This often results in dissatisfied patients, nurses and doctors, escalating waiting lists, inefficient resource usage and undesirable waiting times. The objective of this study is to use Operational Research methodologies to enhance the performance of the operating theatre by improving elective patient planning using robust scheduling and improving the overall responsiveness to emergency patients by solving the disruption management and rescheduling problem. OT scheduling considers two types of patients: elective and emergency. Elective patients are selected from a waiting list and scheduled in advance based on resource availability and a set of objectives. This type of scheduling is referred to as ‘offline scheduling’. Disruptions to this schedule can occur for various reasons including variations in length of treatment, equipment restrictions or breakdown, unforeseen delays and the arrival of emergency patients, which may compete for resources. Emergency patients consist of acute patients requiring surgical intervention or in-patients whose conditions have deteriorated. These may or may not be urgent and are triaged accordingly. Most hospitals reserve theatres for emergency cases, but when these or other resources are unavailable, disruptions to the elective schedule result, such as delays in surgery start time, elective surgery cancellations or transfers to another institution. Scheduling of emergency patients and the handling of schedule disruptions is an ‘online’ process typically handled by OT staff. This means that decisions are made ‘on the spot’ in a ‘real-time’ environment. There are three key stages to this study: (1) Analyse the performance of the operating theatre department using simulation. Simulation is used as a decision support tool and involves changing system parameters and elective scheduling policies and observing the effect on the system’s performance measures; (2) Improve viability of elective schedules making offline schedules more robust to differences between expected treatment times and actual treatment times, using robust scheduling techniques. This will improve the access to care and the responsiveness to emergency patients; (3) Address the disruption management and rescheduling problem (which incorporates emergency arrivals) using innovative robust reactive scheduling techniques. The robust schedule will form the baseline schedule for the online robust reactive scheduling model.