Synthesis of 4-arm star poly(L-Lactide) oligomers using an in situ-generated calcium-based initiator

Using an in situ-generated calcium-based initiating species derived from pentaerythritol, the bulk synthesis of well-defined 4-arm star poly(L-lactide) oligomers has been studied in detail. The substitution of the traditional initiator, stannous octoate with calcium hydride allowed the synthesis of oligomers that had both low PDIs and a comparable number of polymeric arms (3.7 – 3.9) to oligomers of similar molecular weight. Investigations into the degree of control observed during the course of the polymerization found that the insolubility of pentaerythritol in molten L-lactide resulted in an uncontrolled polymerization only when the feed mole ratio of L-lactide to pentaerythritol was 13. At feed ratios of 40 and greater, a pseudo-living polymerization was observed. As part of this study, in situ FT-Raman spectroscopy was demonstrated to be a suitable method to monitor the kinetics of the ring-opening polymerization (ROP) of lactide. The advantages of using this technique rather than FT-IR-ATR and 1H NMR for monitoring L-lactide consumption during polymerization are discussed.

A review of the economic consequences of a policy of universal leucodepletion as compared to existing practices

Leucodepletion, the removal of leucocytes from blood products improves the safety of blood transfusion by reducing adverse events associated with the incidental non-therapeutic transfusion of leucocytes. Leucodepletion has been shown to have clinical benefit for immuno-suppressed patients who require transfusion. The selective leucodepletion of blood products by bed side filtration for these patients has been widely practiced. This study investigated the economic consequences in Queensland of moving from a policy of selective leucodepletion to one of universal leucodepletion, that is providing all transfused patients with blood products leucodepleted during the manufacturing process. Using an analytic decision model a cost-effectiveness analysis was conducted. An ICER of $16.3M per life year gained was derived. Sensitivity analysis found this result to be robust to uncertainty in the parameters used in the model. This result argues against moving to a policy of universal leucodepletion. However during the course of the study the policy decision for universal leucodepletion was made and implemented in Queensland in October 2008. This study has concluded that cost-effectiveness is not an influential factor in policy decisions regarding quality and safety initiatives in the Australian blood sector.

Translation and news making : a study of contemporary arabic television

Arabic satellite television has recently attracted tremendous attention in both the academic and professional worlds, with a special interest in Aljazeera as a curious phenomenon in the Arab region. Having made a household name for itself worldwide with the airing of the Bin Laden tapes, Aljazeera has set out to deliberately change the culture of Arabic journalism, as it has been repeatedly stated by its current General Manager Waddah Khanfar, and to shake up the Arab society by raising awareness to issues never discussed on television before and challenging long-established social and cultural values and norms while promoting, as it claims, Arab issues from a presumably Arab perspective. Working within the meta-frame of democracy, this Qatari-based network station has been received with mixed reactions ranging from complete support to utter rejection in both the west and the Arab world. This research examines the social semiotics of Arabic television and the socio-cultural impact of translation-mediated news in Arabic satellite television, with the aim to carry out a qualitative content analysis, informed by framing theory, critical linguistic analysis, social semiotics and translation theory, within a re-mediation framework which rests on the assumption that a medium “appropriates the techniques, forms and social significance of other media and attempts to rival or refashion them in the name of the real" (Bolter and Grusin, 2000: 66). This is a multilayered research into how translation operates at two different yet interwoven levels: translation proper, that is the rendition of discourse from one language into another at the text level, and translation as a broader process of interpretation of social behaviour that is driven by linguistic and cultural forms of another medium resulting in new social signs generated from source meaning reproduced as target meaning that is bound to be different in many respects. The research primarily focuses on the news media, news making and reporting at Arabic satellite television and looks at translation as a reframing process of news stories in terms of content and cultural values. This notion is based on the premise that by its very nature, news reporting is a framing process, which involves a reconstruction of reality into actualities in presenting the news and providing the context for it. In other words, the mediation of perceived reality through a media form, such as television, actually modifies the mind’s ordering and internal representation of the reality that is presented. The research examines the process of reframing through translation news already framed or actualized in another language and argues that in submitting framed news reports to the translation process several alterations take place, driven by the linguistic and cultural constraints and shaped by the context in which the content is presented. These alterations, which involve recontextualizations, may be intentional or unintentional, motivated or unmotivated. Generally, they are the product of lack of awareness of the dynamics and intricacies of turning a message from one language form into another. More specifically, they are the result of a synthesis process that consciously or subconsciously conforms to editorial policy and cultural interpretive frameworks. In either case, the original message is reproduced and the news is reframed. For the case study, this research examines news broadcasts by the now world-renowned Arabic satellite television station Aljazeera, and to a lesser extent the Lebanese Broadcasting Corporation (LBC) and Al- Arabiya where access is feasible, for comparison and crosschecking purposes. As a new phenomenon in the Arab world, Arabic satellite television, especially 24-hour news and current affairs, provides an interesting area worthy of study, not only for its immediate socio-cultural and professional and ethical implications for the Arabic media in particular, but also for news and current affairs production in the western media that rely on foreign language sources and translation mediation for international stories.

Making the processes of designing explicit within an information technology environment

In this paper, technology is described as involving processes whereby resources are utilised to satisfy human needs or to take advantage of opportunities, to develop practical solutions to problems. This study, set within one type of technology context, information technology, investigated how, through a one semester undergraduate university course, elements of technological processes were made explicit to students. While it was acknowledged in the development and implementation of this course that students needed to learn technical skills, technological skills and knowledge, including design, were seen as vital also, to enable students to think about information technology from a perspective that was not confined and limited to `technology as hardware and software'. This paper describes how the course, set within a three year program of study, was aimed at helping students to develop their thinking and their knowledge about design processes in an explicit way. An interpretive research approach was used and data sources included a repertory grid `survey'; student interviews; video recordings of classroom interactions, audio recordings of lectures, observations of classroom interactions made by researchers; and artefacts which included students' journals and portfolios. The development of students' knowledge about design practices is discussed and reflections upon student knowledge development in conjunction with their learning experiences are made. Implications for ensuring explicitness of design practice within information technology contexts are presented, and the need to identify what constitutes design knowledge is argued.

Patterns of engagement in workplace learning amongst employees from social sectors

Continuous learning and development has become increasingly important in the information age. However, employees with limited formal education in lower status occupations may be disadvantaged in their opportunities for development, as their jobs tend to require more limited knowledge and skills. In mature age, such workers may be subject to cumulative disadvantage with respect to work related learning and development, as well as negative stereotyping. This thesis concerns work related learning and development from a lifespan development psychology perspective. Development across the lifespan is grounded in biocultural co-constructivism. That is, the reciprocal influences of the individual and environment produce change in the individual. Existing theories and models of adaptive development attempt to explain how developmental resources are allocated across the lifespan. These included the Meta- theory of Selective Optimisation with Compensation, Dual Process Model of Self Regulation, and Developmental Regulation via Optimisation and Primary and Secondary Control. These models were integrated to create the Model of Adaptive Development for Work Related Learning. The Learning and Development Survey (LDS) was constructed to measure the hypothesised processes of adaptive development for work related learning, which were individual goal selection, individual goal engagement, individual goal disengagement, organisational opportunities (selection and engagement), and organisational constraints. Data collection was undertaken in two phases: the pilot study and the main study. The objective of the pilot study was to test the LDS on a target population of 112 employees from a local government organisation. Exploratory factor analysis reduced the pilot version of the survey to 38 items encompassing eight constructs which covered the processes of the model of adaptive development for work related learning. In the main study, the Revised Learning and Development Survey (R-LDS) was administered to another group of 137 employees from the local government organisation, as well as 110 employees from a private healthcare organisation. The purpose of the main study was to validate the R-LDS on two different groups to provide evidence of stability, and compare survey scores according to age and occupational status to determine construct validity. Findings from the main study indicated that only four constructs of the R-LDS were stable, which were organisational opportunities – selection, individual goal engagement, organisational constraints – disengagement and organisational opportunities – engagement. In addition, MANOVA studies revealed that the demographic variables affected organisational opportunities and constraints in the workplace, although individual goal engagement was not influenced by age. The findings from the pilot and main study partially supported the model of adaptive development for work related learning. Given that only four factors displayed adequate reliability in terms of internal consistency and stability, the findings suggest that individual goal selection and individual goal disengagement are less relevant to work related learning and development. Some recent research which emerged during the course of the current study has suggested that individual goal selection and individual goal disengagement are more relevant when goal achievement is impeded by biological constraints such as ageing. However, correlations between the retained factors support the model of adaptive development for work related learning, and represent the role of biocultural co-constructivism in development. Individual goal engagement was positively correlated with both opportunity factors (selection and engagement), while organisational constraints – disengagement was negatively correlated with organisational opportunities – selection. Demographic findings indicated that higher occupational status was associated with more opportunities for development. Age was associated with fewer opportunities or greater constraints for development, especially for lower status workers.

Investigation of highly regulated promoters for the production of recombinant proteins in plants

Plants have been identified as promising expression systems for the commercial production of recombinant proteins. Plant-based protein production or “biofarming” offers a number of advantages over traditional expression systems in terms of scale of production, the capacity for post-translation processing, providing a product free of contaminants and cost effectiveness. A number of pharmaceutically important and commercially valuable proteins, such as antibodies, biopharmaceuticals and industrial enzymes are currently being produced in plant expression systems. However, several challenges still remain to improve recombinant protein yield with no ill effect on the host plant. The ability for transgenic plants to produce foreign proteins at commercially viable levels can be directly related to the level and cell specificity of the selected promoter driving the transgene. The accumulation of recombinant proteins may be controlled by a tissue-specific, developmentally-regulated or chemically-inducible promoter such that expression of recombinant proteins can be spatially- or temporally- controlled. The strict control of gene expression is particularly useful for proteins that are considered toxic and whose expression is likely to have a detrimental effect on plant growth. To date, the most commonly used promoter in plant biotechnology is the cauliflower mosaic virus (CaMV) 35S promoter which is used to drive strong, constitutive transgene expression in most organs of transgenic plants. Of particular interest to researchers in the Centre for Tropical Crops and Biocommodities at QUT are tissue-specific promoters for the accumulation of foreign proteins in the roots, seeds and fruit of various plant species, including tobacco, banana and sugarcane. Therefore this Masters project aimed to isolate and characterise root- and seed-specific promoters for the control of genes encoding recombinant proteins in plant-based expression systems. Additionally, the effects of matching cognate terminators with their respective gene promoters were assessed. The Arabidopsis root promoters ARSK1 and EIR1 were selected from the literature based on their reported limited root expression profiles. Both promoters were analysed using the PlantCARE database to identify putative motifs or cis-acting elements that may be associated with this activity. A number of motifs were identified in the ARSK1 promoter region including, WUN (wound-inducible), MBS (MYB binding site), Skn-1, and a RY core element (seed-specific) and in the EIR1 promoter region including, Skn-1 (seed-specific), Box-W1 (fungal elicitor), Aux-RR core (auxin response) and ABRE (ABA response). However, no previously reported root-specific cis-acting elements were observed in either promoter region. To confirm root specificity, both promoters, and truncated versions, were fused to the GUS reporter gene and the expression cassette introduced into Arabidopsis via Agrobacterium-mediated transformation. Despite the reported tissue-specific nature of these promoters, both upstream regulatory regions directed constitutive GUS expression in all transgenic plants. Further, similar levels of GUS expression from the ARSK1 promoter were directed by the control CaMV 35S promoter. The truncated version of the EIR1 promoter (1.2 Kb) showed some differences in the level of GUS expression compared to the 2.2 Kb promoter. Therefore, this suggests an enhancer element is contained in the 2.2 Kb upstream region that increases transgene expression. The Arabidopsis seed-specific genes ATS1 and ATS3 were selected from the literature based on their seed-specific expression profiles and gene expression confirmed in this study as seed-specific by RT-PCR analysis. The selected promoter regions were analysed using the PlantCARE database in order to identify any putative cis elements. The seed-specific motifs GCN4 and Skn-1 were identified in both promoter regions that are associated with elevated expression levels in the endosperm. Additionaly, the seed-specific RY element and the ABRE were located in the ATS1 promoter. Both promoters were fused to the GUS reporter gene and used to transform Arabidopsis plants. GUS expression from the putative promoters was consitutive in all transgenic Arabidopsis tissue tested. Importantly, the positive control FAE1 seed-specific promoter also directed constitutive GUS expression throughout transgenic Arabidopsis plants. The constitutive nature seen in all of the promoters used in this study was not anticipated. While variations in promoter activity can be caused by a number of influencing factors, the variation in promoter activity observed here would imply a major contributing factor common to all plant expression cassettes tested. All promoter constructs generated in this study were based on the binary vector pCAMBIA2300. This vector contains the plant selection gene (NPTII) under the transcriptional control of the duplicated CaMV 35S promoter. This CaMV 35S promoter contains two enhancer domains that confer strong, constitutive expression of the selection gene and is located immediately upstream of the promoter-GUS fusion. During the course of this project, Yoo et al. (2005) reported that transgene expression is significantly affected when the expression cassette is located on the same T-DNA as the 35S enhancer. It was concluded, the trans-acting effects of the enhancer activate and control transgene expression causing irregular expression patterns. This phenomenon seems the most plausible reason for the constitutive expression profiles observed with the root- and seed-specific promoters assessed in this study. The expression from some promoters can be influenced by their cognate terminator sequences. Therefore, the Arabidopsis ARSK1, EIR1, ATS1 and ATS3 terminator sequences were isolated and incorporated into expression cassettes containing the GUS reporter gene under the control of their cognate promoters. Again, unrestricted GUS activity was displayed throughout transgenic plants transformed with these reporter gene fusions. As previously discussed constitutive GUS expression was most likely due to the trans-acting effect of the upstream CaMV 35S promoter in the selection cassette located on the same T-DNA. The results obtained in this study make it impossible to assess the influence matching terminators with their cognate promoters have on transgene expression profiles. The obvious future direction of research continuing from this study would be to transform pBIN-based promoter-GUS fusions (ie. constructs containing no CaMV 35S promoter driving the plant selection gene) into Arabidopsis in order to determine the true tissue specificity of these promoters and evaluate the effects of their cognate 3’ terminator sequences. Further, promoter truncations based around the cis-elements identified here may assist in determining whether these motifs are in fact involved in the overall activity of the promoter.

Incidental walking activity is sufficient to induce time-dependent conditioning of the Achilles tendon

The Achilles tendon has been seen to exhibit time-dependent conditioning when isometric muscle actions were of a prolonged duration, compared to those involved in dynamic activities, such as walking. Since, the effect of short duration muscle activation associated with dynamic activities is yet to be established, the present study aimed to investigate the effect of incidental walking activity on Achilles tendon diametral strain. Eleven healthy male participants refrained from physical activity in excess of the walking required to carry out necessary daily tasks and wore an activity monitor during the 24 h study period. Achilles tendon diametral strain, 2 cm proximal to the calcaneal insertion, was determined from sagittal sonograms. Baseline sonographic examinations were conducted at ∼08:00 h followed by replicate examinations at 12 and 24 h. Walking activity was measured as either present (1) or absent (0) and a linear weighting function was applied to account for the proximity of walking activity to tendon examination time. Over the course of the day the median (min, max) Achilles tendon diametral strain was −11.4 (4.5, −25.4)%. A statistically significant relationship was evident between walking activity and diametral strain (P < 0.01) and this relationship improved when walking activity was temporally weighted (AIC 131 to 126). The results demonstrate that the short yet repetitive loads generated during activities of daily living, such as walking, are sufficient to induce appreciable time-dependant conditioning of the Achilles tendon. Implications arise for the in vivo measurement of Achilles tendon properties and the rehabilitation of tendinopathy.

What causes childhood leukaemia? Some beliefs of parents of affected children

The theories of parents about the cause of their children's leukaemia have been documented in the course of a case-control study. From a sample of 175 children who were diagnosed as having acute lymphoblastic leukaemia, 91.4% of their parents put forward their theories. Some of these theories were related clearly to material that had been published and therefore had some scientific validity. Other theories often had no apparent scientific basis. Persons who are involved in the care of children with leukaemia should be aware of the wide variety of theories that are held by their parents so that they may provide counselling which could be of help in the relief of feelings of anxiety or guilt among the parents. Parents should always be afforded the opportunity to put forward their own theories so that they may be discussed on a rational basis. It is conceivable that some parents might put forward new hypotheses about leukaemogenesis that could be tested scientifically.

Dynamics of in vitro polymer degradation of polycaprolactone-based scaffolds : accelerated versus simulated physiological conditions

The increasing use of biodegradable devices in tissue engineering and regenerative medicine means it is essential to study and understand their degradation behaviour. Accelerated degradation systems aim to achieve similar degradation profiles within a shorter period of time, compared with standard conditions. However, these conditions only partially mimic the actual situation, and subsequent analyses and derived mechanisms must be treated with caution and should always be supported by actual long-term degradation data obtained under physiological conditions. Our studies revealed that polycaprolactone (PCL) and PCL-composite scaffolds degrade very differently under these different degradation conditions, whilst still undergoing hydrolysis. Molecular weight and mass loss results differ due to the different degradation pathways followed (surface degradation pathway for accelerated conditions and bulk degradation pathway for simulated physiological conditions). Crystallinity studies revealed similar patterns of recrystallization dynamics, and mechanical data indicated that the scaffolds retained their functional stability, in both instances, over the course of degradation. Ultimately, polymer degradation was shown to be chiefly governed by molecular weight, crystallinity susceptibility to hydrolysis and device architecture considerations whilst maintaining its thermodynamic equilibrium.

Culture independent analysis of greyback canegrub-associated microflora and microbial community comparison using subtractive hybridisation

Greyback canegrubs cost the Australian sugarcane industry around $13 million per annum in damage and control. A novel and cost effective biocontrol bacterium could play an important role in the integrated pest management program currently in place to reduce damage and control associated costs. During the course of this project, terminal restriction fragment length polymorphism (TRFLP), 16-S rDNA cloning, suppressive subtractive hybridisation (SSH) and entomopathogen-specific PCR screening were used to investigate the little studied canegrub-associated microflora in an attempt to discover novel pathogens from putatively-diseased specimens. Microflora associated with these soil-dwelling insects was found to be both highly diverse and divergent between individual specimens. Dominant members detected in live specimens were predominantly from taxa of known insect symbionts while dominant sequences amplified from dead grubs were homologous to putativelysaprophytic bacteria and bacteria able to grow during refrigeration. A number of entomopathogenic bacteria were identified such as Photorhabdus luminescens and Pseudomonas fluorescens. Dead canegrubs prior to decomposition need to be analysed if these bacteria are to be isolated. Novel strategies to enrich putative pathogen-associated sequences (SSH and PCR screening) were shown to be promising approaches for pathogen discovery and the investigation of canegrubsassociated microflora. However, due to inter- and intra-grub-associated community diversity, dead grub decomposition and PCR-specific methodological limitations (PCR bias, primer specificity, BLAST database restrictions, 16-S gene copy number and heterogeneity), recommendations have been made to improve the efficiency of such techniques. Improved specimen collection procedures and utilisation of emerging high-throughput sequencing technologies may be required to examine these complex communities in more detail. This is the first study to perform a whole-grub analysis and comparison of greyback canegrub-associated microbial communities. This work also describes the development of a novel V3-PCR based SSH technique. This was the first SSH technique to use V3-PCR products as a starting material and specifically compare bacterial species present in a complex community.

An investigation of foot and ankle problems experienced by nurses

Relatively little information has been reported about foot and ankle problems experienced by nurses, despite anecdotal evidence which suggests they are common ailments. The purpose of this study was to improve knowledge about the prevalence of foot and ankle musculoskeletal disorders (MSDs) and to explore relationships between these MSDs and proposed risk factors. A review of the literature relating to work-related MSDs, MSDs in nursing, foot and lower-limb MSDs, screening for work-related MSDs, foot discomfort, footwear and the prevalence of foot problems in the community was undertaken. Based on the review, theoretical risk factors were proposed that pertained to the individual characteristics of the nurses, their work activity or their work environment. Three studies were then undertaken. A cross-sectional survey of 304 nurses, working in a large tertiary paediatric hospital, established the prevalence of foot and ankle MSDs. The survey collected information about self-reported risk factors of interest. The second study involved the clinical examination of a subgroup of 40 nurses, to examine changes in body discomfort, foot discomfort and postural sway over the course of a single work shift. Objective measurements of additional risk factors, such as individual foot posture (arch index) and the hardness of shoe midsoles, were performed. A final study was used to confirm the test-retest reliability of important aspects of the survey and key clinical measurements. Foot and ankle problems were the most common MSDs experienced by nurses in the preceding seven days (42.7% of nurses). They were the second most common MSDs to cause disability in the last 12 months (17.4% of nurses), and the third most common MSDs experienced by nurses in the last 12 months (54% of nurses). Substantial foot discomfort (Visual Analogue Scale (VAS) score of 50mm or more) was experienced by 48.5% of nurses at sometime in the last 12 months. Individual risk factors, such as obesity and the number of self-reported foot conditions (e.g., callouses, curled toes, flat feet) were strongly associated with the likelihood of experiencing foot problems in the last seven days or during the last 12 months. These risk factors showed consistent associations with disabling foot conditions and substantial foot discomfort. Some of these associations were dependent upon work-related risk factors, such as the location within the hospital and the average hours worked per week. Working in the intensive care unit was associated with higher odds of experiencing foot problems within the last seven days, foot problems in the last 12 months and foot problems that impaired activity in the last 12 months. Changes in foot discomfort experienced within a day, showed large individual variability. Fifteen of the forty nurses experienced moderate/substantial foot discomfort at the end of their shift (VAS 25+mm). Analysis of the association between risk factors and moderate/substantial foot discomfort revealed that foot discomfort was less likely for nurses who were older, had greater BMI or had lower foot arches, as indicated by higher arch index scores. The nurses’ postural sway decreased over the course of the work shift, suggesting improved body balance by the end of the day. These findings were unexpected. Further clinical studies examining individual nurses on several work shifts are needed to confirm these results, particularly due to the small sample size and the single measurement occasion. There are more than 280,000 nurses registered to practice in Australia. The nursing workforce is ageing and the prevalence of foot problems will increase. If the prevalence estimates from this study are extrapolated to the profession generally, more than 70,000 hospital nurses have experienced substantial foot discomfort and 25-30,000 hospital nurses have been limited in their activity due to foot problems during the last 12 months. Nurses with underlying foot conditions were more likely to report having foot problems at work. Strategies to prevent or manage foot conditions exist and they should be disseminated to nurses. Obesity is a significant risk factor for foot and ankle MSDs and these nurses may need particular assistance to manage foot problems. The risk of foot problems for particular groups of nurses, e.g. obese nurses, may vary depending upon the location within the hospital. Further research is needed to confirm the findings of this study. Similar studies should be conducted in other occupational groups that require workers to stand for prolonged periods.

Swept frequency biompedance analysis for the determination of body water compartments

Bioelectrical impedance analysis, (BIA), is a method of body composition analysis first investigated in 1962 which has recently received much attention by a number of research groups. The reasons for this recent interest are its advantages, (viz: inexpensive, non-invasive and portable) and also the increasing interest in the diagnostic value of body composition analysis. The concept utilised by BIA to predict body water volumes is the proportional relationship for a simple cylindrical conductor, (volume oc length2/resistance), which allows the volume to be predicted from the measured resistance and length. Most of the research to date has measured the body's resistance to the passage of a 50· kHz AC current to predict total body water, (TBW). Several research groups have investigated the application of AC currents at lower frequencies, (eg 5 kHz), to predict extracellular water, (ECW). However all research to date using BIA to predict body water volumes has used the impedance measured at a discrete frequency or frequencies. This thesis investigates the variation of impedance and phase of biological systems over a range of frequencies and describes the development of a swept frequency bioimpedance meter which measures impedance and phase at 496 frequencies ranging from 4 kHz to 1 MHz. The impedance of any biological system varies with the frequency of the applied current. The graph of reactance vs resistance yields a circular arc with the resistance decreasing with increasing frequency and reactance increasing from zero to a maximum then decreasing to zero. Computer programs were written to analyse the measured impedance spectrum and determine the impedance, Zc, at the characteristic frequency, (the frequency at which the reactance is a maximum). The fitted locus of the measured data was extrapolated to determine the resistance, Ro, at zero frequency; a value that cannot be measured directly using surface electrodes. The explanation of the theoretical basis for selecting these impedance values (Zc and Ro), to predict TBW and ECW is presented. Studies were conducted on a group of normal healthy animals, (n=42), in which TBW and ECW were determined by the gold standard of isotope dilution. The prediction quotients L2/Zc and L2/Ro, (L=length), yielded standard errors of 4.2% and 3.2% respectively, and were found to be significantly better than previously reported, empirically determined prediction quotients derived from measurements at a single frequency. The prediction equations established in this group of normal healthy animals were applied to a group of animals with abnormally low fluid levels, (n=20), and also to a group with an abnormal balance of extra-cellular to intracellular fluids, (n=20). In both cases the equations using L2/Zc and L2/Ro accurately and precisely predicted TBW and ECW. This demonstrated that the technique developed using multiple frequency bioelectrical impedance analysis, (MFBIA), can accurately predict both TBW and ECW in both normal and abnormal animals, (with standard errors of the estimate of 6% and 3% for TBW and ECW respectively). Isotope dilution techniques were used to determine TBW and ECW in a group of 60 healthy human subjects, (male. and female, aged between 18 and 45). Whole body impedance measurements were recorded on each subject using the MFBIA technique and the correlations between body water volumes, (TBW and ECW), and heighe/impedance, (for all measured frequencies), were compared. The prediction quotients H2/Zc and H2/Ro, (H=height), again yielded the highest correlation with TBW and ECW respectively with corresponding standard errors of 5.2% and 10%. The values of the correlation coefficients obtained in this study were very similar to those recently reported by others. It was also observed that in healthy human subjects the impedance measured at virtually any frequency yielded correlations not significantly different from those obtained from the MFBIA quotients. This phenomenon has been reported by other research groups and emphasises the need to validate the technique by investigating its application in one or more groups with abnormalities in fluid levels. The clinical application of MFBIA was trialled and its capability of detecting lymphoedema, (an excess of extracellular fluid), was investigated. The MFBIA technique was demonstrated to be significantly more sensitive, (P<.05), in detecting lymphoedema than the current technique of circumferential measurements. MFBIA was also shown to provide valuable information describing the changes in the quantity of muscle mass of the patient during the course of the treatment. The determination of body composition, (viz TBW and ECW), by MFBIA has been shown to be a significant improvement on previous bioelectrical impedance techniques. The merit of the MFBIA technique is evidenced in its accurate, precise and valid application in animal groups with a wide variation in body fluid volumes and balances. The multiple frequency bioelectrical impedance analysis technique developed in this study provides accurate and precise estimates of body composition, (viz TBW and ECW), regardless of the individual's state of health.

Implementation and evaluation of a new model of nursing practice in radiation oncology

Patients undergoing radiation therapy for cancer face a series of challenges that require support from a multidisciplinary team which includes radiation oncology nurses. However, the specific contribution of nursing, and the models of care that best support the delivery of nursing interventions in the radiotherapy setting, is not well described. In this case study, the Interaction Model of Client Health Behaviour and the associated principles of person-centred care were incorporated into a new model of care that was implemented in one radiation oncology setting in Brisbane, Australia. The new model of care was operationalised through a Primary Nursing/Collaborative Practice framework. To evaluate the impact of the new model for patients and health professionals, multiple sources of data were collected from patients and clinical staff prior to, during, and 18 months following introduction of the practice redesign. One cohort of patients and clinical staff completed surveys incorporating measures of key outcomes immediately prior to implementation of the model, while a second cohort of patients and clinical staff completed these same surveys 18 months following introduction of the model. In-depth interviews were also conducted with nursing, medical and allied health staff throughout the implementation phase to obtain a more comprehensive account of the processes and outcomes associated with implementing such a model. From the patients’ perspectives, this study demonstrated that, although adverse effects of radiotherapy continue to affect patient well-being, patients continue to be satisfied with nursing care in this specialty, and that they generally reported high levels of functioning despite undergoing a curative course of radiotherapy. From the health professionals’ perspective, there was evidence of attitudinal change by nursing staff within the radiotherapy department which reflected a greater understanding and appreciation of a more person-centred approach to care. Importantly, this case study has also confirmed that a range of factors need to be considered when redesigning nursing practice in the radiotherapy setting, as the challenges associated with changing traditional practices, ensuring multidisciplinary approaches to care, and resourcing a new model were experienced. The findings from this study suggest that the move from a relatively functional approach to a person-centred approach in the radiotherapy setting has contributed to some improvements in the provision of individualised and coordinated patient care. However, this study has also highlighted that primary nursing may be limited in its approach as a framework for patient care unless it is supported by a whole team approach, an appropriate supportive governance model, and sufficient resourcing. Introducing such a model thus requires effective education, preparation and ongoing support for the whole team. The challenges of providing care in the context of complex interdisciplinary relationships have been highlighted by this study. Aspects of this study may assist in planning further nursing interventions for patients undergoing radiotherapy for cancer, and continue to enhance the contribution of the radiation oncology nurse to improved patient outcomes.

Spatial analysis of melioidosis distribution in a suburban area

Burkholderia pseudomallei, the causative agent of melioidosis is associated with soil. This study used a geographic information system (GIS) to determine the spatial distribution of clinical cases of melioidosis in the endemic suburban region of Townsville in Australia. A total of 65 cases over the period 1996–2008 were plotted using residential address. Two distinct groupings were found. One was around the base of a hill in the city centre and the other followed the old course of a major waterway in the region. Both groups (accounting for 43 of the 65 cases examined) are in areas expected to have particularly wet topsoils following intense rainfall, due to soil type or landscape position.

Cross-talk of subchondral bone osteoblasts and articular cartilage chondrocytes : a new insight in understanding osteoarthritis pathogenesis

Osteoarthritis (OA) is the most common musculoskeletal disorder and represents a major health burden to society. In the course of the pathological development of OA, articular cartilage chondrocytes (ACCs) undergo atypical phenotype changes characterized by the expression of hypertrophic differentiation markers. Also, the adjacent subchondral bone shows signs of abnormal mineral density and enhanced production of bone turnover markers, indicative of osteoblast dysfunction. Collectively these findings indicate that the pathological changes typical of OA, involve alterations of the phenotypic properties of cells in both the subchondral bone and articular cartilage. However, the mechanism(s) by which these changes occur during OA development are not completely understood. The purpose of this project was to address the question of how subchondral bone osteoblasts (SBOs) and ACCs interact with each other with respect to regulation of respective cells’ phenotypic properties and in particular the involvement of mitogen activated protein kinase (MAPK) signalling pathways under normal and OA joint condition. We also endeavoured to test the influence of cross-talk between SBOs and ACCs isolated from normal and OA joint on matrix metalloproteinase (MMP) expression. For this purpose tissues from the knees of OA patients and normal controls were collected to isolate SBOs and ACCs. The cellular cross-talk of SBOs and ACCs were studied by means of both direct and indirect co-culture systems, which made it possible to identify the role of both membrane bound and soluble factors. Histology, immunohistochemistry, qRT-PCR, zymography, ELISA and western blotting were some of the techniques applied to distinguish the changes in the co-cultured vs. non co-cultured cells. The MAPK signalling pathways were probed by using targeted MAPK inhibitors, and their activity monitored by western blot analysis using phospho MAPK specific antibodies. Our co-culture studies demonstrated that OA ACCs enhanced the SBOs differentiation compared to normal ACCs. We demonstrated that OA ACCs induced these phenotypic changes in the SBOs via activating an ERK1/2 signalling pathway. The findings from this study thus provided clear evidence that OA ACCs play an integral role in altering the SBO phenotype. In the second study, we tested the influence of normal SBOs and OA SBOs on ACCs phenotype changes. The results showed that OA SBOs increased the hypertrophic gene expression in co-cultured ACCs compared to normal SBOs, a phenotype which is considered as pathological to the health and integrity of articular cartilage. It was demonstrated that these phenotype changes occurred via de-activation of p38 and activation of ERK1/2 signaling pathways. These findings suggest that the pathological interaction of OA SBOs with ACCs is mediated by cross-talking between ERK1/2 and p38 pathways, resulting in ACCs undergoing hypertrophic differentiation. Subsequent experiments to determine the effect on MMP regulation, of SBOs and ACCs cross-talk, revealed that co-culturing OA SBOs with ACCs significantly enhanced the proteolytic activity and expression of MMP-2 and MMP-9. In turn, co-culture of OA ACCs with SBOs led to abundant MMP-2 expression in SBOs. Furthermore, we showed that the addition of ERK1/2 and JNK inhibitors reversed the elevated MMP-2 and MMP-9 production which otherwise resulted from the interactions of OA SBOs-ACCs. Thus, this study has demonstrated that the altered interactions between OA SBOs-ACCs are capable of triggering the pathological pathways leading to degenerative changes seen in the osteoarthritic joint. In conclusion, the body of work presented in this dissertation has given clear in vitro evidence that the altered bi-directional communication of SBOs and ACCs may play a role in OA development and that this process was mediated by MAPK signalling pathways. Targeting these altered interactions by the use of MAPK inhibitors may provide the scientific rationale for the development of novel therapeutic strategies in the treatment and management of OA.