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.

Sink or Swim? : Revising Ophelia in contemporary young adult fiction

Shakespeare’s Hamlet has in recent years been used by a number of young adult novels to define and authorise representations of gendered adolescent subjectivity. In so doing, these novels attend not only to Shakespeare’s play but also to other adaptations of the play. For example, the long cultural history of Ophelia being used as a template for depicting adolescent femininity as risky or dangerous is as influential as the play itself in early twenty-first century novels. This paper reads such novels for the ways in which codes of gender and of genre circulate in adolescent fiction when linked explicitly with Shakespearean texts and traditions.

Citizenship, community, public space and the marginalisation of children and young people

Throughout Australia (and in comparable urban contexts around the world) public spaces may be said to be under attack by developers and also attempts by civic authorities to regulate, restrict, rebrand and reframe them. A consequence of the increasingly security driven, privatised and surveilled nature of public space is the exclusion and displacement of those considered flawed and unwelcome in the ‘spectacular’ consumption spaces of many major urban centres. In the name of urban regeneration, processes of securitisation, ‘gentrification’ and creative cities discourses can refashion public space as sites of selective inclusion and exclusion. In this context of monitoring and control procedures, children and young people’s use of space in parks, neighbourhoods, shopping malls and streets is often viewed as a threat to the social order, requiring various forms of punitive and/or remedial action. This paper discusses developments in the surveillance, governance and control of public space used by children and young people in particular and the capacity for their displacement and marginality, diminishing their sense of place and belonging, and right to public space as an expression of their civil, political and social citizenship(s).

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.

Through-focus performance with multifocal contact lenses : effect of binocularity, pupil diameter and inherent ocular aberrations

Purpose to evaluate the effects of the wearer’s pupil size and spherical aberration on visual performance with centre-near, aspheric multifocal contact lenses (MFCLs). The advantage of binocular over monocular vision was also investigated. Methods Twelve young volunteers, with an average age of 27±5 years, participated in the study. LogMAR Visual Acuity (VA) was measured under cycloplegia for a range of defocus levels (from +3.0 to -3.0D, in 0.5D steps) with no correction and with three aspheric MFCLs (Air Optix Aqua Multifocal, Ciba Vision, Duluth, GA, US) with a centre-near design, providing correction for “Low”, “Med” and “High” near demands. Measurements were performed for all combinations of the following conditions: i) artificial pupils of 6mm and 3mm diameter, ii) binocular and monocular (dominant eye) vision. Depth-of-focus (DOF) was calculated from the VA vs. defocus curves. Ocular aberrations under cycloplegia were measured using iTrace. Results VA at -3.0D defocus (simulating near performance) was statistically higher for the 3mm than for the 6mm pupil (p=0.006), and for binocular rather than for monocular vision (p<0.001). Similarly, DOF was better for the 3mm pupil (p=0.002) and for binocular viewing conditions (p<0.001, ANOVA). Both VA at –3.0D defocus and DOF increased as the “addition” of the MFCL correction increased. Finally, with the centre-near MFCLs a linear correlation was found between VA at –3.0D defocus and the wearer’s ocular spherical aberration (R2=0.20 p<0.001 for 6mm data), with the eyes exhibiting the higher positive spherical aberration experiencing lower VAs. By contrast, no correlation was found between VA and spherical aberration at 0.00D defocus (distance vision). Conclusions Both near VA and depth-of-focus improve with these MFCLs, with the effects being more pronounced for small pupils and binocular than for monocular vision. Coupling of the wearer’s ocular spherical aberration with the aberration profiles provided by MFCLs affects their functionality.

Effect of text type on near work-induced contrast adaptation in myopic and emmetropic young adults

Purpose Contrast adaptation has been speculated to be an error signal for emmetropization. Myopic children exhibit higher contrast adaptation than emmetropic children. This study aimed to determine whether contrast adaptation varies with the type of text viewed by emmetropic and myopic young adults. Methods Baseline contrast sensitivity was determined in 25 emmetropic and 25 spectacle-corrected myopic young adults for 0.5, 1.2, 2.7, 4.4, and 6.2 cycles per degree (cpd) horizontal sine wave gratings. The adults spent periods looking at a 6.2 cpd high-contrast horizontal grating and reading lines of English and Chinese text (these texts comprised 1.2 cpd row and 6 cpd stroke frequencies). The effects of these near tasks on contrast sensitivity were determined, with decreases in sensitivity indicating contrast adaptation. Results Contrast adaptation was affected by the near task (F2,672 = 43.0; P < 0.001). Adaptation was greater for the grating task (0.13 ± 0.17 log unit, averaged across all frequencies) than reading tasks, but there was no significant difference between the two reading tasks (English 0.05 ± 0.13 log unit versus Chinese 0.04 ± 0.13 log unit). The myopic group showed significantly greater adaptation (by 0.04, 0.04, and 0.05 log units for English, Chinese, and grating tasks, respectively) than the emmetropic group (F1,48 = 5.0; P = 0.03). Conclusions In young adults, reading Chinese text induced similar contrast adaptation as reading English text. Myopes exhibited greater contrast adaptation than emmetropes. Contrast adaptation, independent of text type, might be associated with myopia development.

Receptor tyrosine kinases and their activation in melanoma

Receptor tyrosine kinases (RTKs) and their downstream signalling pathways have long been hypothesized to play key roles in melanoma development. A decade ago, evidence was derived largely from animal models, RTK expression studies and detection of activated RAS isoforms in a small fraction of melanomas. Predictions that overexpression of specific RTKs implied increased kinase activity and that some RTKs would show activating mutations in melanoma were largely untested. However, technological advances including rapid gene sequencing, siRNA methods and phospho-RTK arrays now give a more complete picture. Mutated forms of RTK genes including KIT, ERBB4, the EPH and FGFR families and others are known in melanoma. Additional over- or underexpressed RTKs and also protein tyrosine phosphatases (PTPs) have been reported, and activities measured. Complex interactions between RTKs and PTPs are implicated in the abnormal signalling driving aberrant growth and survival in malignant melanocytes, and indeed in normal melanocytic signalling including the response to ultraviolet radiation. Kinases are considered druggable targets, so characterization of global RTK activity in melanoma should assist the rational development of tyrosine kinase inhibitors for clinical use. © 2011 John Wiley & Sons A/S.

Punk’s fairy godfather : Go-Between John Willsteed on Lou Reed

Obituary on the death of Lou Reed, member of The Velvet Underground and acclaimed solo artist.

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.

Bail and remand for young people in Australia : a national research project

Funded and endorsed by the Australasian Juvenile Justice Administrators, this is one of the first national scale research reports into the bail and remand practices for young Australians. A young person can be placed in custody on remand (ie refused bail) after being arrested by police in relation to a suspected criminal offence, before entering a plea, while awaiting trial, during trial or awaiting sentence. Although custodial remand plays an important role in Western criminal justice systems, minimising the unnecessary use of remand is important given the obligations Australia has under several UN instruments to use, as a last resort, youth detention of any kind. This research identifies trends in the use of custodial remand and explores the factors that influence its use for young people nationally and in each of Australia’s jurisdictions.

Submission to the inquiry into the high level of involvement of Indigenous juveniles and young adults in the criminal justice system

Introduction • The Australian Institute of Criminology (AIC) is Australia's national research and knowledge centre on crime and justice. • The Institute seeks to promote justice and reduce crime by undertaking and communicating evidence-based research to inform policy and practice. • The AIC is governed by the Criminology Research Act and has been in operation since 1973. • The AIC is pleased to have the opportunity to contribute to the Committee's Inquiry into the high level of involvement of Indigenous juveniles and young adults in the criminal justice system. • There is a great deal of evidence to demonstrate that Indigenous young people are significantly over-represented at every stage of the criminal justice system in Australia.

“We’re not like these weird feather boa-covered AIDS-spreading monsters” : How LGBT young people and service providers think riskiness informs LGBT youth–police interactions

Research has suggested that lesbian, gay, bisexual and transgender (LGBT) young people are “at-risk” of victimization and/or legally “risky.” Relatively few studies have examined the social construction of risk in “risk factor” research and whether risk as a concept influences the everyday lives of LGBT young people. This article reports how 35 LGBT young people and seven service provider staff in Brisbane, Queensland, Australia perceived LGBT youth–police interactions as reflecting discourses about LGBT riskiness and danger. The participants specifically note how they thought looking at-risk and/or looking risky informed their policing experiences. The article concludes with recommendations for improving future policing practice.

Talk in activity during young children’s use of digital technologies at home

Internet-connected tablets and smart phones are being used increasingly by young children. Little is known, however, about their social interactions with family members when engaged with these technologies. This article examines video-recorded interactions between a father and his two young children, one aged 18 months using an iPhone and one aged three years accessing an iPad. Drawing on Ethnomethodology and Conversation Analysis, analysis establishes ways the family members engage and disengage in talk so as to manage their individual activity with mobile devices and accomplish interaction with each other. Findings are relevant for understanding children’s everyday practices with mobile technologies.

Testing an extended theory of planned behavior to predict young people's intentions to join a bone marrow donor registry

An extended theory of planned behavior (TPB) was used to understand the factors, particularly control perceptions and affective reactions, given conflicting findings in previous research, informing younger people's intentions to join a bone marrow registry. Participants (N  = 174) completed attitude, subjective norm, perceived behavioral control (PBC), moral norm, anticipated regret, self-identity, and intention items for registering. The extended TPB (except PBC) explained 67.2% of variance in intention. Further testing is needed as to the volitional nature of registering. Moral norm, anticipated regret, and self-identity are likely intervention targets for increasing younger people's bone marrow registry participation.