HER2 positive gastric and gastroesophageal adenocarcinoma; An Irish tertiary center experience

Background: Trastuzumab has been approved for patients with human epidermal growth factor receptor 2 (HER2) over expression and gene amplification metastatic gastric cancer. Here we present the prevalence of HER2 positive gastric cancer in an Irish population, the use of Trastuzumab in first line and beyond progression. Methods: The study was conducted in St James's Hospital, Dublin. A retrospective analysis of the date of patients with HER2 positive gastric cancer over a period of 3 years was carried out. Her2 positive was defined as immunohistochemistry (IHC) score of +3, of IHC score of +2 and increased gene copy number by fluorescence in situ hybridization (FISH). Overall survival was calculated from the day of initiation of treatment with Trastuzumab until death. Results: During the study period 140 patients with gastric and gastro-esophageal junction adenocarcinoma were treated. Out of those, 30 (21.4%) had HER2 positive disease. Among HER2 positive disease patients 18 (12.8%) were treated with first line Trastuzumab containing regimen with a median overall survival of 13 months. Nine (50%) developed progressive disease while on Trastuzumab and of those, 4 (22.2%) patients continued on Trastuzumab beyond progression, two (11.1%) of whom achieved stable disease and a prolonged survival. Conclusion: HER2 positivity rate in an Irish population with advanced gastric and gastro-esophageal junction adenocarcinoma is 21.4%. Treatment with Trastuzumab in the first line in combination with chemotherapy is a reasonable approach. Continuation of Trastuzumab beyond progression is a feasible strategy that requires further exploration.

Dacomitinib versus erlotinib in patients with EGFR-mutated advanced nonsmall-cell lung cancer (NSCLC): Pooled subset analyses from two randomized trials

Background: The irreversible epidermal growth factor receptor (EGFR) inhibitors have demonstrated efficacy in NSCLC patients with activating EGFR mutations, but it is unknown if they are superior to the reversible inhibitors. Dacomitinib is an oral, small-molecule irreversible inhibitor of all enzymatically active HER family tyrosine kinases. Methods: The ARCHER 1009 (NCT01360554) and A7471028 (NCT00769067) studies randomized patients with locally advanced/metastatic NSCLC following progression with one or two prior chemotherapy regimens to dacomitinib or erlotinib. EGFR mutation testing was performed centrally on archived tumor samples. We pooled patients with exon 19 deletion and L858R EGFR mutations from both studies to compare the efficacy of dacomitinib to erlotinib. Results: One hundred twenty-one patients with any EGFR mutation were enrolled; 101 had activating mutations in exon 19 or 21. For patients with exon19/21 mutations, the median progression-free survival was 14.6 months [95% confidence interval (CI) 9.0–18.2] with dacomitinib and 9.6 months (95% CI 7.4–12.7) with erlotinib [unstratified hazard ratio (HR) 0.717 (95% CI 0.458–1.124), two-sided log-rank, P = 0.146]. The median survival was 26.6 months (95% CI 21.6–41.5) with dacomitinib versus 23.2 months (95% CI 16.0–31.8) with erlotinib [unstratified HR 0.737 (95% CI 0.431–1.259), two-sided log-rank, P = 0.265]. Dacomitinib was associated with a higher incidence of diarrhea and mucositis in both studies compared with erlotinib. Conclusions: Dacomitinib is an active agent with comparable efficacy to erlotinib in the EGFR mutated patients. The subgroup with exon 19 deletion had favorable outcomes with dacomitinib. An ongoing phase III study will compare dacomitinib to gefitinib in first-line therapy of patients with NSCLC harboring common activating EGFR mutations (ARCHER 1050; NCT01774721). Clinical trials number: ARCHER 1009 (NCT01360554) and A7471028 (NCT00769067).

2nd ESMO Consensus Conference in Lung Cancer: Locally advanced stage III 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 2nd 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 non-small-cell lung cancer (NSCLC) in each of four areas: pathology and molecular biomarkers, first-line/second and further lines of treatment in advanced disease, early-stage disease and locally advanced disease. For each question, recommendations were made including reference to the grade of recommendation and level of evidence. This consensus paper focuses on locally advanced disease.

Representational change and strategy use in children's number line estimation during the first years of primary school

Background: The objective of this study was to scrutinize number line estimation behaviors displayed by children in mathematics classrooms during the first three years of schooling. We extend existing research by not only mapping potential logarithmic-linear shifts but also provide a new perspective by studying in detail the estimation strategies of individual target digits within a number range familiar to children. Methods: Typically developing children (n = 67) from Years 1 – 3 completed a number-to-position numerical estimation task (0-20 number line). Estimation behaviors were first analyzed via logarithmic and linear regression modeling. Subsequently, using an analysis of variance we compared the estimation accuracy of each digit, thus identifying target digits that were estimated with the assistance of arithmetic strategy. Results: Our results further confirm a developmental logarithmic-linear shift when utilizing regression modeling; however, uniquely we have identified that children employ variable strategies when completing numerical estimation, with levels of strategy advancing with development. Conclusion: In terms of the existing cognitive research, this strategy factor highlights the limitations of any regression modeling approach, or alternatively, it could underpin the developmental time course of the logarithmic-linear shift. Future studies need to systematically investigate this relationship and also consider the implications for educational practice.

Breastfeeding self-efficacy of women using second-line strategies for healthy term infants in the first week postpartum : an Australian observational study

Background Breastfeeding self-efficacy (BFSE) supports breastfeeding initiation and duration. Challenges to breastfeeding may undermine BFSE, but second-line strategies including nipple shields, syringe, cup, supply line and bottle feeding may support breastfeeding until challenges are resolved. The primary aim of this study was to examine BFSE in a sample of women using second-line strategies for feeding healthy term infants in the first week postpartum. Methods A retrospective self-report study was conducted using the Breastfeeding Self-Efficacy Scale - Short Form (BSES-SF), demographic and infant feeding questionnaires. Breastfeeding women who gave birth to a singleton healthy term infant at one private metropolitan birthing facility in Australia from November 2008 to February 2009 returned anonymous questionnaires by mail. Results A total of 128 (73 multiparous, 55 primiparous) women participated in the study. The mean BSES-SF score was 51.18 (Standard deviation, SD: 12.48). The median BSES-SF score was 53. Of women using a second-line strategy, 16 exceeded the median, and 42 were below. Analyses using Kruskal-Wallis tests confirmed this difference was statistically significant (H = 21.569, p = 0.001). The rate of second-line strategy use was 48%. The four most commonly used second-line strategies were: bottles with regular teats (77%); syringe feeding (44%); bottles with wide teats (34%); and nipple shields (27%). Seven key challenges were identified that contributed to the decision to use second-line strategies, including: nipple pain (40%); unsettled infant (40%); insufficient milk supply (37%); fatigue (37%); night nursery care (25%); infant weight loss > 10% (24%); and maternal birth associated pain (20%). Skin-to-skin contact at birth was commonly reported (93%). At seven days postpartum 124 women (97%) were continuing to breastfeed. Conclusions The high rate of use of second-line strategies identified in this study and high rate of breastfeeding at day seven despite lower BFSE indicate that such practices should not be overlooked by health professionals. The design of this study does not enable determination of cause-effect relationships to identify factors which contribute to use of second-line strategies. Nevertheless, the significantly lower BSES-SF score of women using a second-line strategy highlights this group of women have particular needs that require attention.

Discovery and characterization of IGFBP-mediated endocytosis in the human retinal pigment epithelial cell line ARPE-19

Insulin-like growth factor binding proteins (IGFBPs) are prime regulators of IGF-action in numerous cell types including the retinal pigment epithelium (RPE). The RPE performs several functions essential for vision, including growth factor secretion and waste removal via a phagocytic process mediated in part by vitronectin (Vn). In the course of studying the effects of IGFBPs on IGF-mediated VEGF secretion and Vn-mediated phagocytosis in the RPE cell line ARPE-19, we have discovered that these cells avidly ingest synthetic microspheres (2.0 μm diameter) coated with IGFBPs. Given the novelty of this finding and the established role for endocytosis in mediating IGFBP actions in other cell types, we have explored the potential role of candidate cell surface receptors. Moreover, we have examined the role of key IGFBP structural motifs, by comparing responses to three members of the IGFBP family (IGFBP-3, IGFBP-4 and IGFBP-5) which display overlapping variations in primary structure and glycosylation status. Coating of microspheres (FluoSpheres®, sulfate modified polystyrene filled with a fluorophore) was conducted at 37 °C for 1 h using 20 μg/mL of test protein, followed by extensive washing. Binding of proteins was confirmed using a microBCA assay. The negative control consisted of microspheres treated with 0.1% bovine serum albumin (BSA), and all test samples were post-treated with BSA in an effort to coat any remaining free protein binding sites, which might otherwise encourage non-specific interactions with the cell surface. Serum-starved cultures of ARPE-19 cells were incubated with microspheres for 24 h, using a ratio of approximately 100 microspheres per cell. Uptake of microspheres was quantified using a fluorometer and was confirmed visually by confocal fluorescence microscopy. The ARPE-19 cells displayed little affinity for BSA-treated microspheres, but avidly ingested large quantities of those pre-treated with Vn (ANOVA; p < 0.001). Strong responses were also observed towards recombinant formulations of non-glycosylated IGFBP-3, glycosylated IGFBP-3 and glycosylated IGFBP-5 (all p < 0.001), while glycosylated IGFBP-4 induced a relatively minor response (p < 0.05). The response to IGFBP-3 was unaffected in the presence of excess soluble IGFBP-3, IGF-I or Vn. Likewise, soluble IGFBP-3 did not induce uptake of BSA-treated microspheres. Antibodies to either the transferrin receptor or type 1 IGF-receptor displayed slight inhibitory effects on responses to IGFBPs and Vn. Heparin abolished responses to Vn, IGFBP-5 and non-glycosylated IGFBP-3, but only partially inhibited the response to glycosylated IGFBP-3. Our results demonstrate for the first time IGFBP-mediated endocytosis in ARPE-19 cells and suggest roles for the IGFBP-heparin-binding domain and glycosylation status. These findings have important implications for understanding the mechanisms of IGFBP actions on the RPE, and in particular suggest a role for IGFBP-endocytosis.

The development of an on-line module for students on “Working in Inter-cultural Teams”

Since 2005 QUT through a number of large Teaching and Learning Grants has sponsored a range of teamwork learning initiatives to assist students to develop the teamwork skills demanded by industry. After a suite of six online team learning modules was developed, first year unit coordinators requested an additional module to address the challenges of working with the diverse range of social, cultural and personal values that students from different backgrounds bring to student teams. The Intercultural Teams module asks students to map themselves against a Cultural Orientations Framework so they can understand their own cultural beliefs. By learning about other cultural orientations and comparing and analysing their effects, team members can develop communication and team process management strategies to leverage their differences to realise effective and creative outcomes. The interactive session will demonstrate the elements of the Intercultural Teams module and ask participants to consider ways the module can be integrated into classroom learning to support the development of students’ intercultural competencies.

The importance of a triple bottom line approach for safeguarding urban water quality

Water environments are greatly valued in urban areas as ecological and aesthetic assets. However, it is the water environment that is most adversely affected by urbanisation. Urban land use coupled with anthropogenic activities alters the stream flow regime and degrade water quality with urban stormwater being a significant source of pollutants. Unfortunately, urban water pollution is difficult to evaluate in terms of conventional monetary measures. True costs extend beyond immediate human or the physical boundaries of the urban area and affect the function of surrounding ecosystems. Current approaches for handling stormwater pollution and water quality issues in urban landscapes are limited as these are primarily focused on ‘end-of-pipe’ solutions. The approaches are commonly based either on, insufficient design knowledge, faulty value judgements or inadequate consideration of full life cycle costs. It is in this context that the adoption of a triple bottom line approach is advocated to safeguard urban water quality. The problem of degradation of urban water environments can only be remedied through innovative planning, water sensitive engineering design and the foresight to implement sustainable practices. Sustainable urban landscapes must be designed to match the triple bottom line needs of the community, starting with ecosystem services first such as the water cycle, then addressing the social and immediate ecosystem health needs, and finally the economic performance of the catchment. This calls for a cultural change towards urban water resources rather than the current piecemeal and single issue focus approach. This paper discusses the challenges in safeguarding urban water environments and the limitations of current approaches. It then explores the opportunities offered by integrating innovative planning practices with water engineering concepts into a single cohesive framework to protect valuable urban ecosystem assets. Finally, a series of recommendations are proposed for protecting urban water resources within the context of a triple bottom line approach.

Advances in vegetation management for power line corridor monitoring using aerial remote sensing techniques

This paper presents a comprehensive discussion of vegetation management approaches in power line corridors based on aerial remote sensing techniques. We address three issues 1) strategies for risk management in power line corridors, 2) selection of suitable platforms and sensor suite for data collection and 3) the progress in automated data processing techniques for vegetation management. We present initial results from a series of experiments and, challenges and lessons learnt from our project.

A biologically inspired object spectral-texture descriptor and its application to vegetation classification in power-line corridors

The use of appropriate features to represent an output class or object is critical for all classification problems. In this paper, we propose a biologically inspired object descriptor to represent the spectral-texture patterns of image-objects. The proposed feature descriptor is generated from the pulse spectral frequencies (PSF) of a pulse coupled neural network (PCNN), which is invariant to rotation, translation and small scale changes. The proposed method is first evaluated in a rotation and scale invariant texture classification using USC-SIPI texture database. It is further evaluated in an application of vegetation species classification in power line corridor monitoring using airborne multi-spectral aerial imagery. The results from the two experiments demonstrate that the PSF feature is effective to represent spectral-texture patterns of objects and it shows better results than classic color histogram and texture features.

Mission unreachable : how Jaman is shaping the future of on-line distribution

Perhaps the most innovative of all independent OLD ventures specialising in ROW content is Jaman. Founded in 2007 by IT entrepreneur Gaurav Dhillon, and based in San Mateo, California, Jaman is a quality specialist distributor of non-Hollywood films. As of late 2010, Jaman had 1.8 million registered users and attracts viewers from most countries in the world. 75% of all use is generated from outside the U.S. Jaman does very well in English speaking parts of the world, particularly current and former Commonwealth countries. The United Kingdom accounts for 29% of users, North America (U.S. and Canada) 26%, and India represents 23%. Jaman is sometimes referred to as ‘social cinema’: a website which brings together the critique and review of a cinephile website (the forums of Rue-morgue.com for cinefantastique movie fans for example) with the social interaction, community and functionality of a social media site (for example Facebook.com). Jaman could be considered a pioneer in this space; a first mover in wrapping commercial movie downloading in an interactive social experience.

An example of cognitive obstacles in advanced integration: the case of scalar line integrals

Cognitive obstacles that arise in the teaching and learning of scalar line integrals, derived from cognitive aids provided to students when first learning about integration of single variable functions are described. A discussion of how and why the obstacles cause students problems is presented and possible strategies to overcome the obstacles are outlined.

Fast power line detection and localization using steerable filter for active UAV guidance

In this paper we present a fast power line detection and localisation algorithm as well as propose a high-level guidance architecture for active vision-based Unmanned Aerial Vehicle (UAV) guidance. The detection stage is based on steerable filters for edge ridge detection, followed by a line fitting algorithm to refine candidate power lines in images. The guidance architecture assumes an UAV with an onboard Gimbal camera. We first control the position of the Gimbal such that the power line is in the field of view of the camera. Then its pose is used to generate the appropriate control commands such that the aircraft moves and flies above the lines. We present initial experimental results for the detection stage which shows that the proposed algorithm outperforms two state-of-the-art line detection algorithms for power line detection from aerial imagery.

Designing a new robust on-line secondary path modeling technique for feedforward active noise control systems

Several approaches have been introduced in the literature for active noise control (ANC) systems. Since the filtered-x least-mean-square (FxLMS) algorithm appears to be the best choice as a controller filter, researchers tend to improve performance of ANC systems by enhancing and modifying this algorithm. This paper proposes a new version of the FxLMS algorithm, as a first novelty. In many ANC applications, an on-line secondary path modeling method using white noise as a training signal is required to ensure convergence of the system. As a second novelty, this paper proposes a new approach for on-line secondary path modeling on the basis of a new variable-step-size (VSS) LMS algorithm in feed forward ANC systems. The proposed algorithm is designed so that the noise injection is stopped at the optimum point when the modeling accuracy is sufficient. In this approach, a sudden change in the secondary path during operation makes the algorithm reactivate injection of the white noise to re-adjust the secondary path estimate. Comparative simulation results shown in this paper indicate the effectiveness of the proposed approach in reducing both narrow-band and broad-band noise. In addition, the proposed ANC system is robust against sudden changes of the secondary path model.

Characterisation of enterovirus 71 replication kinetics in human colorectal cell line, HT29

Hand, Foot and Mouth Disease (HFMD), a contagious viral disease that commonly affects infants and children with blisters and flu like symptoms, is caused by a group of enteroviruses such as Enterovirus 71 (EV71) and coxsackievirus A16 (CA16). However some HFMD caused by EV71 may further develop into severe neurological complications such as encephalitis and meningitis. The route of transmission was postulated that the virus transmit from one person to another through direct contact of vesicular fluid or droplet from the infected or via faecal-oral route. To this end, this study utilised a human colorectal adenocarcinoma cell line (HT29) with epithelioid morphology as an in vitro model for the investigation of EV71 replication kinetics. Using qPCR, viral RNA was first detected in HT29 cells as early as 12 h post infection (hpi) while viral protein was first detected at 48 hpi. A significant change in HT29 cells’ morphology was also observed after 48 hpi. Furthermore HT29 cell viability also significantly decreased at 72 hpi. Together, data from this study demonstrated that co-culture of HT29 with EV71 is a useful in vitro model to study the pathogenesis of EV71