883 resultados para Diffuse adherence
Resumo:
Despite its potential multiple contributions to sustainable policy objectives, urban transit is generally not widely used by the public in terms of its market share compared to that of automobiles, particularly in affluent societies with low-density urban forms like Australia. Transit service providers need to attract more people to transit by improving transit quality of service. The key to cost-effective transit service improvements lies in accurate evaluation of policy proposals by taking into account their impacts on transit users. If transit providers knew what is more or less important to their customers, they could focus their efforts on optimising customer-oriented service. Policy interventions could also be specified to influence transit users’ travel decisions, with targets of customer satisfaction and broader community welfare. This significance motivates the research into the relationship between urban transit quality of service and its user perception as well as behaviour. This research focused on two dimensions of transit user’s travel behaviour: route choice and access arrival time choice. The study area chosen was a busy urban transit corridor linking Brisbane central business district (CBD) and the St. Lucia campus of The University of Queensland (UQ). This multi-system corridor provided a ‘natural experiment’ for transit users between the CBD and UQ, as they can choose between busway 109 (with grade-separate exclusive right-of-way), ordinary on-street bus 412, and linear fast ferry CityCat on the Brisbane River. The population of interest was set as the attendees to UQ, who travelled from the CBD or from a suburb via the CBD. Two waves of internet-based self-completion questionnaire surveys were conducted to collect data on sampled passengers’ perception of transit service quality and behaviour of using public transit in the study area. The first wave survey is to collect behaviour and attitude data on respondents’ daily transit usage and their direct rating of importance on factors of route-level transit quality of service. A series of statistical analyses is conducted to examine the relationships between transit users’ travel and personal characteristics and their transit usage characteristics. A factor-cluster segmentation procedure is applied to respodents’ importance ratings on service quality variables regarding transit route preference to explore users’ various perspectives to transit quality of service. Based on the perceptions of service quality collected from the second wave survey, a series of quality criteria of the transit routes under study was quantitatively measured, particularly, the travel time reliability in terms of schedule adherence. It was proved that mixed traffic conditions and peak-period effects can affect transit service reliability. Multinomial logit models of transit user’s route choice were estimated using route-level service quality perceptions collected in the second wave survey. Relative importance of service quality factors were derived from choice model’s significant parameter estimates, such as access and egress times, seat availability, and busway system. Interpretations of the parameter estimates were conducted, particularly the equivalent in-vehicle time of access and egress times, and busway in-vehicle time. Market segmentation by trip origin was applied to investigate the difference in magnitude between the parameter estimates of access and egress times. The significant costs of transfer in transit trips were highlighted. These importance ratios were applied back to quality perceptions collected as RP data to compare the satisfaction levels between the service attributes and to generate an action relevance matrix to prioritise attributes for quality improvement. An empirical study on the relationship between average passenger waiting time and transit service characteristics was performed using the service quality perceived. Passenger arrivals for services with long headways (over 15 minutes) were found to be obviously coordinated with scheduled departure times of transit vehicles in order to reduce waiting time. This drove further investigations and modelling innovations in passenger’ access arrival time choice and its relationships with transit service characteristics and average passenger waiting time. Specifically, original contributions were made in formulation of expected waiting time, analysis of the risk-aversion attitude to missing desired service run in the passengers’ access time arrivals’ choice, and extensions of the utility function specification for modelling passenger access arrival distribution, by using complicated expected utility forms and non-linear probability weighting to explicitly accommodate the risk of missing an intended service and passenger’s risk-aversion attitude. Discussions on this research’s contributions to knowledge, its limitations, and recommendations for future research are provided at the concluding section of this thesis.
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Sol-gel synthesis in varied gravity is only a relatively new topic in the literature and further investigation is required to explore its full potential as a method to synthesise novel materials. Although trialled for systems such as silica, the specific application of varied gravity synthesis to other sol-gel systems such as titanium has not previously been undertaken. Current literature methods for the synthesis of sol-gel material in reduced gravity could not be applied to titanium sol-gel processing, thus a new strategy had to be developed in this study. To successfully conduct experiments in varied gravity a refined titanium sol-gel chemical precursor had to be developed which allowed the single solution precursor to remain un-reactive at temperatures up to 50oC and only begin to react when exposed to a pressure decrease from a vacuum. Due to the new nature of this precursor, a thorough characterisation of the reaction precursors was subsequently undertaken with the use of techniques such as Nuclear Magnetic Resonance, Infra-red and UV-Vis spectroscopy in order to achieve sufficient understanding of precursor chemistry and kinetic stability. This understanding was then used to propose gelation reaction mechanisms under varied gravity conditions. Two unique reactor systems were designed and built with the specific purpose to allow the effects of varied gravity (high, normal, reduced) during synthesis of titanium sol-gels to be studied. The first system was a centrifuge capable of providing high gravity environments of up to 70 g’s for extended periods, whilst applying a 100 mbar vacuum and a temperature of 40-50oC to the reaction chambers. The second system to be used in the QUT Microgravity Drop Tower Facility was also required to provide the same thermal and vacuum conditions used in the centrifuge, but had to operate autonomously during free fall. Through the use of post synthesis characterisation techniques such as Raman Spectroscopy, X-Ray diffraction (XRD) and N2 adsorption, it was found that increased gravity levels during synthesis, had the greatest effect on the final products. Samples produced in reduced and normal gravity appeared to form amorphous gels containing very small particles with moderate surface areas. Whereas crystalline anatase (TiO2), was found to form in samples synthesised above 5 g with significant increases in crystallinity, particle size and surface area observed when samples were produced at gravity levels up to 70 g. It is proposed that for samples produced in higher gravity, an increased concentration gradient of water is forms at the bottom of the reacting film due to forced convection. The particles formed in higher gravity diffuse downward towards this excess of water, which favours the condensation reaction of remaining sol gel precursors with the particles promoting increased particle growth. Due to the removal of downward convection in reduced gravity, particle growth due to condensation reaction processes are physically hindered hydrolysis reactions favoured instead. Another significant finding from this work was that anatase could be produced at relatively low temperatures of 40-50oC instead of the conventional method of calcination above 450oC solely through sol-gel synthesis at higher gravity levels. It is hoped that the outcomes of this research will lead to an increased understanding of the effects of gravity on chemical synthesis of titanium sol-gel, potentially leading to the development of improved products suitable for diverse applications such as semiconductor or catalyst materials as well as significantly reducing production and energy costs through manufacturing these materials at significantly lower temperatures.
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Despite the Revised International Prognostic Index's (R-IPI) undoubted utility in diffuse large B-cell lymphoma (DLBCL), significant clinical heterogeneity within R-IPI categories persists. Emerging evidence indicates that circulating host immunity is a robust and R-IPI independent prognosticator, most likely reflecting the immune status of the intratumoral microenvironment. We hypothesized that direct quantification of immunity within lymphomatous tissue would better permit stratification within R-IPI categories. We analyzed 122 newly diagnosed consecutive DLBCL patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemo-immunotherapy. Median follow-up was 4 years. As expected, the R-IPI was a significant predictor of outcome with 5-year overall survival (OS) 87% for very good, 87% for good, and 51% for poor-risk R-IPI scores (P < 0.001). Consistent with previous reports, systemic immunity also predicted outcome (86% OS for high lymphocyte to monocyte ratio [LMR], versus 63% with low LMR, P = 0.01). Multivariate analysis confirmed LMR as independently prognostic. Flow cytometry on fresh diagnostic lymphoma tissue, identified CD4+ T-cell infiltration as the most significant predictor of outcome with ≥23% infiltration dividing the cohort into high and low risk groups with regard to event-free survival (EFS, P = 0.007) and OS (P = 0.003). EFS and OS were independent of the R-IPI and LMR. Importantly, within very good/good R-IPI patients, CD4+ T-cells still distinguished patients with different 5 year OS (high 96% versus low 63%, P = 0.02). These results illustrate the importance of circulating and local intratumoral immunity in DLBCL treated with R-CHOP.
Resumo:
We employed a Hidden-Markov-Model (HMM) algorithm in loss of heterozygosity (LOH) analysis of high-density single nucleotide polymorphism (SNP) array data from Non-Hodgkin’s lymphoma (NHL) entities, follicular lymphoma (FL), and diffuse large B-cell lymphoma (DLBCL). This revealed a high frequency of LOH over the chromosomal region 11p11.2, containing the gene encoding the protein tyrosine phosphatase receptor type J (PTPRJ). Although PTPRJ regulates components of key survival pathways in B-cells (i.e., BCR, MAPK, and PI3K signaling), its role in B-cell development is poorly understood. LOH of PTPRJ has been described in several types of cancer but not in any hematological malignancy. Interestingly, FL cases with LOH exhibited down-regulation of PTPRJ, in contrast no significant variation of expression was shown in DLBCLs. In addition, sequence screening in Exons 5 and 13 of PTPRJ identified the G973A (rs2270993), T1054C (rs2270992), A1182C (rs1566734), and G2971C (rs4752904) coding SNPs (cSNPs). The A1182 allele was significantly more frequent in FLs and in NHLs with LOH. Significant over-representation of the C1054 (rs2270992) and the C2971 (rs4752904) alleles were also observed in LOH cases. A haplotype analysis also revealed a significant lower frequency of haplotype GTCG in NHL cases, but it was only detected in cases with retention. Conversely, haplotype GCAC was over-representated in cases with LOH. Altogether, these results indicate that the inactivation of PTPRJ may be a common lymphomagenic mechanism in these NHL subtypes and that haplotypes in PTPRJ gene may play a role in susceptibility to NHL, by affecting activation of PTPRJ in these B-cell lymphomas.
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Recent developments in genomic technologies have resulted in increased understanding of pathogenic mechanisms and emphasized the importance of central survival pathways. Here, we use a novel bioinformatic based integrative genomic profiling approach to elucidate conserved mechanisms of lymphomagenesis in the three commonest non-Hodgkin's lymphoma (NHL) entities: diffuse large B-cell lymphoma, follicular lymphoma, and B-cell chronic lymphocytic leukemia. By integrating genome-wide DNA copy number analysis and transcriptome profiling of tumor cohorts, we identified genetic lesions present in each entity and highlighted their likely target genes. This revealed a significant enrichment of components of both the apoptosis pathway and the mitogen activated protein kinase pathway, including amplification of the MAP3K12 locus in all three entities, within the set of genes targeted by genetic alterations in these diseases. Furthermore, amplification of 12p13.33 was identified in all three entities and found to target the FOXM1 oncogene. Amplification of FOXM1 was subsequently found to be associated with an increased MYC oncogenic signaling signature, and siRNA-mediated knock-down of FOXM1 resulted in decreased MYC expression and induced G2 arrest. Together, these findings underscore genetic alteration of the MAPK and apoptosis pathways, and genetic amplification of FOXM1 as conserved mechanisms of lymphomagenesis in common NHL entities. Integrative genomic profiling identifies common central survival mechanisms and highlights them as attractive targets for directed therapy.
Resumo:
Background Loss of heterozygosity (LOH) is an important marker for one of the 'two-hits' required for tumor suppressor gene inactivation. Traditional methods for mapping LOH regions require the comparison of both tumor and patient-matched normal DNA samples. However, for many archival samples, patient-matched normal DNA is not available leading to the under-utilization of this important resource in LOH studies. Here we describe a new method for LOH analysis that relies on the genome-wide comparison of heterozygosity of single nucleotide polymorphisms (SNPs) between cohorts of cases and un-matched healthy control samples. Regions of LOH are defined by consistent decreases in heterozygosity across a genetic region in the case cohort compared to the control cohort. Methods DNA was collected from 20 Follicular Lymphoma (FL) tumor samples, 20 Diffuse Large B-cell Lymphoma (DLBCL) tumor samples, neoplastic B-cells of 10 B-cell Chronic Lymphocytic Leukemia (B-CLL) patients and Buccal cell samples matched to 4 of these B-CLL patients. The cohort heterozygosity comparison method was developed and validated using LOH derived in a small cohort of B-CLL by traditional comparisons of tumor and normal DNA samples, and compared to the only alternative method for LOH analysis without patient matched controls. LOH candidate regions were then generated for enlarged cohorts of B-CLL, FL and DLBCL samples using our cohort heterozygosity comparison method in order to evaluate potential LOH candidate regions in these non-Hodgkin's lymphoma tumor subtypes. Results Using a small cohort of B-CLL samples with patient-matched normal DNA we have validated the utility of this method and shown that it displays more accuracy and sensitivity in detecting LOH candidate regions compared to the only alternative method, the Hidden Markov Model (HMM) method. Subsequently, using B-CLL, FL and DLBCL tumor samples we have utilised cohort heterozygosity comparisons to localise LOH candidate regions in these subtypes of non-Hodgkin's lymphoma. Detected LOH regions included both previously described regions of LOH as well as novel genomic candidate regions. Conclusions We have proven the efficacy of the use of cohort heterozygosity comparisons for genome-wide mapping of LOH and shown it to be in many ways superior to the HMM method. Additionally, the use of this method to analyse SNP microarray data from 3 common forms of non-Hodgkin's lymphoma yielded interesting tumor suppressor gene candidates, including the ETV3 gene that was highlighted in both B-CLL and FL.
Resumo:
The t(14;18)(q21;q34) BCL2 translocation is a common genetic alteration in follicular and diffuse large B-cell lymphoma. However, it is not invariably associated with BCL2 gene overexpression due to undefined mechanisms that regulate expression from the proximal immunoglobulin heavy-chain (IgH) promoter. The BACH2 transcriptional repressor is able to modulate activity of this promoter. Here we have shown that, in tumor samples with BCL2 translocation, those with high levels of BACH2 had significantly lower BCL2 transcript abundance compared to those with low levels of BACH2. This indicates that BACH2 may be partially responsible for regulation of BCL2 expression from the t(14;18)(q21;q34) translocation.
Resumo:
FOXP1 is a transcriptional repressor that has been proposed to repress the expression of some NFκB-responsive genes. Furthermore, truncated forms of FOXP1 have been associated with a subtype of Diffuse Large B-cell Lymphoma characterised by constitutive NFκB activity, indicating that they may inhibit this repression. We have shown that FL tumors have increased relative abundance of truncated FOXP1 isoforms and this is associated with increased expression of NFκB-associated genes. Our results provide strong evidence that relative FOXP1 isoform abundance is associated with NFκB activity in FL, and could potentially be used as a marker for this gene signature.
Resumo:
Background & aims: - Excess adiposity (overweight) is one of numerous risk factors for cardiometabolic disease. Most risk reduction strategies for overweight rely on weight loss through dietary energy restriction. However, since the evidence base for long-term successful weight loss interventions is scant, it is important to identify strategies for risk reduction independent of weight loss. The aim of this study was to compare the effects of isoenergetic substitution of dietary saturated fat (SFA) with monounsaturated fat (MUFA) via macadamia nuts on coronary risk compared to usual diet in overweight adults. Methods: - A randomised controlled trial design, maintaining usual energy intake, but manipulating dietary lipid profile in a group of 64 (54 female, 10 male) overweight (BMI > 25), otherwise healthy, subjects. For the intervention group, energy intakes of usual (baseline) diets were calculated from multiple 3 day diet diaries, and SFA was replaced with MUFA (target: 50%E from fat as MUFA) by altering dietary SFA sources and adding macadamia nuts to the diet. Both control and intervention groups received advice on national guidelines for physical activity and adhered to the same protocol for diet diary record keeping and trial consultations. Anthropometric and clinical measures were taken at baseline and at 10 weeks. Results: A significant increase in brachial artery flow-mediated dilation (p < 0.05) was seen in the monounsaturated diet group at week 10 compared to baseline. This corresponded to significant decreases in waist circumference, total cholesterol (p < 0.05), plasma leptin and ICAM-1 (p < 0.01). Conclusions: - In patient subgroups where adherence to dietary energy-reduction is poor, isoenergetic interventions may improve endothelial function and other coronary risk factors without changes in body weight. This trial was registered with the Australia New Zealand Clinical Trial Registry (ACTRN12607000106437).
Resumo:
PURPOSE Current research on errors in health care focuses almost exclusively on system and clinician error. It tends to exclude how patients may create errors that influence their health. We aimed to identify the types of errors that patients can contribute and help manage, especially in primary care. METHODS Eleven nominal group interviews of patients and primary health care professionals were held in Auckland, New Zealand, during late 2007. Group members reported and helped to classify types of potential error by patients. We synthesized the ideas that emerged from the nominal groups into a taxonomy of patient error. RESULTS Our taxonomy is a 3-level system encompassing 70 potential types of patient error. The first level classifies 8 categories of error into 2 main groups: action errors and mental errors. The action errors, which result in part or whole from patient behavior, are attendance errors, assertion errors, and adherence errors. The mental errors, which are errors in patient thought processes, comprise memory errors, mindfulness errors, misjudgments, and—more distally—knowledge deficits and attitudes not conducive to health. CONCLUSION The taxonomy is an early attempt to understand and recognize how patients may err and what clinicians should aim to influence so they can help patients act safely. This approach begins to balance perspectives on error but requires further research. There is a need to move beyond seeing patient, clinician, and system errors as separate categories of error. An important next step may be research that attempts to understand how patients, clinicians, and systems interact to cocreate and reduce errors.
Resumo:
The effectiveness of structural elements employed for stormwater mitigation such as bioretention basins and constructed wetlands depend on the compatibility between their design specifications and actual stormwater quality and quantity characteristics. These structural elements are commonly designed to accommodate the initial portion of runoff considering the occurrence of first flush. Therefore, the effectiveness of stormwater quality treatment primarily depends on the in-depth knowledge of the first flush phenomenon and the ability to provide appropriate treatment. The current scientific knowledge relating to first flush is limited primarily due to research investigations being undertaken based on lumped rainfall and runoff parameters. This paper presents the outcomes of an in-depth study undertaken of the first flush phenomenon using a set of indicators which are not only innovative, but is also able to accurately represent the characteristics of the different sectors in a runoff hydrograph. The analysis undertaken confirmed that pollutant wash-off during the initial 10% of runoff volume was critical for the occurrence of first flush. Typically first flush was found to last up to 40% of the runoff volume. The study outcomes provide new knowledge to enhance the effectiveness of structural stormwater treatment measures.
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The current approach for protecting the receiving water environment from urban stormwater pollution is the adoption of structural measures commonly referred to as Water Sensitive Urban Design (WSUD). The treatment efficiency of WSUD measures closely depends on the design of the specific treatment units. As stormwater quality can be influenced by rainfall characteristics, the selection of appropriate rainfall events for treatment design is essential to ensure the effectiveness of WSUD systems. Based on extensive field investigation of four urban residential catchments and computer modelling, this paper details a technically robust approach for the selection of rainfall events for stormwater treatment design using a three-component model. The modelling outcomes indicate that selecting smaller average recurrence interval (ARI) events with high intensity-short duration as the threshold for the treatment system design is the most feasible since these events cumulatively generate a major portion of the annual pollutant load compared to the other types of rainfall events, despite producing a relatively smaller runoff volume. This implies that designs based on small and more frequent rainfall events rather than larger rainfall events would be appropriate in the context of efficiency in treatment performance, cost-effectiveness and possible savings in land area needed.
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Residential balcony design influences speech interference levels caused by road traffic noise and a simplified design methodology is needed for optimising balcony acoustic treatments. This research comprehensively assesses speech interference levels and benefits of nine different balcony designs situated in urban street canyons through the use of a combined direct, specular reflection and diffuse reflection path theoretical model. This thesis outlines the theory, analysis and results that lead up to the presentation of a practical design guide which can be used to predict the acoustic effects of balcony geometry and acoustic treatments in streets with variable geometry and acoustic characteristics.
Resumo:
Non-periodic structural variation has been found in the high Tc cuprates, YBa2Cu3O7-x and Hg0.67Pb0.33Ba2Ca2Cu 3O8+δ, by image analysis of high resolution transmission electron microscope (HRTEM) images. We use two methods for analysis of the HRTEM images. The first method is a means for measuring the bending of lattice fringes at twin planes. The second method is a low-pass filter technique which enhances information contained by diffuse-scattered electrons and reveals what appears to be an interference effect between domains of differing lattice parameter in the top and bottom of the thin foil. We believe that these methods of image analysis could be usefully applied to the many thousands of HRTEM images that have been collected by other workers in the high temperature superconductor field. This work provides direct structural evidence for phase separation in high Tc cuprates, and gives support to recent stripes models that have been proposed to explain various angle resolved photoelectron spectroscopy and nuclear magnetic resonance data. We believe that the structural variation is a response to an opening of an electronic solubility gap where holes are not uniformly distributed in the material but are confined to metallic stripes. Optimum doping may occur as a consequence of the diffuse boundaries between stripes which arise from spinodal decomposition. Theoretical ideas about the high Tc cuprates which treat the cuprates as homogeneous may need to be modified in order to take account of this type of structural variation.