Estimating the effects of environmental exposures using a weighted mean of monitoring stations

The health effects of environmental hazards are often examined using time series of the association between a daily response variable (e.g., death) and a daily level of exposure (e.g., temperature). Exposures are usually the average from a network of stations. This gives each station equal importance, and negates the opportunity for some stations to be better measures of exposure. We used a Bayesian hierarchical model that weighted stations using random variables between zero and one. We compared the weighted estimates to the standard model using data on health outcomes (deaths and hospital admissions) and exposures (air pollution and temperature) in Brisbane, Australia. The improvements in model fit were relatively small, and the estimated health effects of pollution were similar using either the standard or weighted estimates. Spatial weighted exposures would be probably more worthwhile when there is either greater spatial detail in the health outcome, or a greater spatial variation in exposure.

From slum to suburbia : examining a spectrum of planned and unplanned urban morphology in humid sub-tropical regions of the world

The current rapid urban growth throughout the world manifests in various ways and historically cities have grown, similarly, alternately or simultaneously between planned extensions and organic informal settlements (Mumford, 1989). Within cities different urban morphological regions can reveal different contexts of economic growth and/or periods of dramatic social/technological change (Whitehand, 2001, 105). Morpho-typological study of alternate contexts can present alternative models and contribute to the present discourse which questions traditional paradigms of urban planning and design (Todes et al, 2010). In this study a series of cities are examined as a preliminary exploration into the urban morphology of cities in ‘humid subtropical’ climates. From an initial set of twenty, six cities were selected: Sao Paulo, Brazil; Jacksonville, USA; Maputo, Mozambique; Kanpur, India; Hong Kong, China; and Brisbane, Australia. The urban form was analysed from satellite imagery at a constant scale. Urban morphological regions (types) were identified as those demonstrating particular consistant characteristics of form (density, typology and pattern) different to their surroundings when examined at a constant scale. This analysis was correlated against existing data and literature discussing the proliferation of two types of urban development, ‘informal settlement’ (defined here as self-organised communities identifiable but not always synonymous with ‘slums’) and ‘suburbia’ (defined here as master planned communities of generally detached houses prevalent in western society) - the extreme ends of a hypothetical spectrum from ‘planned’ to ‘spontaneous’ urban development. Preliminary results show some cities contain a wide variety of urban form ranging from the highly organic ‘self-organised’ type to the highly planned ‘master planned community’ (in the case of Sao Paulo) while others tend to fall at one end of the planning spectrum or the other (more planned in the cases of Brisbane and Jacksonville; and both highly planned and highly organic in the case of Maputo). Further research will examine the social, economical and political drivers and controls which lead to this diversity or homogeneity of urban form and speculates on the role of self-organisation as a process for the adaptation of urban form.

Prognostic significance of IGF and ECM induced signalling proteins in breast cancer patients

Breast cancer is a leading contributor to the burden of disease in Australia. Fortunately, the recent introduction of diverse therapeutic strategies have improved the survival outcome for many women. Despite this, the clinical management of breast cancer remains problematic as not all approaches are sufficiently sophisticated to take into account the heterogeneity of this disease and are unable to predict disease progression, in particular, metastasis. As such, women with good prognostic outcomes are exposed to the side effects of therapies without added benefit. Furthermore, women with aggressive disease for whom these advanced treatments would deliver benefit cannot be distinguished and opportunities for more intensive or novel treatment are lost. This study is designed to identify novel factors associated with disease progression, and the potential to inform disease prognosis. Frequently overlooked, yet common mediators of disease are the interactions that take place between the insulin-like growth factor (IGF) system and the extracellular matrix (ECM). Our laboratory has previously demonstrated that multiprotein insulin-like growth factor-I (IGF-I): insulin-like growth factor binding protein (IGFBP): vitronectin (VN) complexes stimulate migration of breast cancer cells in vitro, via the cooperative involvement of the insulin-like growth factor type I receptor (IGF-IR) and VN-binding integrins. However, the effects of IGF and ECM protein interactions on the dissemination and progression of breast cancer in vivo are unknown. It was hypothesised that interactions between proteins required for IGF induced signalling events and those within the ECM contribute to breast cancer metastasis and are prognostic and predictive indicators of patient outcome. To address this hypothesis, semiquantitative immunohistochemistry (IHC) analyses were performed to compare the extracellular and subcellular distribution of IGF and ECM induced signalling proteins between matched normal, primary cancer, and metastatic cancer among archival formalin-fixed paraffin-embedded (FFPE) breast tissue samples collected from women attending the Princess Alexandra Hospital, Brisbane. Multivariate Cox proportional hazards (PH) regression survival models in conjunction with a modified „purposeful selection of covariates. method were applied to determine the prognostic potential of these proteins. This study provides the first in-depth, compartmentalised analysis of the distribution of IGF and ECM induced signalling proteins. As protein function and protein localisation are closely correlated, these findings provide novel insights into IGF signalling and ECM protein function during breast cancer development and progression. Distinct IGF signalling and ECM protein immunoreactivity was observed in the stroma and/or in subcellular locations in normal breast, primary cancer and metastatic cancer tissues. Analysis of the presence and location of stratifin (SFN) suggested a causal relationship in ECM remodelling events during breast cancer development and progression. The results of this study have also suggested that fibronectin (FN) and ¥â1 integrin are important for the formation of invadopodia and epithelial-to-mesenchymal transition (EMT) events. Our data also highlighted the importance of the temporal and spatial distribution of IGF induced signalling proteins in breast cancer metastasis; in particular, SFN, enhancer-of-split and hairy-related protein 2 (SHARP-2), total-akt/protein kinase B 1 (Total-AKT1), phosphorylated-akt/protein kinase B (P-AKT), extracellular signal-related kinase-1 and extracellular signal-related kinase-2 (ERK1/2) and phosphorylated-extracellular signal-related kinase-1 and extracellular signal-related kinase-2 (P-ERK1/2). Multivariate survival models were created from the immunohistochemical data. These models were found to fit well with these data with very high statistical confidence. Numerous prognostic confounding effects and effect modifications were identified among elements of the ECM and IGF signalling cascade and corroborate the survival models. This finding provides further evidence for the prognostic potential of IGF and ECM induced signalling proteins. In addition, the adjusted measures of associations obtained in this study have strengthened the validity and utility of the resulting models. The findings from this study provide insights into the biological interactions that occur during the development of breast tissue and contribute to disease progression. Importantly, these multivariate survival models could provide important prognostic and predictive indicators that assist the clinical management of breast disease, namely in the early identification of cancers with a propensity to metastasise, and/or recur following adjuvant therapy. The outcomes of this study further inform the development of new therapeutics to aid patient recovery. The findings from this study have widespread clinical application in the diagnosis of disease and prognosis of disease progression, and inform the most appropriate clinical management of individuals with breast cancer.

Semantic judgement of medical concepts : combining syntagmatic and paradigmatic information with the tensor encoding model

This paper outlines a novel approach for modelling semantic relationships within medical documents. Medical terminologies contain a rich source of semantic information critical to a number of techniques in medical informatics, including medical information retrieval. Recent research suggests that corpus-driven approaches are effective at automatically capturing semantic similarities between medical concepts, thus making them an attractive option for accessing semantic information. Most previous corpus-driven methods only considered syntagmatic associations. In this paper, we adapt a recent approach that explicitly models both syntagmatic and paradigmatic associations. We show that the implicit similarity between certain medical concepts can only be modelled using paradigmatic associations. In addition, the inclusion of both types of associations overcomes the sensitivity to the training corpus experienced by previous approaches, making our method both more effective and more robust. This finding may have implications for researchers in the area of medical information retrieval.

Association between ambient ultraviolet radiation and risk of esophageal cancer

OBJECTIVES: Ecological studies have suggested an inverse relationship between latitude and risks of some cancers. However, associations between solar ultraviolet radiation (UVR) exposure and esophageal cancer risk have not been fully explored. We therefore investigated the association between nevi, freckles, and measures of ambient UVR over the life-course with risks of esophageal cancers. METHODS: We compared estimated lifetime residential ambient UVR among Australian patients with esophageal cancer (330 esophageal adenocarcinoma (EAC), 386 esophago-gastric junction adenocarcinoma (EGJAC), and 279 esophageal squamous cell carcinoma (ESCC)), and 1471 population controls. We asked people where they had lived at different periods of their life, and assigned ambient UVR to each location based on measurements from NASA's Total Ozone Mapping Spectrometer database. Freckling and nevus burden were self-reported. We used multivariable logistic regression models to estimate the magnitude of associations between phenotype, ambient UVR, and esophageal cancer risk. RESULTS: Compared with population controls, patients with EAC and EGJAC were less likely to have high levels of estimated cumulative lifetime ambient UVR (EAC odds ratio (OR) 0.59, 95% confidence interval (CI) 0.35-0.99, EGJAC OR 0.55, 0.34-0.90). We found no association between UVR and risk of ESCC (OR 0.91, 0.51-1.64). The associations were independent of age, sex, body mass index, education, state of recruitment, frequency of reflux, smoking status, alcohol consumption, and H. pylori serostatus. Cases with EAC were also significantly less likely to report high levels of nevi than controls. CONCLUSIONS: These data show an inverse association between ambient solar UVR at residential locations and risk of EAC and EGJAC, but not ESCC.

How activation, entanglement, and searching a semantic network contribute to event memory

Free association norms indicate that words are organized into semantic/associative neighborhoods within a larger network of words and links that bind the net together. We present evidence indicating that memory for a recent word event can depend on implicitly and simultaneously activating related words in its neighborhood. Processing a word during encoding primes its network representation as a function of the density of the links in its neighborhood. Such priming increases recall and recognition and can have long lasting effects when the word is processed in working memory. Evidence for this phenomenon is reviewed in extralist cuing, primed free association, intralist cuing, and single-item recognition tasks. The findings also show that when a related word is presented to cue the recall of a studied word, the cue activates it in an array of related words that distract and reduce the probability of its selection. The activation of the semantic network produces priming benefits during encoding and search costs during retrieval. In extralist cuing recall is a negative function of cue-to-distracter strength and a positive function of neighborhood density, cue-to-target strength, and target-to cue strength. We show how four measures derived from the network can be combined and used to predict memory performance. These measures play different roles in different tasks indicating that the contribution of the semantic network varies with the context provided by the task. We evaluate spreading activation and quantum-like entanglement explanations for the priming effect produced by neighborhood density.

Feasibility of agent-based modelling of articular cartilage including a conceptual representation of its structure

Articular cartilage is a complex structure with an architecture in which fluid-swollen proteoglycans constrained within a 3D network of collagen fibrils. Because of the complexity of the cartilage structure, the relationship between its mechanical behaviours at the macroscale level and its components at the micro-scale level are not completely understood. The research objective in this thesis is to create a new model of articular cartilage that can be used to simulate and obtain insight into the micro-macro-interaction and mechanisms underlying its mechanical responses during physiological function. The new model of articular cartilage has two characteristics, namely: i) not use fibre-reinforced composite material idealization ii) Provide a framework for that it does probing the micro mechanism of the fluid-solid interaction underlying the deformation of articular cartilage using simple rules of repartition instead of constitutive / physical laws and intuitive curve-fitting. Even though there are various microstructural and mechanical behaviours that can be studied, the scope of this thesis is limited to osmotic pressure formation and distribution and their influence on cartilage fluid diffusion and percolation, which in turn governs the deformation of the compression-loaded tissue. The study can be divided into two stages. In the first stage, the distributions and concentrations of proteoglycans, collagen and water were investigated using histological protocols. Based on this, the structure of cartilage was conceptualised as microscopic osmotic units that consist of these constituents that were distributed according to histological results. These units were repeated three-dimensionally to form the structural model of articular cartilage. In the second stage, cellular automata were incorporated into the resulting matrix (lattice) to simulate the osmotic pressure of the fluid and the movement of water within and out of the matrix; following the osmotic pressure gradient in accordance with the chosen rule of repartition of the pressure. The outcome of this study is the new model of articular cartilage that can be used to simulate and study the micromechanical behaviours of cartilage under different conditions of health and loading. These behaviours are illuminated at the microscale level using the socalled neighbourhood rules developed in the thesis in accordance with the typical requirements of cellular automata modelling. Using these rules and relevant Boundary Conditions to simulate pressure distribution and related fluid motion produced significant results that provided the following insight into the relationships between osmotic pressure gradient and associated fluid micromovement, and the deformation of the matrix. For example, it could be concluded that: 1. It is possible to model articular cartilage with the agent-based model of cellular automata and the Margolus neighbourhood rule. 2. The concept of 3D inter connected osmotic units is a viable structural model for the extracellular matrix of articular cartilage. 3. Different rules of osmotic pressure advection lead to different patterns of deformation in the cartilage matrix, enabling an insight into how this micromechanism influences macromechanical deformation. 4. When features such as transition coefficient were changed, permeability (representing change) is altered due to the change in concentrations of collagen, proteoglycans (i.e. degenerative conditions), the deformation process is impacted. 5. The boundary conditions also influence the relationship between osmotic pressure gradient and fluid movement at the micro-scale level. The outcomes are important to cartilage research since we can use these to study the microscale damage in the cartilage matrix. From this, we are able to monitor related diseases and their progression leading to potential insight into drug-cartilage interaction for treatment. This innovative model is an incremental progress on attempts at creating further computational modelling approaches to cartilage research and other fluid-saturated tissues and material systems.

Investigation into the noise map based on traffic flow prediction in the citywide road network

As one of the measures for decreasing road traffic noise in a city, the control of the traffic flow and the physical distribution is considered. To conduct the measure effectively, the model for predicting the traffic flow in the citywide road network is necessary. In this study, the existing model named AVENUE was used as a traffic flow prediction model. The traffic flow model was integrated with the road vehicles' sound power model and the sound propagation model, and the new road traffic noise prediction model was established. As a case study, the prediction model was applied to the road network of Tsukuba city in Japan and the noise map of the city was made. To examine the calculation accuracy of the noise map, the calculated values of the noise at the main roads were compared with the measured values. As a result, it was found that there was a possibility that the high accuracy noise map of the city could be made by using the noise prediction model developed in this study.

Classification of railway bridges based on criticality and vulnerability factors

Bridges are currently rated individually for maintenance and repair action according to the structural conditions of their elements. Dealing with thousands of bridges and the many factors that cause deterioration, makes this rating process extremely complicated. The current simplified but practical methods are not accurate enough. On the other hand, the sophisticated, more accurate methods are only used for a single or particular bridge type. It is therefore necessary to develop a practical and accurate rating system for a network of bridges. The first most important step in achieving this aim is to classify bridges based on the differences in nature and the unique characteristics of the critical factors and the relationship between them, for a network of bridges. Critical factors and vulnerable elements will be identified and placed in different categories. This classification method will be used to develop a new practical rating method for a network of railway bridges based on criticality and vulnerability analysis. This rating system will be more accurate and economical as well as improve the safety and serviceability of railway bridges.

Estimating the effects of ambient temperature on mortality : methodological challenges and proposed solutions

The health impacts of exposure to ambient temperature have been drawing increasing attention from the environmental health research community, government, society, industries, and the public. Case-crossover and time series models are most commonly used to examine the effects of ambient temperature on mortality. However, some key methodological issues remain to be addressed. For example, few studies have used spatiotemporal models to assess the effects of spatial temperatures on mortality. Few studies have used a case-crossover design to examine the delayed (distributed lag) and non-linear relationship between temperature and mortality. Also, little evidence is available on the effects of temperature changes on mortality, and on differences in heat-related mortality over time. This thesis aimed to address the following research questions: 1. How to combine case-crossover design and distributed lag non-linear models? 2. Is there any significant difference in effect estimates between time series and spatiotemporal models? 3. How to assess the effects of temperature changes between neighbouring days on mortality? 4. Is there any change in temperature effects on mortality over time? To combine the case-crossover design and distributed lag non-linear model, datasets including deaths, and weather conditions (minimum temperature, mean temperature, maximum temperature, and relative humidity), and air pollution were acquired from Tianjin China, for the years 2005 to 2007. I demonstrated how to combine the case-crossover design with a distributed lag non-linear model. This allows the case-crossover design to estimate the non-linear and delayed effects of temperature whilst controlling for seasonality. There was consistent U-shaped relationship between temperature and mortality. Cold effects were delayed by 3 days, and persisted for 10 days. Hot effects were acute and lasted for three days, and were followed by mortality displacement for non-accidental, cardiopulmonary, and cardiovascular deaths. Mean temperature was a better predictor of mortality (based on model fit) than maximum or minimum temperature. It is still unclear whether spatiotemporal models using spatial temperature exposure produce better estimates of mortality risk compared with time series models that use a single site’s temperature or averaged temperature from a network of sites. Daily mortality data were obtained from 163 locations across Brisbane city, Australia from 2000 to 2004. Ordinary kriging was used to interpolate spatial temperatures across the city based on 19 monitoring sites. A spatiotemporal model was used to examine the impact of spatial temperature on mortality. A time series model was used to assess the effects of single site’s temperature, and averaged temperature from 3 monitoring sites on mortality. Squared Pearson scaled residuals were used to check the model fit. The results of this study show that even though spatiotemporal models gave a better model fit than time series models, spatiotemporal and time series models gave similar effect estimates. Time series analyses using temperature recorded from a single monitoring site or average temperature of multiple sites were equally good at estimating the association between temperature and mortality as compared with a spatiotemporal model. A time series Poisson regression model was used to estimate the association between temperature change and mortality in summer in Brisbane, Australia during 1996–2004 and Los Angeles, United States during 1987–2000. Temperature change was calculated by the current day's mean temperature minus the previous day's mean. In Brisbane, a drop of more than 3 �C in temperature between days was associated with relative risks (RRs) of 1.16 (95% confidence interval (CI): 1.02, 1.31) for non-external mortality (NEM), 1.19 (95% CI: 1.00, 1.41) for NEM in females, and 1.44 (95% CI: 1.10, 1.89) for NEM aged 65.74 years. An increase of more than 3 �C was associated with RRs of 1.35 (95% CI: 1.03, 1.77) for cardiovascular mortality and 1.67 (95% CI: 1.15, 2.43) for people aged < 65 years. In Los Angeles, only a drop of more than 3 �C was significantly associated with RRs of 1.13 (95% CI: 1.05, 1.22) for total NEM, 1.25 (95% CI: 1.13, 1.39) for cardiovascular mortality, and 1.25 (95% CI: 1.14, 1.39) for people aged . 75 years. In both cities, there were joint effects of temperature change and mean temperature on NEM. A change in temperature of more than 3 �C, whether positive or negative, has an adverse impact on mortality even after controlling for mean temperature. I examined the variation in the effects of high temperatures on elderly mortality (age . 75 years) by year, city and region for 83 large US cities between 1987 and 2000. High temperature days were defined as two or more consecutive days with temperatures above the 90th percentile for each city during each warm season (May 1 to September 30). The mortality risk for high temperatures was decomposed into: a "main effect" due to high temperatures using a distributed lag non-linear function, and an "added effect" due to consecutive high temperature days. I pooled yearly effects across regions and overall effects at both regional and national levels. The effects of high temperature (both main and added effects) on elderly mortality varied greatly by year, city and region. The years with higher heat-related mortality were often followed by those with relatively lower mortality. Understanding this variability in the effects of high temperatures is important for the development of heat-warning systems. In conclusion, this thesis makes contribution in several aspects. Case-crossover design was combined with distribute lag non-linear model to assess the effects of temperature on mortality in Tianjin. This makes the case-crossover design flexibly estimate the non-linear and delayed effects of temperature. Both extreme cold and high temperatures increased the risk of mortality in Tianjin. Time series model using single site’s temperature or averaged temperature from some sites can be used to examine the effects of temperature on mortality. Temperature change (no matter significant temperature drop or great temperature increase) increases the risk of mortality. The high temperature effect on mortality is highly variable from year to year.

A study of postdiagnosis breast cancer concerns for women living in rural and remote Queensland. Part II : support issues

This paper presents the recent findings from a study on the postdiagnosis support needs of women with breast cancer living in rural and remote Queensland. The findings presented in this discussion focus on support needs from the perspective of the women experiencing breast cancer as well as health service providers. The tyranny of distance imposes unique hardships, such as separation from family and friends, during a time of great vulnerability for treatment, the need to travel long distances for support and follow-up services, and extra financial burdens, which can combine to cause strains on the marital relationship and family cohesion. Positive indications are, however, that the rural communities operate on strong, informal networks of support. This network of family, friends and community can, and does, play an active role in the provision of emotional and practical support.

The challenges of managing complexity in projects : an Australian perspective

Project Management (PM) as an academic field is relatively new in Australian universities. Moreover, the field is distributed across four main areas: business (management), built environment and construction, engineering and more recently ICT (information systems). At an institutional level, with notable exceptions, there is little engagement between researchers working in those individual areas. Consequently, an initiative was launched in 2009 to create a network of PM researchers to build a disciplinary base for PM in Australia. The initiative took the form of a bi-annual forum. The first forum established the constituency and spread of PM research in Australia (Sense et al., 2011). This special issue of IJPM arose out of the second forum, held in 2012, that explored the notion of an Australian perspective on PM. At the forum, researchers were invited to collaborate to explore issues, methodological approaches, and theoretical positions underpinning their research and to answer the question: is there a distinctly Australian research agenda which responds to the current challenges of large and complex projects in our region? From a research point of view, it was abundantly clear at the forum that many of the issues facing Australian researchers are shared around the world. However, what emerged from the forum as the Australian perspective was a set of themes and research issues that dominate the Australia research agenda.

Spatiotemporal model or time series model for assessing city-wide temperature effects on mortality?

Most studies examining the temperature–mortality association in a city used temperatures from one site or the average from a network of sites. This may cause measurement error as temperature varies across a city due to effects such as urban heat islands. We examined whether spatiotemporal models using spatially resolved temperatures produced different associations between temperature and mortality compared with time series models that used non-spatial temperatures. We obtained daily mortality data in 163 areas across Brisbane city, Australia from 2000 to 2004. We used ordinary kriging to interpolate spatial temperature variation across the city based on 19 monitoring sites. We used a spatiotemporal model to examine the impact of spatially resolved temperatures on mortality. Also, we used a time series model to examine non-spatial temperatures using a single site and the average temperature from three sites. We used squared Pearson scaled residuals to compare model fit. We found that kriged temperatures were consistent with observed temperatures. Spatiotemporal models using kriged temperature data yielded slightly better model fit than time series models using a single site or the average of three sites' data. Despite this better fit, spatiotemporal and time series models produced similar associations between temperature and mortality. In conclusion, time series models using non-spatial temperatures were equally good at estimating the city-wide association between temperature and mortality as spatiotemporal models.

Planning for sustainability of non motorised public transport in a developing city

Most large cities around the world are undergoing rapid transport sector development to cater for increased urbanization. Subsequently the issues of mobility, access equity, congestion, operational safety and above all environmental sustainability are becoming increasingly crucial in transport planning and policy making. The popular response in addressing these issues has been demand management, through improvement of motorised public transport (MPT) modes (bus, train, tram) and non-motorized transport (NMT) modes (walk, bicycle); improved fuel technology. Relatively little attention has however been given to another readily available and highly sustainable component of the urban transport system, non-motorized public transport (NMPT) such as the pedicab that operates on a commercial basis and serves as an NMT taxi; and has long standing history in many Asian cities; relatively stable in existence in Latin America; and reemerging and expanding in Europe, North America and Australia. Consensus at policy level on the apparent benefits, costs and management approach for NMPT integration has often been a major transport planning problem. Within this context, this research attempts to provide a more complete analysis of the current existence rationale and possible future, or otherwise, of NMPT as a regular public transport system. The analytical process is divided into three major stages. Stage 1 reviews the status and role condition of NMPT as regular public transport on a global scale- in developing cities and developed cities. The review establishes the strong ongoing and future potential role of NMPT in major developing cities. Stage 2 narrows down the status review to a case study city of a developing country in order to facilitate deeper role review and status analysis of the mode. Dhaka, capital city of Bangladesh, has been chosen due to its magnitude of NMPT presence. The review and analysis reveals the multisectoral and dominant role of NMPT in catering for the travel need of Dhaka transport users. The review also indicates ad-hoc, disintegrated policy planning in management of NMPT and the need for a planning framework to facilitate balanced integration between NMPT and MT in future. Stage 3 develops an integrated, multimodal planning framework (IMPF), based on a four-step planning process. This includes defining the purpose and scope of the planning exercise, determining current deficiencies and preferred characteristics for the proposed IMPF, selection of suitable techniques to address the deficiencies and needs of the transport network while laying out the IMPF and finally, development of a delivery plan for the IMPF based on a selected layout technique and integration approach. The output of the exercise is a planning instrument (decision tool) that can be used to assign a road hierarchy in order to allocate appropriate traffic to appropriate network type, particularly to facilitate the operational balance between MT and NMT. The instrument is based on a partial restriction approach of motorised transport (MT) and NMT, structured on the notion of functional hierarchy approach, and distributes/prioritises MT and NMT such that functional needs of the network category is best complemented. The planning instrument based on these processes and principles offers a six-level road hierarchy with a different composition of network-governing attributes and modal priority, for the current Dhaka transport network, in order to facilitate efficient integration of NMT with MT. A case study application of the instrument on a small transport network of Dhaka also demonstrates the utility, flexibility and adoptability of the instrument in logically allocating corridors with particular positions in the road hierarchy paradigm. Although the tool is useful in enabling balanced distribution of NMPT with MT at different network levels, further investigation is required with reference to detailed modal variations, scales and locations of a network to further generalise the framework application.

A transcription factor map as revealed by a genome-wide gene expression analysis of whole-blood mRNA transcriptome in multiple sclerosis

Background Several lines of evidence suggests that transcription factors are involved in the pathogenesis of Multiple Sclerosis (MS) but a complete mapping the whole network has been elusive. One of the reasons is that there are several clinical subtypes of MS and transcription factors which may be involved in one subtype may not be in others. We investigated the possibility that this network could be mapped using microarray technologies and modern bioinformatics methods on a dataset from whole blood in 99 untreated MS patients (36 Relapse Remitting MS, 43 Primary Progressive MS, and 20 Secondary Progressive MS) and 45 age-matched healthy controls, Methodology/Principal Findings We have used two different analytical methodologies: a differential expression analysis and a differential co-expression analysis, which have converged on a significant number of regulatory motifs that seem to be statistically overrepresented in genes which are either differentially expressed (or differentially co-expressed) in cases and controls (e.g. V$KROX_Q6, p-value < 3.31E-6; V$CREBP1_Q2, p-value < 9.93E-6, V$YY1_02, p-value < 1.65E-5). Conclusions/significance: Our analysis uncovered a network of transcription factors that potentially dysregulate several genes in MS or one or more of its disease subtypes. Analysing the published literature we have found that these transcription factors are involved in the early T-lymphocyte specification and commitment as well as in oligodendrocytes dedifferentiation and development. The most significant transcription factors motifs were for the Early Growth response EGR/KROX family, ATF2, YY1 (Yin and Yang 1), E2F-1/DP-1 and E2F-4/DP-2 heterodimers, SOX5, and CREB and ATF families.