Relationship between EGFR expression, EGFR mutation status, and the efficacy of chemotherapy plus cetuximab in FLEX study patients with advanced non-small-cell lung cancer

INTRODUCTION: The phase III FLEX study (NCT00148798) in advanced non-small-cell lung cancer indicated that the survival benefit associated with the addition of cetuximab to cisplatin and vinorelbine was limited to patients whose tumors expressed high levels of epidermal growth factor receptor (EGFR) (immunohistochemistry score of >/=200; scale 0-300). We assessed whether the treatment effect was also modulated in FLEX study patients by tumor EGFR mutation status. METHODS: A tumor mutation screen of EGFR exons 18 to 21 included 971 of 1125 (86%) FLEX study patients. Treatment outcome in low and high EGFR expression groups was analyzed across efficacy endpoints according to tumor EGFR mutation status. RESULTS: Mutations in EGFR exons 18 to 21 were detected in 133 of 971 tumors (14%), 970 of which were also evaluable for EGFR expression level. The most common mutations were exon 19 deletions and L858R (124 of 133 patients; 93%). In the high EGFR expression group (immunohistochemistry score of >/=200), a survival benefit for the addition of cetuximab to chemotherapy was demonstrated in patients with EGFR wild-type (including T790M mutant) tumors. Although patient numbers were small, those in the high EGFR expression group whose tumors carried EGFR mutations may also have derived a survival benefit from the addition of cetuximab to chemotherapy. Response data suggested a cetuximab benefit in the high EGFR expression group regardless of EGFR mutation status. CONCLUSIONS: The survival benefit associated with the addition of cetuximab to first-line chemotherapy for advanced non-small-cell lung cancer expressing high levels of EGFR is not limited by EGFR mutation status.

Second ESMO consensus conference on lung cancer : pathology and molecular biomarkers for non-small-cell lung cancer

To complement the existing treatment guidelines for all tumour types, ESMO organises consensus conferences to focus on specific issues in each type of tumour. The Second ESMO Consensus Conference on Lung Cancer was held on 11-12 May 2013 in Lugano. A total of 35 experts met to address several questions on management of patients with nonsmall- cell lung cancer (NSCLC) in each of four areas: pathology and molecular biomarkers, early stage disease, locally advanced disease and advanced (metastatic) disease. For each question, recommendations were made including reference to the grade of recommendation and level of evidence. This consensus paper focuses on recommendations for pathology and molecular biomarkers in relation to the diagnosis of lung cancer, primarily non-small-cell carcinomas.

Tailored silica coated Ag nanoparticles for non-invasive surface enhanced Raman spectroscopy of biomolecular targets

Silica coated Ag nanoparticles with defined surface plasmon resonances are used to selectively detect and analyze protein cofactors in solution and on interfaces via surface enhanced resonance Raman spectroscopy. The silica coating has a surprisingly small effect on optical amplification but minimizes unwanted interactions between the protein and the nanoparticle.

The emergent imperatives from a design-led innovation engagement within the mining industry

This research seeks a better and more detailed understanding of the processes of implementing design-led innovation in the mining equipment technology services (METS) sector, in a context where the traditional approach to manufacturing is being challenged. This longitudinal research specifically investigated the barriers to design-led innovation and opportunities that developed throughout this research, to understand how the organisation and culture of a METS company evolved, in order to progress towards design-led change. The significance of these findings is shown in the combined implementation of design imperatives leading towards design-led change at all business levels of an organisational structure.

Predicting the likelihood of non-healing : a venous leg ulcer risk assessment tool

This project developed, validated and tested reliability of a risk assessment tool to predict the risk of failure to heal of patients with venous leg ulcers within 24 weeks. The risk assessment tool will allow clinicians to be able to determine realistic outcomes for their patients, promote early healing and potentially avoid weeks of inappropriate therapy. The tool will also assist in addressing specific risk factors and guide decisions on early, alternative, tailored interventions.

The effect of the addition of hip strengthening exercises to a lumbopelvic exercise programme for the treatment of non-specific low back pain : a randomized controlled trial

Objectives To compare the efficacy of two exercise programs in reducing pain and disability for individuals with non-specific low back pain and to examine the underlying mechanical factors related to pain and disability for individuals with NSLBP. Design A single-blind, randomized controlled trial. Methods: Eighty participants were recruited from eleven community-based general medical practices and randomized into two groups completing either a lumbopelvic motor control or a combined lumbopelvic motor control and progressive hip strengthening exercise therapy program. All participants received an education session, 6 rehabilitation sessions including real time ultrasound training, and a home based exercise program manual and log book. The primary outcomes were pain (0-100mm visual analogue scale), and disability (Oswestry Disability Index V2). The secondary outcomes were hip strength (N/kg) and two-dimensional frontal plane biomechanics (°) measure during the static Trendelenburg test and while walking. All outcomes were measured at baseline and at 6-week follow up. Results There was no statistical difference in the change in pain (xˉ = -4.0mm, t= -1.07, p =0.29, 95%CI -11.5, 3.5) or disability (xˉ = -0.3%, t= -0.19, p =0.85, 95%CI -3.5, 2.8) between groups. Within group comparisons revealed clinically meaningful reductions in pain for both Group One (xˉ =-20.9mm, 95%CI -25.7, -16.1) and Group Two (xˉ =-24.9, 95%CI -30.8, -19.0). Conclusion Both exercise programs had similar efficacy in reducing pain. The addition of hip strengthening exercises to a motor control exercise program does not appear to result in improved clinical outcome for pain for individuals with non-specific low back pain.

Geochemistry-based coral palaeoclimate studies and the potential of ‘non-traditional’ (non-massive Porites) corals : recent developments and future progression

Understanding the natural variability of the Earth's climate system and accurately identifying potential anthropogenic influences requires long term, geographically distributed records of key climate indicators, such as temperature and precipitation that extend prior to the last 400. years of the Holocene. Reef corals provide an excellent source of high resolution climate records, and importantly represent the tropical marine environment where palaeoclimate data are urgently required. Recent decades have seen significant improvement in our understanding of coral biomineralisation, the associated uptake of geochemical proxies and methods of identifying and understanding the effects of both early and late, post depositional diagenetic alteration. These processes all have significant implications for interpreting geochemical proxies relevant to palaeoclimatic reconstructions. This paper reviews the current 'state of the art' in terms of coral based palaeoclimate reconstructions and highlights a key remaining problem. The majority of coral based palaeoclimate research has been derived from massive colonies of Porites. However, massive Porites are not globally abundant and may not provide material of a particular age of interest in those regions where they are present. Therefore, there is great potential for alternate coral genera to act as complimentary climate archives. While it remains critical to consider five key factors - vital effects, differential growth morphologies, geochemical heterogeneity in the skeletal ultrastructure, transfer equation selection and diagenetic screening of skeletal material - in order to allow the highest level of accuracy in coral palaeoclimate reconstructions, it is also important to develop alternate taxa for palaeoclimate studies in regions where Porites colonies are absent or rare. Currently as many as nine genera other than Porites have proven at least limited utility in palaeothermometry, most of which are found in the Atlantic/Caribbean region where massive Porites do not exist. Even branching taxa such as Acropora have significant potential to preserve environmental archives. Increasing this capability will greatly expand the number of potential geochemical archives available for longer term temporal records of palaeoclimate.

Investigating the mediating effects of emotional intelligence and coping on problem behaviours in adolescents

This study explored the mediating effect of emotional intelligence (EI) and coping strategies on problem behaviours in Australian adolescents. One hundred and forty-five adolescents (60 boys and 85 girls with a mean age of 12.02 years) completed self-report instruments of EI, stress coping strategies, and problem behaviours. The relationships between Emotional Management and Control and engagement in internalising and externalising behaviours were found to be mediated by the use of non-productive coping strategies. Mediation models of the relationship between problem behaviours and the Understanding Emotions and Emotional Recognition and Expression dimensions were found to be only partially mediated by the engagement in problem-focused and non-productive coping strategies. The results are discussed in regards to how coping strategies utilised in adolescence may produce more or less adaptive patterns of coping during adulthood. The development of emotional abilities may be required to improve coping outcomes for adolescents, which in turn may produce better psychological outcomes for adolescents in the long term.

Understanding Uncertainties in Non-Linear Population Trajectories: A Bayesian Semi-Parametric Hierarchical Approach to Large-Scale Surveys of Coral Cover

Recently, attempts to improve decision making in species management have focussed on uncertainties associated with modelling temporal fluctuations in populations. Reducing model uncertainty is challenging; while larger samples improve estimation of species trajectories and reduce statistical errors, they typically amplify variability in observed trajectories. In particular, traditional modelling approaches aimed at estimating population trajectories usually do not account well for nonlinearities and uncertainties associated with multi-scale observations characteristic of large spatio-temporal surveys. We present a Bayesian semi-parametric hierarchical model for simultaneously quantifying uncertainties associated with model structure and parameters, and scale-specific variability over time. We estimate uncertainty across a four-tiered spatial hierarchy of coral cover from the Great Barrier Reef. Coral variability is well described; however, our results show that, in the absence of additional model specifications, conclusions regarding coral trajectories become highly uncertain when considering multiple reefs, suggesting that management should focus more at the scale of individual reefs. The approach presented facilitates the description and estimation of population trajectories and associated uncertainties when variability cannot be attributed to specific causes and origins. We argue that our model can unlock value contained in large-scale datasets, provide guidance for understanding sources of uncertainty, and support better informed decision making

Youth off the Streets "Our Place, Walgett Youth and Young Families Project" Project Evaluation.

The Project: • YOTS is a major youth specific agency established in 1991. It is a non-denominational, non-discriminatory and not-for-profit organisation, providing a wide range of services and offering a full continuum of care. It seeks to build on the strengths and positive aspects of marginalised young people and communities. • The 'Our Place, Walgett Youth and Young Families Project' further develops an existing YOTS capacity to provide services to Aboriginal young people. • The project adopted an action-research and community development model in which YOTS worked in partnership with the Youth Sub-committee of the Walgett Interagency. • Specific goals/objectives of the program were to: Coordinate youth and young family activities in partnership with local services and the community to build self-esteem, pride, resilience, motivation and skills; Contribute to the prevention and reduction of homelessness, unstable and unsafe housing and disruptive mobility (Walgett/Redfern) in youth and young families; Increase and improve collaborative engagement between youth and family focused services; and, research, adapt and implement Australian and international best-practice homelessness prevention/reduction initiatives to contribute to new models of practice relevant to rural and regional areas. • The project centred around an out-reach model that focused on providing a safe space with relevant structured activities coordinated by YOTS youth and family workers. Through community and service provider consultation, it was proposed that local services could coordinate strategies and activities and run them, where possible, from the centre, providing ease of access in a safe and supportive context. • Specific activities included: Implementing regular meetings with the stakeholders and community representatives; Developing a Terms of Reference for YOTS presence in the Walgett community; Undertaking a community consultation prior to finalising program activities; Implementing a range of recreational activities (sports, music, arts and crafts) early on in the activity; Implementing young family support initiatives; implementing a volunteering program, including volunteer support to young families through intergenerational volunteering; running a series of Culture and Healing Camps in partnership with local Elders and other services; Running a series of Music Camps; Providing alternative education support and referrals in partnership with local schools; Researching, identifying and adapting other best-practice models.

Going live : building academic capacity in blended learning using web-conferencing technologies

This paper reports on a current initiative at Queensland University of Technology to provide timely, flexible and sustainable training and support to academic staff in blended learning and associated techno-pedagogies via a web-conferencing classroom and collaboration tool, Elluminate Live!. This technology was first introduced to QUT in 2008 as part of the university‘s ongoing commitment to meeting the learning needs of diverse student cohorts. The centralised Learning Design team, in collaboration with the university‘s department of eLearning Services, was given the task of providing training and support to academic staff in the effective use of the technology for teaching and learning, as part of the team‘s ongoing brief to support and enhance the provision of blended learning throughout the university. The resulting program, ―Learning Design Live‖ (LDL) is informed by Rogers‘ theory of innovation and diffusion (2003) and structured according to Wilson‘s framework for faculty development (2007). This paper discusses the program‘s design and structure, considers the program‘s impact on academic capacity in blended learning within the institution, and reflects on future directions for the program and emerging insights into blended learning and participant engagement for both staff and students.

Dynamic digital posters : making the most of collaborative learning spaces

Academic and professional staff at Queensland University of Technology (QUT) have been faced with the challenge of how to create engaging student experiences in collaborative learning spaces. In 2013 a new Bachelor of Science course was implemented focusing on inquiry-based, collaborative and active learning. Student groups in two of the first year units carried out a poster assessment task. This paper provides a preliminary evaluation of the assessment approach used, whereby students created dynamic digital posters to capitalise on the affordances of the learning space.

An exploration of advertising engagement, advertising avoidance and privacy concerns on social networking sites

This thesis examines perceptions of advertising on social networking sites (SNS), in particular consumers' privacy concerns, advertising engagement and advertising avoidance. It contributes to the understanding of social media by providing results of a longitudinal investigation of consumer perceptions of advertising, a topography of engagement and avoidance triggers and a three dimensional model of advertising avoidance on SNS. This research used a mixed methodology, employing Critical Incident Technique, In-depth interviews and online surveys.

CoWs, Google and online possibilities : creating digital posters to enhance student engagement

A new Bachelor of Science (BSc) course was introduced at Queensland University of Technology (QUT) in 2013 and focused on inquiry-based, collaborative and active learning. Two of the first year units required that students carry out a group poster assessment task. This poster provides a preliminary evaluation from an academic staff perspective of the assessment approach used, whereby students created digital posters to utilise the affordances of new learning spaces. The digital posters approach was first introduced to a group of academic staff from the Science and Engineering Faculty (SEF) in 2012 during a professional development program to explicitly develop skills and shared understandings of teaching in collaborative learning spaces (Steel & Andrews, 2012). Considerations were given to the pedagogical requirements of a poster assessment task, the affordances of the learning space and an identification of possible benefits of using Google Sites to create digital posters. Positive feedback from this group (as highlighted in the quotes shown) and subsequent approval from unit coordinators for two of the new first year BSc units meant that the approach was adopted for Semester 1, 2013 with approximately 360 students in each unit.

Non-destructive DNA extraction from Chironomidae, including of fragile pupal exuviae, extends analysable collections and enhances vouchering

It is well established that the traditional taxonomy and nomenclature of Chironomidae relies on adult males whose usually characteristic genitalia provide evidence of species distinction. In the early days some names were based on female adults of variable distinctiveness – but females are difficult to identify (Ekrem et al. 2010) and many of these names remain dubious. In Russia especially, a system based on larval morphology grew in parallel to the conventional adult-based system. The systems became reconciled with the studies that underlay the production of the Holarctic generic keys to Chironomidae, commencing notably with the larval volume (Wiederholm, 1983). Ever since Thienemann’s pioneering studies, it has been evident that the pupa, notably the cast skins (exuviae) provide a wealth of features that can aid in identification (e.g. Wiederholm, 1986). Furthermore, the pupae can be readily associated with name-bearing adults when a pharate (‘cloaked’) adult stage is visible within the pupa. Association of larvae with the name-bearing later stages has been much more difficult, time-consuming and fraught with risk of failure. Yet it is identification of the larval stage that is needed by most applied researchers due to the value of the immature stages of the family in aquatic monitoring for water quality, although the pupal stage also has advocates (reviewed by Sinclair & Gresens, 2008). Few use the adult stage for such purposes as their provenance and association with the water body can be verified only by emergence trapping, and sampling of adults lies outside regular aquatic monitoring protocols.