Advances in our understanding of osteoarthritis (OA) have made development of sensitive measurement tools a priority. The literature review in this thesis found that one of the measurement tools, arthroscopy, had not been fully evaluated. This body of work evaluated the performance of arthroscopic assessments of articular cartilage (AC) in early OA with specific reference to the OMERACT filter. Preliminary studies in plastic knee arthroscopy simulation models found that estimates of AC lesion area had poor accuracy and reliability. Measurements of lesion diameter were greatly improved by the use of specially designed measurement probes but these did not prove feasible in vivo. Ovine studies evaluated discriminant and criterion validity. Biomechanical assessments served as the gold standard for AC stiffness while macroscopic, thickness and histologic assessments were used for gross structural damage. An hybrid gold standard assessment was devised to validate arthroscopic estimates of Severity and Extent of chondropathy. Arthroscopic global assessments discriminated between normal and very early OA but discrimination between different states of OA was less impressive. Assessments of the Severity of chondropathy had acceptable accuracy and moderate reliability. While arthroscopy could not examine the entire articular surface and estimates of Extent of chondropathy were subject to very large error they broadly resembled those of the hybrid gold standard assessment and they enhanced composite score performance. Composite score validity was further improved by inclusion of estimates of chondro-osteophyte. An empirical approach to composite algorithm weighting to optimise discriminant validity was developed. This approach compared favourably with previously described methods. Composite scores proved best at discriminating between normal and very early OA but were also capable of detecting small changes in OA. Arthroscopic asessments of AC damage meet the OMERACT filter criteria of Truth and Discrimination. Assessments using current arthroscopic technology should include estimates of the Extent of all grades of chondropathy. The optimal scoring algorithm should be determined empirically. Arthroscopic assessments using existing technology may be used to validate noninvasive assessments of the Severity chondropathy but not of Extent. Future efforts to improve arthroscopic assessments of AC should focus on reducing random error associated with estimates of extent.

The iron content of industrial minerals can be reduced by physical and chemical processing. Chemical processing is very efficient to achieve a high degree of iron removal at minimum operating cost. Both inorganic acids and organic acids have been used for clay refining. However, due to environmental pollution and contamination of products with the SO42- and Cl-, inorganic acids should be avoided as much as possible. This research investigated the use of oxalic acid to dissolve iron oxides and the dissolution characteristics of natural iron oxides. The dissolution of iron oxides in oxalic acid was found to be very slow at temperatures ranging from 25??? to 60???, but increased rapidly at a temperature above 90oC with increasing oxalic acid concentration, whereas the pH caused the reaction rate to decrease at pH&gt2.5 and improved the rate from pH 1 to pH 2.5. The iron oxides such as goethite (??-FeOOH), lepidocrocite (??-FeOOH) and iron hydroxide (Fe(OH)3) can be dissolved faster at the presence of magnetite which exhibits an induction period at the initial stage and showed the bell-shaped curves for the dissolution. In titration tests, however, the increase of temperature causes an increase in solubility of the oxalate complexes, resulting in an increased stability of ionized species in solution. During the addition of NaOH, NaHC2O4???H2O was precipitated without forming Na2C2O4???H2O, but it was re-dissolved at pH&gt4.0. On the other hand with NH4OH, NH4HC2O4???H2O and (NH4) 2C2O4???H2O co-precipitated at pH 0.93, but also re-dissolved at over pH 2.03. The reaction temperature was found not to affect the removal of iron from the ferric oxalate complex solution using lime. Iron is removed as iron hydroxide and calcium oxalate is then precipitated during the iron removal step. The formation of Fe(OH)3 in the solution was affected by the dissociation of Ca(OH)2. The thermodynamics of sodium, ammonium and iron oxalate complexes were investigated and the standard free energy, ??Go was calculated using thermodynamic data and solubility products. The dissolution of pure hematite by oxalate was found to follow a shrinking core model of which the kinetic step of the reaction is the controlled mechanism.

By elucidating the origins of the banlieue rouge, a belt of communist-dominated suburbs surrounding Paris that arose during the interwar years and reached its apogee under the Fourth Republic, this thesis addresses the problem of why twentieth-century France was home to a pro-Soviet communist party with mass support. Specifically, a local study of the PCF in Arcueil and Cachan, two neighbouring communes south of Paris with divergent political evolutions since World War I, is used to discern how and why the Parti communiste fran??ais (PCF) came to exert hegemony in the working-class suburbs of Paris. After surveying the historiography of communism in France and beyond, this thesis concludes that the communist banlieue rouge was born of working-class alienation from bourgeois society that was nourished by a communist counter-society that was contingent upon the PCF???s capacity to adapt and respond to local circumstances. Using archival sources and statistical analysis, it demonstrates that in Arcueil and Cachan rapid suburbanisation and an attendant proletarianisation created the pre-conditions for the rise of the PCF. This study finds that during the interwar period the PCF rapidly emerged as an electoral force in both suburbs as it set about laying the foundations of a communist counter-society, especially in Arcueil where it won control of local government in 1935. In Arcueil, the PCF spearheaded the local Resistance movement during World War II and then under the Fourth Republic went on to consolidate a nascent communist communal identity, while in Cachan its influence fell victim to Cold War politics. The pre-conditions for the rise of communism were apparent earlier and to a greater degree in Arcueil, an industrialised, working-class suburb with long-standing radical traditions, than in the traditionally conservative Cachan. In Arcueil, the PCF was more successful than its counterpart in Cachan at exploiting an alienation that was not only part of the deep-seated historical traditions of the French working class but was also part of everyday life f or workers forced to live in miserable conditions. In suburbs such as Arcueil, suburban working-class pride at being a social outcast was conflated with communism to create a durable communist communal identity.

Ectomycorrhizal fungi are able to ameliorate heavy metal stress to host trees in polluted soils. Their sensitivity or tolerance to heavy metals is usually examined based on growth and proliferation on heavy metal amended media. However, there are no data on cellular effects of heavy metals and detoxification in live cells of these fungi. Organelle morphology has recently been recognized as an indication of cellular health and its changes can be used to assess cytotoxicity. The aim of this study was, therefore, to investigate short term effects of common heavy metal pollutants, Zn2+ and Ni2+ on the morphology of vacuoles, mitochondria and microtubules in hyphal tip cells of two Paxillus involutus strains. Vacuoles, mitochondria and microtubules were labeled with Oregon Green?? 488 carboxylic acid diacetate, 3,3'-dihexyloxacarbocyanine iodide ((DiOC6(3)) and anti-??- tubulin antibodies, respectively. They were treated with 0-1 mmol L-1 NiSO4 or 0-100 mmol L-1 ZnSO4 or K2SO4 (SO4 2- control) and examined by fluorescence microscopy. Vacuoles and mitochondria in untreated hyphal tip cells of strain P2 which originated from a heavy metal-rich soil were motile and tubular forming networks. Exposure to the metals caused tubular vacuole thickening and vesiculation as well as fragmentation of tubular mitochondria in living hyphal tip cells. The highest K2SO4 concentration also had severe effects on mitochondria. These effects were metal, concentration and exposure time dependent. NiSO4 caused these effects at a hundred fold lower concentration than ZnSO4 and induced severe microtubule disruption. Vacuole tubularity recovered after removal of the metal solutions depending on the metal, concentration and exposure time. Mitochondrial tubularity recovered to pretreatment morphology in a shorter time and even during exposure to the highest metal concentration. Vacuoles of strain P46 which originated from a non-polluted soil were pleomorphic, but mainly spherical with occasional tubular interconnections. The vacuoles were too sensitive to UV light exposure required for fluorescence microscopy to investigate their response to heavy metals. The mitochondrial network and microtubules resembled those of strain P2. The highest ZnSO4 and NiSO4 concentrations caused similar trends in response of mitochondria and microtubules of the two strains. However, mitochondria of strain P46 were less sensitive at lower metal concentrations. The highest K2SO4 concentration had more severe effects on mitochondria of strain P46 than in strain P2 from which tubularity was not recovered. This investigation is the first to reveal that heavy metals affect organelle morphology in two strains of an ectomycorrhizal fungus. Nickel effects on the organelles are likely to result from microtubule disruption. Metal induced mitochondrial fragmentation is possibly an apoptotic response and the recovery of tubular organelle networks suggests cellular detoxification.

Neuromelanin (NM) is a dark polymer pigment present in specific populations of catecholaminergic neurons in the brain. Interest in this pigment has rekindled in recent years because of a hypothesised link between NM and the especial vulnerability of NM-containing neurons to cell death in Parkinson???s disease (PD). Many aspects of the biology of NM are yet to be characterised. It is not known if NM like the similar melanin of the skin is synthesised via an enzymatic pathway or solely through autoxidation as has traditionally been thought. Examination of the ultrastructure of NM granules showed that in contrast to peripheral melanosomes, an electron-lucent lipid component was present that represented 30% of pigment volume. The identity of the lipid component of NM has remained unclear since it was first suggested that NM contained lipid in the 1960???s. NM lipid was biochemically isolated from the substantia nigra of 32 human brains. Using reversed-phase high performance liquid chromatography, atmospheric pressure chemical ionisation mass spectrometry and 1H- and 13C NMR techniques, it was shown for the first time that the NM lipid is the polyisoprenoid dolichol. The age-related development and regulation of NM has not previously been described. Optical density and area measurements of unstained NM in ventral substantia nigra neurons spanning the ages of 24 weeks to 95 years old demonstrated three developmental phases. NM was not present at birth and initiation of pigmentation began at approximately 3 years of age, followed by a period of increasing pigment granule number and colouration until age 20. In PD brain, the ultrastructure of NM demonstrated that the amount of lipid did not change. However, filipin staining showed a reduction of cholesterol in PD NM containing neurons. In addition, immunogold staining of ??-synuclein demonstrated that this protein redistributed to the NM lipid in PD brain. The finding of phases in the development of NM, and the identification of lipid species in NM suggest that NM biology is regulated. This thesis has also demonstrated changes in the lipid and associated proteins in PD, suggesting NM???s chemical composition alters which may have functional consequences that contribute to PD.

Platelet-derived growth factor (PDGF) has been implicated in the pathogenesis of vascular occlusive disorders such as atherosclerosis and restenosis, in part due to its regulation of smooth muscle cell (SMC) phenotype. The molecular mechanisms regulating the expression of PDGF-receptor-?? (PDGF-R-??), which binds all known dimeric forms of PDGF except PDGF-DD, are poorly understood. Here it is demonstrated that PDGF-R-?? protein and transcriptional regulation in SMCs is under the positive regulatory influence of the zinc finger nuclear protein, Sp1. An atypical G-rich Sp1-binding element from -61 to -52 bp (-61G10 - 52) upstream of the transcriptional start site, was identified in the PDGF-R-?? promoter via electrophoretic mobility shift, competition and supershift analysis. Mutation of this sequence ablated endogenous Sp1 binding and activation of the PDGF-R-?? promoter. In addition to Sp1 regulation of PDGF-R-??, it was shown that fibroblast growth factor-2 (FGF-2) represses PDGF-R-?? transcription, mRNA and protein expression in SMCs. The FGF-2-induced inhibition of PDGF-R-?? was rescued by block of extracellular signal-regulated kinase-1/2 (ERK1/2) signaling. Interestingly, mutation of the aforementioned novel Sp1-response-element blocked FGF-2-induced repression of PDGF-R-?? transcription. FGF-2 was also shown to stimulate Sp1 phosphorylation in an ERK1/2-dependent manner, enhancing its interaction with the PDGF-R-?? promoter. Further analysis revealed that mutations of residues Thr453 and Thr739 in Sp1 resulted in loss of FGF-2-mediated repression of PDGF-R-?? transcription. These findings demonstrate that FGF-2 stimulates ERK1/2- dependent Sp1 phosphorylation, thereby repressing PDGF-R-?? transcription via Sp1 binding the -61/-52 element in the PDGF-R-?? promoter. Thus, phosphorylation triggered by FGF-2, switches Sp1 from an activator to a repressor of PDGF-R-?? transcription, a finding previously unreported in any Sp1-dependent gene. It is also shown in this thesis that the proto-oncogene Ets-1 controls PDGF-R-?? transcription and mRNA expression in SMCs. Mutational, electrophoretic mobility shift and chromatin immunoprecipitation assays revealed the existence of a reverse Ets binding motif (-45TTCC-42) in the proximal region of the PDGFR- ?? promoter which bound both recombinant and endogenous Ets-1. Ets-1- inducible PDGF-R-?? expression was dependent upon the integrity of both the - 45TTCC-42 motif and the previously identified -61G10 -52 element, which resides upstream of -45TTCC-42 and mediates Sp1 induction. Hydrogen peroxide (H2O2) at nanomolar concentrations, stimulated levels of Ets-1 and increased PDGF-R- ?? transcription and mRNA expression without affecting Sp1 expression. Disruption of the -45TTCC-42 motif or -61G10 -52 element blocked H2O2 activation of the PDGF-R-?? promoter. These studies identify a functional Ets motif in the PDGF-R-?? promoter which plays a pivotal role in agonist-inducible PDGF-R-?? transcription. The interplay between transcription factors such as Sp1 and Ets- 1 in the promoter of genes can exert profound influences on gene regulation. Modulating gene expression affects biological processes such as SMC proliferation and phenotype changes, which contributes to changes in vessel integrity, a hallmark of atherosclerosis. This study provides a greater insight in the functional consequences of Sp1 and Ets-1 interplay in PDGF-R-?? gene regulation and in general, provides a greater understanding of the functional regulation of cooperating transcription factors.

It is known in many gold operations that less than 2% of the cyanide consumed accounts for the gold and silver dissolution. The majority of the cyanide is consumed by minerals contained in the gold ore to produce many different cyanide soluble complexes or used in converting cyanide to other related species such as thiocyanate and cyanate. The high costs associated with cyanide and thiocyanate detoxification and excessive cyanide utilisation encountered when treating ores with high cyanide consumption constitutes a significant proportion of the overall processing costs. This study examines the possibility of recovering free cyanide from thiocyanate using a process based on the Acidification-Volatilisation-Regeneration (AVR) circuit in conjunction with a pre-concentration stage using commercially available ionexchange resin. From thermodynamic modelling based on the STABCAL program it was found that it was thermodynamically possible to recover cyanide from thiocyanate if the oxidation of cyanide to cyanate can be stopped. Addition of copper to the system found that the majority of the thiocyanate exists as copper(I) thiocyanate (CuSCN) solid. Using ion-exchange resins can be an effective way to concentrate thiocyanate from tailing solutions or slurries. Four different models were successfully used to model the equilibria between thiocyanate and chloride on commercial ion-exchange resins. By normalising the equilibria data when applying the Mass action law the equilibria becomes independent of ionic strength within the range of concentration considered. An advantage of this is that only one unique equilibrium constant is used to describe the ion-exchange process. The electrochemical and kinetic studies showed that the reaction between thiocyanate and hydrogen peroxide is catalysed by hydrogen ions. Secondly under acidic conditions the rate of cyanide recovery by the AVR circuit was faster than at higher pH conditions. The overall reaction of thiocyanate with respect to the concentration of thiocyanate and hydrogen peroxide is an overall third order reaction. The derived third order rate expression is first order with respect to thiocyanate concentration and second order with respect to hydrogen peroxide concentration. Previous studies showed that the production of cyanide inhibits the reactions between thiocyanate and hydrogen peroxide, but by removing cyanide from the reaction by air stripping, this was not observed. Addition of copper to the system did not show a catalytic effect on the reaction but it was found that copper (II) ions suppresses competing reactions that occurred without affecting the reaction between thiocyanate and hydrogen peroxide.

In this thesis, multiple-response sequences (MRSs) are examined. These are a language classroom practice in which two or more students respond to a teacher???s question or other elicitation. The study uses tools of Conversation Analysis to investigate over 38 hours of classroom talk- in-interaction in TESOL classes comprising monolingual adult Korean learners. Classes were recorded on audio and video in Seoul, South Korea and Sydney, Australia. About 1050 cases of MRSs were found and analysed. In the study, four distinct major types of multiple responses (MRs) are identified. These are: the identical MR, in which two or more students provide the same response; the complementary MR, in which two or more students??? responses provide essent ially the same meaning, but in different forms; the collaborative MR, in which two or more students collectively provide various parts of the response in the construction of a single response; and the competitive MR, in which two or more students provide responses that diverge from one another. The study also examines complex MRs, which are combinations of the basic four types, and expanded sequences, in which MRs occur in preparatory stage or post-expansion sequences. It was found that the teacher and students can produce highly complex, co-ordinated and orderly talk in the course of MRSs. The study also considers MRSs as a potential locus for second language learning. The relevance of this study to some major theories of second language acquisition is discussed, in particular in relation to social interaction in the classroom.Finally, some suggestions for future research in the area are presented.

Since the early stages of the Hawke government, Australia???s taxation system has been modified with a view to attracting additional capital into the domestic venture capital market. In December 2002, the Howard government enacted the Taxation Laws Amendment (Venture Capital) Act 2002 (Cth) and the Venture Capital Act 2002 (Cth). This legislative package created a prospective concession primarily aimed at qualifying limited partnerships who participate in the Australian venture capital market. Subject to a rather stringent qualification criteria, such partnerships are treated as fiscally transparent for the purposes of Australian taxation law. In addition, the gains made upon the disposal of portfolio investments by these partnerships may not be subject to Australian capital gains tax (&quotCGT&quot) or otherwise assessable as ordinary income. The central concept of these measures is the venture capital limited partnership (&quotVCLP&quot), and other fund of fund organisational forms which are founded on the limited partnership. For this reason, the provisions of the Taxation Laws Amendment (Venture Capital) Act 2002 (Cth) and the Venture Capital Act 2002 (Cth) are collectively identified as the &quotVCLP Concessions&quot. This thesis has been prepared as a rigorous assessment of the VCLP Concessions. It draws upon an analysis of the nature and structure of venture capital investing to determine whether the particular features of the VCLP Concessions appropriately cater for the needs of prospective foreign investors. The efficacy and appropriateness of the VCLP Concessions from a policy perspective is also examined. Recommendations are provided which, if enacted, would address regions of structural inconsistency and improve the functioning of this concessional regime.

Issue Addressed: Access block (the prolonged wait for an inpatient hospital bed after emergency department (ED) treatment) is regarded as one of the major issues currently facing emergency medicine both in Australia and internationally. At this tertiary referral hospital review of existing data has indicated that access block has continued to increase in recent years, with a sharp rise in emergency access problems since July 1999 and is now identified as a system wide problem. Objective: This research thesis sought to explore four main areas of inquiry concerning access issues within this hospital. The first objective was to determine the current bed capacity of this hospital and identify the percentage of access block within this system. The second objective was to seek an understanding of hospital clinicians??? experiences of access block and to identify the factors they perceive directly influence patient access to acute in-patient care. The third objective was to identify change strategies to improve patient access. The final objective was to determine whether collaborative participation and involvement of clinicians would lead to a change in hospital culture and foster a collective ownership of access block as a hospital wide problem. Method: In a participatory action research inquiry, hospital clinicians within this hospital were invited to be co-researchers. The process of concurrent investigation and action followed a five- part sequence of entry, issue identification, planning, action and reflection. Both qualitative and quantitative research methods were used including in-depth semi structured interviews, focus groups, process mapping, control charts and statistical analysis. Results: The research findings revealed a consistently high level of access block experienced by this hospital with bed occupancy rates in excess of 90%. During the study, hospital clinicians??? became actively involved in identifying major access issues. Six main delay categories evolved: Access delays due to limited imaging and diagnostic services, patient transport delays, barriers within the patient discharges process, insufficient access and availability to transitional, hostel, rehabilitation and nursing home beds and delays due to poor internal processes within the wards. Multi-disciplinary working parties were formed to implement six intervention strategies identified by the hospital clinicians. These included: the development of a patient access database and hospital wide alert system for code red status, the design of a pharmacy discharge prescription tracking system, the establishment of a patient discharge lounge, a quality study of the aged care assessment team within the ED and the formation of a transport working group to evaluate an electronic transport booking system within the hospital. Conclusion: In recording the qualitative process involved in gaining hospital clinicians??? perceptions of the problem of access block some indicators of engagement and empowerment were documented. The success of this participatory action approach is based on the simple principal that those that are doing the job are in the best position to change or improve it.