COX-derived prostanoid pathways in gastrointestinal cancer development and progression : novel targets for prevention and intervention

Arachidonic acid metabolism through cyclooxygenase (COX) pathways leads to the generation of biologically active eicosanoids. Eicosanoid expression levels vary during development and progression of gastrointestinal (GI) malignancies. COX-2 is the major COX-isoform responsible for G.I. cancer development/progression. COX-2 expression increases during progression from a normal to cancerous state. Evidence from observational studies has demonstrated that chronic NSAID use reduces the risk of cancer development, while both incidence and risk of death due to G.I. cancers were significantly reduced by daily aspirin intake. A number of randomized controlled trials (APC trial, Prevention of Sporadic Adenomatous Polyps trial, APPROVe trial) have also shown a significant protective effect in patients receiving selective COX-2 inhibitors. However, chronic use of selective COX-2 inhibitors at high doses was associated with increased cardiovascular risk, while NSAIDs have also been associated with increased risk. More recently, downstream effectors of COX-signaling have been investigated in cancer development/progression. PGE 2, which binds to both EP and PPAR receptors, is the major prostanoid implicated in the carcinogenesis of G.I. cancers. The role of TXA 2 in G.I. cancers has also been examined, although further studies are required to uncover its role in carcinogenesis. Other prostanoids investigated include PGD 2 and its metabolite 15d-PGJ2, PGF 1α and PGI 2. Targeting these prostanoids in G.I. cancers has the promise of avoiding cardiovascular toxicity associated with chronic selective COX-2 inhibition, while maintaining anti-tumor reactivity.A progressive sequence from normal to pre-malignant to a malignant state has been identified in G.I. cancers. In this review, we will discuss the role of the COX-derived prostanoids in G.I. cancer development and progression. Targeting these downstream prostanoids for chemoprevention and/or treatment of G.I. cancers will also be discussed. Finally, we will highlight the latest pre-clinical technologies as well as avenues for future investigation in this highly topical research field. © 2011 Elsevier B.V.

Shifting global power and shifting state power

The adoption of the Declaration on the Rights of Indigenous Peoples (DRIP) by the United Nations General Assembly in September 2007 has been heralded by many as a major breakthrough in the promotion of Indigenous rights under international law. Many however are sceptical as to whether DRIP actually promotes Indigenous rights or rather limits them in ways that serve the interests of nation states thereby diminishing the universality of human rights with respect to Indigenous peoples. This paper will examine how shifts in global power from the United States to the BRIC nations (Brazil, Russia, India and China) are likely to impact on the realisation of the right of self determination for Indigenous peoples. It will start by outlining the right of self determination as articulated in the Declaration, and in particular how the United States and its allies - the CANZUS group (Canada, Australia, New Zealand and United States) - were influential in shaping its form and content. The paper will then assess the extent to which the right to self determination is realised in Australia, the United States and the BRJC nations to provide an indication of the likely future direction of recognition and realisation of Indigenous rights at a global level.

The effects and interactions of GABAergic and dopaminergic agents in the prevention of form deprivation myopia by brief periods of normal vision

Intravitreal injections of GABA antagonists, dopamine agonists and brief periods of normal vision have been shown separately to inhibit form-deprivation myopia (FDM). Our study had three aims: (i) establish whether GABAergic agents modify the myopia protective effect of normal vision, (ii) investigate the receptor sub-type specificity of any observed effect, and (iii) consider an interaction with the dopamine (DA) system. Prior to the period of normal vision GABAergic agents were applied either (i) individually, (ii) in combination with other GABAergic agents (an agonist with an antagonist), or (iii) in combination with DA agonists and antagonists. Water injections were given to groups not receiving drug treatments so that all experimental eyes received intravitreal injections. As shown previously, constant form-deprivation resulted in high myopia and when diffusers were removed for 2 h per day the period of normal vision greatly reduced the FDM that developed. GABA agonists inhibited the protective effect of normal vision whereas antagonists had the opposite effect. GABAA/C agonists and D2 DA antagonists when used in combination were additive in suppressing the protective effect of normal vision. A D2 DA agonist restored some of the protective effect of normal vision that was inhibited by a GABA agonist (muscimol). The protective effect of normal vision against form-deprivation is modifiable by both the GABAergic and DAergic pathways.

Communication Interception Technology (CIT) and its use in the fight against Transnational Organised Crime (TOC) in Australia : a review of the literature

In recent times, technology has advanced in such a manner that the world can now communicate in means previously never thought possible. Transnational organised crime groups, who have exploited these new technologies as basis for their criminal success, however, have not overlooked this development, growth and globalisation. Law enforcement agencies have been confronted with an unremitting challenge as they endeavour to intercept, monitor and analyse these communications as a means of disrupting the activities of criminal enterprises. The challenge lies in the ability to recognise and change tactics to match an increasingly sophisticated adversary. The use of communication interception technology, such as phone taps or email interception, is a tactic that when used appropriately has the potential to cause serious disruption to criminal enterprises. Despite the research that exists on CIT and TOC, these two bodies of knowledge rarely intersect. This paper builds on current literature, drawing them together to provide a clearer picture of the use of CIT in an enforcement and intelligence capacity. It provides a review of the literature pertaining to TOC, the structure of criminal enterprises and the vulnerability of communication used by these crime groups. Identifying the current contemporary models of policing it reviews intelligence-led policing as the emerging framework for modern policing. Finally, it assesses the literature concerning CIT, its uses within Australia and the limitations and arguments that exist. In doing so, this paper provides practitioners with a clearer picture of the use, barriers and benefits of using CIT in the fight against TOC. It helps to bridge the current gaps in modern policing theory and offers a perspective that can help drive future research.

Effective punishment experiences : the need for a more comprehensive approach to conceptualising behavioural punishers and reinforcers in a road safety context

Determining what consequences are likely to serve as effective punishment for any given behaviour is a complex task. This chapter focuses specifically on illegal road user behaviours and the mechanisms used to punish and deter them. Traffic law enforcement has traditionally used the threat and/or receipt of legal sanctions and penalties to deter illegal and risky behaviours. This process represents the use of positive punishment, one of the key behaviour modification mechanisms. Behaviour modification principles describe four types of reinforcers: positive and negative punishments and positive and negative reinforcements. The terms ‘positive’ and ‘negative’ are not used in an evaluative sense here. Rather, they represent the presence (positive) or absence (negative) of stimuli to promote behaviour change. Punishments aim to inhibit behaviour and reinforcements aim to encourage it. This chapter describes a variety of punishments and reinforcements that have been and could be used to modify illegal road user behaviours. In doing so, it draws on several theoretical perspectives that have defined behavioural reinforcement and punishment in different ways. Historically, the main theoretical approach used to deter risky road use has been classical deterrence theory which has focussed on the perceived certainty, severity and swiftness of penalties. Stafford and Warr (1993) extended the traditional deterrence principles to include the positive reinforcement concept of punishment avoidance. Evidence of the association between punishment avoidance experiences and behaviour has been established for a number of risky road user behaviours including drink driving, unlicensed driving, and speeding. We chose a novel way of assessing punishment avoidance by specifying two sub-constructs (detection evasion and punishment evasion). Another theorist, Akers, described the idea of competing reinforcers, termed differential reinforcement, within social learning theory (1977). Differential reinforcement describes a balance of reinforcements and punishments as influential on behaviour. This chapter describes comprehensive way of conceptualising a broad range of reinforcement and punishment concepts, consistent with Akers’ differential reinforcement concept, within a behaviour modification framework that incorporates deterrence principles. The efficacy of three theoretical perspectives to explain self-reported speeding among a sample of 833 Australian car drivers was examined. Results demonstrated that a broad range of variables predicted speeding including personal experiences of evading detection and punishment for speeding, intrinsic sensations, practical benefits expected from speeding, and an absence of punishing effects from being caught. Not surprisingly, being younger was also significantly related to more frequent speeding, although in a regression analysis, gender did not retain a significant influence once all punishment and reinforcement variables were entered. The implications for speed management, as well as road user behaviour modification more generally, are discussed in light of these findings. Overall, the findings reported in this chapter suggest that a more comprehensive approach is required to manage the behaviour of road users which does not rely solely on traditional legal penalties and sanctions.

Comparing outcomes of a school based injury prevention intervention for low-medium risk adolescents with high-risk adoelscents

High-risk adolescents are shown to jeopardise their future social and health functioning as well as placing themselves and others at immediate risk of harm. The challenge of “reaching” high-risk adolescents, who are often marginalised, is considerable. There is a positive relationship between age and risk taking behaviors during adolescence. This study examines outcomes (alcohol use, transport risk behaviors, violence) of a school based intervention (SPIY) by comparing low-medium risk adolescents with high-risk adolescents over a six month period.

Skin cancer prevention and fashion – frontier bedfellows

Problem Queensland has the highest rates of skin cancer in the world, even after wide-ranging public programs promoting sun safety awareness. To-date, public awareness campaigns on the dangers of excessive sun exposure have been highly successful. For adolescents, however, where a significant amount of lifetime sun exposure occurs, perilous exposure still ensues, despite awareness of the risks. New frontier approaches are required to target this key audience cluster, for this significant national problem. Approach For the majority of adolescents, being part of a collective norm defines their visual, attitudinal and behavioural actions and fashion has been validated as one of the most powerful forces that can form, shape and bolster these norms. Considering clothing is the easiest method to limit the amount of skin exposed to UV, fashion (in its many subtle, yet influential guises) is proposed as an avenue to advance positive sun safe practices for adolescents. Through an action-led methodology, this research explores the potential of fashion, as one of the key parts of a complex equation, to be a prime driver to facilitate sun safety for adolescents. Findings This paper advocates that fashion, as distinguishable from clothing, has the potential to positively influence sun protective behaviour. The findings go further and recommend the use of fashion as a stealth driver for sun safety advancement, for adolescents in particular, via shifts in norms of beauty and targeted generational communication strategies. This frontier approach has the potential to significantly reduce risky sun exposure in adolescence.

Crime, justice and social democracy : proceedings of the second international conference, 2013, volume 1

The refereed papers contained in this set of conference proceedings were presented at the 2nd International Conference on Crime, Justice and Social Democracy, hosted by the Crime and Justice Research Centre, Faculty of Law, QUT. The conference attracted an impressive list of internationally distinguished keynote and panel speakers from the United Kingdom, United States, Australia, New Zealand, Canada and this time Latin America, as well as high quality paper submissions.

A proposed approach to monitor private-sector policies and practices related to food environments, obesity and non-communicable disease prevention

Private-sector organizations play a critical role in shaping the food environments of individuals and populations. However, there is currently very limited independent monitoring of private-sector actions related to food environments. This paper reviews previous efforts to monitor the private sector in this area, and outlines a proposed approach to monitor private-sector policies and practices related to food environments, and their influence on obesity and non-communicable disease (NCD) prevention. A step-wise approach to data collection is recommended, in which the first (‘minimal’) step is the collation of publicly available food and nutrition-related policies of selected private-sector organizations. The second (‘expanded’) step assesses the nutritional composition of each organization's products, their promotions to children, their labelling practices, and the accessibility, availability and affordability of their products. The third (‘optimal’) step includes data on other commercial activities that may influence food environments, such as political lobbying and corporate philanthropy. The proposed approach will be further developed and piloted in countries of varying size and income levels. There is potential for this approach to enable national and international benchmarking of private-sector policies and practices, and to inform efforts to hold the private sector to account for their role in obesity and NCD prevention.

Making prevention matter : a survey of child sexual abuse prevention programs in Australia

Throughout Australia, there is considerable concern about the prevalence of child sexual abuse. Sexual abuse is experienced by over 3,500 Australian children each year, causing long-term psychological, health and social problems to children, their families and communities, and significant economic costs to society as a whole. In many countries, the provision of school-based programs has been a core strategy in efforts to prevent child sexual abuse. However, little is known about the range of programs in use in Australia, the numbers of children who have received programs, and the contents and methods used in program delivery. This presentation reports on a detailed National survey of child sexual abuse prevention programs currently used in Australian primary schools. An online survey was conducted over a six-month period from November 2011 to April 2012 yielding detailed data from 38 programs. The presentation will provide an overview of: the scope and reach of programs; program content, teaching strategies and resources; barriers and facilitators to program adoption by schools; and program evaluation strategies.

Development of an evidence-based framework to guide injury prevention interventions for off-road motorcyclists

There is little research on off-road motorcycle and all-terrain vehicle riders though injury levels are high. This thesis identified formal responsibility for monitoring injuries, targeting young male and recreational riders, promotion of family members as models, and controlled and accessible riding locations as ways to increase safety. These recommendations were based on analysis of Queensland hospitalisation records, rider personal reports and survey responses.