How technological change affects power relations in global markets : remote developers in the console and mobile games industry

This paper focuses on Australian development firms in the console and mobile games industry in order to understand how small firms in a geographically remote and marginal position in the global industry are able to relate to global firms and capture revenue share. This paper shows that, while technological change in the games industry has resulted in the emergence of new industry segments based on transactional rather than relational forms of economic coordination, in which we might therefore expect less asymmetrical power relations, lead firms retain a position of power in the global games entertainment industry relative to remote developers. This has been possible because lead firms in the emerging mobile devices market have developed and sustained bottlenecks in their segment of the industry through platform competition and the development of an intensely competitive ecosystem of developers. Our research shows the critical role of platform competition and bottlenecks in influencing power asymmetries within global markets.

The impact of heatwaves on mortality and emergency hospital admissions from non-external causes in Brisbane, Australia

Objectives Heatwaves can have significant health consequences resulting in increased mortality and morbidity. However, their impact on people living in tropical/subtropical regions remains largely unknown. This study assessed the impact of heatwaves on mortality and emergency hospital admissions (EHAs) from non-external causes (NEC) in Brisbane, a subtropical city in Australia. Methods We acquired daily data on weather, air pollution and EHAs for patients aged 15 years and over in Brisbane between January 1996 and December 2005, and on mortality between January 1996 and November 2004. A locally derived definition of heatwave (daily maximum ≥37°C for 2 or more consecutive days) was adopted. Case–crossover analyses were used to assess the impact of heatwaves on cause-specific mortality and EHAs. Results During heatwaves, there was a statistically significant increase in NEC mortality (OR 1.46; 95% CI 1.21 to 1.77), cardiovascular mortality (OR 1.89; 95% CI 1.44 to 2.48), diabetes mortality in those aged 75+ (OR 9.96; 95% CI 1.02 to 96.85), NEC EHAs (OR 1.15; 95% CI 1.07 to 1.23) and EHAs from renal diseases (OR 1.41; 95% CI 1.09 to 1.83). The elderly were found to be particularly vulnerable to heatwaves (eg, for NEC EHAs, OR 1.24 for 65–74-year-olds and 1.39 for those aged 75+). Conclusions Significant increases in NEC mortality and EHAs were observed during heatwaves in Brisbane where people are well accustomed to hot summer weather. The most vulnerable were the elderly and people with cardiovascular, renal or diabetic disease.

Higher-order non-linear analysis of steel structures. Part I : elastic second-order formulation

This paper presents a higher-order beam-column formulation that can capture the geometrically non-linear behaviour of steel framed structures which contain a multiplicity of slender members. Despite advances in computational frame software, analyses of large frames can still be problematic from a numerical standpoint and so the intent of the paper is to fulfil a need for versatile, reliable and efficient non-linear analysis of general steel framed structures with very many members. Following a comprehensive review of numerical frame analysis techniques, a fourth-order element is derived and implemented in an updated Lagrangian formulation, and it is able to predict flexural buckling, snap-through buckling and large displacement post-buckling behaviour of typical structures whose responses have been reported by independent researchers. The solutions are shown to be efficacious in terms of a balance of accuracy and computational expediency. The higher-order element forms a basis for augmenting the geometrically non-linear approach with material non-linearity through the refined plastic hinge methodology described in the companion paper.

Higher-order non-linear analysis of steel structures. Part II : refined plastic hinge formulation

In the companion paper, a fourth-order element formulation in an updated Lagrangian formulation was presented to handle geometric non-linearities. The formulation of the present paper extends this to include material non-linearity by proposing a refined plastic hinge approach to analyse large steel framed structures with many members, for which contemporary algorithms based on the plastic zone approach can be problematic computationally. This concept is an advancement of conventional plastic hinge approaches, as the refined plastic hinge technique allows for gradual yielding, being recognized as distributed plasticity across the element section, a condition of full plasticity, as well as including strain hardening. It is founded on interaction yield surfaces specified analytically in terms of force resultants, and achieves accurate and rapid convergence for large frames for which geometric and material non-linearity are significant. The solutions are shown to be efficacious in terms of a balance of accuracy and computational expediency. In addition to the numerical efficiency, the present versatile approach is able to capture different kinds of material and geometric non-linearities on general applications of steel structures, and thereby it offers an efficacious and accurate means of assessing non-linear behaviour of the structures for engineering practice.

Is sedation by non-anaesthetists really safe?

I read with great interest the editorial recently published in the British Journal of Anaesthesia that questioned whether sedation by non-anaesthetists is really safe. The authors noted their ‘grave concerns’ about the emerging practice of non-anaesthetist administered propofol (NAAP) during electrophysiology procedures. I offer the following insights into this issue.

The informed manager : exploring absorptive capacity in the non-profit sector

Being across new knowledge is critical to the survival of individual businesses. This study explored the way in which managers of small social services in Queensland identified important new knowledge and brought this into their organisations. New knowledge was found to be highly valued by managers with key resources allocated to knowledge seeking processes particularly in response to regulatory change. Knowledge absorption involved accessing multiple sources, and external professional networks were found to be critical to understanding and integrating new knowledge. The research highlighted the challenges in securing new knowledge and the importance of managers professional links.

Selection and monitoring of navigation modes for an autonomous rover

Considering the wide spectrum of situations that it may encounter, a robot navigating autonomously in outdoor environments needs to be endowed with several operating modes, for robustness and efficiency reasons. Indeed, the terrain it has to traverse may be composed of flat or rough areas, low cohesive soils such as sand dunes, concrete road etc. . .Traversing these various kinds of environment calls for different navigation and/or locomotion functionalities, especially if the robot is endowed with different locomotion abilities, such as the robots WorkPartner, Hylos [4], Nomad or the Marsokhod rovers. Numerous rover navigation techniques have been proposed, each of them being suited to a particular environment context (e.g. path following, obstacle avoidance in more or less cluttered environments, rough terrain traverses...). However, seldom contributions in the literature tackle the problem of selecting autonomously the most suited mode [3]. Most of the existing work is indeed devoted to the passive analysis of a single navigation mode, as in [2]. Fault detection is of course essential: one can imagine that a proper monitoring of the Mars Exploration Rover Opportunity could have avoided the rover to be stuck during several weeks in a dune, by detecting non-nominal behavior of some parameters. But the ability to recover the anticipated problem by switching to a better suited navigation mode would bring higher autonomy abilities, and therefore a better overall efficiency. We propose here a probabilistic framework to achieve this, which fuses environment related and robot related information in order to actively control the rover operations.

From “anytime, anywhere” to “here and now”: place and time restrictions in mobile narratives to enhance situated engagement of mobile users

The usage of the mobile Internet has increased tremendously within the last couple of years, and thereby the vision of accessing information anytime, anywhere has become more realistic and a dominant design principle for providing content. However, this study challenges this paradigm of unlimited and unrestricted access, and explores the question whether constraints and restrictions can positively influence the motivation and enticement of mobile users to engage with location-specific content. Restrictions, such as a particular time or location that gives a user access to content, may be used to foster participation and engagement, as well as to support content production and to enhance the user’s experience. In order to explore this, a Mobile Narrative and a Narrative Map have been created. For the former, the access to individual chapters of the story was restricted. Authors can specify constraints, such as a location or time, which need to be met by the reader if they want to read the story. This concept allows creative writers of the story to exploit the fact that the reader’s context is known, by intensifying the user experience and integrating this knowledge into the writing process. The latter, the Narrative Map, provides users with extracts from stories or information snippets about authors at relevant locations. In both concepts, a feedback channel was also integrated, on which location, time, and size constraints were imposed. In a user-centred design process involving authors and potential readers, those concepts have been implemented, followed by an evaluation comprising four user studies. The results show that restrictions and constraints can indeed lead to more enticing and engaging user experiences, and restricted contribution opportunities can lead to a higher motivation to participate as well as to an improved quality of submissions. These findings are relevant for future developments in the area of mobile narratives and creative writing, as well as for common mobile services that aim for enticing user experiences.

A near-to-far non-parametric learning approach for estimating traversability in deformable terrain

It is well recognized that many scientifically interesting sites on Mars are located in rough terrains. Therefore, to enable safe autonomous operation of a planetary rover during exploration, the ability to accurately estimate terrain traversability is critical. In particular, this estimate needs to account for terrain deformation, which significantly affects the vehicle attitude and configuration. This paper presents an approach to estimate vehicle configuration, as a measure of traversability, in deformable terrain by learning the correlation between exteroceptive and proprioceptive information in experiments. We first perform traversability estimation with rigid terrain assumptions, then correlate the output with experienced vehicle configuration and terrain deformation using a multi-task Gaussian Process (GP) framework. Experimental validation of the proposed approach was performed on a prototype planetary rover and the vehicle attitude and configuration estimate was compared with state-of-the-art techniques. We demonstrate the ability of the approach to accurately estimate traversability with uncertainty in deformable terrain.

Motion planning and stochastic control with experimental validation on a planetary rover

Motion planning for planetary rovers must consider control uncertainty in order to maintain the safety of the platform during navigation. Modelling such control uncertainty is difficult due to the complex interaction between the platform and its environment. In this paper, we propose a motion planning approach whereby the outcome of control actions is learned from experience and represented statistically using a Gaussian process regression model. This model is used to construct a control policy for navigation to a goal region in a terrain map built using an on-board RGB-D camera. The terrain includes flat ground, small rocks, and non-traversable rocks. We report the results of 200 simulated and 35 experimental trials that validate the approach and demonstrate the value of considering control uncertainty in maintaining platform safety.

Capturing complex, non-linear team behaviours during competitive football performance

This study investigated changes in the complexity (magnitude and structure of variability) of the collective behaviours of association football teams during competitive performance. Raw positional data from an entire competitive match between two professional teams were obtained with the ProZone® tracking system. Five compound positional variables were used to investigate the collective patterns of performance of each team including: surface area, stretch index, team length, team width, and geometrical centre. Analyses involve the coefficient of variation (%CV) and approximate entropy (ApEn), as well as the linear association between both parameters. Collective measures successfully captured the idiosyncratic behaviours of each team and their variations across the six time periods of the match. Key events such as goals scored and game breaks (such as half time and full time) seemed to influence the collective patterns of performance. While ApEn values significantly decreased during each half, the %CV increased. Teams seem to become more regular and predictable, but with increased magnitudes of variation in their organisational shape over the natural course of a match.

IL-23R is epigenetically regulated and modulated by chemotherapy in non-small cell lung cancer

The Interleukin-23 (IL-23)/IL-23R signaling axis is an important inflammatory pathway, involved in the stimulation and regulation of the T helper (Th) 17 lymphocytes, resulting in the production of IL-17. Aside from auto-immunity, this cytokine has also been linked to carcinogenesis and polymorphisms in the IL-23R gene are associated with an increased risk for the development of a number of different cancers. Activation of the IL-23 pathway results in the up-regulation of STAT3 and it is thought that the pathological consequences associated with this are in part due to the production of IL-17. We have previously identified IL-23A as pro-proliferative and epigenetically regulated in non-small cell lung cancer (NSCLC). The current study aims to evaluate IL-23R in greater detail in NSCLC. We demonstrate that IL-23R is expressed and epigenetically regulated in NSCLC through histone post-translation modifications and CpG island methylation. In addition, Gemcitabine treatment, a chemotherapy drug used in the treatment of NSCLC, resulted in the up-regulation of the IL-23R. Furthermore, Apilimod (STA 5326), a small molecule which blocks the expression of IL-23 and IL-12, reduced the proliferative capacity of NSCLC cells, particularly in the adenocarcinoma (A549) sub-type. Apilimod is currently undergoing investigation in a number of clinical trials for the treatment of auto-immune conditions such as Crohn's disease and Rheumatoid Arthritis. Our results may have implications for treating NSCLC patients with Gemcitabine or epigenetic targeted therapies. However, Apilimod may possibly provide a new treatment avenue for NSCLC patients. Work is currently ongoing to further delineate the IL-23/IL-23R axis in this disease.

Thromboxane synthase expression and correlation with VEGF and angiogenesis in non-small cell lung cancer

Background Thromboxane synthase (TXS) metabolizes prostaglandin H2 into thromboxanes, which are biologically active on cancer cells. TXS over-expression has been reported in a range of cancers, and associated with angiogenesis and poor outcome. TXS has been identified as a potential therapeutic target in NSCLC. This study examines a link between TXS expression, angiogenesis, and survival in NSCLC. Methods TXS and VEGF metabolite levels were measured in NSCLC serum samples (n=46) by EIA. TXB2 levels were correlated with VEGF. A 204-patient TMA was stained for TXS, VEGF, and CD-31 expression. Expression was correlated with a range of clinical parameters, including overall survival. TXS expression was correlated with VEGF and CD-31. Stable TXS clones were generated and the effect of overexpression on tumor growth and angiogenesis markers was examined in-vitro and in-vivo (xenograft mouse model). Results Serum TXB2 levels were correlated with VEGF (p<0.05). TXS and VEGF were expressed to a varying degree in NSCLC tissue. TXS was associated with VEGF (p<0.0001) and microvessel density (CD-31; p<0.05). TXS and VEGF expression levels were higher in adenocarcinoma (p<0.0001) and female patients (p<0.05). Stable overexpression of TXS increased VEGF secretion in-vitro. While no significant association with patient survival was observed for either TXS or VEGF in our patient cohort, TXS overexpression significantly (p<0.05) increased tumor growth in-vivo. TXS overexpression was also associated with higher levels of VEGF, microvessel density, and reduced apoptosis in xenograft tumors. Conclusion TXS promotes tumor growth in-vivo in NSCLC, an effect which is at least partly mediated through increased tumor angiogenesis.

High coexpression of both EGFR and IGF1R correlates with poor patient prognosis in resected non-small-cell lung cancer

Background Recent experimental and biomarker evidence indicates that the epidermal growth factor receptor (EGFR) and insulin-like growth factor receptor 1 (IGF1R) interact in the pathogenesis of malignant epithelial tumors, including lung cancer. This study examines the expression of both receptors and their prognostic significance in surgically resected non-small-cell lung cancer (NSCLC). Methods EGFR and IGF1R expression were evaluated in 184 patients with NSCLC (83 squamous cell carcinomas [SCCs], 83 adenocarcinomas [ADCs], and 18 other types) using immunohistochemical (IHC) analysis. Expression of both receptors was examined in matched fresh frozen normal and tumor tissues from 40 patients with NSCLC (20 SCCs and 20 ADCs) by Western blot analysis. Results High EGFR expression was detected in 51% of patients, and SCCs had higher EGFR expression than did non-SCCs (57.4% vs. 42.5%; P =.028). High IGF1R expression was observed in 53.8% of patients, with SCC having higher expression than non-SCC (62.6% vs. 37.3%; P =.0004). A significant association was shown between EGFR and IGF1R protein overexpression (P <.005). Patients with high expression of both receptors had a poorer overall survival (OS) (P =.04). Higher EGFR and IGF1R expression was detected in resected tumors relative to matched normal tissues (P =.0004 and P =.0009), with SCC having higher expression levels than ADC. Conclusion Our findings indicate a close interrelationship between EGFR and IGF1R. Coexpression of both receptors correlates with poor survival. This subset of patients may benefit from treatments cotargeting EGFR and IGF1R. © 2014 Elsevier Inc. All rights reserved.

Targeted therapies in non-small cell lung cancer

The majority of non-small cell lung cancer (NSCLC) patients present with advanced disease and with a 5 year survival rate of <15% for these patients, treatment outcomes are considered extremely disappointing. Standard chemotherapy regimens provide some improvement to ~40% of patients. However, intrinsic and acquired chemoresistance are a significant problem and hinder sustained long term benefits of such treatments. Advances in proteomic and genomic profiling have increased our understanding of the aberrant molecular mechanisms that are driving an individual's tumour. The increased sensitivity of these technologies has enabled molecular profiling at the stage of initial biopsy thus paving the way for a more personalised approach to the treatment of cancer patients. Improvements in diagnostics together with a wave of new targeted small molecule inhibitors and monoclonal antibodies have revolutionised the treatment of cancer. To date there are essentially three targeted agents approved for clinical use in NSCLC. The tyrosine kinase inhibitor (TKI) erlotinib, which targets the epidermal growth factor receptor (EGFR) TK domain, has proven to be an effective treatment strategy in patients who harbour activating mutations in the EGFR TK domain. Bevacizumab a monoclonal antibody targeting the vascular endothelial growth factor (VEGF) can improve survival, response rates, and progression-free survival when used in combination with chemotherapy. Crizotinib, a small-molecule drug, inhibits the tyrosine kinase activity of the echinoderm microtubule-associated protein-like 4 anaplastic lymphoma kinase (EML4-ALK) fusion protein, resulting in decreased tumour cell growth, migration, and invasiveness in patients with locally advanced or metastatic NSCLC. The clinical relevance of several other targeted agents are under investigation in distinct molecular subsets of patients with key "driver" mutations including: KRAS, HER2, BRAF, MET, PIK3CA, AKT1,MAP2K1, ROS1 and RET. Often several pathways are activated simultaneously and crosstalk between pathways allows tumour cells to escape the inhibition of a single targeted agent. This chapter will explore the clinical development of currently available targeted therapies for NSCLC as well as those in clinical trials and will examine the synergy between cytotoxic therapies.