Identification and characterization of novel proteolytic interactions of prostate cancer-expressed kallikrein-related peptidases, type II transmembrane serine proteases and matrix metalloproteinases

This study investigated interactions of protein-cleaving enzymes (or proteases) that promote prostate cancer progression. It provides the first evidence of a novel regulatory network of protease activity at the surface of cells. The proteases kallikrein-related peptidases 4 and 14, and matrix metalloproteinases 3 and 9 are cleaved at the cell surface by the cell surface proteases hepsin and TMPRSS2. These cleavage events potentially regulate activation of downstream targets of kallikrein 4 and 14 such as cell surface signalling via the protease-activated receptors (PARs) and cell growth-promoting factors such as hepatocyte-growth factor.

Linking spatial stock dynamics and economics: Evaluation of indicators and fishery management for the travelling eastern king prawn (Melicertus plebejus)

Reduced economic circumstances havemoved management goals towards higher profit, rather than maximum sustainable yields in several Australian fisheries. The eastern king prawn is one such fishery, for which we have developed new methodology for stock dynamics, calculation of model-based and data-based reference points and management strategy evaluation. The fishery is notable for the northward movement of prawns in eastern Australian waters, from the State jurisdiction of New South Wales to that of Queensland, as they grow to spawning size, so that vessels fishing in the northern deeper waters harvest more large prawns. Bioeconomic fishing data were standardized for calibrating a length-structured spatial operating model. Model simulations identified that reduced boat numbers and fishing effort could improve profitability while retaining viable fishing in each jurisdiction. Simulations also identified catch rate levels that were effective for monitoring in simple within-year effort-control rules. However, favourable performance of catch rate indicators was achieved only when a meaningful upper limit was placed on total allowed fishing effort. Themethods and findings will allow improved measures for monitoring fisheries and inform decision makers on the uncertainty and assumptions affecting economic indicators.

Predatory police : the roles of ethics and networks as mediating factors

The institution the police force has been established to protect citizens and their property from harm and predatory opportunism. However, there have been occasions when the very people assigned to protect become part of the predatory force against society. Predatory policing occurs when the police use their powers to extort money in the form of bribes. While, the concept is receiving attention in Europe but there have not been any direct studies in Australia. To overcome this research deficit and determine the extent, if any, of predatory policing in Australia data is interrogated from four police corruption inquiries in the Australian states of Queensland, New South Wales, Victoria and Western Australia. In addition, it examines the role of the type of networks used by corrupt police officers. The synthesis and application of public corruption and network literatures to the predatory policing domain provides new and relevant insights to assist those responsible for the administration of our institutions of justice. The paper concludes with a framework, drawn from the first stage of the project, to assist in the conceptualisation and monitoring of this public problem.

Multilineage differentiation potential of bone and cartilage cells derived from explant culture

To date, mesenchymal stem cells (MSCs) from various tissues have been reported, but the yield and differentiation potential of different tissue-derived MSCs is still not clear. This study was undertaken in an attempt to investigate the multilineage stem cell potential of bone and cartilage explant cultures in comparison with bone marrow derived mesenchymal stem cells (BMSCs). The results showed that the surface antigen expression of tissue-derived cells was consistent with that of mesenchymal stem cells, such as lacking the haematopoietic and common leukocyte markers (CD34, CD45) while expressing markers related to adhesion (CD29, CD166) and stem cells (CD90, CD105). The tissue-derived cells were able to differentiate into osteoblast, chondrocyte and adipocyte lineage pathways when stimulated in the appropriate differentiating conditions. However, compared with BMSCs, tissue-derived cells showed less capacity for multilineage differentiation when the level of differentiation was assessed in monolayer culture by analysing the expression of tissue-specific genes by reverse transcription polymerase chain reaction (RT-PCR) and histology. In high density pellet cultures, tissue-derived cells were able to differentiate into chondrocytes, expressing chondrocyte markers such as proteoglycans, type II collagen and aggrecan. Taken together, these results indicate that cells derived from tissue explant cultures reserved certain degree of differentiation properties of MSCs in vitro.

The relationship between subjective appetite sensations, markers of inflammation and appetite in dialysis patients

Background: Poor appetite is a marker of morbidity and mortality in hemodialysis patients, making it an important area for research. Visual analog scales (VAS) can capture a range of subjective sensations related to appetite (such as hunger, desire to eat or fullness), but have not been commonly used to measure appetite in dialysis patients. The aim of this study was to explore the association between retrospective ratings of appetite using VAS and a range of clinical variables as well as biomarkers of appetite in hemodialysis patients.----- Methods: 28 hemodialysis patients (mean age 61±17y, 50% male, median dialysis vintage 19.5(4-101) months) rated their appetite using VAS for hunger, fullness and desire to eat and a 5-point categorical scale measuring general appetite. Blood levels of the appetite peptides leptin, ghrelin and peptide YY were also measured.----- Results: Hunger ratings measured by VAS were significantly (p<0.05) correlated with a range of clinical, nutritional and inflammatory markers: age (r=-0.376), co-morbidities, (r=-0.380) PG-SGA score (r=-0.451), weight (r=-0.375), fat-free mass (r=-0.435), C-Reactive Protein (CRP) (r=-0.383) and Intercellular adhesion molecule (sICAM-1) (r=-0.387). There was a consistent relationship between VAS and appetite on a 5-point categorical scale for questions of hunger, and a similar trend for desire to eat, but not for fullness. Neither method of measuring subjective appetite correlated with appetite peptides.----- Conclusions: Retrospective ratings of hunger on a VAS are associated with a range of clinical variables and further studies are warranted to support their use as a method of measuring appetite in dialysis patients.

The role of fluid and emotional intelligence in malingering

The purpose of the present study was to examine the role of fluid (gf), social (SI) and emotional intelligence (EI) in faking the Beck Depression Inventory (2nd ed., BDI-II). Twenty-two students and 26 non-students completed Raven’s Advanced Progressive Matrices (APM), a social insight test, the Schutte et al. self-report EI scale, and the BDI-II under honest and faking instructions. Results were consistent with a new model of successful faking, in which a participant’s original response must be manipulated into a strategic response, which must match diagnostic criteria. As hypothesised, the BDI-II could be faked, and gf was not related to faking ability. Counter to expectations, however, SI and EI were not related to faking ability. A second study explored why EI failed to facilitate faking. Forty-nine students and 50 non-students completed the EI measure, the Marlowe-Crown Scale and the Levenson et al. Psychopathy Scale. As hypothesised, EI was negatively correlated with psychopathy, but EI showed no relationship with socially desirable responding. It was concluded that in the first experiment, high-EI people did fake effectively, but high-psychopathy people (who had low EI) were also faking effectively, resulting in a distribution that showed no advantage to high EI individuals.

Development of rapid and highly resolving combinatorial genotyping schemes for Campylobacter jejuni and Campylobacter coli

Campylobacter jejuni followed by Campylobacter coli contribute substantially to the economic and public health burden attributed to food-borne infections in Australia. Genotypic characterisation of isolates has provided new insights into the epidemiology and pathogenesis of C. jejuni and C. coli. However, currently available methods are not conducive to large scale epidemiological investigations that are necessary to elucidate the global epidemiology of these common food-borne pathogens. This research aims to develop high resolution C. jejuni and C. coli genotyping schemes that are convenient for high throughput applications. Real-time PCR and High Resolution Melt (HRM) analysis are fundamental to the genotyping schemes developed in this study and enable rapid, cost effective, interrogation of a range of different polymorphic sites within the Campylobacter genome. While the sources and routes of transmission of campylobacters are unclear, handling and consumption of poultry meat is frequently associated with human campylobacteriosis in Australia. Therefore, chicken derived C. jejuni and C. coli isolates were used to develop and verify the methods described in this study. The first aim of this study describes the application of MLST-SNP (Multi Locus Sequence Typing Single Nucleotide Polymorphisms) + binary typing to 87 chicken C. jejuni isolates using real-time PCR analysis. These typing schemes were developed previously by our research group using isolates from campylobacteriosis patients. This present study showed that SNP + binary typing alone or in combination are effective at detecting epidemiological linkage between chicken derived Campylobacter isolates and enable data comparisons with other MLST based investigations. SNP + binary types obtained from chicken isolates in this study were compared with a previously SNP + binary and MLST typed set of human isolates. Common genotypes between the two collections of isolates were identified and ST-524 represented a clone that could be worth monitoring in the chicken meat industry. In contrast, ST-48, mainly associated with bovine hosts, was abundant in the human isolates. This genotype was, however, absent in the chicken isolates, indicating the role of non-poultry sources in causing human Campylobacter infections. This demonstrates the potential application of SNP + binary typing for epidemiological investigations and source tracing. While MLST SNPs and binary genes comprise the more stable backbone of the Campylobacter genome and are indicative of long term epidemiological linkage of the isolates, the development of a High Resolution Melt (HRM) based curve analysis method to interrogate the hypervariable Campylobacter flagellin encoding gene (flaA) is described in Aim 2 of this study. The flaA gene product appears to be an important pathogenicity determinant of campylobacters and is therefore a popular target for genotyping, especially for short term epidemiological studies such as outbreak investigations. HRM curve analysis based flaA interrogation is a single-step closed-tube method that provides portable data that can be easily shared and accessed. Critical to the development of flaA HRM was the use of flaA specific primers that did not amplify the flaB gene. HRM curve analysis flaA interrogation was successful at discriminating the 47 sequence variants identified within the 87 C. jejuni and 15 C. coli isolates and correlated to the epidemiological background of the isolates. In the combinatorial format, the resolving power of flaA was additive to that of SNP + binary typing and CRISPR (Clustered regularly spaced short Palindromic repeats) HRM and fits the PHRANA (Progressive hierarchical resolving assays using nucleic acids) approach for genotyping. The use of statistical methods to analyse the HRM data enhanced sophistication of the method. Therefore, flaA HRM is a rapid and cost effective alternative to gel- or sequence-based flaA typing schemes. Aim 3 of this study describes the development of a novel bioinformatics driven method to interrogate Campylobacter MLST gene fragments using HRM, and is called ‘SNP Nucleated Minim MLST’ or ‘Minim typing’. The method involves HRM interrogation of MLST fragments that encompass highly informative “Nucleating SNPS” to ensure high resolution. Selection of fragments potentially suited to HRM analysis was conducted in silico using i) “Minimum SNPs” and ii) the new ’HRMtype’ software packages. Species specific sets of six “Nucleating SNPs” and six HRM fragments were identified for both C. jejuni and C. coli to ensure high typeability and resolution relevant to the MLST database. ‘Minim typing’ was tested empirically by typing 15 C. jejuni and five C. coli isolates. The association of clonal complexes (CC) to each isolate by ‘Minim typing’ and SNP + binary typing were used to compare the two MLST interrogation schemes. The CCs linked with each C. jejuni isolate were consistent for both methods. Thus, ‘Minim typing’ is an efficient and cost effective method to interrogate MLST genes. However, it is not expected to be independent, or meet the resolution of, sequence based MLST gene interrogation. ‘Minim typing’ in combination with flaA HRM is envisaged to comprise a highly resolving combinatorial typing scheme developed around the HRM platform and is amenable to automation and multiplexing. The genotyping techniques described in this thesis involve the combinatorial interrogation of differentially evolving genetic markers on the unified real-time PCR and HRM platform. They provide high resolution and are simple, cost effective and ideally suited to rapid and high throughput genotyping for these common food-borne pathogens.

Chemical functionalities of high and low sulfur Australian coals : a case study using micro attenuated total reflectance–fourier transform infrared (ATR–FTIR) spectrometry

The macerals in bituminous coals with varying organic sulfur content from the Early Permian Greta Coal Measures at three locations (Southland Colliery, Drayton Colliery and the Cranky Corner Basin), in and around the Sydney Basin (Australia), have been studied using light-element electron microprobe (EMP) analysis and micro-ATR–FTIR. Electron microprobe analysis of individual macerals reveals that the vitrinite in both the Cranky Corner Basin and Drayton Colliery (Puxtrees seam) samples have similar carbon contents (ca. 78% C in telocollinite), suggesting that they are of equivalent rank. However, the Cranky Corner coals have anomalously low vitrinite reflectance (down to 0.45%) vs. the Drayton materials (ca. 0.7%). They also have very high organic S content (3–6.5%) and lower O content (ca. 10%) than the equivalent macerals in the Drayton sample (0.7% S and 15.6% O). A study was carried out to investigate the impacts of the high organic S on the functional groups of the macerals in these two otherwise iso-rank, stratigraphically-equivalent seams. An iso-rank low-S coal from the overlying Wittingham Coal Measures near Muswellbrook and coals of slightly higher rank from the Greta Coal Measures at Southland Colliery near Cessnock were also evaluated using the same techniques to extend the data set. Although the telocollinite in the Drayton and Cranky Corner coals have very similar carbon content (ca.78% C), the ATR–FTIR spectra of the vitrinite and inertinite macerals in these respectively low S and high S coals show some distinct differences in IR absorbance from various aliphatic and aromatic functional groups. The differences in absorbance of the aliphatic stretching bands (2800–3000 cm−1) and the aromatic carbon (CC) peak at 1606 cm−1 are very obvious. Compared to that of the Drayton sample (0.7% S and 15% O), the telocollinite of the Cranky Corner coal (6% S and 10% O) clearly shows: (i) less absorbance from OH groups, represented by a broad region around 3553 cm−1, (ii) much stronger aliphatic C–H absorbance (stretching modes around 3000–2800 cm−1 and bending modes around 1442 cm−1) and (iii) less absorbance from aromatic carbon functional groups (peaking at 1606 cm−1). Evaluation of the iso-rank Drayton and Cranky Corner coals shows that: (i) the aliphatic C–H absorbances decrease with increasing oxygen content but increase with increasing organic S content and (ii) the aromatic H to aliphatic H ratio (Har/Hali) for the telocollinite increases with (organic) O%, but decreases progressively with increasing organic S. The high organic S content in the maceral appears to be accompanied by a greater proportion of aliphatic functional groups, possibly as a result of some of the O within maceral ring structures in the high S coal samples being replaced.

The contribution of physical activity and sedentary behaviours to the growth and development of children and adolescents : implications for overweight and obesity

The obesity epidemic is a global trend and is of particular concern in children. Recent reports have highlighted the severity of obesity in children by suggesting: “today's generation of children will be the first for over a century for whom life expectancy falls.” This review assesses the evidence that identifies the important role of physical activity in the growth, development and physical health of young people, owing to its numerous physical and psychological health benefits. Key issues, such as “does a sedentary lifestyle automatically lead to obesity” and “are levels of physical activity in today's children less than physical activity levels in children from previous generations?”, are also discussed. Today's environment enforces an inactive lifestyle that is likely to contribute to a positive energy balance and childhood obesity. Whether a child or adolescent, the evidence is conclusive that physical activity is conducive to a healthy lifestyle and prevention of disease. Habitual physical activity established during the early years may provide the greatest likelihood of impact on mortality and longevity. It is evident that environmental factors need to change if physical activity strategies are to have a significant impact on increasing habitual physical activity levels in children and adolescents. There is also a need for more evidence-based physical activity guidelines for children of all ages. Efforts should be concentrated on facilitating an active lifestyle for children in an attempt to put a stop to the increasing prevalence of obese children

An examination of the base rates of post-concussion symptoms : the influence of demographics and depression

Post-concussion syndrome (PCS) is a controversial constellation of cognitive, emotional, and physical symptoms that some patients experience following a mild traumatic brain injury or concussion. PCS-like symptoms are commonly found in individuals with depression, pain, and stress, as well as healthy individuals. This study investigated the base rate of PCS symptoms in a healthy sample of 96 participants and examined the relationship between these symptoms, depression, and sample demographics. PCS symptoms were assessed using the British-Columbia Post-Concussion Symptom Inventory. Depression was measured using the Beck Depression Inventory II. Results demonstrated that: The base rate of PCS was very high; there was a strong positive relationship between depression and PCS; and demographic characteristics were not related to PCS in this sample. These findings are broadly consistent with literature suggesting a significant role for non-neurological factors in the expression of PCS symptomatology. This study adds to the growing body of literature that calls for caution in the clinical interpretation of results from PCS symptom inventories.

Children, Obesity and Exercise: Prevention, Treatment and Management of Childhood and Adolescent Obesity

Throughout the developed world there is an increasing prevalence of childhood obesity. Because of this increase, and awareness of the risks to long term health that childhood obesity presents, the phenomena is now described by many as a global epidemic. Children, Obesity and Exercise provides sport, exercise and medicine students and professionals with an accessible and practical guide to understanding and managing childhood and adolescent obesity. It covers: overweight, obesity and body composition; physical activity, growth and development; psycho-social aspects of childhood obesity; physical activity behaviours; eating behaviours; measuring childrens behaviour; interventions for prevention and management of childhood obesity. Children, Obesity and Exercise addresses the need for authoritative advice and innovative approaches to the prevention and management of this chronic problem.

Effects of Sweetness and Energy in Drinks on Food Intake Following Exercise

Exercise is known to cause physiological changes that could affect the impact of nutrients on appetite control. This study was designed to assess the effect of drinks containing either sucrose or high-intensity sweeteners on food intake following exercise. Using a repeated-measures design, three drink conditions were employed: plain water (W), a low-energy drink sweetened with artificial sweeteners aspartame and acesulfame-K (L), and a high-energy, sucrose-sweetened drink (H). Following a period of challenging exercise (70% VO2 max for 50 min), subjects consumed freely from a particular drink before being offered a test meal at which energy and nutrient intakes were measured. The degree of pleasantness (palatability) of the drinks was also measured before and after exercise. At the test meal, energy intake following the artificially sweetened (L) drink was significantly greater than after water and the sucrose (H) drinks (p < 0.05). Compared with the artificially sweetened (L) drink, the high-energy (H) drink suppressed intake by approximately the energy contained in the drink itself. However, there was no difference between the water (W) and the sucrose (H) drink on test meal energy intake. When the net effects were compared (i.e., drink + test meal energy intake), total energy intake was significantly lower after the water (W) drink compared with the two sweet (L and H) drinks. The exercise period brought about changes in the perceived pleasantness of the water, but had no effect on either of the sweet drinks. The remarkably precise energy compensation demonstrated after the higher energy sucrose drink suggests that exercise may prime the system to respond sensitively to nutritional manipulations. The results may also have implications for the effect on short-term appetite control of different types of drinks used to quench thirst during and after exercise.

Didiman: Australian agricultural extension officers in the territory of Papua and New Guinea, 1945-1975

Historically, the development philosophy for the two Territories of Papua and New Guinea (known as TPNG, formerly two territories, Papua and New Guinea) was equated with economic development, with a focus on agricultural development. To achieve the modification or complete change in indigenous farming systems the Australian Government’s Department of External Territories adopted and utilised a programme based on agricultural extension. Prior to World War II, under Australian administration, the economic development of these two territories, as in many colonies of the time, was based on the institution of the plantation. Little was initiated in agriculture development for indigenous people. This changed after World War II to a rationale based on the promotion and advancement of primary industry, but also came to include indigenous farmers. To develop agriculture within a colony it was thought that a modification to, or in some cases the complete transformation of, existing farming systems was necessary to improve the material welfare of the population. It was also seen to be a guarantee for the future national interest of the sovereign state after independence was granted. The Didiman and Didimisis became the frontline, field operatives of this theoretical model of development. This thesis examines the Didiman’s field operations, the structural organisation of agricultural administration and the application of policy in the two territories.

Influences of age and mechanical stability on volume, microstructure, and mineralization of the fracture callus during bone healing : Is osteoclast activity the key to age-related impaired healing?

Earlier studies have shown that the influence of fixation stability on bone healing diminishes with advanced age. The goal of this study was to unravel the relationship between mechanical stimulus and age on callus competence at a tissue level. Using 3D in vitro micro-computed tomography derived metrics, 2D in vivo radiography, and histology, we investigated the influences of age and varying fixation stability on callus size, geometry, microstructure, composition, remodeling, and vascularity. Compared were four groups with a 1.5-mm osteotomy gap in the femora of Sprague–Dawley rats: Young rigid (YR), Young semirigid (YSR), Old rigid (OR), Old semirigid (OSR). Hypothesis was that calcified callus microstructure and composition is impaired due to the influence of advanced age, and these individuals would show a reduced response to fixation stabilities. Semirigid fixations resulted in a larger ΔCSA (Callus cross-sectional area) compared to rigid groups. In vitro μCT analysis at 6 weeks postmortem showed callus bridging scores in younger animals to be superior than their older counterparts (pb0.01). Younger animals showed (i) larger callus strut thickness (pb0.001), (ii) lower perforation in struts (pb0.01), and (iii) higher mineralization of callus struts (pb0.001). Callus mineralization was reduced in young animals with semirigid fracture fixation but remained unaffected in the aged group. While stability had an influence, age showed none on callus size and geometry of callus. With no differences observed in relative osteoid areas in the callus ROI, old as well as semirigid fixated animals showed a higher osteoclast count (pb0.05). Blood vessel density was reduced in animals with semirigid fixation (pb0.05). In conclusion, in vivo monitoring indicated delayed callus maturation in aged individuals. Callus bridging and callus competence (microstructure and mineralization) were impaired in individuals with an advanced age. This matched with increased bone resorption due to higher osteoclast numbers. Varying fixator configurations in older individuals did not alter the dominant effect of advanced age on callus tissue mineralization, unlike in their younger counterparts. Age-associated influences appeared independent from stability. This study illustrates the dominating role of osteoclastic activity in age-related impaired healing, while demonstrating the optimization of fixation parameters such as stiffness appeared to be less effective in influencing healing in aged individuals.

Comparing exercise prescribed with exercise completed : effects of gender and mode of exercise

The purpose of this study was to compare the amount of exercise prescribed with the amount completed between two different modes of training intervention and between the sexes. Thirty-two men (mean age = 39.1 years, body mass index = 32.9 kg · m-2) and women (mean age = 39.6 years, body mass index = 32.1 kg · m-2) were prescribed traditional resistance training or light-resistance circuit training for 16 weeks. Lean mass and fat mass were determined by dual-energy X-ray absorptiometry at weeks 1 and 16. A completion index was calculated to provide a measure of the extent to which participants completed exercise training relative to the amount of exercise prescribed. The absolute amount of exercise completed by the circuit training group was significantly greater than the amount prescribed (P < 0.0001). The resistance training group consistently under-completed relative to the amount prescribed, but the difference was not significant. The completion index for the circuit training group (26 ± 21.7%) was significantly different from that of the resistance training group (-7.4 ± 3.0%). The completion index was not significantly different between men and women in either group. These data suggest that overweight and obese individuals participating in light-resistance circuit training complete more exercise than is prescribed. Men and women do not differ in the extent to which they over- or under-complete prescribed exercise.