The cytochrome P-450 isoenzyme CYP2E1 in the biological processing of industrial chemicals : consequences for occupational and environmental medicine

The importance of the isoform CYP2E1 of the human cytochrome P-450 superfamily of enzymes for occupational and environmental medicine is derived from its unique substrate spectrum that includes a number of highly important high-production chemicals, such as aliphatic and aromatic hydrocarbons, solvents and industrial monomers (i.a. alkanes, alkenes, aromatic and halogenated hydrocarbons). Many polymorphic genes, such as CYP2E1, show considerable differences in allelic distribution between different human populations. The polymorphic nature of the human CYP2E1 gene is significant for inter-individual differences in toxicity of its substrates. Since the substrate spectrum of CYP2E1 includes many compounds of basic relevance to industrial toxicology, a rationale for metabolic interactions of different CYP2E1 substrates is provided. In-depth research into the inter-individual phenotypic differences of human CYP2E1 enzyme activities was enabled by the recognition that the 6-hydroxylation of the drug chlorzoxazone is mediated by CYP2E1. Studies on CYP2E1 phenotyping have pointed to inter-individual variations in enzyme activities. There are consistent ethnic differences in CYP2E1 enzyme expression, mostly demonstrated between European and Japanese populations, which point to a major impact of genetic factors. The most frequently studied genetic polymorphisms are the restriction fragment length polymorphisms PstI/RsaI (mutant allele: CYP2E1*5B) located in the 5′-flanking region of the gene, as well as the DraI polymorphism (mutant allele: CYP2E1*6) located in intron 6. These polymorphisms are partly related, as they form the common allele designated CYP2E1*5A. Striking inter-ethnic differences between Europeans and Asians appear with respect to the frequencies of the CYP2E1*5A allele (only approximately 5% of Europeans are heterozygous, but 37% of Asians are, whilst 6% of Asians are homozygous). Available studies indicate a wide variation in human CYP2E1 expression, which are very likely based on complex gene-environment interactions. Major inter-ethnic differences are apparent on the genotyping and the phenotyping levels. Selected cases are presented where inter-ethnic variations of CYP2E1 may provide likely explanations for unexplained findings concerning industrial chemicals that are CYP2E1 substrates. Possible consequences of differential inter-individual and inter-ethnic susceptibilities are related to individual expressions of clinical symptoms of chemical toxicity, to results of biological monitoring of exposed workers, and to the interpretation of results of epidemiological or molecular-epidemiological studies.

Markers of genetic susceptibility in human environmental hygiene and toxicology : the role of selected CYP, NAT and GST genes

Inherited genetic traits co-determine the susceptibility of an individual to a toxic chemical. Special emphasis has been put on individual responses to environmental and industrial carcinogens, but other chronic diseases are of increasing interest. Polymorphisms of relevant xenobiotic metabolising enzymes may be used as toxicological susceptibility markers. A growing number of genes encoding enzymes involved in biotransformation of toxicants and in cellular defence against toxicant-induced damage to the cells has been identified and cloned, leading to increased knowledge of allelic variants of genes and genetic defects that may result in a differential susceptibility toward environmental toxicants. "Low penetrating" polymorphisms in metabolism genes tend to be much more common in the population than allelic variants of "high penetrating" cancer genes, and are therefore of considerable importance from a public health point of view. Positive associations between cancer and CYP1A1 alleles, in particular the *2C I462V allele, were found for tissues following the aerodigestive tract. Again, in most cases, the effect of the variant CYP1A1 allele becomes apparent or clearer in connection with the GSTM1 null allele. The CYP1B1 codon 432 polymorphism (CYP1B1*3) has been identified as a susceptibility factor in smoking-related head-and-neck squameous cell cancer. The impact of this polymorphic variant of CYP1B1 on cancer risk was also reflected by an association with the frequency of somatic mutations of the p53 gene. Combined genotype analysis of CYP1B1 and the glutathione transferases GSTM1 or GSTT1 has also pointed to interactive effects. Of particular interest for the industrial and environmental field is the isozyme CYP2E1. Several genotypes of this isozyme have been characterised which seem to be associated with different levels of expression of enzyme activity. The acetylator status for NAT2 can be determined by genotyping or by phenotyping. In the pathogenesis of human bladder cancer due to occupational exposure to "classical" aromatic amines (benzidine, 4-aminodiphenyl, 1-naphthylamine) acetylation by NAT2 is regarded as a detoxication step. Interestingly, the underlying European findings of a higher susceptibility of slow acetylators towards aromatic amines are in contrast to findings in Chinese workers occupationally exposed to aromatic amines which points to different mechanisms of susceptibility between European and Chinese populations. Regarding human bladder cancer, the hypothesis has been put forward that genetic polymorphism of GSTM1 might be linked with the occurrence of this tumour type. This supports the hypothesis that exposure to PAH might causally be involved in urothelial cancers. The human polymorphic GST catalysing conjugation of halomethanes, dihalomethanes, ethylene oxide and a number of other industrial compounds could be characterised as a class theta enzyme (GSTT1) by means of molecular biology. "Conjugator" and "non-conjugator" phenotypes are coincident with the presence and absence of the GSTT1 gene. There are wide variations in the frequencies of GSTT1 deletion (GSTT1 *0/0) among different ethnicities. Human phenotyping is facilitated by the GST activity towards methyl bromide or ethylene oxide in erythrocytes which is representative of the metabolic GSTT1 competence of the entire organism. Inter-individual variations in xenobiotic metabolism capacities may be due to polymorphisms of the genes coding for the enzymes themselves or of the genes coding for the receptors or transcription factors which regulate the expression of the enzymes. Also, polymorphisms in several regions of genes may cause altered ligand affinity, transactivation activity or expression levels of the receptor subsequently influencing the expression of the downstream target genes. Studies of individual susceptibility to toxicants and gene-environment interaction are now emerging as an important component of molecular epidemiology.

Genetic susceptibility to environmental toxicants : the interface between human and experimental studies in the development of new toxicological concepts

The growing knowledge of the genetic polymorphisms of enzymes metabolising xenobiotics in humans and their connections with individual susceptibility towards toxicants has created new and important interfaces between human epidemiology and experimental toxicology. The results of molecular epidemiological studies may provide new hypotheses and concepts, which call for experimental verification, and experimental concepts may obtain further proof by molecular epidemiological studies. If applied diligently, these possibilities may be combined to lead to new strategies of human-oriented toxicological research. This overview will present some outstanding examples for such strategies taken from the practically very important field of occupational toxicology. The main focus is placed on the effects of enzyme polymorphisms of the xenobiotic metabolism in association with the induction of bladder cancer and renal cell cancer after exposure to occupational chemicals. Also, smoking and induction of head and neck squamous cell cancer are considered.

The influence of fleet safety climate on occupational driver behaviours

The concepts of traffic safety culture and climate hold considerable impact on road safety outcomes. Data sourced from four Australian organisations revealed a five factor structure that was consistent with previous research, which were: management commitment; work demands; relationships; appropriateness of rules; and communication. Correlation and regression analyses were conducted to identify which aspects of fleet safety climate were related to driver behaviours. The findings suggest that organisations may be able to reduce the likelihood of employees engaging in unsafe driving behaviours as a result of fatigue or distractions through increasing aspects of fleet safety climate, including: management commitment; level of trust; safety communication; appropriateness of work demands; and appropriateness of safety policies and procedures. To assist practitioners in enhancing fleet safety climate and managing occupational road risks, recommendations are made based on these findings, such as fostering a supportive environment of mutual responsibility.

Investigating the link between transit oriented development and sustainable travel behavior in Brisbane : a case-control study

The purpose of this research is to empirically test the prevailing view that transit oriented development enhances the use of more sustainable modes of transport using Brisbane, Australia as a case. Transit oriented development has been adopted as a new policy tool to reduce car-based travel worldwide. Despite being a billion dollar investment, the impacts of transit oriented development on promoting sustainable travel behavior is not conclusive. The research uses a case-control approach to empirically investigate this relationship based on travel behavior data collected from 88 individuals living in two contrasting neighborhoods in Brisbane: Kelvin Grove Urban Village – a transit oriented development, and Annerley – a traditional suburb (non-transit oriented development). A comparative investigation of travel behavior was subsequently conducted using distance travelled by modes and purposes between the neighborhoods. Results show that the availability of opportunity and services located within the transit oriented development reduces the car use by 5% and increases the use of active transport by 4%. The findings in this research support the implementation of TOD policies in Brisbane.

Tales of science and defiance : the case for co-learning and collaboration in bridging the science/emotion divide in water recycling debates

Although science is generally assumed to be well integrated into rational decision-making models, it can be used to destabilise consultative processes, particularly when emotions are involved. Water policies are often seen as debates over technical and engineering issues, but can be highly controversial. Recycled water proposals, in particular, can create highly emotive conflicts. Through a case study regarding the rejection of recycled water proposals in the south-east Queensland, Australia, we explore the influence of science and emotions in contemporary water planning. We highlight the dangers inherent in promoting technical water planning issues at the expense of appropriate consideration of citizen concerns. Combining the science–policy interface and stakeholder engagement literatures, we advocate for collaborative decision-making processes that accommodate emotions and value judgements. A more collaborative stakeholder engagement model, founded on the principles of co-learning, has the potential to broaden the decision-making base and to promote better and more inclusive decision-making.

The security and privacy of usage policies and provenance logs in an Information Accountability Framework

The potential benefits of shared eHealth records systems are promising for the future of improved healthcare. However, the uptake of such systems is hindered by concerns over the security and privacy of patient information. The use of Information Accountability and so called Accountable-eHealth (AeH) systems has been proposed to balance the privacy concerns of patients with the information needs of healthcare professionals. However, a number of challenges remain before AeH systems can become a reality. Among these is the need to protect the information stored in the usage policies and provenance logs used by AeH systems to define appropriate use of information and hold users accountable for their actions. In this paper, we discuss the privacy and security issues surrounding these accountability mechanisms, define valid access to the information they contain, discuss solutions to protect them, and verify and model an implementation of the access requirements as part of an Information Accountability Framework.

Environmental, personal, and genetic determinants of response to vitamin D supplementation in older adults

CONTEXT AND OBJECTIVE: Suboptimal vitamin D status can be corrected by vitamin D supplementation, but individual responses to supplementation vary. We aimed to examine genetic and nongenetic determinants of change in serum 25-hydroxyvitamin D (25(OH)D) after supplementation. DESIGN AND PARTICIPANTS: We used data from a pilot randomized controlled trial in which 644 adults aged 60 to 84 years were randomly assigned to monthly doses of placebo, 30 000 IU, or 60 000 IU vitamin D3 for 12 months. Baseline characteristics were obtained from a self-administered questionnaire. Eighty-eight single-nucleotide polymorphisms (SNPs) in 41 candidate genes were genotyped using Sequenom MassArray technology. Serum 25(OH)D levels before and after the intervention were measured using the Diasorin Liaison platform immunoassay. We used linear regression models to examine associations between genetic and nongenetic factors and change in serum 25(OH)D levels. RESULTS: Supplement dose and baseline 25(OH)D level explained 24% of the variability in response to supplementation. Body mass index, self-reported health status, and ambient UV radiation made a small additional contribution. SNPs in CYP2R1, IRF4, MC1R, CYP27B1, VDR, TYRP1, MCM6, and HERC2 were associated with change in 25(OH)D level, although only CYP2R1 was significant after adjustment for multiple testing. Models including SNPs explained a similar proportion of variability in response to supplementation as models that included personal and environmental factors. CONCLUSION: Stepwise regression analyses suggest that genetic variability may be associated with response to supplementation, perhaps suggesting that some people might need higher doses to reach optimal 25(OH)D levels or that there is variability in the physiologically normal level of 25(OH)D.

Australian Library and Information Association Course Accreditation Review 2013

This report has been prepared for the Australian Library and Information Association (ALIA) in response to the request to undertake a literature review and environmental scan to inform discussions of the issues associated with professional accreditation. ALIA is the peak body which develops and monitors the professional standards that ensure the high quality of graduates entering the library and information services (LIS) profession in Australia. The report presents a themed discussion of the issues identified in the literature review and environmental scan to build a full picture of the role of course accreditation in LIS education. This is set against developments in the wider context of quality assurance in Australian tertiary education, to analyse the implications of this changing environment for ALIA’s accreditation policies and ractices.

The affect heuristic and public support for three types of wood smoke mitigation policies

This study applied the affect heuristic model to investigate key psychological factors (affective associations, perceived benefits, and costs of wood heating) contributing to public support for three distinct types of wood smoke mitigation policies: education, incentives, and regulation. The sample comprised 265 residents of Armidale, an Australian regional community adversely affected by winter wood smoke pollution. Our results indicate that residents with stronger positive affective associations with wood heating expressed less support for wood smoke mitigation policies involving regulation. This relationship was fully mediated by expected benefits and costs associated with wood heating. Affective associations were unrelated to public support for policies involving education and incentives, which were broadly endorsed by all segments of the community, and were more strongly associated with rational considerations. Latent profile analysis revealed no evidence to support the proposition that some community members experience internal “heart versus head” conflicts in which their positive affective associations with wood heating would be at odds with their risk judgments about the dangers of wood smoke pollution. Affective associations and cost/benefit judgments were very consistent with each other.

A sunburnt country – storms, surges and sea levels : of insurance and flooding rains

Increasing population pressures and life-style choices are resulting in more people living in areas that are at risk of inundation from rising sea levels and flooding. However, following natural disaster events, such as the 2011 Queensland floods, many Australians discovered they were uninsured. Either their insurance policies did not cover flood; or multiple (and confusing) water-related definitions led them to believe they had cover when they did not. Several theories are analysed to try to explain what is a world-wide underinsurance problem but these do not provide an answer to the problem. This research focuses on uncovering the reasons consumers fail to adequately insure for flood and other water-related events. Recent Australian legislative attempts to overcome insureds’ confusion of water related definitions are examined for this purpose. The authors conclude that Australian and other) legislators should set a maximum premium for a minimum amount of flood and sea related cover; and restrict the building and style of homes in flood prone areas.

Use of contract models to improve environmental outcomes in transport infrastructure construction

The type of contract model may have a significant influence on achieving project objectives, including environmental and climate change goals. This research investigates non-standard contract models impacting greenhouse gas emissions (GHG) in transport infrastructure construction in Australia. The research is based on the analysis of two case studies: an Early Contractor Involvement (ECI) contract and a Design and Construct (D&C) contract with GHG reduction requirements embedded in the contractor selection. Main findings support the use of ECIs for better integrating decisions made during the planning phase with the construction activities, and improve environmental outcomes while achieving financial and time savings. Key words: greenhouse gases reduction; road construction; contracting; ECI; D&C

Practical analysis of big acoustic sensor data for environmental monitoring

Monitoring the environment with acoustic sensors is an effective method for understanding changes in ecosystems. Through extensive monitoring, large-scale, ecologically relevant, datasets can be produced that can inform environmental policy. The collection of acoustic sensor data is a solved problem; the current challenge is the management and analysis of raw audio data to produce useful datasets for ecologists. This paper presents the applied research we use to analyze big acoustic datasets. Its core contribution is the presentation of practical large-scale acoustic data analysis methodologies. We describe details of the data workflows we use to provide both citizen scientists and researchers practical access to large volumes of ecoacoustic data. Finally, we propose a work in progress large-scale architecture for analysis driven by a hybrid cloud-and-local production-grade website.