Cyclooxygenase-2 protein levels are independent of epidermal growth factor receptor expression or activation in operable non-small cell lung cancer

Both cyclooxygenase (COX)-2 and epidermal growth factor receptor (EGFR) are thought to play important roles in the pathogenesis of non-small cell lung cancer (NSCLC). A number of in vitro studies have postulated a link between EGFR activation and subsequent COX-2 upregulation. The relationship between these factors has not been established in patients with NSCLC. COX-2 and EGFR expression were studied in 172 NSCLC specimens using standard immunohistochemical techniques. Western blotting was used to determine COX-2 and EGFR levels in five NSCLC cell lines. The effect of treatment with EGF on COX-2 expression in A549 cells was assessed. Results: Both EGFR and COX-2 are overexpressed in NSCLC. The predominant pattern of COX-2 and EGFR staining was cytoplasmic. Membranous EGFR staining was seen in 23.3% of cases. There was no relationship between COX-2 and EGFR expression and survival or any clinicopathological features. No correlation was seen between EGFR expression and COX-2 expression in the immunohistochemical series or in the cell lines. Treatment with EGF did not upregulate COX-2 levels in A549 cells, either in serum free or serum-supplemented conditions. Conclusions: Although COX-2 and EGFR are over-expressed in NSCLC neither was of prognostic significance in this series of cases. There is no correlation between these two factors in either tumour samples or cell lines. Although these factors show no correlation in NSCLC, they remain potential, though independent targets for treatment. © 2004 Elsevier Ireland Ltd. All rights reserved.

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.

Association between maternal depressive symptoms in the early postnatal period and responsiveness in feeding at child age 2 years

Maternal depression is a known risk factor for poor outcomes for children. Pathways to these poor outcomes relate to reduced maternal responsiveness or sensitivity to the child. Impaired responsiveness potentially impacts the feeding relationship and thus may be a risk factor for inappropriate feeding practices. The aim of this study was to examine the longitudinal relationships between self-reported maternal post-natal depressive symptoms at child age 4 months and feeding practices at child age 2 years in a community sample. Participants were Australian first-time mothers allocated to the control group of the NOURISH randomized controlled trial when infants were 4 months old. Complete data from 211 mothers (of 346 allocated) followed up when their children were 2 years of age (51% girls) were available for analysis. The relationship between Edinburgh Postnatal Depression Scale (EPDS) score (child age 4 months) and child feeding practices (child age 2 years) was tested using hierarchical linear regression analysis adjusted for maternal and child characteristics. Higher EPDS score was associated with less responsive feeding practices at child age 2 years: greater pressure [β = 0.18, 95% confidence interval (CI): 0.04–0.32, P = 0.01], restriction (β = 0.14, 95% CI: 0.001–0.28, P = 0.05), instrumental (β = 0.14, 95% CI: 0.005–0.27, P = 0.04) and emotional (β = 0.15, 95% CI: 0.01–0.29, P = 0.03) feeding practices (ΔR2 values: 0.02–0.03, P < 0.05). This study provides evidence for the proposed link between maternal post-natal depressive symptoms and lower responsiveness in child feeding. These findings suggest that the provision of support to mothers experiencing some levels of depressive symptomatology in the early post-natal period may improve responsiveness in the child feeding relationship.

Playing with Grammar in the Early Years : Learning about Language in the Australian Curriculum : English

As teacher/researchers interested in the pursuit of socially-just outcomes in early childhood education, the form and function of language occupies a special position in our work. We believe that mastering a range of literacy competences includes not only the technical skills for learning, but also the resources for viewing and constructing the world (Freire and Macdeo, 1987). Rather than seeing knowledge about language as the accumulation of technical skills alone, the viewpoint to which we subscribe treats knowledge about language as a dialectic that evolves from, is situated in, and contributes to a social arena (Halliday, 1978). We do not shy away from this position just because children are in the early years of schooling. In ‘Playing with Grammar’, we focus on the Foundation to Year 2 grouping, in line with the Australian Curriculum, Assessment and Reporting Authority’s (hereafter ACARA) advice on the ‘nature of learners’ (ACARA, 2013). With our focus on the early years of schooling comes our acknowledgement of the importance and complexity of play. At a time where accountability in education has moved many teachers to a sense of urgency to prove language and literacy achievement (Genishi and Dyson, 2009), we encourage space to revisit what we know about literature choices and learning experiences and bring these together to facilitate language learning. We can neither ignore, nor overemphasise, the importance of play for the development of language through: the opportunities presented for creative use and practice; social interactions for real purposes; and, identifying and solving problems in the lives of young children (Marsh and Hallet, 2008). We argue that by engaging young children in opportunities to play with language we are ultimately empowering them to be active in their language learning and in the process fostering a love of language and the intricacies it holds. Our goal in this publication is to provide a range of highly practical strategies for scaffolding young children through some of the Content Descriptions from the Australian Curriculum English Version 5.0, hereafter AC:E V5.0 (ACARA, 2013). This recently released curriculum offers a new theoretical approach to building children’s knowledge about language. The AC:E V5.0 uses selected traditional terms through an approach developed in systemic functional linguistics (see Halliday and Matthiessen, 2004) to highlight the dynamic forms and functions of multimodal language in texts. For example, the following statement, taken from the ‘Language: Knowing about the English language’ strand states: English uses standard grammatical terminology within a contextual framework, in which language choices are seen to vary according to the topics at hand, the nature and proximity of the relationships between the language users, and the modalities or channels of communication available (ACARA, 2013). Put simply, traditional grammar terms are used within a functional framework made up of field, tenor, and mode. An understanding of genre is noted with the reference to a ‘contextual framework’. The ‘topics at hand’ concern the field or subject matter of the text. The ‘relationships between the language users’ is a description of tenor. There is reference to ‘modalities’, such as spoken, written or visual text. We posit that this innovative approach is necessary for working with contemporary multimodal and cross-cultural texts (see Exley and Mills, 2012). We believe there is enormous power in using literature to expose children to the richness of language and in turn develop language and literacy skills. Taking time to look at language patterns within actual literature is a pathway to ‘…capture interest, stir the imagination and absorb the [child]’ into the world of language and literacy (Saxby, 1993, p. 55). In the following three sections, we have tried to remain faithful to our interpretation of the AC:E V5.0 Content Descriptions without giving an exhaustive explanation of the grammatical terms. Other excellent tomes, such as Derewianka (2011), Humphrey, Droga and Feez (2012), and Rossbridge and Rushton (2011) provide these more comprehensive explanations as does the AC:E V5.0 Glossary. We’ve reproduced some of the AC:E V5.0 glossary at the end of this publication. Our focus is on the structure and unfolding of the learning experiences. We outline strategies for working with children in Foundation, Year 1 and Year 2 by providing some demonstration learning experiences based on texts we’ve selected, but maintain that the affordances of these strategies will only be realised when teaching and learning is purposively tied to authentic projects in local contexts. We strongly encourage you not to use only the resource texts we’ve selected, but to capitalise upon your skill for identifying the language features in the texts you and the children are studying and adapt some of the strategies we have outlined. Each learning experience is connected to one of the Content Descriptions from the AC:E V5.0 and contains an experience specific purpose, a suggested resource text and a sequence for the experience that always commences with an orientation to text followed by an examination of a particular grammatical resource. We expect that each of these learning experiences will take a couple if not a few teaching episodes to work through, especially if children are meeting a concept for the first time. We hope you use as much, or as little, of each experience as is needed. Our plans allow for focused discussion, shared exploration and opportunities to revisit the same text for the purpose of enhancing meaning making. We do not want the teaching of grammar to slip into a crisis of irrelevance or to be seen as a series of worksheet drills with finite answers. Strategies for effective practice, however, have much portability. We are both very keen to hear from teachers who are adopting and adapting these learning experiences in their classrooms. Please email us on b.exley@qut.edu.au or lkervin@uow.edu.au. We’d love to continue the conversation with you over time.

The role of sleepiness, sleep disorders, and the work environment on heavy-vehicle crashes in 2 Australian states

Heavy-vehicle driving involves a challenging work environment and a high crash rate. We investigated the associations of sleepiness, sleep disorders, and work environment (including truck characteristics) with the risk of crashing between 2008 and 2011 in the Australian states of New South Wales and Western Australia. We conducted a case-control study of 530 heavy-vehicle drivers who had recently crashed and 517 heavy-vehicle drivers who had not. Drivers' crash histories, truck details, driving schedules, payment rates, sleep patterns, and measures of health were collected. Subjects wore a nasal flow monitor for 1 night to assess for obstructive sleep apnea. Driving schedules that included the period between midnight and 5:59 am were associated with increased likelihood of crashing (odds ratio = 3.42, 95% confidence interval: 2.04, 5.74), as were having an empty load (odds ratio = 2.61, 95% confidence interval: 1.72, 3.97) and being a less experienced driver (odds ratio = 3.25, 95% confidence interval: 2.37, 4.46). Not taking regular breaks and the lack of vehicle safety devices were also associated with increased crash risk. Despite the high prevalence of obstructive sleep apnea, it was not associated with the risk of a heavy-vehicle nonfatal, nonsevere crash. Scheduling of driving to avoid midnight-to-dawn driving and the use of more frequent rest breaks are likely to reduce the risk of heavy-vehicle nonfatal, nonsevere crashes by 2–3 times.

Percutaneous coronary intervention with drug-eluting stents or coronary artery bypass surgery in subjects with type 2 diabetes : evaluation of: Farkouth ME, Domanski M, Sleeper LA, et al. Strategies for multivessel revascularization in patients with diabetes. N Engl J Med 2012;367(25):2375-84, and Contini GA, Nicolini F, Fortuna D, et al. Five-year outcomes of surgical or percutaneous myocardial revascularization in diabetic patients. Int J Cardiol 2012. [Epub ahead of print]

There is debate as to whether percutaneous coronary intervention (PCI) with drug-eluting stents or coronary artery bypass surgery (CABG) is the best procedure for subjects with type 2 diabetes and coronary artery disease requiring revascularization. There is some evidence that following these procedures there is less further revascularization with CABG than PCI in subjects with diabetes. Two recent studies; the FREEDOM (Future Revascularization Evaluation in patients with Diabetes mellitus: Optimal Management of Multivessel Disease) trial, and a trial using a real world diabetic population from a Registry, have shown that the benefits of CABG over PCI in subjects with type 2 diabetes extends to lower rates of death and myocardial infarct, in addition to lower rates of revascularization. However, the rates of stroke may be higher with CABG than PCI with drug-eluting stents in this population. Thus, if CABG is going to be preferred to PCI in subjects with type 2 diabetes and multivessel coronary disease, consideration should be given to how to reduce the rates of stroke with CABG.

Directory of World Cinema : Australia and New Zealand 2

Building on and bringing up to date the material presented in the first installment of Directory of World Cinema : Australia and New Zealand, this volume continues the exploration of the cinema produced in Australia and New Zealand since the beginning of the twentieth century. Among the additions to this volume are in-depth treatments of the locations that feature prominently in the countries' cinema. Essays by leading critics and film scholars consider the significance in films of the outback and the beach, which is evoked as a liminal space in Long Weekend and a symbol of death in Heaven's Burning, among other films. Other contributions turn the spotlight on previously unexplored genres and key filmmakers, including Jane Campion, Rolf de Heer, Charles Chauvel, and Gillian Armstrong.

An extracellular signal-regulated kinase 2 survival pathway mediates resistance of human mesothelioma cells to asbestos-induced injury

We hypothesized that normal human mesothelial cells acquire resistance to asbestos-induced toxicity via induction of one or more epidermal growth factor receptor (EGFR) - linked survival pathways (phosphoinositol-3-kinase/AKT/ mammalian target of rapamycin and extracellular signal - regulated kinase [ERK] 1/2) during simian virus 40 (SV40) transformation and carcinogenesis. Both isolated HKNM-2 mesothelial cells and a telomerase-immortalized mesothelial line (LP9/TERT-1) were more sensitive to crocidolite asbestos toxicity than an SV40 Tag-immortalized mesothelial line (MET5A) and malignant mesothelioma cell lines (HMESO and PPM Mill). Whereas increases in phosphorylation of AKT (pAKT) were observed in MET5A cells in response to asbestos, LP9/TERT-1 cells exhibited dose-related decreases in pAKT levels. Pretreatment with an EGFR phosphorylation or mitogen-activated protein kinase kinase 1/2 inhibitor abrogated asbestos-induced phosphorylated ERK (pERK) 1/2 levels in both LP9/TERT-1 and MET5A cells as well as increases in pAKT levels in MET5A cells. Transient transfection of small interfering RNAs targeting ERK1, ERK2, or AKT revealed that ERK1/2 pathways were involved in cell death by asbestos in both cell lines. Asbestos-resistant HMESO or PPM Mill cells with high endogenous levels of ERKs or AKT did not show dose-responsive increases in pERK1/ERK1, pERK2/ERK2, or pAKT/AKT levels by asbestos. However, small hairpin ERK2 stable cell lines created from both malignant mesothelioma lines were more sensitive to asbestos toxicity than shERK1 and shControl lines, and exhibited unique, tumor-specific changes in endogenous cell death - related gene expression. Our results suggest that EGFR phosphorylation is causally linkedto pERK and pAKT activation by asbestos in normal and SV40 Tag - immortalized human mesothelial cells. They also indicate that ERK2 plays a role in modulating asbestos toxicity by regulating genes critical to cell injury and survival that are differentially expressed in human mesotheliomas.

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.

Bounded rationality and voting decisions over 160 years : voter behavior and increasing complexity in decision-making

Using a quasi-natural voting experiment encompassing a 160-year period (1848–2009) in Switzerland, we investigate whether a higher level of complexity leads to increased reliance on trusted parliamentary representatives. We find that when more referenda are held on the same day, constituents are more likely to refer to parliamentary recommendations when making their decisions. This finding holds true even when we narrow our focus to referenda with a relatively lower voter turnout on days on which more than one referendum is held. We also demonstrate that when constituents face a higher level of complexity, they follow the parliamentary recommendations rather than those of interest groups. "Viewed as a geometric figure, the ant’s path is irregular, complex, hard to describe. But its complexity is really a complexity in the surface of the beach, not a complexity in the ant." ([1] p. 51)

RNA silencing in plants: Yesterday, today, and tomorrow

RNA silencing has become a major focus of molecular biology and biomedical research around the world. This is highlighted by a simple PubMed search for “RNA silencing,” which retrieves almost 9,000 articles. Interest in gene silencing-related mechanisms stemmed from the early 1990s, when this phenomenon was first noted as a surprise observation by plant scientists during the course of plant transformation experiments, in which the introduction of a transgene into the genome led to the silencing of both the transgene and homologous endogenes. From these initial studies, plant biologists have continued to generate a wealth of information into not only gene silencing mechanisms but also the complexity of these biological pathways as well as revealing their multilevel interactions with one another. The plant biology community has also made significant advancements in exploiting RNA silencing as a powerful tool for gene function studies and crop improvements. In this article, we (1) review the rich history of gene silencing research and the knowledge it has generated into our understanding of this fundamental mechanism of gene regulation in plants; (2) describe examples of the current applications of RNA silencing in crop plants; and (3) discuss improvements in RNA silencing technology and its potential application in plant science.

Community media 2.0 : a report from the 'Co-Creative Communities' forum

Participatory digital culture presents major challenges to all traditional media outlets, but it presents very direct challenges to the community broadcast sector, which was established from the outset as local, community-driven and participatory. These and other issues were the focus of a recent forum at the Australian Centre for the Moving Image in Melbourne (Co-Creative Communities, 8–9 November 2012). The forum was part of a national research project, which has been exploring how Australian community arts and media organisations are responding to participatory digital culture, social media and user-led innovation. Focusing on the organisations who presented at the symposium, the paper examines how community-interest media is making the most of new and social media platforms. It considers examples of participatory digital media that have emerged from the community broadcast sector, but it also considers local, collaborative, community-interest media projects developed by public broadcasters and organisations involved in arts, social justice and development. Drawing on forum transcripts and follow-up research the essay describes some of the key trends shaping how community-interest media organisations and independent producers are working with participatory digital culture, and with what success.

RNA Silencing in Plants

RNA silencing-related mechanisms have been documented in almost all living organisms and RNA silencing is now used as board term to describe the vast array of related processes involving RNA–RNA, RNA–DNA, RNA–protein or protein–protein interactions that ultimately result in the repression of gene expression. In plants, the parallel RNA silencing pathways have evolved to extraordinary levels of complexity and diversity, playing crucial roles in providing protection against invading nucleic acids derived from viruses or replicating transposons, controlling chromatin modifications as well as regulating endogenous gene expression to ensure normal plant growth and development. The aims of this chapter are (1) to provide an overview of the initial curious observations of RNA silencing-related phenomena in plants, (2) to outline the parallel gene silencing pathways of plants, and (3) to discuss current applications of RNA silencing technologies to not only study but also modify plant development