Assessing health risk associated with airborne polycyclic aromatic hydrocarbons by chemometrics and toxic equivalency factors

Some polycyclic aromatic hydrocarbons (PAHs) are ubiquitous in air and have been implicated as carcinogenic materials. Therefore, literature is replete with studies that are focused on their occurrence and profiles in indoor and outdoor air samples. However, because the relative potency of individual PAHs vary widely, health risks associated with the presence of PAHs in a particular environment cannot be extrapolated directly from the concentrations of individual PAHs in that environment. In addition, database on the potency of PAH mixtures is currently limited. In this paper, we have utilized multi-criteria decision making methods (MCDMs) to simultaneously correlate PAH-related health risk in some microenvironments to the concentration levels, ethoxyresorufin-O-deethylase (EROD) activity induction equivalency factors and toxic equivalency factors (TEFs) of PAHs found in those microenvironments. The results showed that the relative risk associated with PAHs in different air samples depends on the index used. Nevertheless, this approach offers a promising tool that could help identify microenvironments of concern and assist the prioritisation of control strategies.

A model for assessing and correcting construction project health

Abstract Maintaining the health of a construction project can help to achieve the desired outcomes of the project. An analogy is drawn to the medical process of a human health check where it is possible to broadly diagnose health in terms of a number of key areas such as blood pressure or cholesterol level. Similarly it appears possible to diagnose the current health of a construction project in terms of a number of Critical Success Factors (CSFs) and key performance indicators (KPIs). The medical analogy continues into the detailed investigation phase where a number of contributing factors are evaluated to identify possible causes of ill health and through the identification of potential remedies to return the project to the desired level of health. This paper presents the development of a model that diagnoses the immediate health of a construction project, investigates the factors which appear to be causing the ill health and proposes a remedy to return the project to good health. The proposed model uses the well-established continuous improvement management model (Deming, 1986) to adapt the process of human physical health checking to construction project health.

Membrane associated transporter protein gene (SLC45A2) and the genetic basis of normal human pigmentation variation

This work is concerned with the genetic basis of normal human pigmentation variation. Specifically, the role of polymorphisms within the solute carrier family 45 member 2 (SLC45A2 or membrane associated transporter protein; MATP) gene were investigated with respect to variation in hair, skin and eye colour ― both between and within populations. SLC45A2 is an important regulator of melanin production and mutations in the gene underly the most recently identified form of oculocutaneous albinism. There is evidence to suggest that non-synonymous polymorphisms in SLC45A2 are associated with normal pigmentation variation between populations. Therefore, the underlying hypothesis of this thesis is that polymorphisms in SLC45A2 will alter the function or regulation of the protein, thereby altering the important role it plays in melanogenesis and providing a mechanism for normal pigmentation variation. In order to investigate the role that SLC45A2 polymorphisms play in human pigmentation variation, a DNA database was established which collected pigmentation phenotypic information and blood samples of more than 700 individuals. This database was used as the foundation for two association studies outlined in this thesis, the first of which involved genotyping two previously-described non-synonymous polymorphisms, p.Glu272Lys and p.Phe374Leu, in four different population groups. For both polymorphisms, allele frequencies were significantly different between population groups and the 272Lys and 374Leu alleles were strongly associated with black hair, brown eyes and olive skin colour in Caucasians. This was the first report to show that SLC45A2 polymorphisms were associated with normal human intra-population pigmentation variation. The second association study involved genotyping several SLC45A2 promoter polymorphisms to determine if they also played a role in pigmentation variation. Firstly, the transcription start site (TSS), and hence putative proximal promoter region, was identified using 5' RNA ligase mediated rapid amplification of cDNA ends (RLM-RACE). Two alternate TSSs were identified and the putative promoter region was screened for novel polymorphisms using denaturing high performance liquid chromatography (dHPLC). A novel duplication (c.–1176_–1174dupAAT) was identified along with other previously described single nucleotide polymorphisms (c.–1721C>G and c.–1169G>A). Strong linkage disequilibrium ensured that all three polymorphisms were associated with skin colour such that the –1721G, +dup and –1169A alleles were associated with olive skin in Caucasians. No linkage disequilibrium was observed between the promoter and coding region polymorphisms, suggesting independent effects. The association analyses were complemented with functional data, showing that the –1721G, +dup and –1169A alleles significantly decreased SLC45A2 transcriptional activity. Based on in silico bioinformatic analysis that showed these alleles remove a microphthalmia-associated transcription factor (MITF) binding site, and that MITF is a known regulator of SLC45A2 (Baxter and Pavan, 2002; Du and Fisher, 2002), it was postulated that SLC45A2 promoter polymorphisms could contribute to the regulation of pigmentation by altering MITF binding affinity. Further characterisation of the SLC45A2 promoter was carried out using luciferase reporter assays to determine the transcriptional activity of different regions of the promoter. Five constructs were designed of increasing length and their promoter activity evaluated. Constitutive promoter activity was observed within the first ~200 bp and promoter activity increased as the construct size increased. The functional impact of the –1721G, +dup and –1169A alleles, which removed a MITF consensus binding site, were assessed using electrophoretic mobility shift assays (EMSA) and expression analysis of genotyped melanoblast and melanocyte cell lines. EMSA results confirmed that the promoter polymorphisms affected DNA-protein binding. Interestingly, however, the protein/s involved were not MITF, or at least MITF was not the protein directly binding to the DNA. In an effort to more thoroughly characterise the functional consequences of SLC45A2 promoter polymorphisms, the mRNA expression levels of SLC45A2 and MITF were determined in melanocyte/melanoblast cell lines. Based on SLC45A2’s role in processing and trafficking TYRP1 from the trans-Golgi network to stage 2 melanosmes, the mRNA expression of TYRP1 was also investigated. Expression results suggested a coordinated expression of pigmentation genes. This thesis has substantially contributed to the field of pigmentation by showing that SLC45A2 polymorphisms not only show allele frequency differences between population groups, but also contribute to normal pigmentation variation within a Caucasian population. In addition, promoter polymorphisms have been shown to have functional consequences for SLC45A2 transcription and the expression of other pigmentation genes. Combined, the data presented in this work supports the notion that SLC45A2 is an important contributor to normal pigmentation variation and should be the target of further research to elucidate its role in determining pigmentation phenotypes. Understanding SLC45A2’s function may lead to the development of therapeutic interventions for oculocutaneous albinism and other disorders of pigmentation. It may also help in our understanding of skin cancer susceptibility and evolutionary adaptation to different UV environments, and contribute to the forensic application of pigmentation phenotype prediction.

Urban sustainability and growth management in south-east Asian city-regions : the case of Kuala Lumpur and Hong Kong

Major South-East Asian city-regions have experienced considerable physical, economic and social transformations during the past three decades. The rapid pace of globalisation and economic restructuring has resulted in these city-regions receiving the full impact of urbanisation pressures. In an attempt to ease these pressures, city-regions such as Bangkok, Seoul, Tokyo, Taipei, Hong Kong, Singapore and Kuala Lumpur have advocate growth management approaches giving particular interest to urban sustainability. These approaches promote efforts to achieve the triple bottom line sustainability by balancing economic and social development, and environmental protection, and putting more emphasis on compact and optimum development of urban forms. This paper evaluates the case of two South-East Asian city-regions, Kuala Lumpur and Hong Kong, and assesses their experiences in managing their urban forms whilst promoting sustainable patterns of urban development. The findings show that sustainable urban development initiatives employing a top down approach has yielded encouraging results in these case study city-regions. However the need for a more concerted effort towards the overall sustainability agenda still remains vital.

Promoting sustainable urban development in fast growing city-regions : practices from Kuala Lumpur and Hong Kong

The Asia‐Pacific region is characterised by rapid population growth and urbanisation. These trends often result in an increasing consumption of land, which in turn lead to spatially expansive and discontinuous urban development. As a consequence, local communities and the environment face strong pressures. Many cities in the region have developed policies to tackle the issue of rapid growth and its associated consequences, for example climate change. The broad aim of this paper is to identify the nature, trends and strategies of growth management in major Asia‐Pacific city‐regions, and their implications for natural resource management and infrastructure provision. More specifically, this research seeks to provide insights on sustainable urban development practice, particularly on the promotion of compact urbanisation within the Asia‐Pacific’s fastest growing regions. The methodology of the paper includes a detailed literature review and a comparative analysis of existing strategies and policies. The literature review focuses on the key concepts related to sustainable urban growth management. It also includes existing applications of urban growth management approaches and planning information system in managing growth. Following the literature review, the paper undertakes a comparative analysis of the strategies of major Asia‐Pacific city‐regions of Kuala Lumpur and Hong Kong in terms of their approaches to sustainable urban development. The findings of the paper provide a clear understanding of the necessity of sustainable urban development practices. It contributes to the development of a substantial base for further research. Ultimately, this research aims to shed light on sustainable urban development by providing insights on the management of growth, natural resources and urban infrastructures.

Exploratory spatial analysis of social and environmental factors associated with the incidence of Ross River Virus in Brisbane, Australia

We used geographic information systems and a spatial analysis approach to explore the pattern of Ross River virus (RRV) incidence in Brisbane, Australia. Climate, vegetation and socioeconomic data in 2001 were obtained from the Australian Bureau of Meteorology, the Brisbane City Council and the Australian Bureau of Statistics, respectively. Information on the RRV cases was obtained from the Queensland Department of Health. Spatial and multiple negative binomial regression models were used to identify the socioeconomic and environmental determinants of RRV transmission. The results show that RRV activity was primarily concentrated in the northeastern, northwestern, and southeastern regions in Brisbane. Multiple negative binomial regression models showed that the spatial pattern of RRV disease in Brisbane seemed to be determined by a combination of local ecologic, socioeconomic, and environmental factors.