202 resultados para Site investigations
Resumo:
Motor vehicle emissions have been identified as one of the major contributors of fine and ultrafine particles (UFP) in urban areas. Schools located near major roads could potentially be exposed to high levels of UPFs and school classroom is an important microenvironment where significant exposure to UFPs is likely to occur. Most of the research conducted to date has investigated the relationship between indoor and outdoor particle number concentration (PNC) in schools based on one outdoor location, which may introduce a level of error when calculating the variation of total UPFs, and can result in the underestimation or overestimation of indoor to outdoor (I/O) ratio values.
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HtrA is a complex, multimeric chaperone and serine protease important for the virulence and survival of many bacteria. Chlamydia trachomatis is an obligate, intracellular bacterial pathogen that is responsible for severe disease pathology. C. trachomatis HtrA (CtHtrA) has been shown to be highly expressed in laboratory models of disease. In this study, molecular modelling of CtHtrA protein active site structure identified putative S1-S3 subsite residues I242, I265, and V266. These residues were altered by site-directed mutagenesis, and these changes were shown to considerably reduce protease activity on known substrates and resulted in a narrower and distinct range of substrates compared to wild type. Bacterial two-hybrid analysis revealed that CtHtrA is able to interact in vivo with a broad range of protein sequences with high affinity. Notably, however, the interaction was significantly altered in 35 out of 69 clones when residue V266 was mutated, indicating that this residue has an important function during substrate binding.
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Background Total hip arthroplasty (THA) is a commonly performed procedure and numbers are increasing with ageing populations. One of the most serious complications in THA are surgical site infections (SSIs), caused by pathogens entering the wound during the procedure. SSIs are associated with a substantial burden for health services, increased mortality and reduced functional outcomes in patients. Numerous approaches to preventing these infections exist but there is no gold standard in practice and the cost-effectiveness of alternate strategies is largely unknown. Objectives The aim of this project was to evaluate the cost-effectiveness of strategies claiming to reduce deep surgical site infections following total hip arthroplasty in Australia. The objectives were: 1. Identification of competing strategies or combinations of strategies that are clinically relevant to the control of SSI related to hip arthroplasty 2. Evidence synthesis and pooling of results to assess the volume and quality of evidence claiming to reduce the risk of SSI following total hip arthroplasty 3. Construction of an economic decision model incorporating cost and health outcomes for each of the identified strategies 4. Quantification of the effect of uncertainty in the model 5. Assessment of the value of perfect information among model parameters to inform future data collection Methods The literature relating to SSI in THA was reviewed, in particular to establish definitions of these concepts, understand mechanisms of aetiology and microbiology, risk factors, diagnosis and consequences as well as to give an overview of existing infection prevention measures. Published economic evaluations on this topic were also reviewed and limitations for Australian decision-makers identified. A Markov state-transition model was developed for the Australian context and subsequently validated by clinicians. The model was designed to capture key events related to deep SSI occurring within the first 12 months following primary THA. Relevant infection prevention measures were selected by reviewing clinical guideline recommendations combined with expert elicitation. Strategies selected for evaluation were the routine use of pre-operative antibiotic prophylaxis (AP) versus no use of antibiotic prophylaxis (No AP) or in combination with antibiotic-impregnated cement (AP & ABC) or laminar air operating rooms (AP & LOR). The best available evidence for clinical effect size and utility parameters was harvested from the medical literature using reproducible methods. Queensland hospital data were extracted to inform patients’ transitions between model health states and related costs captured in assigned treatment codes. Costs related to infection prevention were derived from reliable hospital records and expert opinion. Uncertainty of model input parameters was explored in probabilistic sensitivity analyses and scenario analyses and the value of perfect information was estimated. Results The cost-effectiveness analysis was performed from a health services perspective using a hypothetical cohort of 30,000 THA patients aged 65 years. The baseline rate of deep SSI was 0.96% within one year of a primary THA. The routine use of antibiotic prophylaxis (AP) was highly cost-effective and resulted in cost savings of over $1.6m whilst generating an extra 163 QALYs (without consideration of uncertainty). Deterministic and probabilistic analysis (considering uncertainty) identified antibiotic prophylaxis combined with antibiotic-impregnated cement (AP & ABC) to be the most cost-effective strategy. Using AP & ABC generated the highest net monetary benefit (NMB) and an incremental $3.1m NMB compared to only using antibiotic prophylaxis. There was a very low error probability that this strategy might not have the largest NMB (<5%). Not using antibiotic prophylaxis (No AP) or using both antibiotic prophylaxis combined with laminar air operating rooms (AP & LOR) resulted in worse health outcomes and higher costs. Sensitivity analyses showed that the model was sensitive to the initial cohort starting age and the additional costs of ABC but the best strategy did not change, even for extreme values. The cost-effectiveness improved for a higher proportion of cemented primary THAs and higher baseline rates of deep SSI. The value of perfect information indicated that no additional research is required to support the model conclusions. Conclusions Preventing deep SSI with antibiotic prophylaxis and antibiotic-impregnated cement has shown to improve health outcomes among hospitalised patients, save lives and enhance resource allocation. By implementing a more beneficial infection control strategy, scarce health care resources can be used more efficiently to the benefit of all members of society. The results of this project provide Australian policy makers with key information about how to efficiently manage risks of infection in THA.
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Background. One of the promising avenues for development of vaccines against Human immunodeficiency virus type 1 (HIV-1) and other human pathogens is the use of plasmid-based DNA vaccines. However, relatively large doses of plasmid must be injected for a relatively weak response. We investigated whether genome elements from Porcine circovirus type 1 (PCV-1), an apathogenic small ssDNA-containing virus, had useful expression-enhancing properties that could allow dose-sparing in a plasmid vaccine. Results. The linearised PCV-1 genome inserted 5' of the CMV promoter in the well-characterised HIV-1 plasmid vaccine pTHgrttnC increased expression of the polyantigen up to 2-fold, and elicited 3-fold higher CTL responses in mice at 10-fold lower doses than unmodified pTHgrttnC. The PCV-1 capsid gene promoter (Pcap) alone was equally effective. Enhancing activity was traced to a putative composite host transcription factor binding site and a "Conserved Late Element" transcription-enhancing sequence previously unidentified in circoviruses. Conclusions. We identified a novel PCV-1 genome-derived enhancer sequence that significantly increased antigen expression from plasmids in in vitro assays, and improved immunogenicity in mice of the HIV-1 subtype C vaccine plasmid, pTHgrttnC. This should allow significant dose sparing of, or increased responses to, this and other plasmid-based vaccines. We also report investigations of the potential of other circovirus-derived sequences to be similarly used. © 2011 Tanzer et al; licensee BioMed Central Ltd.
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Urban renewal is a significant issue in developed urban areas, with a particular problem for urban planners being redevelopment of land to meet demand whilst ensuring compatibility with existing land use. This paper presents a geographic information systems (GIS)-based decision support tool (called LUDS) to quantitatively assess land-use suitability for site redevelopment in urban renewal areas. This consists of a model for the suitability analysis and an affiliated land-information database for residential, commercial, industrial, G/I/C (government/institution/community) and open space land uses. Development has occurred with support from interviews with industry experts, focus group meetings and an experimental trial, combined with several advanced techniques and tools, including GIS data processing and spatial analysis, multi-criterion analysis, as well as the AHP method for constructing the model and database. As demonstrated in the trial, LUDS assists planners in making land-use decisions and supports the planning process in assessing urban land-use suitability for site redevelopment. Moreover, it facilitates public consultation (participatory planning) by providing stakeholders with an explicit understanding of planners' views.
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Exponential growth of genomic data in the last two decades has made manual analyses impractical for all but trial studies. As genomic analyses have become more sophisticated, and move toward comparisons across large datasets, computational approaches have become essential. One of the most important biological questions is to understand the mechanisms underlying gene regulation. Genetic regulation is commonly investigated and modelled through the use of transcriptional regulatory network (TRN) structures. These model the regulatory interactions between two key components: transcription factors (TFs) and the target genes (TGs) they regulate. Transcriptional regulatory networks have proven to be invaluable scientific tools in Bioinformatics. When used in conjunction with comparative genomics, they have provided substantial insights into the evolution of regulatory interactions. Current approaches to regulatory network inference, however, omit two additional key entities: promoters and transcription factor binding sites (TFBSs). In this study, we attempted to explore the relationships among these regulatory components in bacteria. Our primary goal was to identify relationships that can assist in reducing the high false positive rates associated with transcription factor binding site predictions and thereupon enhance the reliability of the inferred transcription regulatory networks. In our preliminary exploration of relationships between the key regulatory components in Escherichia coli transcription, we discovered a number of potentially useful features. The combination of location score and sequence dissimilarity scores increased de novo binding site prediction accuracy by 13.6%. Another important observation made was with regards to the relationship between transcription factors grouped by their regulatory role and corresponding promoter strength. Our study of E.coli ��70 promoters, found support at the 0.1 significance level for our hypothesis | that weak promoters are preferentially associated with activator binding sites to enhance gene expression, whilst strong promoters have more repressor binding sites to repress or inhibit gene transcription. Although the observations were specific to �70, they nevertheless strongly encourage additional investigations when more experimentally confirmed data are available. In our preliminary exploration of relationships between the key regulatory components in E.coli transcription, we discovered a number of potentially useful features { some of which proved successful in reducing the number of false positives when applied to re-evaluate binding site predictions. Of chief interest was the relationship observed between promoter strength and TFs with respect to their regulatory role. Based on the common assumption, where promoter homology positively correlates with transcription rate, we hypothesised that weak promoters would have more transcription factors that enhance gene expression, whilst strong promoters would have more repressor binding sites. The t-tests assessed for E.coli �70 promoters returned a p-value of 0.072, which at 0.1 significance level suggested support for our (alternative) hypothesis; albeit this trend may only be present for promoters where corresponding TFBSs are either all repressors or all activators. Nevertheless, such suggestive results strongly encourage additional investigations when more experimentally confirmed data will become available. Much of the remainder of the thesis concerns a machine learning study of binding site prediction, using the SVM and kernel methods, principally the spectrum kernel. Spectrum kernels have been successfully applied in previous studies of protein classification [91, 92], as well as the related problem of promoter predictions [59], and we have here successfully applied the technique to refining TFBS predictions. The advantages provided by the SVM classifier were best seen in `moderately'-conserved transcription factor binding sites as represented by our E.coli CRP case study. Inclusion of additional position feature attributes further increased accuracy by 9.1% but more notable was the considerable decrease in false positive rate from 0.8 to 0.5 while retaining 0.9 sensitivity. Improved prediction of transcription factor binding sites is in turn extremely valuable in improving inference of regulatory relationships, a problem notoriously prone to false positive predictions. Here, the number of false regulatory interactions inferred using the conventional two-component model was substantially reduced when we integrated de novo transcription factor binding site predictions as an additional criterion for acceptance in a case study of inference in the Fur regulon. This initial work was extended to a comparative study of the iron regulatory system across 20 Yersinia strains. This work revealed interesting, strain-specific difierences, especially between pathogenic and non-pathogenic strains. Such difierences were made clear through interactive visualisations using the TRNDifi software developed as part of this work, and would have remained undetected using conventional methods. This approach led to the nomination of the Yfe iron-uptake system as a candidate for further wet-lab experimentation due to its potential active functionality in non-pathogens and its known participation in full virulence of the bubonic plague strain. Building on this work, we introduced novel structures we have labelled as `regulatory trees', inspired by the phylogenetic tree concept. Instead of using gene or protein sequence similarity, the regulatory trees were constructed based on the number of similar regulatory interactions. While the common phylogentic trees convey information regarding changes in gene repertoire, which we might regard being analogous to `hardware', the regulatory tree informs us of the changes in regulatory circuitry, in some respects analogous to `software'. In this context, we explored the `pan-regulatory network' for the Fur system, the entire set of regulatory interactions found for the Fur transcription factor across a group of genomes. In the pan-regulatory network, emphasis is placed on how the regulatory network for each target genome is inferred from multiple sources instead of a single source, as is the common approach. The benefit of using multiple reference networks, is a more comprehensive survey of the relationships, and increased confidence in the regulatory interactions predicted. In the present study, we distinguish between relationships found across the full set of genomes as the `core-regulatory-set', and interactions found only in a subset of genomes explored as the `sub-regulatory-set'. We found nine Fur target gene clusters present across the four genomes studied, this core set potentially identifying basic regulatory processes essential for survival. Species level difierences are seen at the sub-regulatory-set level; for example the known virulence factors, YbtA and PchR were found in Y.pestis and P.aerguinosa respectively, but were not present in both E.coli and B.subtilis. Such factors and the iron-uptake systems they regulate, are ideal candidates for wet-lab investigation to determine whether or not they are pathogenic specific. In this study, we employed a broad range of approaches to address our goals and assessed these methods using the Fur regulon as our initial case study. We identified a set of promising feature attributes; demonstrated their success in increasing transcription factor binding site prediction specificity while retaining sensitivity, and showed the importance of binding site predictions in enhancing the reliability of regulatory interaction inferences. Most importantly, these outcomes led to the introduction of a range of visualisations and techniques, which are applicable across the entire bacterial spectrum and can be utilised in studies beyond the understanding of transcriptional regulatory networks.
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Teachers often have difficulty implementing inquiry-based activities, leading to the arousal of negative emotions. In this multicase study of beginning physics teachers in Australia, we were interested in the extent to which their expectations were realized and how their classroom experiences while implementing extended experimental investigations (EEIs) produced emotional states that mediated their teaching practices. Against rhetoric of fear expressed by their senior colleagues, three of the four teachers were surprised by the positive outcomes from their supervision of EEIs for the first time. Two of these teachers experienced high intensity positive emotions in response to their students’ success. When student actions / outcomes did not meet their teachers’ expectations, frustration, anger, and disappointment were experienced by the teachers, as predicted by a sociological theory of human emotions (Turner, 2007). Over the course of the EEI projects, the teachers’ practices changed along with their emotional states and their students’ achievements. We account for similarities and differences in the teachers’ emotional experiences in terms of context, prior experience, and expectations. The findings from this study provide insights into effective supervision practices that can be used to inform new and experienced teachers alike.
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Attention Deficit Hyperactivity Disorder is a diagnostic term now indelibly scored on the public psyche. In some quarters, a diagnosis of “ADHD” is regarded with derision. In others it is welcomed with relief. Despite intense multi-disciplinary research, the jury is still out with regards to the “truth” of ADHD. Not surprisingly, the rapid increase in diagnosis over the past fifteen years, coupled with an exponential rise in the prescription of restricted class psychopharmaceuticals has stirred virulent debate. Provoking the most interest, it seems, are questions regarding causality. Typically, these revolve around possible antecedents for “disorderly” behaviour – bad food, bad tv and bad parents. Very seldom is the institution of schooling ever in the line of sight. To investigate this gap, I draw on Foucault to question what might be happening in schools and how this may be contributing to the definition, recognition and classification of particular children as a particular kind of “disorderly”.
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A pressing cost issue facing construction is the procurement of off-site pre-manufactured assemblies. In order to encourage Australian adoption of off-site manufacture (OSM), a new approach to underlying processes is required. The advent of object oriented digital models for construction design assumes intelligent use of data. However, the construction production system relies on traditional methods and data sources and is expected to benefit from the application of well-established business process management techniques. The integration of the old and new data sources allows for the development of business process models which, by capturing typical construction processes involving OSM, provides insights into such processes. This integrative approach is the foundation of research into the use of OSM to increase construction productivity in Australia. The purpose of this study is to develop business process models capturing the procurement, resources and information flow of construction projects. For each stage of the construction value chain, a number of sub-processes are identified. Business Process Modelling Notation (BPMN), a mainstream business process modelling standard, is used to create base-line generic construction process models. These models identify OSM decision-making points that could provide cost reductions in procurement workflow and management systems. This paper reports on phase one of an on-going research aiming to develop a proto-type workflow application that can provide semi-automated support to construction processes involving OSM and assist in decision-making in the adoption of OSM thus contributing to a sustainable built environment.
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Many construction industry decision-makers believe there is a lack of off-site manufacture (OSM) adoption for non-residential construction in Australia. Identification of construction business process was considered imperative in order to assist decision-makers to increase OSM utilisation. The premise that domain knowledge can be re-used to provide an intervention point in the construction process led a team of researchers to construct simple base-line process models for the complete construction process, segmented into six phases. Sixteen domain knowledge industry experts were asked to review the construction phase base-line models to answer the question “Where in the process illustrated by this base-line model phase is an OSM task?”. Through an iterative and generative process a number of off-site manufacture intervention points were identified and integrated into the process models. The re-use of industry expert domain knowledge provided suggestions for new ways to do basic tasks thus facilitating changes to current practice. It is expected that implementation of the new processes will lead to systemic industry change and thus a growth in productivity due to increased adoption of OSM.
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Background: Surgical site infection (SSI) is associated with substantial costs for health services, reduced quality of life, and functional outcomes. The aim of this study was to evaluate the cost-effectiveness of strategies claiming to reduce the risk of SSI in hip arthroplasty in Australia. Methods: Baseline use of antibiotic prophylaxis (AP) was compared with no antibiotic prophylaxis (no AP), antibiotic-impregnated cement (AP þ ABC), and laminar air operating rooms (AP þ LOR). A Markov model was used to simulate long-term health and cost outcomes of a hypothetical cohort of 30,000 total hip arthroplasty patients from a health services perspective. Model parameters were informed by the best available evidence. Uncertainty was explored in probabilistic sensitivity and scenario analyses. Results: Stopping the routine use of AP resulted in over Australian dollars (AUD) $1.5 million extra costs and a loss of 163 quality-adjusted life years (QALYs). Using antibiotic cement in addition to AP (AP þ ABC)generated an extra 32 QALYs while saving over AUD $123,000. The use of laminar air operating rooms combined with routine AP (AP þ LOR) resulted in an AUD $4.59 million cost increase and 127 QALYs lost compared with the baseline comparator. Conclusion: Preventing deep SSI with antibiotic prophylaxis and antibiotic-impregnated cement has shown to improve health outcomes among hospitalized patients, save lives, and enhance resource allocation. Based on this evidence, the use of laminar air operating rooms is not recommended.
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Pro-anorexia Internet sites aim to promote, support and discuss anorexia nervosa. Media coverage has raised concerns that sites may increase the level of eating disorders. This research examines the meaning of participation in a pro-anorexia Internet site and its relationship with disordered eating by using an interpretative phenomenological analysis of fifteen separate message ‘threads’ followed over a six-week period. Four themes were identified: (1) tips and techniques; (2) ‘ana’ v. anorexia nervosa; (3) social support; and (4) need for anorexia. Findings suggest participation was multi-purpose, providing a coping function in relation to weight loss, and the contribution of sites to increased levels of eating disorders is not inevitable.
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This dissertation analyses how physical objects are translated into digital artworks using techniques which can lead to ‘imperfections’ in the resulting digital artwork that are typically removed to arrive at a ‘perfect’ final representation. The dissertation discusses the adaptation of existing techniques into an artistic workflow that acknowledges and incorporates the imperfections of translation into the final pieces. It presents an exploration of the relationship between physical and digital artefacts and the processes used to move between the two. The work explores the 'craft' of digital sculpting and the technology used in producing what the artist terms ‘a naturally imperfect form’, incorporating knowledge of traditional sculpture, an understanding of anatomy and an interest in the study of bones (Osteology). The outcomes of the research are presented as a series of digital sculptural works, exhibited as a collection of curiosities in multiple mediums, including interactive game spaces, augmented reality (AR), rapid prototype prints (RP) and video displays.
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Particulate matter research is essential because of the well known significant adverse effects of aerosol particles on human health and the environment. In particular, identification of the origin or sources of particulate matter emissions is of paramount importance in assisting efforts to control and reduce air pollution in the atmosphere. This thesis aims to: identify the sources of particulate matter; compare pollution conditions at urban, rural and roadside receptor sites; combine information about the sources with meteorological conditions at the sites to locate the emission sources; compare sources based on particle size or mass; and ultimately, provide the basis for control and reduction in particulate matter concentrations in the atmosphere. To achieve these objectives, data was obtained from assorted local and international receptor sites over long sampling periods. The samples were analysed using Ion Beam Analysis and Scanning Mobility Particle Sizer methods to measure the particle mass with chemical composition and the particle size distribution, respectively. Advanced data analysis techniques were employed to derive information from large, complex data sets. Multi-Criteria Decision Making (MCDM), a ranking method, drew on data variability to examine the overall trends, and provided the rank ordering of the sites and years that sampling was conducted. Coupled with the receptor model Positive Matrix Factorisation (PMF), the pollution emission sources were identified and meaningful information pertinent to the prioritisation of control and reduction strategies was obtained. This thesis is presented in the thesis by publication format. It includes four refereed papers which together demonstrate a novel combination of data analysis techniques that enabled particulate matter sources to be identified and sampling site/year ranked. The strength of this source identification process was corroborated when the analysis procedure was expanded to encompass multiple receptor sites. Initially applied to identify the contributing sources at roadside and suburban sites in Brisbane, the technique was subsequently applied to three receptor sites (roadside, urban and rural) located in Hong Kong. The comparable results from these international and national sites over several sampling periods indicated similarities in source contributions between receptor site-types, irrespective of global location and suggested the need to apply these methods to air pollution investigations worldwide. Furthermore, an investigation into particle size distribution data was conducted to deduce the sources of aerosol emissions based on particle size and elemental composition. Considering the adverse effects on human health caused by small-sized particles, knowledge of particle size distribution and their elemental composition provides a different perspective on the pollution problem. This thesis clearly illustrates that the application of an innovative combination of advanced data interpretation methods to identify particulate matter sources and rank sampling sites/years provides the basis for the prioritisation of future air pollution control measures. Moreover, this study contributes significantly to knowledge based on chemical composition of airborne particulate matter in Brisbane, Australia and on the identity and plausible locations of the contributing sources. Such novel source apportionment and ranking procedures are ultimately applicable to environmental investigations worldwide.
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This paper presents an alternative approach to image segmentation by using the spatial distribution of edge pixels as opposed to pixel intensities. The segmentation is achieved by a multi-layered approach and is intended to find suitable landing areas for an aircraft emergency landing. We combine standard techniques (edge detectors) with novel developed algorithms (line expansion and geometry test) to design an original segmentation algorithm. Our approach removes the dependency on environmental factors that traditionally influence lighting conditions, which in turn have negative impact on pixel-based segmentation techniques. We present test outcomes on realistic visual data collected from an aircraft, reporting on preliminary feedback about the performance of the detection. We demonstrate consistent performances over 97% detection rate.