Sustained release and osteogenic potential of heparan sulfate-doped fibrin glue scaffolds within a rat cranial model

This paper explores the potential therapeutic role of the naturally occurring sugar heparan sulfate (HS) for the augmentation of bone repair. Scaffolds comprising fibrin glue loaded with 5 lg of embryonically derived HS were assessed, firstly as a release-reservoir, and secondly as a scaffold to stimulate bone regeneration in a critical size rat cranial defect. We show HS-loaded scaffolds have a uniform distribution of HS, which was readily released with a typical burst phase, quickly followed by a prolonged delivery lasting several days. Importantly, the released HS contributed to improved wound healing over a 3-month period as determined by microcomputed tomography (lCT) scanning, histology, histomorphometry, and PCR for osteogenic markers. In all cases, only minimal healing was observed after 1 and 3 months in the absence of HS. In contrast, marked healing was observed by 3 months following HS treatment, with nearly full closure of the defect site. PCR analysis showed significant increases in the gene expression of the osteogenic markers Runx2, alkaline phosphatase, and osteopontin in the heparin sulfate group compared with controls. These results further emphasize the important role HS plays in augmenting wound healing, and its successful delivery in a hydrogel provides a novel alternative to autologous bone graft and growth factorbased therapies.

Case-control study of early childhood caries in Australia

The aim of this case-control study of 617 children was to investigate early childhood caries (ECC) risk indicators in a non-fluoridated region in Australia. ECC cases were recruited from childcare facilities, public hospitals and private specialist clinics to source children from different socioeconomic backgrounds. Non-ECC controls were recruited from the same childcare facilities. A multinomial logistic modelling approach was used for statistical analysis. The results showed that a large percentage of children tested positive for Streptococcus mutans if their mothers also tested positive. A common risk indicator found in ECC children from childcare facilities and public hospitals was visible plaque (OR 4.1, 95% CI 1.0-15.9, and OR 8.7, 95% CI 2.3-32.9, respectively). Compared to ECC-free controls, the risk indicators specific to childcare cases were enamel hypoplasia (OR 4.2, 95% CI 1.0-18.3), difficulty in cleaning child's teeth (OR 6.6, 95% CI 2.2-19.8), presence of S. mutans (OR 4.8, 95% CI 0.7-32.6), sweetened drinks (OR 4.0, 95% CI 1.2-13.6) and maternal anxiety (OR 5.1, 95% CI 1.1-25.0). Risk indicators specific to public hospital cases were S. mutans presence in child (OR 7.7, 95% CI 1.3-44.6) or mother (OR 8.1, 95% CI 0.9-72.4), ethnicity (OR 5.6, 95% CI 1.4-22.1), and access of mother to pension or health care card (OR 20.5, 95% CI 3.5-119.9). By contrast, a history of chronic ear infections was found to be protective for ECC in childcare children (OR 0.28, 95% CI 0.09-0.82). The biological, socioeconomic and maternal risk indicators demonstrated in the present study can be employed in models of ECC that can be usefully applied for future longitudinal studies.

Effects of lead exposure on hippocampal metabotropic glutamate receptor subtype 3 and 7 in developmental rats

Background A complete explanation of the mechanisms by which Pb2+ exerts toxic effects on developmental central nervous system remains unknown. Glutamate is critical to the developing brain through various subtypes of ionotropic or metabotropic glutamate receptors (mGluRs). Ionotropic N-methyl-D-aspartate receptors have been considered as a principal target in lead-induced neurotoxicity. The relationship between mGluR3/mGluR7 and synaptic plasticity had been verified by many recent studies. The present study aimed to examine the role of mGluR3/mGluR7 in lead-induced neurotoxicity. Methods Twenty-four adult and female rats were randomly selected and placed on control or 0.2% lead acetate during gestation and lactation. Blood lead and hippocampal lead levels of pups were analyzed at weaning to evaluate the actual lead content at the end of the exposure. Impairments of short -term memory and long-term memory of pups were assessed by tests using Morris water maze and by detection of hippocampal ultrastructural alterations on electron microscopy. The impact of lead exposure on mGluR3 and mGluR7 mRNA expression in hippocampal tissue of pups were investigated by quantitative real-time polymerase chain reaction and its potential role in lead neurotoxicity were discussed. Results Lead levels of blood and hippocampi in the lead-exposed rats were significantly higher than those in the controls (P < 0.001). In tests using Morris Water Maze, the overall decrease in goal latency and swimming distance was taken to indicate that controls had shorter latencies and distance than lead-exposed rats (P = 0.001 and P < 0.001 by repeated-measures analysis of variance). On transmission electron microscopy neuronal ultrastructural alterations were observed and the results of real-time polymerase chain reaction showed that exposure to 0.2% lead acetate did not substantially change gene expression of mGluR3 and mGluR7 mRNA compared with controls. Conclusion Exposure to lead before and after birth can damage short-term and long-term memory ability of young rats and hippocampal ultrastructure. However, the current study does not provide evidence that the expression of rat hippocampal mGluR3 and mGluR7 can be altered by systemic administration of lead during gestation and lactation, which are informative for the field of lead-induced developmental neurotoxicity noting that it seems not to be worthwhile to include mGluR3 and mGluR7 in future studies. Background

Electronic telephone directory listings : preferred sampling frame for a population-based study of childhood cancer in Australia

PURPOSE: We report our telephone-based system for selecting community control series appropriate for a complete Australia-wide series of Ewing's sarcoma cases. METHODS: We used electronic directory random sampling to select age-matched controls. The sampling has all listed telephone numbers on an up-dated CD-Rom. RESULTS: 95% of 2245 telephone numbers selected were successfully contacted. The mean number of attempts needed was 1.94, 58% answering at the first attempt. On average, we needed 4.5 contacts per control selected. Calls were more likely to be successful (reach a respondent) when made in the evening (except Saturdays). The overall response rate among contacted telephone numbers was 92.8%. Participation rates among female and male respondents were practically the same. The exclusion of unlisted numbers (13.5% of connected households) and unconnected households (3.7%) led to potential selection bias. However, restricting the case series to listed cases only, plus having external information on the direction of potential bias allow meaningful interpretation of our data. CONCLUSION: Sampling from an electronic directory is convenient, economical and simple, and gives a very good yield of eligible subjects compared to other methods.

Managing the winds of change

Environmental impacts caused during Australia's comparatively recent settlement by Europeans are evident. Governments (both Commonwealth and States) have been largely responsible for requiring landholders – through leasehold development conditions and taxation concessions – to conduct clearing that is now perceived as damage. Most governments are now demanding resource protection. There is a measure of bewilderment (if not resentment) among landholders because of this change. The more populous States, where most overall damage has been done (i.e. Victoria and New South Wales), provide most support for attempts to stop development in other regions where there has been less damage. Queensland, i.e. the north-eastern quarter of the continent, has been relatively slow to develop. It also holds the largest and most diverse natural environments. Tree clearing is an unavoidable element of land development, whether to access and enhance native grasses for livestock or to allow for urban developments (with exotic tree plantings). The consequences in terms of regulations are particularly complex because of the dynamic nature of vegetation. The regulatory terms used in current legislation – such as 'Endangered' and 'Of concern' – depend on legally-defined, static baselines. Regrowth and fire damage are two obvious causes of change. A less obvious aspect is succession, where ecosystems change naturally over long timeframes. In the recent past, the Queensland Government encouraged extensive tree-clearing e.g. through the State Brigalow Development Scheme (mostly 1962 to 1975) which resulted in the removal of some 97% of the wide-ranging mature forests of Acacia harpophylla. At the same time, this government controls National Parks and other reservations (occupying some 4% of the State's 1.7 million km2 area) and also holds major World Heritage Areas (such as the Great Barrier Reef and the Wet Tropics Rainforest) promulgated under Commonwealth legislation. This is a highly prescriptive approach, where the community is directed on the one hand to develop (largely through lease conditions) and on the other to avoid development (largely by unusable reserves). Another approach to development and conservation is still possible in Queensland. For this to occur, however, a more workable and equitable solution than has been employed to date is needed, especially for the remote lands of this State. This must involve resident landholders, who have the capacity (through local knowledge, infrastructure and daily presence) to undertake most costeffectively sustainable land-use management (with suitable attention to ecosystems requiring special conservation effort), that is, provided they have the necessary direction, encouragement and incentive to do so.

Flexible high-power multi DC-DC converters for train systems

This thesis reports on the investigations, simulations and analyses of novel power electronics topologies and control strategies. The research is financed by an Australian Research Council (ARC) Linkage (07-09) grant. Therefore, in addition to developing original research and contributing to the available knowledge of power electronics, it also contributes to the design of a DC-DC converter for specific application to the auxiliary power supply in electric trains. Specifically, in this regard, it contributes to the design of a 7.5 kW DC-DC converter for the industrial partner (Schaffler and Associates Ltd) who supported this project. As the thesis is formatted as a ‘thesis by publication’, the contents are organized around published papers. The research has resulted in eleven papers, including seven peer reviewed and published conference papers, one published journal paper, two journal papers accepted for publication and one submitted journal paper (provisionally accepted subject to few changes). In this research, several novel DC-DC converter topologies are introduced, analysed, and tested. The similarity of all of the topologies devised lies in their ‘current circulating’ switching state, which allows them to store some energy in the inductor, as extra inductor current. The stored energy may be applied to enhance the performance of the converter in the occurrence of load current or input voltage disturbances. In addition, when there is an alternating load current, the ability to store energy allows the converter to perform satisfactorily despite frequently and highly varying load current. In this research, the capability of current storage has been utilised to design topologies for specific applications, and the enhancement of the performance of the considered applications has been illustrated. The simplest DC-DC converter topology, which has a ‘current circulating’ switching state, is the Positive Buck-Boost (PBB) converter (also known as the non-inverting Buck-Boost converter). Usually, the topology of the PBB converter is operating as a Buck or a Boost converter in applications with widely varying input voltage or output reference voltage. For example, in electric railways (the application of our industrial partner), the overhead line voltage alternates from 1000VDC to 500VDC and the required regulated voltage is 600VDC. In the course of this research, our industrial partner (Schaffler and Associates Ltd) industrialized a PBB converter–the ‘Mudo converter’–operating at 7.5 kW. Programming the onboard DSP and testing the PBB converter in experimental and nominal power and voltage was part of this research program. In the earlier stages of this research, the advantages and drawbacks of utilization of the ‘current circulating’ switching state in the positive Buck-Boost converter were investigated. In brief, the advantages were found to be robustness against input voltage and current load disturbances, and the drawback was extra conduction and switching loss. Although the robustness against disturbances is desirable for many applications, the price of energy loss must be minimized to attract attention to the utilization of the PBB converter. In further stages of this research, two novel control strategies for different applications were devised to minimise the extra energy loss while the advantages of the positive Buck-Boost converter were fully utilized. The first strategy is Smart Load Controller (SLC) for applications with pre-knowledge or predictability of input voltage and/or load current disturbances. A convenient example of these applications is electric/hybrid cars where a master controller commands all changes in loads and voltage sources. Therefore, the master controller has a pre-knowledge of the load and input voltage disturbances so it can apply the SLC strategy to utilize robustness of the PBB converter. Another strategy aiming to minimise energy loss and maximise the robustness in the face of disturbance is developed to cover applications with unexpected disturbances. This strategy is named Dynamic Hysteresis Band (DHB), and is used to manipulate the hysteresis band height after occurrence of disturbance to reduce dynamics of the output voltage. When no disturbance has occurred, the PBB converter works with minimum inductor current and minimum energy loss. New topologies based on the PBB converter have been introduced to address input voltage disturbances for different onboard applications. The research shows that the performance of applications of symmetrical/asymmetrical multi-level diode-clamped inverters, DC-networks, and linear-assisted RF amplifiers may be enhanced by the utilization of topologies based on the PBB converter. Multi-level diode-clamped inverters have the problem of DC-link voltage balancing when the power factor of their load closes to unity. This research has shown that this problem may be solved with a suitable multi-output DC-DC converter supplying DClink capacitors. Furthermore, the multi-level diode-clamped inverters supplied with asymmetrical DC-link voltages may improve the quality of load voltage and reduce the level of Electromagnetic Interference (EMI). Mathematical analyses and experiments on supplying symmetrical and asymmetrical multi-level inverters by specifically designed multi-output DC-DC converters have been reported in two journal papers. Another application in which the system performance can be improved by utilization of the ‘current circulating’ switching state is linear-assisted RF amplifiers in communicational receivers. The concept of ‘linear-assisted’ is to divide the signal into two frequency domains: low frequency, which should be amplified by a switching circuit; and the high frequency domain, which should be amplified by a linear amplifier. The objective is to minimize the overall power loss. This research suggests using the current storage capacity of a PBB based converter to increase its bandwidth, and to increase the domain of the switching converter. The PBB converter addresses the industrial demand for a DC-DC converter for the application of auxiliary power supply of a typical electric train. However, after testing the industrial prototype of the PBB converter, there were some voltage and current spikes because of switching. To attenuate this problem without significantly increasing the switching loss, the idea of Active Gate Signalling (AGS) is presented. AGS suggests a smart gate driver that selectively controls the switching process to reduce voltage/current spikes, without unacceptable reduction in the efficiency of switching.

Do warnings deter rather than produce more sophisticated malingering?

Following Youngjohn, Lees-Haley, and Binder's (1999) comment on Johnson and Lesniak-Karpiak's (1997) study that warnings lead to more subtle malingering, researchers have sought to better understand warning effects. However, such studies have been largely atheoretical and may have confounded warning and coaching. This study examined the effect on malingering of a warning that was based on criminological-sociological concepts derived from the rational choice model of deterrence theory. A total of 78 participants were randomly assigned to a control group, an unwarned simulator group, or one of two warned simulator groups. The warning groups comprised low- and high-level conditions depending on warning intensity. Simulator participants received no coaching about how to fake tests. Outcome variables were scores derived from the Test of Memory Malingering and Wechsler Memory Scale-III. When the rate of malingering was compared across the four groups, a high-level warning effect was found such that warned participants were significantly less likely to exaggerate than unwarned simulators. In an exploratory follow-up analysis, the warned groups were divided into those who reported malingering and those who did not report malingering, and the performance of these groups was compared to that of unwarned simulators and controls. Using this approach, results showed that participants who were deterred from malingering by warning performed no worse than controls. However, on a small number of tests, self-reported malingerers in the low-level warning group appeared less impaired than unwarned simulators. This pattern was not observed in the high-level warning condition. Although cautious interpretation of findings is necessitated by the exploratory nature of some analyses, overall results suggest that using a carefully designed warning may be useful for reducing the rate of malingering. The combination of some noteworthy effect sizes, despite low power and the small size of some groups, suggests that further investigation of the effects of warnings needs to continue to determine their effect more fully.

Dragline automation - a decade of development : shared autonomy for improving mining equipment productivity

Draglines are massive machines commonly used in surface mining to strip overburden, revealing the targeted minerals for extraction. Automating some or all of the phases of operation of these machines offers the potential for significant productivity and maintenance benefits. The mining industry has a history of slow uptake of automation systems due to the challenges contained in the harsh, complex, three-dimensional (3D), dynamically changing mine operating environment. Robotics as a discipline is finally starting to gain acceptance as a technology with the potential to assist mining operations. This article examines the evolution of robotic technologies applied to draglines in the form of machine embedded intelligent systems. Results from this work include a production trial in which 250,000 tons of material was moved autonomously, experiments demonstrating steps towards full autonomy, and teleexcavation experiments in which a dragline in Australia was tasked by an operator in the United States.

Coordinating aerial robots and sensor networks for localization and navigation

We consider multi-robot systems that include sensor nodes and aerial or ground robots networked together. We describe two cooperative algorithms that allow robots and sensors to enhance each other's performance. In the first algorithm, an aerial robot assists the localization of the sensors. In the second algorithm, a localized sensor network controls the navigation of an aerial robot. We present physical experiments with an flying robot and a large Mica Mote sensor network.

Challenges in land use planning around Australian airports

The privatization of major Australian airports in the late 1990s unleashed an unprecedented development wave as corporate lessees implemented ambitious business plans. While planning and environmental regulations governing on-airport development were significantly enhanced, there has been national disquiet about a governance regime that remains under the auspices of the federal government and is not effectively integrated into state and local decision-making machinery. Tensions in major airport regions have been exacerbated by the building of highly conspicuous non-aeronautical developments approved with no determining input by local decision-makers as well as the growing pressures on off-airport locations for aviation-related development. This paper canvasses this context and overviews the evolving structure of planning controls for Australia’s privatized federal airports. A range of issues surfacing through the National Aviation Policy Review process in 2008–2009 is described.

Polydipsia : a feature of peritoneal dialysis

Background Some dialysis patients fail to comply with their fluid restriction causing problems due to volume overload. These patients sometimes blame excessive thirst. There has been little work in this area and no work documenting polydipsia among peritoneal dialysis (PD) patients. Methods We measured motivation to drink and fluid consumption in 46 haemodialysis patients (HD), 39 PD patients and 42 healthy controls (HC) using a modified palmtop computer to collect visual analogue scores at hourly intervals. Results Mean thirst scores were markedly depressed on the dialysis day (day 1) for HD (P<0.0001). The profile for day 2 was similar to that of HC. PD generated consistently higher scores than HD day 1 and HC (P = 0.01 vs. HC and P<0.0001 vs HD day 1). Reported mean daily water consumption was similar for HD and PD with both significantly less than HC (P<0.001 for both). However, measured fluid losses were similar for PD and HC whilst HD were lower (P<0.001 for both) suggesting that the PD group may have underestimated their fluid intake. Conclusion Our results indicate that HD causes a protracted period of reduced thirst but that the population's thirst perception is similar to HC on the interdialytic day despite a reduced fluid intake. In contrast, the PD group recorded high thirst scores throughout the day and were apparently less compliant with their fluid restriction. This is potentially important because the volume status of PD patients influences their survival.

Cholecystokinin and leptin: their influence upon the eating behaviour and nutrient intake of dialysis patients

Background We have used serial visual analogue scores to demonstrate disturbances of the appetite profile in dialysis patients. This is potentially important as dialysis patients are prone to malnutrition yet have a lower nutrient intake than controls. Appetite disturbance may be influenced by accumulation of appetite inhibitors such as leptin and cholecystokinin (CCK) in dialysis patients. Methods Fasting blood samples were drawn from 43 controls, 50 haemodialysis (HD) and 39 peritoneal dialysis (PD) patients to measure leptin and CCK. Hunger and fullness scores were derived from profiles compiled using hourly visual analogue scores. Nutrient intake was derived from 3 day dietary records. Results Fasting CCK was elevated for PD (6.73 ± 4.42 ng/l vs control 4.99 ± 2.23 ng/l, P < 0.05; vs HD 4.43 ± 2.15 ng/l, P < 0.01). Fasting CCK correlated with the variability of the hunger (r = 0.426, P = 0.01) and fullness (r = 0.52, P = 0.002) scores for PD. There was a notable relationship with the increase in fullness after lunch for PD (r = 0.455, P = 0.006). When well nourished PD patients were compared with their malnourished counterparts, CCK was higher in the malnourished group (P = 0.004). Leptin levels were higher for the dialysis patients than controls (HD and PD, P < 0.001) with pronounced hyperleptinaemia evident in some PD patients. Control leptin levels demonstrated correlation with fullness scores (e.g. peak fullness, r = 0.45, P = 0.007) but the dialysis patients did not. PD nutrient intake (energy and protein intake, r = -0.56, P < 0.0001) demonstrated significant negative correlation with leptin. Conclusion Increased CCK levels appear to influence fullness and hunger perception in PD patients and thus may contribute to malnutrition. Leptin does not appear to affect perceived appetite in dialysis patients but it may influence nutrient intake in PD patients via central feeding centres.

Disturbed appetite and nutrient intake in peritoneal dialysis patients

OBJECTIVE Malnutrition is common among peritoneal dialysis (PD) patients. Reduced nutrient intake contributes to this. It has long been assumed that this reflects disturbed appetite. We set out to define the appetite profiles of a group of PD patients using a novel technique. DESIGN Prospective, cross-sectional comparison of PD patients versus controls. SETTING Teaching hospital dialysis unit. PATIENTS 39 PD patients and 42 healthy controls. INTERVENTION Visual analog ratings were recorded at hourly intervals to generate daily profiles for hunger and fullness. Summary statistics were generated to compare the groups. Food intake was measured using 3-day dietary records. MAIN OUTCOME MEASURES Hunger and fullness profiles. Derived hunger and fullness scores. RESULTS Controls demonstrated peaks of hunger before mealtimes, with fullness scores peaking after meals. The PD profiles had much reduced premeal hunger peaks. A postmeal reduction in hunger was evident, but the rest of the trace was flat. The PD fullness profile was also flatter than in the controls. Mean scores were similar despite the marked discrepancy in the profiles. The PD group had lower peak hunger and less diurnal variability in their hunger scores. They also demonstrated much less change in fullness rating around mealtimes, while the mean and peak fullness scores were little different. The reported nutrient intake was significantly lower for PD. CONCLUSION The data suggest that PD patients normalize their mean appetite perception at a lower level of nutrient intake than controls, suggesting that patient-reported appetite may be misleading in clinical practice. There is a loss of the usual daily variation for the PD group, which may contribute to their reduced food intake. The technique described here could be used to assess the impact of interventions upon the abnormal PD appetite profile.

A novel technique to demonstrate disturbed appetite profiles in haemodialysis patients

Background Malnutrition is common among dialysis patients and is associated with an adverse outcome. One cause of this is a persistent reduction in nutrient intake, suggesting an abnormality of appetite regulation. Methods We used a novel technique to describe the appetite profile in 46 haemodialysis (HD) patients and 40 healthy controls. The Electronic Appetite Rating System (EARS) employs a palmtop computer to collect hourly ratings of motivation to eat and mood. We collected data on hunger, desire to eat, fullness, and tiredness. HD subjects were monitored on the dialysis day and the interdialytic day. Controls were monitored for 1 or 2 days. Results Temporal profiles of motivation to eat for the controls were similar on both days. Temporal profiles of motivation to eat for the HD group were lower on the dialysis day. Mean HD scores were not significantly different from controls. Dietary records indicated that dialysis patients consumed less food than controls. Conclusions Our data indicate that the EARS can be used to monitor subjective appetite states continuously in a group of HD patients. A HD session reduces hunger and desire to eat. Patients feel more tired after dialysis. This does not correlate with their hunger score, but does correlate with their fullness rating. Nutrient intake is reduced, suggesting a resetting of appetite control for the HD group. The EARS may be useful for intervention studies.