Epidermal growth factor receptors and cyclooxygenase-2 in the pathogenesis of non-small cell lung cancer : potential targets for chemoprevention and systemic therapy

The epidermal growth factor receptor (EGFR) is part of a family of plasma membrane receptor tyrosine kinases that control many important cellular functions, from growth and proliferation to cell death. Cyclooxygenase (COX)-2 is an enzyme which catalyses the conversion of arachidonic acid to prostagladins and thromboxane. It is induced by various inflammatory stimuli, including the pro-inflammatory cytokines, Interleukin (IL)-1β, Tumour Necrosis Factor (TNF)-α and IL-2. Both EGFR and COX-2 are over-expressed in non-small cell lung cancer (NSCLC) and have been implicated in the early stages of tumourigenesis. This paper considers their roles in the development and progression of lung cancer, their potential interactions, and reviews the recent progress in cancer therapies that are directed toward these targets. An increasing body of evidence suggests that selective inhibitors of both EGFR and COX-2 are potential therapeutic agents for the treatment of NSCLC, in the adjuvant, metastatic and chemopreventative settings. © 2002 Elsevier Science Ireland Ltd. All rights reserved.

Randomized phase II study of cetuximab plus cisplatin/vinorelbine compared with cisplatin/vinorelbine alone as first-line therapy in EGFR-expressing advanced non-small-cell lung cancer

Background: The Lung Cancer Cetuximab Study is an open-label, randomized phase II pilot study of cisplatin and vinorelbine combined with the epidermal growth factor receptor (EGFR)-targeted monoclonal antibody cetuximab versus cisplatin and vinorelbine alone, in patients with advanced EGFR-expressing, non-small-cell lung cancer (NSCLC). End points of the study are activity, safety and pharmacokinetics. Patients and methods: Following randomization, for a maximum of eight cycles, patients received three-weekly cycles of cisplatin (80 mg/m2, day 1) and vinorelbine (25 mg/m2 on days 1 and 8) alone or following cetuximab treatment (initial dose 400 mg/m, followed by 250 mg/m2 weekly thereafter). Results: Eighty-six patients were randomly allocated to the study (43 per arm). Confirmed response rates were 28% in the cisplatin/vinorelbine arm (A) and 35% in the cetuximab plus cisplatin/vinorelbine arm (B). Median progression-free survival (PFS) was 4.6 months in arm A and 5.0 months in arm B, with PFS rates at 12 months of 0% and 15%, respectively. Median survival was 7.3 months in arm A and 8.3 months in arm B. The 24-month survival rates were 0% and 16%, respectively. The cetuximab combination was well tolerated. Conclusion: In the first-line treatment of advanced NSCLC, the combination of cetuximab plus cisplatin/vinorelbine demonstrated an acceptable safety profile and the potential to improve activity over cisplatin/vinorelbine alone. © 2007 European Society for Medical Oncology.

Child eating behaviour outcomes of an early feeding intervention to reduce risk indicators for child obesity : the NOURISH RCT

Objective Describe parent-reported child eating behaviour and maternal parenting impact outcomes of an infant feeding intervention to reduce child obesity risk. Design and Methods An assessor masked Randomised Controlled Trial (RCT) with concealed allocation of individual mother-infant dyads. The NOURISH RCT enrolled 698 first-time mothers (mean age 30.1 years, SD=5.3) with healthy term infants (51% female) aged 4.3 months (SD=1.0) at baseline. Outcomes were assessed six months post-intervention when the children were 2-years old. Mothers reported on child eating behaviours using the Child Eating Behaviour Questionnaire (CEBQ), food preferences and dietary intake using a 24-hour telephone recall. Parenting was assessed using five scales validated for use in Australia. Results Intervention effects were evident on the CEBQ overall (MANOVA P=.002) and 4/8 subscales: child satiety responsiveness (P=.03), fussiness (P=.01), emotional overeating (P<.01), and food responsiveness (P=.06). Intervention children ‘liked’ more fruits (P<.01) and fewer non-core foods and beverages (Ps=.06, .03). The intervention mothers reported greater ‘autonomy encouragement’ (P=.002) Conclusions Anticipatory guidance on protective feeding practices appears to have modest positive impacts on child eating behaviours that are postulated to reduce future obesity risk.

The influence of perpetrator and victim intoxication on perceivers' ratings of a sexual perpetrator's own awareness of wrongdoing for his sexually aggressive behaviour

Rape-perception studies have examined the influence of alcohol intoxication on perpetrator blame attributions: However, no studies have examined how intoxication affects perceptions of a sexual perpetrator’s awareness of the wrongfulness of his behaviour despite its relevance to the conceptualisation of responsibility and blame. This experiment investigated the impact of perpetrator and victim intoxication on perceptions of a perpetrator’s own awareness of wrongdoing for acquaintance rape. Undergraduate students (N = 314) read one of four rape-scenarios in which intoxication was manipulated and rated the perpetrator’s awareness of the consequences and wrongfulness of his sexual aggression. Findings supported the hypothesis that participants would assign less awareness of wrongdoing to an intoxicated, compared to sober, perpetrator. Further, males ascribed more awareness of wrongdoing to the perpetrator of an intoxicated, compared to sober, victim. Findings indicate that intoxicated sexual perpetrators are seen as not fully aware of the nature and consequences of their crime.

Phase II trial of Oxaliplatin and 5-Fluorouracil/Leucovorin combination in epithelial ovarian carcinoma relapsing within 2 years of platinum-based therapy

Objective To evaluate the efficacy and toxicity of Oxaliplatin and 5-Fluorouracil (5-FU)/Leucovorin (LV) combination in ovarian cancer relapsing within 2 years of prior platinum-based chemotherapy in a phase II trial. Methods Eligible patients had at least one prior platinum-based chemotherapy regimen, elevated CA-125 ≥ 60 IU/l, radiological evidence of disease progression and adequate hepatic, renal and bone marrow function. Patients with raised CA-125 levels alone as marker of disease relapse were not eligible. Oxaliplatin (85 mg/m 2) was given on day 1, and 5-Fluorouracil (370 mg/m 2) and Leucovorin (30 mg) was given on days 1 and 8 of a 14-day cycle. Results Twenty-seven patients were enrolled. The median age was 57 years (range 42-74 years). The median platinum-free interval (PFI) was 5 months (range 0-17 months) with only 30% of patients being platinum sensitive (PFI > 6 months). Six patients (22%) had two prior regimens of chemotherapy. A total of 191 cycles were administered (median 7; range 2-12). All patients were evaluable for toxicity. The following grade 3/4 toxicities were noted: anemia 4%; neutropenia 15%; thrombocytopenia 11%; neurotoxicity 8%; lethargy 4%; diarrhea 4%; hypokalemia 11%; hypomagnesemia 11%. Among 27 enrolled patients, 20 patients were evaluable for response by WHO criteria and 25 patients were evaluable by Rustin's CA-125 criteria. The overall response rate (RR) by WHO criteria was 30% (95% CI: 15- 52) [three complete responses (CRs) and three partial responses (PRs)]. The CA-125 response rate was 56% (95% CI: 37-73). Significantly, a 25% (95% CI: 9-53) radiological and a 50% (95% CI: 28-72) CA-125 response rate were noted in platinum resistant patients (PFI < 6 months). The median response duration was 4 months (range 3-12) and the median overall survival was 10 months. Conclusion Oxaliplatin and 5-Fluorouracil/ Leucovorin combination has a good safety profile and is active in platinum-pretreated advanced epithelial ovarian cancer. © 2004 Elsevier Inc. All rights reserved.

Atomistic simulation of interfacial behaviour in graphene-polymer nanocomposites

Graphene–polymer nanocomposites have promising properties as new structural and functional materials. The remarkable mechanical property enhancement in these nanocomposites is generally attributed to exceptional mechanical property of graphene and possible load transfer between graphene and polymer matrix. However, the underlying strengthening and toughening mechanisms have not been well understood. In this work, the interfacial behavior of graphene-polyethylene (PE) was investigated using molecular dynamics (MD) method. The interfacial shear force (ISF) and interfacial shear stress (ISS) between graphene and PE matrix were evaluated, taking into account graphene size, the number of graphene layers and the structural defects in graphene. MD results show that the ISS at graphene-PE interface mainly distributes at each end of the graphene nanofiller within the range of 1 nm, and much larger than that at carbon nanotube (CNT)-PE interface. Moreover, it was found that the ISS at graphene-PE interface is sensitive to the layer number.

Robust recognition of human behaviour in challenging environments

Novel techniques have been developed for the automatic recognition of human behaviour in challenging environments using information from visual and infra-red camera feeds. The techniques have been applied to two interesting scenarios: Recognise drivers' speech using lip movements and recognising audience behaviour, while watching a movie, using facial features and body movements. Outcome of the research in these two areas will be useful in the improving the performance of voice recognition in automobiles for voice based control and for obtaining accurate movie interest ratings based on live audience response analysis.

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.

FRC erection stages dynamic behaviour under wind loads

Buffeting response of a cable-stayed bridge under construction is investigated through wind tunnel tests and numerical simulations. Two configurations of the erection stage have been considered and compared in terms of dynamic response and internal forces using the results of the experimental aeroelastic models. Moreover the results of a numerical model able to simulate the simultaneous effects of vortex shedding from tower and aeroelastic response of the deck are compared to the wind tunnel ones.

Exploring the effect of aquatic exercise on behaviour and psychological wellbeing in people with moderate to severe dementia : a pilot study of the Watermemories Swimming Club

Aim To explore the effects of a dementia-specific, aquatic exercise intervention on behavioural and psychological symptoms in people with dementia (BPSD). Method Residents from two aged care facilities in Queensland, Australia, received a 12-week intervention consisting of aquatic exercises for strength, agility, flexibility, balance and relaxation. The Psychological Well-Being in Cognitively Impaired Persons Scale (PW-BCIP) and the Revised Memory and Behaviour Problems Checklist (RMBPC) were completed by registered nurses at baseline, week 6, week 9 and post intervention. Results Ten women and one man (median age = 88.4 years, interquartile range = 12.3) participated. Statistically significant declines in the RMBPC and PW-BCIP were observed over the study period. Conclusion Preliminary evidence suggests that a dementia-specific, aquatic exercise intervention reduces BPSD and improves psychological well-being in people with moderate to severe dementia. With further testing, this innovative intervention may prove effective in addressing some of the most challenging aspects of dementia care.

Punishment Avoidance and Intentional Risky Driving Behaviour : What are the Implications for ‘Getting Away with it’?

Every motorised jurisdiction mandates legal driving behaviour which facilitates driver mobility and road user safety through explicit road rules that are enforced by regulatory authorities such as the Police. In road safety, traffic law enforcement has been very successfully applied to modify road user behaviour, and increasingly technology is fundamental in detecting illegal road user behaviour. Furthermore, there is also sound evidence that highly visible and/or intensive enforcement programs achieve long-term deterrent effects. To illustrate, in Australia random breath testing has considerably reduced the incidence and prevalence of driving whilst under the influence of alcohol. There is, however, evidence that many road rules continue to be broken, including speeding and using a mobile phone whilst driving, and there are many instances where drivers are not detected or sufficiently sanctioned for these transgressions. Furthermore, there is a growing body of evidence suggesting that experiences of punishment avoidance – that is, successful attempts at avoiding punishment such as drivers talking themselves out of a ticket, or changing driving routes to evade detection –are associated with and predictive of the extent of illegal driving behaviour and future illegal driving intentions. Therefore there is a need to better understand the phenomenon of punishment avoidance to enhance our traffic law enforcement procedures and therefore safety of all road users. This chapter begins with a review of the young driver road safety problem, followed by an examination of contemporary deterrence theory to enhance our understanding of both the experiences and implications of punishment avoidance in the road environment. It is noteworthy that in situations where detection and punishment remain relatively rare, such as on extensive road networks, the research evidence suggests that experiences of punishment avoidance may have a stronger influence upon risky driving behaviour than experiences of punishment. Finally, data from a case study examining the risky behaviour of young drivers will be presented, and the implications for ‘getting away with it’ will be discussed.

Concealed texting while driving : what are young people’s beliefs about this risky behaviour?

Making a conscious effort to hide the fact that one is texting while driving (i.e., concealed texting) is a deliberate and risky behaviour involving attention diverted from the road. As the most frequent users of text messaging services and mobile phones while driving, young people appear at heightened crash risk from engaging in this behaviour. First, several small focus group discussions (N = 12) were carried out to elicit the underlying salient beliefs regarding this behaviour, in accordance with the Theory of Planned Behaviour (TPB). Findings from these discussions, in conjunction with available prior evidence regarding general mobile phone use while driving, then informed questionnaire items that assessed young peoples’ beliefs regarding this behaviour, as well as intention to engage in this behaviour in the next week. In the questionnaire phase of the study, participants (N = 171) were aged 17–25 years, owned a mobile phone, and held a current driver’s licence. Results showed that there were significant differences between low and high intenders (to engage in concealed texting while driving) on the behavioural, normative, and control beliefs investigated. Specifically, high intenders were more likely to believe that concealed texting while driving would result in sharing information with others, using time effectively, and were less likely to think that free-flowing traffic would prevent their engagement in this behaviour. By targeting these beliefs, these findings may potentially inform the development of advertising and other public intervention strategies, aimed at ensuring young drivers reconsider their engagement in this risky behaviour.

Awareness of risky behaviour among Chinese drivers

Background In China, as in many developing countries, rapid increases in car ownership and new drivers have been coupled with a large trauma burden. The World Health Organization has identified key risk factors including speeding, drink-driving, helmet and restraint non-use, overloaded vehicles, and fatigued-driving in many rapidly motorising countries, including China. Levels of awareness of these risk factors among road users are not well understood. Although research identifies speeding as the major factor contributing to road crashes in China, there appears to be widespread acceptance of it among the broader community. Purpose To assess self-reported speeding and awareness of crash risk factors among Chinese drivers in Beijing. Methods Car drivers (n=299) were recruited from car washing locations and car parks to complete an anonymous questionnaire. Perceptions of the relative risk of drink-driving, fatigued-driving and speeding, and attitudes towards speeding and self-reported driving speeds were assessed. Results Overall, driving speeds of >10km/hr above posted limits on two road types (60 and 80 km/hour zones) were reported by more than one third of drivers. High-range speeding (i.e., >30 km/hour in a 60 km/hour zone and >40 km/hour in an 80 km/hour zone) was reported by approximately 5% of the sample. Attitudinal measures indicated that approximately three quarters of drivers reported attitudes that were not supportive of speeding. Drink-driving was identified as the most risky behaviour; 18% reported the perception that drink-driving had the same level of danger as speeding and 82% reported it as more dangerous. For fatigued-driving, 1% reported the perception that it was not as dangerous as speeding; 27.4% reported it as the same level and 71.6% perceived it as more dangerous. Conclusion Driving speeds well above posted speed limits were commonly reported by drivers. Speeding was rated as the least dangerous on-road behaviour, compared to drink-driving and fatigued-driving. One third of drivers reported regularly engaging in speeds at least 10km/hr above posted limits, despite speeding being the major reported contributor to crashes. Greater awareness of the risks associated with speeding is needed to help reduce the road trauma burden in China and promote greater speed limit compliance.

Greener workplace : understanding senior management's adoption decisions through the Theory of Planned Behaviour

Human Resources (HR) policies and practices have changed due to global environmental instability. These policies and practices are key factors for successful environmental management. Using the Theory of Planned Behaviour, this article aims to understand the critical factors which influence senior management’s decision to adopt ‘green’ HR practices. Data were collected from 210 organisations in Australia using two separate surveys. Survey one, which was addressed directly to HR managers and directors, contained questions relating to HR policies (the dependent variables), while survey two, which was addressed directly to CEOs and senior managers, contained questions about environmental-related attitudes, subjective norms and perceived control (the independent variables). Results indicated that senior management’s environmental-related attitudes, subjective norms from stakeholders and perceived green resource readiness influenced their decision to adopt green HR initiatives. However, attitudes and green resource readiness in particular had greater impacts than subjective norms. Limitations, implications and future research are also outlined.