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.

Concealing their communication : exploring psychosocial predictors of young drivers’ intentions and engagement in concealed texting

Making a conscious effort to hide the fact that you are texting while driving (i.e., concealed texting) is a deliberate and risky behaviour involving attention diverted away from the road. As the most frequent users of text messaging services and mobile phones while driving, young people appear at heightened risk of crashing from engaging in this behaviour. This study investigated the phenomenon of concealed texting while driving, and utilised an extended Theory of Planned Behaviour (TPB) including the additional predictors of moral norm, mobile phone involvement, and anticipated regret to predict young drivers’ intentions and subsequent behaviour. Participants (n = 171) were aged 17 to 25 years, owned a mobile phone, and had a current driver’s licence. Participants completed a questionnaire measuring their intention to conceal texting while driving, and a follow-up questionnaire a week later to report their behavioural engagement. The results of hierarchical multiple regression analyses showed overall support for the predictive utility of the TPB with the standard constructs accounting for 69% of variance in drivers’ intentions, and the extended predictors contributing an additional 6% of variance in intentions over and above the standard constructs. Attitude, subjective norm, PBC, moral norm, and mobile phone involvement emerged as significant predictors of intentions; and intention was the only significant predictor of drivers’ self-reported behaviour. These constructs can provide insight into key focal points for countermeasures including advertising and other public education strategies aimed at influencing young drivers to reconsider their engagement in this risky behaviour.

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.

Utilising hospital data to inform product safety prioritisation : the application of RAPEX severity rankings in ICD-coded burn data

Background The implementation of the Australian Consumer Law in 2011 highlighted the need for better use of injury data to improve the effectiveness and responsiveness of product safety (PS) initiatives. In the PS system, resources are allocated to different priority issues using risk assessment tools. The rapid exchange of information (RAPEX) tool to prioritise hazards, developed by the European Commission, is currently being adopted in Australia. Injury data is required as a basic input to the RAPEX tool in the risk assessment process. One of the challenges in utilising injury data in the PS system is the complexity of translating detailed clinical coded data into broad categories such as those used in the RAPEX tool. Aims This study aims to translate hospital burns data into a simplified format by mapping the International Statistical Classification of Disease and Related Health Problems (Tenth Revision) Australian Modification (ICD-10-AM) burn codes into RAPEX severity rankings, using these rankings to identify priority areas in childhood product-related burns data. Methods ICD-10-AM burn codes were mapped into four levels of severity using the RAPEX guide table by assigning rankings from 1-4, in order of increasing severity. RAPEX rankings were determined by the thickness and surface area of the burn (BSA) with information extracted from the fourth character of T20-T30 codes for burn thickness, and the fourth and fifth characters of T31 codes for the BSA. Following the mapping process, secondary data analysis of 2008-2010 Queensland Hospital Admitted Patient Data Collection (QHAPDC) paediatric data was conducted to identify priority areas in product-related burns. Results The application of RAPEX rankings in QHAPDC burn data showed approximately 70% of paediatric burns in Queensland hospitals were categorised under RAPEX levels 1 and 2, 25% under RAPEX 3 and 4, with the remaining 5% unclassifiable. In the PS system, prioritisations are made to issues categorised under RAPEX levels 3 and 4. Analysis of external cause codes within these levels showed that flammable materials (for children aged 10-15yo) and hot substances (for children aged <2yo) were the most frequently identified products. Discussion and conclusions The mapping of ICD-10-AM burn codes into RAPEX rankings showed a favourable degree of compatibility between both classification systems, suggesting that ICD-10-AM coded burn data can be simplified to more effectively support PS initiatives. Additionally, the secondary data analysis showed that only 25% of all admitted burn cases in Queensland were severe enough to trigger a PS response.

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.

Young novice drivers and the risky behaviours of parents and friends during the Provisional (intermediate) licence phase : a brief report

Purpose While there is research indicating that many factors influence the young novice driver's increased risk of road crash injury during the earliest stages of their independent driving, there is a need to further understand the relationship between the perceived risky driving behaviour of parents and friends and the risky behaviour of drivers with a Provisional (intermediate) licence. Method As part of a larger research project, 378 drivers aged 17–25 years (M = 18.22, SD = 1.59, 113 males) with a Provisional licence completed an online survey exploring the perceived riskiness of their parents’ and friends’ driving, and the extent to which they pattern (i.e. base) their driving behaviour on the driving of their parents and friends. Results Young drivers who reported patterning their driving on their friends, and who reported they perceived their friends to be risky drivers, reported more risky driving. The risky driving behaviour of young male drivers was associated with the perceived riskiness of their fathers’ driving, whilst for female drivers the perceived riskiness of their mothers’ driving approached significance. Conclusions The development and application of countermeasures targeting the risky behaviour of same-sex parents appears warranted by the robust research findings. In addition, countermeasures need to encourage young people in general to be non-risky drivers; targeting the negative influence of risky peer groups specifically. Social norms interventions may minimise the influence of potentially-overestimated riskiness.

Knowledge and behaviours of drunk driving offenders in Guangzhou, China

Background Alcohol is a major contributor to road crashes in China (Li, Xie, Nie, & Zhang, 2012; Cochrane, & Chen, 2003). Two levels of offence are defined in legislation: the lower level is driving under the influence (DUI, also translated as “drink driving”) and the higher level is driving while intoxicated (DWI, also translated as “drunk driving”, where the driver has BAC>0.08mg/100ml). This study focuses on a 2011 legislative amendment that made drunk driving (DWI) a criminal offence. However, it is not known whether drivers are aware of the law, and whether this knowledge, their exposure to enforcement and the existence of alcohol use disorders relate to their drink driving behaviour. This study explored these relationships in a sample of convicted drunk drivers. Method A survey collected information about offenders’ knowledge and practices related to drunk driving in Guangzhou. The Alcohol Use Disorders Identification Test (AUDIT) (Babor, & Grant, 1989; Chen, & Cheng, 2005) assessed hazardous drinking levels. In total, 101 drunk driving offenders were recruited while in detention. Results Males represented 90% of the sample; the average age was 33.6 years (SD=8.7; range 17-59 years). The average age at which offenders reported starting to drink alcohol was 19.5 years (SD=4.1; range 8-30 years). Driver’s licences had been held for a median of 7 years. Knowledge about legal limits for DUI and DWI offences was surprisingly low, at 27.7% and 40.6% respectively. On average, offenders had experienced 1.5 police alcohol breath tests in the previous year (SD=1.3; range 1-10). AUDIT scores indicated that a substantial proportion of the offenders had high levels of alcohol use disorders. Higher AUDIT scores were found among the least experienced drivers, those with lack of knowledge about the legal limits, and recidivist drunk drivers. Discussion and conclusions Limited awareness of legal alcohol limits might contribute to offending; high levels of alcohol consumption by many offenders suggest that hazardous drinking levels may also contribute. Novice drivers are a concern and their higher AUDIT scores merit some followup. Overall, this study provides important information to assist in refining community education and prevention efforts to align with China’s new regulations.

Utilising hospital data to inform product safety prioritisation : the application of RAPEX severity rankings in ICD-coded Burn Data

Background The implementation of the Australian Consumer Law in 2011 highlighted the need for better use of injury data to improve the effectiveness and responsiveness of product safety (PS) initiatives. In the PS system, resources are allocated to different priority issues using risk assessment tools. The rapid exchange of information (RAPEX) tool to prioritise hazards, developed by the European Commission, is currently being adopted in Australia. Injury data is required as a basic input to the RAPEX tool in the risk assessment process. One of the challenges in utilising injury data in the PS system is the complexity of translating detailed clinical coded data into broad categories such as those used in the RAPEX tool. Aims This study aims to translate hospital burns data into a simplified format by mapping the International Statistical Classification of Disease and Related Health Problems (Tenth Revision) Australian Modification (ICD-10-AM) burn codes into RAPEX severity rankings, using these rankings to identify priority areas in childhood product-related burns data. Methods ICD-10-AM burn codes were mapped into four levels of severity using the RAPEX guide table by assigning rankings from 1-4, in order of increasing severity. RAPEX rankings were determined by the thickness and surface area of the burn (BSA) with information extracted from the fourth character of T20-T30 codes for burn thickness, and the fourth and fifth characters of T31 codes for the BSA. Following the mapping process, secondary data analysis of 2008-2010 Queensland Hospital Admitted Patient Data Collection (QHAPDC) paediatric data was conducted to identify priority areas in product-related burns. Results The application of RAPEX rankings in QHAPDC burn data showed approximately 70% of paediatric burns in Queensland hospitals were categorised under RAPEX levels 1 and 2, 25% under RAPEX 3 and 4, with the remaining 5% unclassifiable. In the PS system, prioritisations are made to issues categorised under RAPEX levels 3 and 4. Analysis of external cause codes within these levels showed that flammable materials (for children aged 10-15yo) and hot substances (for children aged <2yo) were the most frequently identified products. Discussion and conclusions The mapping of ICD-10-AM burn codes into RAPEX rankings showed a favourable degree of compatibility between both classification systems, suggesting that ICD-10-AM coded burn data can be simplified to more effectively support PS initiatives. Additionally, the secondary data analysis showed that only 25% of all admitted burn cases in Queensland were severe enough to trigger a PS response.

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.

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.

Results of the Queensland 2007-2012 roadside drug testing program : the prevalence of three illicit drugs

The purpose of this investigation is to present an overview of roadside drug driving enforcement and detections in Queensland, Australia since the introduction of oral fluid screening. Drug driving is a problematic issue for road safety and investigations of the prevalence and impact of drug driving suggest that, in particular, the use of illicit drugs may increase a driver’s involvement in a road crash when compared to a driver who is drug free. In response to the potential increased crash involvement of drug impaired drivers, Australian police agencies have adopted the use of oral fluid analysis to detect the presence of illicit drugs in drivers. This paper describes the results of roadside drug testing for over 80,000 drivers in Queensland, Australia, from December 2007 to June 2012. It provides unique data on the prevalence of methamphetamine, cannabis and ecstasy in the screened population for the period. When prevalence rates are examined over time, drug driving detection rates have almost doubled from around 2.0% at the introduction of roadside testing operations to just under 4.0% in the latter years. The most common drug type detected was methamphetamine (40.8%) followed by cannabis (29.8%) and methamphetamine/cannabis combination (22.5%). By comparison, the rate of ecstasy detection was very low (1.7%). The data revealed a number of regional, age and gender patterns and variations of drug driving across the state. Younger drivers were more likely to test positive for cannabis whilst older drivers were more likely to test positive for methamphetamine. The overall characteristics of drivers who tested positive to the presence of at least one of the target illicit drugs are they are likely to be male, aged 30-39 years, be driving a car on Friday, Saturday or Sunday between 6:00PM and 6:00AM and to test positive for methamphetamine.

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.

The potential role of lycopene for the prevention and therapy of prostate cancer : from molecular mechanisms to clinical evidence

Lycopene is a phytochemical that belongs to a group of pigments known as carotenoids. It is red, lipophilic and naturally occurring in many fruits and vegetables, with tomatoes and tomato-based products containing the highest concentrations of bioavailable lycopene. Several epidemiological studies have linked increased lycopene consumption with decreased prostate cancer risk. These findings are supported by in vitro and in vivo experiments showing that lycopene not only enhances the antioxidant response of prostate cells, but that it is even able to inhibit proliferation, induce apoptosis and decrease the metastatic capacity of prostate cancer cells. However, there is still no clearly proven clinical evidence supporting the use of lycopene in the prevention or treatment of prostate cancer, due to the only limited number of published randomized clinical trials and the varying quality of existing studies. The scope of this article is to discuss the potential impact of lycopene on prostate cancer by giving an overview about its molecular mechanisms and clinical effects. © 2013 by the authors; licensee MDPI, Basel, Switzerland.