A cluster-randomised intervention trial against Schistosoma japonicum in the Peoples' Republic of China: bovine and human transmission

Background Zoonotic schistosomiasis japonica is a major public health problem in China. Bovines, particularly water buffaloes, are thought to play a major role in the transmission of schistosomiasis to humans in China. Preliminary results (1998–2003) of a praziquantel (PZQ)-based pilot intervention study we undertook provided proof of principle that water buffaloes are major reservoir hosts for S. japonicum in the Poyang Lake region, Jiangxi Province. Methods and Findings Here we present the results of a cluster-randomised intervention trial (2004–2007) undertaken in Hunan and Jiangxi Provinces, with increased power and more general applicability to the lake and marshlands regions of southern China. The trial involved four matched pairs of villages with one village within each pair randomly selected as a control (human PZQ treatment only), leaving the other as the intervention (human and bovine PZQ treatment). A sentinel cohort of people to be monitored for new infections for the duration of the study was selected from each village. Results showed that combined human and bovine chemotherapy with PZQ had a greater effect on human incidence than human PZQ treatment alone. Conclusions The results from this study, supported by previous experimental evidence, confirms that bovines are the major reservoir host of human schistosomiasis in the lake and marshland regions of southern China, and reinforce the rationale for the development and deployment of a transmission blocking anti-S. japonicum vaccine targeting bovines.

Final : report assessing risk and variation in maintenance and rehabilitation costs for road network

This report presents the results of research projects conducted by The Australian Cooperative Research Centre for Construction Innovation, Queensland University of Technology, RMIT University, Queensland Government Department of Main Roads and Queensland Department of Public Works. The research projects aimed at developing a methodology for assessing variation and risk in investment in road network, including the application of the method in assessing road network performance and maintenance and rehabilitation costs for short- and long-term future investment.

Report : review of the literature : maintenance and rehabilitation costs for roads (Risk-based Analysis)

Realistic estimates of short- and long-term (strategic) budgets for maintenance and rehabilitation of road assessment management should consider the stochastic characteristics of asset conditions of the road networks so that the overall variability of road asset data conditions is taken into account. The probability theory has been used for assessing life-cycle costs for bridge infrastructures by Kong and Frangopol (2003), Zayed et.al. (2002), Kong and Frangopol (2003), Liu and Frangopol (2004), Noortwijk and Frangopol (2004), Novick (1993). Salem 2003 cited the importance of the collection and analysis of existing data on total costs for all life-cycle phases of existing infrastructure, including bridges, road etc., and the use of realistic methods for calculating the probable useful life of these infrastructures (Salem et. al. 2003). Zayed et. al. (2002) reported conflicting results in life-cycle cost analysis using deterministic and stochastic methods. Frangopol et. al. 2001 suggested that additional research was required to develop better life-cycle models and tools to quantify risks, and benefits associated with infrastructures. It is evident from the review of the literature that there is very limited information on the methodology that uses the stochastic characteristics of asset condition data for assessing budgets/costs for road maintenance and rehabilitation (Abaza 2002, Salem et. al. 2003, Zhao, et. al. 2004). Due to this limited information in the research literature, this report will describe and summarise the methodologies presented by each publication and also suggest a methodology for the current research project funded under the Cooperative Research Centre for Construction Innovation CRC CI project no 2003-029-C.

Report : development of a methodology for assessing variation in maintenance and rehabilitation costs

In the previous research CRC CI 2001-010-C “Investment Decision Framework for Infrastructure Asset Management”, a method for assessing variation in cost estimates for road maintenance and rehabilitation was developed. The variability of pavement strength collected from a 92km national highway was used in the analysis to demonstrate the concept. Further analysis was conducted to identify critical input parameters that significantly affect the prediction of road deterioration. In addition to pavement strength, rut depth, annual traffic loading and initial roughness were found to be critical input parameters for road deterioration. This report presents a method developed to incorporate other critical parameters in the analysis, such as unit costs, which are suspected to contribute to a certain degree to cost estimate variation. Thus, the variability of unit costs will be incorporated in this analysis. Bruce Highway located in the tropical east coast of Queensland has been identified to be the network for the analysis. This report presents a step by step methodology for assessing variation in road maintenance and rehabilitation cost estimates.

How can preservice teachers be measured against advocated professional teaching standards?

Australia has had many inquiries into teaching and teacher education over the last decade. Standards for teaching have been produced by national education systems with many state systems following suit. The Queensland College of Teachers (QCT) advocates ten professional teaching standards for teachers and preservice teachers. How can preservice teachers be measured against advocated professional standards? This study investigated 106 second-year preservice teachers’ perceptions of their development against the QCT standards. A pretest-posttest survey instrument was developed based on the QCT standards and administered to these preservice teachers before and after their science education coursework. Percentages, ANOVAs and t-tests were generated to analyse the results. Findings indicated that 22 of the 24 paired pretest-posttest items were highly significant (p<.001). Percentage increases ranged from as low as 27% in the pretest to as high as 97% in the posttest, yet, there were two items with lower significance (i.e., working in professional science education teams and supporting students’ participation in society). Understanding preservice teachers’ perceptions of their abilities to implement these standards may be a step towards the process of determining the achievement of teaching standards; however, more rigorous measurements will need to be developed for both teachers and preservice teachers. University coursework and related assessments can provide an indication of achieving these standards, especially authentic assessment of preservice teachers’ practices.

Downtime reduction analysis of the Australia Post flat mail optical character reader

Machine downtime, whether planned or unplanned, is intuitively costly to manufacturing organisations, but is often very difficult to quantify. The available literature showed that costing processes are rarely undertaken within manufacturing organisations. Where cost analyses have been undertaken, they generally have only valued a small proportion of the affected costs, leading to an overly conservative estimate. This thesis aimed to develop a cost of downtime model, with particular emphasis on the application of the model to Australia Post’s Flat Mail Optical Character Reader (FMOCR). The costing analysis determined a cost of downtime of $5,700,000 per annum, or an average cost of $138 per operational hour. The second section of this work focused on the use of the cost of downtime to objectively determine areas of opportunity for cost reduction on the FMOCR. This was the first time within Post that maintenance costs were considered along side of downtime for determining machine performance. Because of this, the results of the analysis revealed areas which have historically not been targeted for cost reduction. Further exploratory work was undertaken on the Flats Lift Module (FLM) and Auto Induction Station (AIS) Deceleration Belts through the comparison of the results against two additional FMOCR analysis programs. This research has demonstrated the development of a methodical and quantifiable cost of downtime for the FMOCR. This has been the first time that Post has endeavoured to examine the cost of downtime. It is also one of the very few methodologies for valuing downtime costs that has been proposed in literature. The work undertaken has also demonstrated how the cost of downtime can be incorporated into machine performance analysis with specific application to identifying high costs modules. The outcome of this report has both been the methodology for costing downtime, as well as a list of areas for cost reduction. In doing so, this thesis has outlined the two key deliverables presented at the outset of the research.

Utilizing robustness of positive buck-boost converter against input voltage and load current disturbances

A Positive Buck- Boost (PBB) converter is a known DC-DC converter that can operate in step up and step down modes. Unlike Buck, Boost, and Inverting Buck Boost converters, the inductor current of a PBB can be controlled independently of its voltage conversion ratio. In other words, the inductor of PBB can be utilised as an energy storage unit in addition to its main function of energy transfer. In this paper, the capability of PBB to store energy has been utilised to achieve robustness against input voltage fluctuations and output current changes. The control strategy has been developed to keep accuracy, affordability, and simplicity acceptable. To improve the efficiency of the system a Smart Load Controller (SLC) has been suggested. Applying SLC extra current storage occurs when there is sudden loads change otherwise little extra current is stored.

Crimes against morality

The purpose of this chapter is to discuss the relationship between crime and morality, with a specific focus on crimes against morality. While we argue that all crimes have a general moral basis, condemned as wrong or bad and proscribed by society, there is a specific group of offences in modern democratic nations labelled crimes against morality. Included within this group are offences related to prostitution, pornography and homosexuality. What do these crimes have in common? Most clearly they tend to have a sexual basis and are often argued to do sexual harm, in both a moral and /or psychological sense, as well as physically. Conversely they are often argued to be victimless crimes, especially when the acts occur between consenting adults. Finally they are considered essentially private acts but they often occur, and are regulated, in the public domain. Most importantly, each of these crimes against morality has only relatively recently (ie in the past 150 years) become identified and regulated by the state as a criminal offence.

Open occupations - Why work should be free

The benefits of openness are widely apparent everywhere except, seemingly, in occupations. Yet the case against occupational licensing still remains strong. Consideration of dynamic costs strengthens the case further.

Contemporary examples where doctors are not immune from non-fatal offences against a person

While it is uncontested that the medical profession makes a valuable contribution to society, doctors should not always be beyond the reach of the criminal law and they should not automatically be treated as God. Doctors should act reasonably and be conscious of their position of trust. In this sense, the notion of “doctors” is construed broadly to include a range of health care professionals such as podiatrists, radiographers, surgeons and general practitioners. This paper will explore contemporary Australian examples where doctors have acted inappropriately and been convicted of non-fatal offences against the person. The physical invasiveness involved in these scenarios varies significantly. In one example, a doctor penetrates a patient’s private body part with a probe for their own sexual gratification, and in another, a doctor covertly visually records a naked patient. The examples will be connected to the theories underpinning criminalisation, particularly social welfare and individual autonomy, with a view to framing guidelines on when doctors should not be immune from non-fatal offences against a person, and thus where the criminal law should respond.

The costs arising from pressure ulcers attributable to malnutrition

Aim To estimate the economic consequences of pressure ulcers attributable to malnutrition. Method Statistical models were developed to predict the number of cases of pressure ulcer, associated bed days lost and the dollar value of these losses in public hospitals in 2002/2003 in Queensland, Australia. The following input parameters were specified and appropriate probability distributions fitted • Number of at risk discharges per annum • Incidence rate for pressure ulcer • Attributable fraction of malnutrition in the development of pressure ulcer • Independent effect of pressure ulcer on length of hospital stay • Opportunity cost of hospital bed day One thousand random re-samples were made and the results expressed as (output) probabilistic distributions. Results The model predicts a mean 16060 (SD 5 671) bed days lost and corresponding mean economic cost of AU$12 968 668 (SD AU$4 924 148) (EUROS 6 925 268 SD 2 629 495; US$ 7 288 391 SD 2 767 371) of pressure ulcer attributable to malnutrition in 2002/2003 in public hospitals in Queensland, Australia. Conclusion The cost of pressure ulcer attributable to malnutrition in bed days and dollar terms are substantial. The model only considers costs of increased length of stay associated with pressure ulcer and not other factors associated with care.

Recombinant protein production using a Tobacco yellow dwarf virus-based episomal expression vector : control of Rep activity

Over the past decade, plants have been used as expression hosts for the production of pharmaceutically important and commercially valuable proteins. Plants offer many advantages over other expression systems such as lower production costs, rapid scale up of production, similar post-translational modification as animals and the low likelihood of contamination with animal pathogens, microbial toxins or oncogenic sequences. However, improving recombinant protein yield remains one of the greatest challenges to molecular farming. In-Plant Activation (InPAct) is a newly developed technology that offers activatable and high-level expression of heterologous proteins in plants. InPAct vectors contain the geminivirus cis elements essential for rolling circle replication (RCR) and are arranged such that the gene of interest is only expressed in the presence of the cognate viral replication-associated protein (Rep). The expression of Rep in planta may be controlled by a tissue-specific, developmentally regulated or chemically inducible promoter such that heterologous protein accumulation can be spatially and temporally controlled. One of the challenges for the successful exploitation of InPAct technology is the control of Rep expression as even very low levels of this protein can reduce transformation efficiency, cause abnormal phenotypes and premature activation of the InPAct vector in regenerated plants. Tight regulation over transgene expression is also essential if expressing cytotoxic products. Unfortunately, many tissue-specific and inducible promoters are unsuitable for controlling expression of Rep due to low basal activity in the absence of inducer or in tissues other than the target tissue. This PhD aimed to control Rep activity through the production of single chain variable fragments (scFvs) specific to the motif III of Tobacco yellow dwarf virus (TbYDV) Rep. Due to the important role played by the conserved motif III in the RCR, it was postulated that such scFvs can be used to neutralise the activity of the low amount of Rep expressed from a “leaky” inducible promoter, thus preventing activation of the TbYDV-based InPAct vector until intentional induction. Such scFvs could also offer the potential to confer partial or complete resistance to TbYDV, and possibly heterologous viruses as motif III is conserved between geminiviruses. Studies were first undertaken to determine the levels of TbYDV Rep and TbYDV replication-associated protein A (RepA) required for optimal transgene expression from a TbYDV-based InPAct vector. Transient assays in a non-regenerable Nicotiana tabacum (NT-1) cell line were undertaken using a TbYDV-based InPAct vector containing the uidA reporter gene (encoding GUS) in combination with TbYDV Rep and RepA under the control of promoters with high (CaMV 35S) or low (Banana bunchy top virus DNA-R, BT1) activity. The replication enhancer protein of Tomato leaf curl begomovirus (ToLCV), REn, was also used in some co-bombardment experiments to examine whether RepA could be substituted by a replication enhancer from another geminivirus genus. GUS expression was observed both quantitatively and qualitatively by fluorometric and histochemical assays, respectively. GUS expression from the TbYDV-based InPAct vector was found to be greater when Rep was expected to be expressed at low levels (BT1 promoter) rather than high levels (35S promoter). GUS expression was further enhanced when Rep and RepA were co-bombarded with a low ratio of Rep to RepA. Substituting TbYDV RepA with ToLCV REn also enhanced GUS expression but more importantly highest GUS expression was observed when cells were co-transformed with expression vectors directing low levels of Rep and high levels of RepA irrespective of the level of REn. In this case, GUS expression was approximately 74-fold higher than that from a non-replicating vector. The use of different terminators, namely CaMV 35S and Nos terminators, in InPAct vectors was found to influence GUS expression. In the presence of Rep, GUS expression was greater using pInPActGUS-Nos rather than pInPActGUS-35S. The only instance of GUS expression being greater from vectors containing the 35S terminator was when comparing expression from cells transformed with Rep, RepA and REnexpressing vectors and either non-replicating vectors, p35SGS-Nos or p35SGS-35S. This difference was most likely caused by an interaction of viral replication proteins with each other and the terminators. These results indicated that (i) the level of replication associated proteins is critical to high transgene expression, (ii) the choice of terminator within the InPAct vector may affect expression levels and (iii) very low levels of Rep can activate InPAct vectors hence controlling its activity is critical. Prior to generating recombinant scFvs, a recombinant TbYDV Rep was produced in E. coli to act as a control to enable the screening for Rep-specific antibodies. A bacterial expression vector was constructed to express recombinant TbYDV Rep with an Nterminal His-tag (N-His-Rep). Despite investigating several purification techniques including Ni-NTA, anion exchange, hydrophobic interaction and size exclusion chromatography, N-His-Rep could only be partially purified using a Ni-NTA column under native conditions. Although it was not certain that this recombinant N-His-Rep had the same conformation as the native TbYDV Rep and was functional, results from an electromobility shift assay (EMSA) showed that N-His-Rep was able to interact with the TbYDV LIR and was, therefore, possibly functional. Two hybridoma cell lines from mice, immunised with a synthetic peptide containing the TbYDV Rep motif III amino acid sequence, were generated by GenScript (USA). Monoclonal antibodies secreted by the two hybridoma cell lines were first screened against denatured N-His-Rep in Western analysis. After demonstrating their ability to bind N-His-Rep, two scFvs (scFv1 and scFv2) were generated using a PCR-based approach. Whereas the variable heavy chain (VH) from both cell lines could be amplified, only the variable light chain (VL) from cell line 2 was amplified. As a result, scFv1 contained VH and VL from cell line 1, whereas scFv2 contained VH from cell line 2 and VL from cell line 1. Both scFvs were first expressed in E. coli in order to evaluate their affinity to the recombinant TbYDV N-His-Rep. The preliminary results demonstrated that both scFvs were able to bind to the denatured N-His-Rep. However, EMSAs revealed that only scFv2 was able to bind to native N-His-Rep and prevent it from interacting with the TbYDV LIR. Each scFv was cloned into plant expression vectors and co-bombarded into NT-1 cells with the TbYDV-based InPAct GUS expression vector and pBT1-Rep to examine whether the scFvs could prevent Rep from mediating RCR. Although it was expected that the addition of the scFvs would result in decreased GUS expression, GUS expression was found to slightly increase. This increase was even more pronounced when the scFvs were targeted to the cell nucleus by the inclusion of the Simian virus 40 large T antigen (SV40) nuclear localisation signal (NLS). It was postulated that the scFvs were binding to a proportion of Rep, leaving a small amount available to mediate RCR. The outcomes of this project provide evidence that very high levels of recombinant protein can theoretically be expressed using InPAct vectors with judicious selection and control of viral replication proteins. However, the question of whether the scFvs generated in this project have sufficient affinity for TbYDV Rep to prevent its activity in a stably transformed plant remains unknown. It may be that other scFvs with different combinations of VH and VL may have greater affinity for TbYDV Rep. Such scFvs, when expressed at high levels in planta, might also confer resistance to TbYDV and possibly heterologous geminiviruses.

An experimental and finite element investigation of the biomechanics of vertebral compression fractures

Osteoporosis is a disease characterized by low bone mass and micro-architectural deterioration of bone tissue, with a consequent increase in bone fragility and susceptibility to fracture. Osteoporosis affects over 200 million people worldwide, with an estimated 1.5 million fractures annually in the United States alone, and with attendant costs exceeding $10 billion dollars per annum. Osteoporosis reduces bone density through a series of structural changes to the honeycomb-like trabecular bone structure (micro-structure). The reduced bone density, coupled with the microstructural changes, results in significant loss of bone strength and increased fracture risk. Vertebral compression fractures are the most common type of osteoporotic fracture and are associated with pain, increased thoracic curvature, reduced mobility, and difficulty with self care. Surgical interventions, such as kyphoplasty or vertebroplasty, are used to treat osteoporotic vertebral fractures by restoring vertebral stability and alleviating pain. These minimally invasive procedures involve injecting bone cement into the fractured vertebrae. The techniques are still relatively new and while initial results are promising, with the procedures relieving pain in 70-95% of cases, medium-term investigations are now indicating an increased risk of adjacent level fracture following the procedure. With the aging population, understanding and treatment of osteoporosis is an increasingly important public health issue in developed Western countries. The aim of this study was to investigate the biomechanics of spinal osteoporosis and osteoporotic vertebral compression fractures by developing multi-scale computational, Finite Element (FE) models of both healthy and osteoporotic vertebral bodies. The multi-scale approach included the overall vertebral body anatomy, as well as a detailed representation of the internal trabecular microstructure. This novel, multi-scale approach overcame limitations of previous investigations by allowing simultaneous investigation of the mechanics of the trabecular micro-structure as well as overall vertebral body mechanics. The models were used to simulate the progression of osteoporosis, the effect of different loading conditions on vertebral strength and stiffness, and the effects of vertebroplasty on vertebral and trabecular mechanics. The model development process began with the development of an individual trabecular strut model using 3D beam elements, which was used as the building block for lattice-type, structural trabecular bone models, which were in turn incorporated into the vertebral body models. At each stage of model development, model predictions were compared to analytical solutions and in-vitro data from existing literature. The incremental process provided confidence in the predictions of each model before incorporation into the overall vertebral body model. The trabecular bone model, vertebral body model and vertebroplasty models were validated against in-vitro data from a series of compression tests performed using human cadaveric vertebral bodies. Firstly, trabecular bone samples were acquired and morphological parameters for each sample were measured using high resolution micro-computed tomography (CT). Apparent mechanical properties for each sample were then determined using uni-axial compression tests. Bone tissue properties were inversely determined using voxel-based FE models based on the micro-CT data. Specimen specific trabecular bone models were developed and the predicted apparent stiffness and strength were compared to the experimentally measured apparent stiffness and strength of the corresponding specimen. Following the trabecular specimen tests, a series of 12 whole cadaveric vertebrae were then divided into treated and non-treated groups and vertebroplasty performed on the specimens of the treated group. The vertebrae in both groups underwent clinical-CT scanning and destructive uniaxial compression testing. Specimen specific FE vertebral body models were developed and the predicted mechanical response compared to the experimentally measured responses. The validation process demonstrated that the multi-scale FE models comprising a lattice network of beam elements were able to accurately capture the failure mechanics of trabecular bone; and a trabecular core represented with beam elements enclosed in a layer of shell elements to represent the cortical shell was able to adequately represent the failure mechanics of intact vertebral bodies with varying degrees of osteoporosis. Following model development and validation, the models were used to investigate the effects of progressive osteoporosis on vertebral body mechanics and trabecular bone mechanics. These simulations showed that overall failure of the osteoporotic vertebral body is initiated by failure of the trabecular core, and the failure mechanism of the trabeculae varies with the progression of osteoporosis; from tissue yield in healthy trabecular bone, to failure due to instability (buckling) in osteoporotic bone with its thinner trabecular struts. The mechanical response of the vertebral body under load is highly dependent on the ability of the endplates to deform to transmit the load to the underlying trabecular bone. The ability of the endplate to evenly transfer the load through the core diminishes with osteoporosis. Investigation into the effect of different loading conditions on the vertebral body found that, because the trabecular bone structural changes which occur in osteoporosis result in a structure that is highly aligned with the loading direction, the vertebral body is consequently less able to withstand non-uniform loading states such as occurs in forward flexion. Changes in vertebral body loading due to disc degeneration were simulated, but proved to have little effect on osteoporotic vertebra mechanics. Conversely, differences in vertebral body loading between simulated invivo (uniform endplate pressure) and in-vitro conditions (where the vertebral endplates are rigidly cemented) had a dramatic effect on the predicted vertebral mechanics. This investigation suggested that in-vitro loading using bone cement potting of both endplates has major limitations in its ability to represent vertebral body mechanics in-vivo. And lastly, FE investigation into the biomechanical effect of vertebroplasty was performed. The results of this investigation demonstrated that the effect of vertebroplasty on overall vertebra mechanics is strongly governed by the cement distribution achieved within the trabecular core. In agreement with a recent study, the models predicted that vertebroplasty cement distributions which do not form one continuous mass which contacts both endplates have little effect on vertebral body stiffness or strength. In summary, this work presents the development of a novel, multi-scale Finite Element model of the osteoporotic vertebral body, which provides a powerful new tool for investigating the mechanics of osteoporotic vertebral compression fractures at the trabecular bone micro-structural level, and at the vertebral body level.

Development of lifetime warranty policies and models for estimating costs

In today's fiercely competitive products market, product warranty has started playing an important role. The warranty period offered by the manufacturer/dealer has been progressively increasing since the beginning of the 20th Century. Currently, a large number of products are being sold with long-term warranty policies in the form of extended warranty, warranty for used products, service contracts and lifetime warranty policies. Lifetime warranties are relatively a new concept. The modelling of failures during the warranty period and the costs for such policies are complex since the lifespan in these policies are not defined well and it is often difficult to tell about life measures for the longer period of coverage due to usage pattern/maintenance activities undertaken and uncertainties of costs over the period. This paper focuses on defining lifetime, developing lifetime warranty policies and models for predicting failures and estimating costs for lifetime warranty policies.