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.

Occupational Health and Safety, Courts and Crime: the legal construction of occupational health and safety offences in Victoria

This book reports on an empirically-based study of the manner in which the Magistrates' Courts in Victoria, construct occupational health and safety (OHS) issues when hearing prosecutions for offences under the Victorian OHS legislation. Prosecution has always been a controversial element in the enforcement armoury of OHS regulators, but at the same time it has long been argued that the low level of fines imposed by courts has had an important chilling effect on the OHS inspectorate's enforcement approaches, and on the impact of OHS legislation. Using a range of empirical research methods, including three samples of OHS prosecutions carried out in the Victorian Magistrates' Courts, Professor Johnstone shows how courts, inspectors, prosecutors and defence counsel are involved in filtering or reshaping OHS issues during the prosecution process, both pre-trial and in court. He argues that OHS offences are constructed by focusing on "events", in most cases incidents resulting in injury or death. This "event-focus" ensures that the attention of the parties is drawn to the details of the incident, and away from the broader context of the event. During the court-based sentencing process defence counsel is able to adopt a range of techniques which isolate the incident from its micro and macro contexts, thereby individualising and decontextualising the incident.

Safety, courts and crime: occupational safety and health prosecutions in the Magistrates' courts

This paper reports on an empirically based study of occupational safety and health prosecutions in the Magistrates' courts in the State of Victoria, Australia. It examines the way in which the courts construct occupational safety and health issues during prosecutions against alleged offenders, and then theorises the role of the criminal law in health and safety regulation. The paper argues that courts, inspectors, prosecutors and defence counsel are involved in filtering or reshaping occupational safety and health issues during the prosecution process, both pre-trial and in court. An analysis of the pattern of investigation of health and safety offences shows that they are constructed by focusing on 'events', in most cases incidents resulting in injury or death. This 'event focus' ensures that the attention of the parties is drawn to the details of the incident and away from the broader context of the event. This broader context includes the way in which work is organised at the workplace and the quality of occupational safety and health management (the micro context), and the pressures within capitalist production systems for occupational safety and health to be subordinated to production imperatives (the macro context). In particular, during the court-based sentencing process, defence counsel is able to adopt a range of 'isolation' techniques that isolate the incident from its micro and macro contexts, thereby individualising and decontextualising the incident. The paper concludes that the legal system plays a key role in decontextualising and individualising health and safety issues, and that this process is part of the 'architecture' of the legal system, and a direct consequence of the 'form of law'.

Challenging the myths about flexible work in the ADF

In May 2011, the Minister for Defence requested a review into the treatment of women in the ADF following allegations of inappropriate conduct at the Australian Defence Force Academy. The Australian Human Rights Commission (AHRC) initiated the review under the leadership of the Federal Sex Discrimination Commissioner, Elizabeth Broderick, who challenged the ADF to improve its culture and build a more inclusive environment for its members. The need for flexible work arrangements (FWAs) emerged as a central issue in the review, not least as a mechanism for improving the recruitment and retention of women in the ADF. The review, and its subsequent audit report, concluded that flexibility would strengthen the ADF but that there were cultural and structural obstacles. This article addresses the uptake of formal and informal FWAs in the ADF. The study is part of an Australian Research Council funded project, led by Queensland University of Technology, which addresses how the timing, location and tasks of work are negotiated in exchanges between managers and employees.

Elucidating the host-pathogen interactions between in vitro human cells and enterovirus 71 in Hand, Foot and Mouth Disease (HFMD)

This study has provided further understanding of the pathogenesis of EV71, one of the major etiological agents associated with significant mortality in Hand, Foot and Mouth disease. Elucidating the host-pathogen interaction and the mechanism that the virus uses to bypass host defence systems to establish infection will aid in the development of potential antiviral therapeutics against EV71.

Field and Service Robotics: Results of the 9th International Conference

The Field and Service Robotics (FSR) conference is a single track conference with a specific focus on field and service applications of robotics technology. The goal of FSR is to report and encourage the development of field and service robotics. These are non-factory robots, typically mobile, that must operate in complex and dynamic environments. Typical field robotics applications include mining, agriculture, building and construction, forestry, cargo handling and so on. Field robots may operate on the ground (of Earth or planets), under the ground, underwater, in the air or in space. Service robots are those that work closely with humans, importantly the elderly and sick, to help them with their lives. The first FSR conference was held in Canberra, Australia, in 1997. Since then the meeting has been held every 2 years in Asia, America, Europe and Australia. It has been held in Canberra, Australia (1997), Pittsburgh, USA (1999), Helsinki, Finland (2001), Mount Fuji, Japan (2003), Port Douglas, Australia (2005), Chamonix, France (2007), Cambridge, USA (2009), Sendai, Japan (2012) and most recently in Brisbane, Australia (2013). This year we had 54 submissions of which 36 were selected for oral presentation. The organisers would like to thank the international committee for their invaluable contribution in the review process ensuring the overall quality of contributions. The organising committee would also like to thank Ben Upcroft, Felipe Gonzalez and Aaron McFadyen for helping with the organisation and proceedings. and proceedings. The conference was sponsored by the Australian Robotics and Automation Association (ARAA), CSIRO, Queensland University of Technology (QUT), Defence Science and Technology Organisation Australia (DSTO) and the Rio Tinto Centre for Mine Automation, University of Sydney.

Antioxidants in Athlete's Basic Nutrition: Considerations towards a Guideline for the Intake of Vitamin C and Vitamin E

Antioxidants in acute physical exercise and exercise training remain a hot topic in sport nutrition, exercise physiology and biology, in general (Jackson, 2008; Margaritis and Rousseau, 2008; Gomez-Cabrera et al., 2012; Nikolaidis et al., 2012). During the past few decades, antioxidants have received attention predominantly as a nutritional strategy for preventing or minimising detrimental effects of reactive oxygen and nitrogen species (RONS), which are generated during and after strenuous exercise (Jackson, 2008, 2009; Powers and Jackson, 2008). Antioxidant supplementation has become a common practice among athletes as a means to (theoretically) reduce oxidative stress, promote recovery and enhance performance (Peternelj and Coombes, 2011). However, until now, requirements of antioxidant micronutrients and antioxidant compounds for athletes training for and competing in different sport events, including marathon running, triathlon races or team sport events involving repeated sprinting, have not been determined sufficiently (Williams et al., 2006; Margaritis and Rousseau, 2008). Crucially, evidence has been emerging that higher dosages of antioxidants may not necessarily be beneficial in this context, but can also elicit detrimental effects by interfering with performance-enhancing (Gomez-Cabrera et al., 2008) and health-promoting training adaptations (Ristow et al., 2009). As originally postulated in a pioneering study on exercise-induced production of RONS by Davies et al. (1982) in the early 1980s, evidence has been increasing in recent years that RONS are not only damaging agents, but also act as signalling molecules for regulating muscle function (Reid, 2001; Jackson, 2008) and for initiating adaptive responses to exercise (Jackson, 2009; Powers et al., 2010). The recognition that antioxidants could, vice versa, interact with the signalling pathways underlying the responses to acute (and repeated) bouts of exercise has contributed important novel aspects to the continued discussion on antioxidant requirements for athletes. In view of the recent advances in this field, it is the aim of this report to examine the current knowledge of antioxidants, in particular of vitamins C and E, in the basic nutrition of athletes. While overviews on related topics including basic mechanisms of exercise-induced oxidative stress, redox biology, antioxidant defence systems and a summary of studies on antioxidant supplementation during exercise training are provided, this does not mean that this report is comprehensive. Several issues of the expanding and multidisciplinary field of antioxidants and exercise are covered elsewhere in this book and/or in the literature. Exemplarily, the reader is referred to reviews on oxidative stress (Konig et al., 2001; Vollaard et al., 2005; Knez et al., 2006; Powers and Jackson, 2008; Nikolaidis et al., 2012), redox-sensitive signalling and muscle function (Reid, 2001; Vollaard et al., 2005; Jackson, 2008; Ji, 2008; Powers and Jackson, 2008; Powers et al., 2010; Radak et al., 2013) and antioxidant supplementation (Williams et al., 2006; Peake et al., 2007; Peternelj and Coombes, 2011) in the context with exercise. Within the scope of the report, we rather aim to address the question regarding requirements of antioxidants, specifically vitamins C and E, during exercise training, draw conclusions and provide practical implications from the recent research.

Well-trained, healthy triathletes experience no adverse health risks regarding oxidative stress and DNA damage by participating in an ultra-endurance event

Also physical exercise in general is accepted to be protective, acute and strenuous exercise has been shown to induce oxidative stress. Enhanced formation of free radicals leads to oxidation of macromolecules and to DNA damage. On the other hand ultra-endurance events which require strenuous exercise are very popular and the number of participants is continuously increasing worldwide. Since only few data exists on Ironman triathletes, who are prototypes of ultra-endurance athletes, this study was aimed at assessing the risk of oxidative stress and DNA damage after finishing a triathlon and to predict a possible health risk. Blood samples of 42 male athletes were taken 2 days before, within 20 min after the race, 1, 5 and 19 days post-race. Oxidative stress marker increased only moderately after the race and returned to baseline after 5 days. Marker of DNA damage measured by the SCGE assay with and without restriction enzymes as well as by the sister chromatid exchange assay did either show no change or deceased within the first day after the race. Due to intake during the race and the release by the cells plasma concentrations of vitamin C and α-tocopherol increased after the event and returned to baseline 1 day after. This study indicates that despite a temporary increase in some oxidative stress markers, there is no persistent oxidative stress and no DNA damage in response to an Ironman triathlon in trained athletes, mainly due to an appropriate antioxidant intake and general protective alterations in the antioxidant defence system.

Cosmo, Cosmolino: Patent law and nanotechnology

Patent law has a significant instrumental and symbolic role in regulating nanotechnology. A 2011 report of the United States Federal Trade Commission noted that ‘the patent system plays a critical role in promoting innovation across industries from biotechnology to nanotechnology, and by entities from large corporations to independent inventors’. This chapter considers the much contested legal, ethical and social issues involved with regulating the patenting of nanotechnology. Section I considers the efforts of patent offices to classify nanotechnology and the empirical evidence about patent filing rates. Section II examines whether there is a ‘tragedy of the anticommons’ emerging in respect of nanotechnology. It contemplates access mechanisms – such as the defence of experimental use, patent pools, open innovation models and technology transfer. Section III explores ethical and social concerns associated with nanotechnology – in particular, issues about the impact upon human health and the environment.

An elegy for Greg Ham: Copyright law, the Kookaburra case, and remix culture

The ‘Kookaburra’ case was a tragic and controversial copyright dispute, highlighting the need for copyright law reform by the Australian Parliament. In the Kookaburra case, a copyright action was brought by Larrikin Records against Men at Work’s song ‘Down Under’, alleging copyright infringement of the ‘Kookaburra’ song composed by Marion Sinclair. The dispute raised a host of doctrinal matters. There was disquiet over the length of the copyright term. There were fierce contests as to the copyright ownership of the ‘Kookaburra’ song. The litigation raised questions about copyright infringement and substantiality – particularly in relation to musical works. The ‘Kookaburra’ case highlighted frailties in Australia’s regime of copyright exceptions. The litigation should spur the Australian Law Reform Commission to make recommendations for law reform in its inquiry Copyright and the Digital Economy. This article provides a critical evaluation of the options of a defence for transformative use; a defence for fair use; and statutory licensing. The ‘Kookaburra’ case also examines the question of appropriate remedies in respect of copyright infringement. The conclusion considers the implications of the Kookaburra case for other forms of musical works – including digital sampling, mash-ups, and creative remixes. It finishes with an elegy for Greg Ham – paying tribute to the multi-instrumentalist for Men at Work.

The issue of consent: For the plaintiff or defendant to prove in trespass to person?

In White v Johnston1 the vexed question of whether it is for a plaintiff to prove lack of consent to a trespass to person or for the defendant to establish consent as defence was considered. The court also considered the principles of assessing an award of exemplary damages...

A fair use project for Australia: Copyright law and creative freedom

This essay provides a critical assessment of the Fair Use Project based at the Stanford Center for Internet and Society. In evaluating the efficacy of the Fair Use Project, it is worthwhile considering the litigation that the group has been involved in, and evaluating its performance. Part 1 outlines the history of the Stanford Center for Internet and Society, and the aims and objectives of the Fair Use Project. Part 2 considers the litigation in Shloss v. Sweeney over a biography concerning Lucia Joyce, the daughter of the avant-garde literary great, James Joyce. Part 3 examines the dispute over the Harry Potter Lexicon. Part 4 looks at the controversy over the Shepard Fairey poster of President Barack Obama, and the resulting debate with Associated Press. Part 5 of the essay considers the intervention of the Fair Use Project as an amicus curiae in the ‘Column case’. Part 6 explores the participation of the Fair Use Project as an amicus curiae in the litigation over 60 Years Later, an unauthorised literary sequel to J.D. Salinger’s The Catcher in the Rye. Part 7 of the essay investigates the role of the Fair Use project in disputes over copyright law and musical works. Part 8 investigates the role of the Fair Use Project as an advocate in disputes over copyright law, fair use, documentary films, and internet videos. The conclusion has main three arguments. First, it contends that Australia should establish a Fair Use Project to support creative artists in litigation over copyright exceptions. Second, it maintains that Australia should adopt a flexible, open-ended defence of fair use, and draw upon the rich jurisprudence in the United States on the fair use doctrine. Finally, this paper argues that support should be given at an international level to the proposal for a Treaty on Access to Knowledge.

After the gold rush: Patent law and biological inventions

In response to scientific breakthroughs in biotechnology, the development of new technologies, and the demands of a hungry capitalist marketplace, patent law has expanded to accommodate a range of biological inventions. There has been much academic and public debate as to whether gene patents have a positive impact upon research and development, health-care, and the protection of the environment. In a satire of prevailing patenting practices, the English poet and part-time casino waitress, Donna MacLean, sought a patent application - GB0000180.0 - in respect of herself. She explained that she had satisfied the usual patent criteria - in that she was novel, inventive, and useful: It has taken 30 years of hard labor for me to discover and invent myself, and now I wish to protect my invention from unauthorized exploitation, genetic or otherwise. I am new: I have led a private existence and I have not made the invention of myself public. I am not obvious (2000: 18). MacLean said she had many industrial applications. ’For example, my genes can be used in medical research to extremely profitable ends - I therefore wish to have sole control of my own genetic material' (2000: 18). She observed in an interview: ’There's a kind of unpleasant, grasping, greedy atmosphere at the moment around the mapping of the human genome ... I wanted to see if a human being could protect their own genes in law' (Meek, 2000). This special issue of Law in Context charts a new era in the long-standing debate over biological inventions. In the wake of the expansion of patentable subject matter, there has been great strain placed upon patent criteria - such as ’novelty', ’inventive step', and ’utility'. Furthermore, there has been a new focus upon legal doctrines which facilitate access to patented inventions - like the defence of experimental use, the ’Bolar' exception, patent pooling, and compulsory licensing. There has been a concerted effort to renew patent law with an infusion of ethical principles dealing with informed consent and benefit sharing. There has also been a backlash against the commercialisation of biological inventions, and a call by some activists for the abolition of patents on genetic inventions. This collection considers a wide range of biological inventions - ranging from micro-organisms, plants and flowers and transgenic animals to genes, express sequence tags, and research tools, as well as genetic diagnostic tests and pharmaceutical drugs. It is thus an important corrective to much policy work, which has been limited in its purview to merely gene patents and biomedical research. This collection compares and contrasts the various approaches of a number of jurisdictions to the legal problems in respect of biological inventions. In particular, it looks at the complexities of the 1998 European Union Directive on the Legal Protection of Biotechnological Inventions, as well as decisions of member states, such as the Netherlands, and peripheral states, like Iceland. The edition considers US jurisprudence on patent law and policy, as well as recent developments in Canada. It also focuses upon recent developments in Australia - especially in the wake of parallel policy inquiries into gene patents and access to genetic resources.

Canadian rhapsody: Copyright law and research libraries

This article considers the ground-breaking Supreme Court of Canada decision in The Law Society of Upper Canada v CCH Canadian Limited. The matter involved legal publishers bringing an action for copyright infringement against the Law Society of Upper Canada for operating a photocopy and custom copy service at the Great Library of Osgoode Hall. The Supreme Court of Canada decision laid down important precedents in relation to originality, authorisation, and the defence of fair dealing. The ruling has been hailed as ’one of the strongest pro-user rights decisions from any high court in the world, showing what it means to do more than pay mere lip service to balance in copyright'. This decision will have important implications for the regulation of new technologies. The approach has been applied in two decisions dealing copyright law and the Internet - the Canadian Federal Court case of BMG Canada v John Doe, and the Supreme Court of Canada ’Tariff 22' case. The Supreme Court of Canada decision in The Law Society of Upper Canada v CCH Canadian Limited provides an impetus to reconsider the judicial interpretation of user rights in Australian jurisprudence.

Robbery under arms: Copyright law and the Australia-United States free trade agreement

TThis article considers the radical, sweeping changes to Australian copyright law wrought by the Australia–United States Free Trade Agreement 2004 (AUSFTA). It contends that the agreement will result in a “piracy of the public domain”. Under this new regime, copyright owners will be able to obtain greater monopoly profits at the expense of Australian consumers, libraries and research institutions, as well as intermediaries, such as Internet service providers. Part One observes that the copyright term extension in Australia to life of the author plus 70 years for works will have a negative economic and cultural impact — with Australia’s net royalty payments estimated to be up to $88 million higher per year. Part Two argues that the adoption of stronger protection of technological protection measures modelled upon the Digital Millennium Copyright Act 1998 (U.S.) will override domestic policy–making processes, such as the Phillips Fox Digital Agenda Review, and judicial pronouncements such as the Stevens v Sony litigation. Part Three questions whether the new safe harbours protection for Internet service providers will adversely affect the sale of Telstra. This article concludes that there is a need for judicial restraint in interpreting the AUSFTA. There is an urgent call for the Federal Government to pass ameliorating reforms — such as an open–ended defence of fair use and a mechanism for orphan works. There is a need for caution in negotiating future bilateral trade agreements — lest the multinational system for the protection of copyright law be undermined.