FGFR2 as a molecular target in endometrial cancer

Although molecularly targeted therapies have been effective in some cancer types, no targeted therapy is approved for use in endometrial cancer. The recent identification of activating mutations in fibroblast growth factor receptor 2 (FGFR2) in endometrial tumors has generated a new avenue for the development of targeted therapeutic agents. The majority of the mutations identified are identical to germline mutations in FGFR2 and FGFR3 that cause craniosynostosis and hypochondroplasia syndromes and result in both ligand-independent and ligand-dependent receptor activation. Mutations that predominantly occur in the endometrioid subtype of endometrial cancer, are mutually exclusive with KRAS mutation, but occur in the presence of PTEN abrogation. In vitro studies have shown that endometrial cancer cell lines with activating FGFR2 mutations are selectively sensitive to a pan-FGFR inhibitor, PD173074. Several agents with activity against FGFRs are currently in clinical trials. Investigation of these agents in endometrial cancer patients with activating FGFR2 mutations is warranted.

Preparing for Research Assessment: Co-evolution and Gamesmanship

In this paper we adopt a complex systems perspective to examine the perturbations caused by the introduction of the Research Quality Framework (RQF) at a research-intensive Australian university. This case is instructive as it 1) presents a Federal policy initiative that attempted to fundamentally alter the recognition and reward mechanism within a regulated funding environment, 2) analyses the strategies of an institution and its research groups as they sought to not only comply with the implementation of the RQF but to maximise their outcome,and 3) it reveals the ways that some actors used this perturbation to advance their own interests. In short, this case represents an instrumental study into the dynamics of how information systems, organisations, and individuals co-evolve in practice as they seek to navigate a complex problem scenario.

A capability model to improve infrastructure asset performance

Infrastructure organizations are operating in an increasingly challenging business environment as a result of globalization, privatization and deregulation. In an external business environment that is constantly changing, extant literature on strategic management advocates the need to focus on factors internal to the organization such as resources and capabilities to sustain their performance. Specifically, they need to develop dynamic capabilities in order to survive and prosper under conditions of change. The aim of this paper is to explore the dynamic capabilities needed in the management of transport infrastructure assets using a multiple case study research strategy. This paper produced a number of findings. First, the empirical evidence showed that the core infrastructure asset management processes are capacity management, options evaluation, procurement & delivery, maintenance management, and asset information management. Second, the study identified five dynamic capabilities namely stakeholder connectivity, cross-functional, relational, technology absorptive and integrated information capability as central to executing the strategic infrastructure asset management processes well. These findings culminate in the development of a capability model to improve the performance of infrastructure assets in an increasingly dynamic business environment.

Incremental entrepreneurship : best practice professionalization across generations

This chapter will introduce Australia’s Dennis family – a case of ‘incremental entrepreneurship’ in the business transition from the first to the second generation. Following the second generation’s formal involvement and ownership in the business, Dennis Family Corporation (DFC) undertook a major professionalization process to formalize the family business and ensure its continued success. The members of the second generation have successfully sustained the entrepreneurial spirit of their family business (albeit in a different style), adding value to the firm in an ‘incremental’ manner. Throughout the chapter there will be a strong emphasis on the family element of DFC and the roles that each family member has played. Bert Dennis, as the founder and incumbent leader of the firm, has witnessed major changes to the business he built from the ground up. His children, in particular his son Grant Dennis as the primary next generation issue champion, have seen the changes from another perspective – ensuring the business remains within the family into the second generation and beyond. The professionalization process was sparked by a commitment from the second generation to continue to ‘make a real go’ of the family business rather than simply liquidating and distributing the assets. The dedication of all the family members to this objective has ensured the success of this process, and ultimately, the longevity of the firm. Although DFC has become more ‘professional’, it has not lost its entrepreneurial character; rather, it has improved the ways in which entrepreneurialism is fostered and pursued in the company. In essence, this case outlines how the implementation of appropriate governance and management practices has allowed the Dennis family to overcome the challenges and maximize the opportunities associated with owning and operating a multigenerational family fi rm. From a theoretical perspective, this case uses the concepts of entrepreneurial orientation (EO) (Lumpkin and Dess 1996) and the resource- based view (RBV) (Habbershon and Williams 1999; Barney 1991; Wernerfelt 1984) to demonstrate how the fi rm has leveraged its familiness to foster an enduring spirit of entrepreneurship and to maintain a sustained competitive advantage.

Weight management and its role in breast cancer rehabilitation

Overweight and obesity are risk factors for post-menopausal breast cancer, and many women diagnosed with breast cancer, irrespective of menopausal status, gain weight after diagnosis. Weight management plays an important role in rehabilitation and recovery since obesity and/or weight gain may lead to poorer breast cancer prognosis, as well as prevalent co-morbid conditions (e.g. cardiovascular disease and diabetes), poorer surgical outcomes (e.g., increased operating and recovery times, higher infection rates, and poorer healing), lymphedema, fatigue, functional decline, and poorer health and overall quality of life. Health care professionals should encourage weight management at all phases of the cancer care continuum as a means to potentially avoid adverse sequelae and late effects, as well as to improve overall health and possibly survival. Comprehensive approaches that involve dietary and behavior modification, and increased aerobic and strength training exercise have shown promise in either preventing weight gain or promoting weight loss, reducing biomarkers associated with inflammation and co-morbidity, and improving lifestyle behaviors, functional status, and quality of life in this high-risk patient population.

An effective approach to verbose queries using a limited dependencies language model

Intuitively, any ‘bag of words’ approach in IR should benefit from taking term dependencies into account. Unfortunately, for years the results of exploiting such dependencies have been mixed or inconclusive. To improve the situation, this paper shows how the natural language properties of the target documents can be used to transform and enrich the term dependencies to more useful statistics. This is done in three steps. The term co-occurrence statistics of queries and documents are each represented by a Markov chain. The paper proves that such a chain is ergodic, and therefore its asymptotic behavior is unique, stationary, and independent of the initial state. Next, the stationary distribution is taken to model queries and documents, rather than their initial distributions. Finally, ranking is achieved following the customary language modeling paradigm. The main contribution of this paper is to argue why the asymptotic behavior of the document model is a better representation then just the document’s initial distribution. A secondary contribution is to investigate the practical application of this representation in case the queries become increasingly verbose. In the experiments (based on Lemur’s search engine substrate) the default query model was replaced by the stable distribution of the query. Just modeling the query this way already resulted in significant improvements over a standard language model baseline. The results were on a par or better than more sophisticated algorithms that use fine-tuned parameters or extensive training. Moreover, the more verbose the query, the more effective the approach seems to become.

An investigation of unique challenges in National Historic relics and scenic sites (NHRSSs) in Chinese research literature 1982-2008 using co-word analysis

National Housing Relics and Scenic Sites (NHRSSs) in China are the equivalent of National Parks in the West but have contrasting features and broader roles when compared to their Western counterparts. By reviewing and analysing more than 370 academic sources, this paper identifies 6 major issue clusters and future challenges that will influence the management of NHRSSs over time. It also provides a number of cases to illustrate the particular features of NHRSSs. Identifying the hot issues and important challenges in Chinese NHRSSs will provide valuable insights into priorities now being discussed in highly populated areas of the World.

Characterisation of the TaNF-Y family of transcription factors in wheat

Light plays a unique role for plants as it is both a source of energy for growth and a signal for development. Light captured by the pigments in the light harvesting complexes is used to drive the synthesis of the chemical energy required for carbon assimilation. The light perceived by photoreceptors activates effectors, such as transcription factors (TFs), which modulate the expression of light-responsive genes. Recently, it has been speculated that increasing the photosynthetic rate could further improve the yield potential of three carbon (C3) crops such as wheat. However, little is currently known about the transcriptional regulation of photosynthesis genes, particularly in crop species. Nuclear factor Y (NF-Y) TF is a functionally diverse regulator of growth and development in the model plant species, with demonstrated roles in embryo development, stress response, flowering time and chloroplast biogenesis. Furthermore, a light-responsive NF-Y binding site (CCAAT-box) is present in the promoter of a spinach photosynthesis gene. As photosynthesis genes are co-regulated by light and co-regulated genes typically have similar regulatory elements in their promoters, it seems likely that other photosynthesis genes would also have light-responsive CCAAT-boxes. This provided the impetus to investigate the NF-Y TF in bread wheat. This thesis is focussed on wheat NF-Y members that have roles in light-mediated gene regulation with an emphasis on their involvement in the regulation of photosynthesis genes. NF-Y is a heterotrimeric complex, comprised of the three subunits NF-YA, NF-YB and NF-YC. Unlike the mammalian and yeast counterparts, each of the three subunits is encoded by multiple genes in Arabidopsis. The initial step taken in this study was the identification of the wheat NF-Y family (Chapter 3). A search of the current wheat nucleotide sequence databases identified 37 NF-Y genes (10 NF-YA, 11 NF-YB, 14 NF-YC & 2 Dr1). Phylogenetic analysis revealed that each of the three wheat NF-Y (TaNF-Y) subunit families could be divided into 4-5 clades based on their conserved core regions. Outside of the core regions, eleven motifs were identified to be conserved between Arabidopsis, rice and wheat NF-Y subunit members. The expression profiles of TaNF-Y genes were constructed using quantitative real-time polymerase chain reaction (RT-PCR). Some TaNF-Y subunit members had little variation in their transcript levels among the organs, while others displayed organ-predominant expression profiles, including those expressed mainly in the photosynthetic organs. To investigate their potential role in light-mediated gene regulation, the light responsiveness of the TaNF-Y genes were examined (Chapters 4 and 5). Two TaNF-YB and five TaNF-YC members were markedly upregulated by light in both the wheat leaves and seedling shoots. To identify the potential target genes of the light-upregulated NF-Y subunit members, a gene expression correlation analysis was conducted using publically available Affymetrix Wheat Genome Array datasets. This analysis revealed that the transcript expression levels of TaNF-YB3 and TaNF-YC11 were significantly correlated with those of photosynthesis genes. These correlated express profiles were also observed in the quantitative RT-PCR dataset from wheat plants grown under light and dark conditions. Sequence analysis of the promoters of these wheat photosynthesis genes revealed that they were enriched with potential NF-Y binding sites (CCAAT-box). The potential role of TaNF-YB3 in the regulation of photosynthetic genes was further investigated using a transgenic approach (Chapter 5). Transgenic wheat lines constitutively expressing TaNF-YB3 were found to have significantly increased expression levels of photosynthesis genes, including those encoding light harvesting chlorophyll a/b-binding proteins, photosystem I reaction centre subunits, a chloroplast ATP synthase subunit and glutamyl-tRNA reductase (GluTR). GluTR is a rate-limiting enzyme in the chlorophyll biosynthesis pathway. In association with the increased expression of the photosynthesis genes, the transgenic lines had a higher leaf chlorophyll content, increased photosynthetic rate and had a more rapid early growth rate compared to the wild-type wheat. In addition to its role in the regulation of photosynthesis genes, TaNF-YB3 overexpression lines flower on average 2-days earlier than the wild-type (Chapter 6). Quantitative RT-PCR analysis showed that there was a 13-fold increase in the expression level of the floral integrator, TaFT. The transcript levels of other downstream genes (TaFT2 and TaVRN1) were also increased in the transgenic lines. Furthermore, the transcript levels of TaNF-YB3 were significantly correlated with those of constans (CO), constans-like (COL) and timing of chlorophyll a/b-binding (CAB) expression 1 [TOC1; (CCT)] domain-containing proteins known to be involved in the regulation of flowering time. To summarise the key findings of this study, 37 NF-Y genes were identified in the crop species wheat. An in depth analysis of TaNF-Y gene expression profiles revealed that the potential role of some light-upregulated members was in the regulation of photosynthetic genes. The involvement of TaNF-YB3 in the regulation of photosynthesis genes was supported by data obtained from transgenic wheat lines with increased constitutive expression of TaNF-YB3. The overexpression of TaNF-YB3 in the transgenic lines revealed this NF-YB member is also involved in the fine-tuning of flowering time. These data suggest that the NF-Y TF plays an important role in light-mediated gene regulation in wheat.

Can transfer of learning be enriched by valuing knowledge transformation and co-creation? Exploring new ways to improve training design

This paper argues that a possible cause of issues with management education outcomes is the fact that most training models operate from a limited ‘transfer’ metaphor. This theoretical paper contends that by reconceptualising existing models, specifically Holton’s transfer of learning model, to incorporate multiple processes and acknowledge the importance of educator- or trainer-student interaction in co-creating knowledge, there is potential to improve training design and ultimately achieve more satisfactory training outcomes.

The rise of co-creative consumers : user experience sharing behaviour in online communities

This thesis examines consumer initiated value co-creation behaviour in the context of convergent mobile online services using a Service-Dominant logic (SD logic) theoretical framework. It focuses on non-reciprocal marketing phenomena such as open innovation and user generated content whereby new viable business models are derived and consumer roles and community become essential to the success of business. Attention to customers. roles and personalised experiences in value co-creation has been recognised in the literature (e.g., Prahalad & Ramaswamy, 2000; Prahalad, 2004; Prahalad & Ramaswamy, 2004). Similarly, in a subsequent iteration of their 2004 version of the foundations of SD logic, Vargo and Lusch (2006) replaced the concept of value co-production with value co-creation and suggested that a value co-creation mindset is essential to underpin the firm-customer value creation relationship. Much of this focus, however, has been limited to firm initiated value co-creation (e.g., B2B or B2C), while consumer initiated value creation, particularly consumer-to-consumer (C2C) has received little attention in the SD logic literature. While it is recognised that not every consumer wishes to make the effort to engage extensively in co-creation processes (MacDonald & Uncles, 2009), some consumers may not be satisfied with a standard product, instead they engage in the effort required for personalisation that potentially leads to greater value for themselves, and which may benefit not only the firm, but other consumers as well. Literature suggests that there are consumers who do, and as a result initiate such behaviour and expend effort to engage in co-creation activity (e.g., Gruen, Osmonbekov and Czaplewski, 2006; 2007 MacDonald & Uncles, 2009). In terms of consumers. engagement in value proposition (co-production) and value actualisation (co-creation), SD logic (Vargo & Lusch, 2004, 2008) provides a new lens that enables marketing scholars to transcend existing marketing theory and facilitates marketing practitioners to initiate service centric and value co-creation oriented marketing practices. Although the active role of the consumer is acknowledged in the SD logic oriented literature, we know little about how and why consumers participate in a value co-creation process (Payne, Storbacka, & Frow, 2008). Literature suggests that researchers should focus on areas such as C2C interaction (Gummesson 2007; Nicholls 2010) and consumer experience sharing and co-creation (Belk 2009; Prahalad & Ramaswamy 2004). In particular, this thesis seeks to better understand consumer initiated value co-creation, which is aligned with the notion that consumers can be resource integrators (Baron & Harris, 2008) and more. The reason for this focus is that consumers today are more empowered in both online and offline contexts (Füller, Mühlbacher, Matzler, & Jawecki, 2009; Sweeney, 2007). Active consumers take initiatives to engage and co-create solutions with other active actors in the market for their betterment of life (Ballantyne & Varey, 2006; Grönroos & Ravald, 2009). In terms of the organisation of the thesis, this thesis first takes a „zoom-out. (Vargo & Lusch, 2011) approach and develops the Experience Co-Creation (ECo) framework that is aligned with balanced centricity (Gummesson, 2008) and Actor-to-Actor worldview (Vargo & Lusch, 2011). This ECo framework is based on an extended „SD logic friendly lexicon. (Lusch & Vargo, 2006): value initiation and value initiator, value-in-experience, betterment centricity and betterment outcomes, and experience co-creation contexts derived from five gaps identified from the SD logic literature review. The framework is also designed to accommodate broader marketing phenomena (i.e., both reciprocal and non-reciprocal marketing phenomena). After zooming out and establishing the ECo framework, the thesis takes a zoom-in approach and places attention back on the value co-creation process. Owing to the scope of the current research, this thesis focuses specifically on non-reciprocal value co-creation phenomena initiated by consumers in online communities. Two emergent concepts: User Experience Sharing (UES) and Co-Creative Consumers are proposed grounded in the ECo framework. Together, these two theorised concepts shed light on the following two propositions: (1) User Experience Sharing derives value-in-experience as consumers make initiative efforts to participate in value co-creation, and (2) Co-Creative Consumers are value initiators who perform UES. Three research questions were identified underpinning the scope of this research: RQ1: What factors influence consumers to exhibit User Experience Sharing behaviour? RQ2: Why do Co-Creative Consumers participate in User Experience Sharing as part of value co-creation behaviour? RQ3: What are the characteristics of Co-Creative Consumers? To answer these research questions, two theoretical models were developed: the User Experience Sharing Behaviour Model (UESBM) grounded in the Theory of Planned Behaviour framework, and the Co-Creative Consumer Motivation Model (CCMM) grounded in the Motivation, Opportunity, Ability framework. The models use SD logic consistent constructs and draw upon multiple streams of literature including consumer education, consumer psychology and consumer behaviour, and organisational psychology and organisational behaviour. These constructs include User Experience Sharing with Other Consumers (UESC), User Experience Sharing with Firms (UESF), Enjoyment in Helping Others (EIHO), Consumer Empowerment (EMP), Consumer Competence (COMP), and Intention to Engage in User Experience Sharing (INT), Attitudes toward User Experience Sharing (ATT) and Subjective Norm (SN) in the UESBM, and User Experience Sharing (UES), Consumer Citizenship (CIT), Relating Needs of Self (RELS) and Relating Needs of Others (RELO), Newness (NEW), Mavenism (MAV), Use Innovativeness (UI), Personal Initiative (PIN) and Communality (COMU) in the CCMM. Many of these constructs are relatively new to marketing and require further empirical evidence for support. Two studies were conducted to underpin the corresponding research questions. Study One was conducted to calibrate and re-specify the proposed models. Study Two was a replica study to confirm the proposed models. In Study One, data were collected from a PC DIY online community. In Study Two, a majority of data were collected from Apple product online communities. The data were examined using structural equation modelling and cluster analysis. Considering the nature of the forums, the Study One data is considered to reflect some characteristics of Prosumers and the Study Two data is considered to reflect some characteristics of Innovators. The results drawn from two independent samples (N = 326 and N = 294) provide empirical support for the overall structure theorised in the research models. The results in both models show that Enjoyment in Helping Others and Consumer Competence in the UESBM, and Consumer Citizenship and Relating Needs in CCMM have significant impacts on UES. The consistent results appeared in both Study One and Study Two. The results also support the conceptualisation of Co-Creative Consumers and indicate Co-Creative Consumers are individuals who are able to relate the needs of themselves and others and feel a responsibility to share their valuable personal experiences. In general, the results shed light on "How and why consumers voluntarily participate in the value co-creation process?. The findings provide evidence to conceptualise User Experience Sharing behaviour as well as the Co-Creative Consumer using the lens of SD logic. This research is a pioneering study that incorporates and empirically tests SD logic consistent constructs to examine a particular area of the logic – that is consumer initiated value co-creation behaviour. This thesis also informs practitioners about how to facilitate and understand factors that engage with either firm or consumer initiated online communities.

Central Queensland Mining Supplies Pty Ltd v Columbia Steel Casting Co Ltd

In Central Queensland Mining Supplies Pty Ltd v Columbia Steel Casting Co Ltd [2011] QSC 183 Applegarth J considered complaints made by the defendant about the approach the plaintiff had taken in its endeavour to comply with its disclosure obligation under r 211 of the Uniform Civil Procedure Rules 1999 (Qld). The judgment also provides an indication of the direction the court is taking in relation to disclosure and document management in matters involving large numbers of documents.

The influence of architecture on degradation and tissue ingrowth into three-dimensional poly(lactic-co-glycolic acid) scaffolds in vitro and in vivo

The in vitro and in vivo degradation properties of poly(lactic-co-glycolic acid) (PLGA) scaffolds produced by two different technologies - thermally induced phase separation (TIPS), and solvent casting and particulate leaching (SCPL) were compared. Over 6 weeks, in vitro degradation produced changes in SCPL scaffold dimension, mass, internal architecture and mechanical properties. TIPS scaffolds produced far less changes in these parameters providing significant advantages over SCPL. In vivo results were based on a microsurgically created arteriovenous (AV) loop sandwiched between two TIPS scaffolds placed in a polycarbonate chamber under rat groin skin. Histologically, a predominant foreign body giant cell response and reduced vascularity was evident in tissue ingrowth between 2 and 8 weeks in TIPS scaffolds. Tissue death occurred at 8 weeks in the smallest pores. Morphometric comparison of TIPS and SCPL scaffolds indicated slightly better tissue ingrowth but greater loss of scaffold structure in SCPL scaffolds. Although advantageous in vitro, large surface area:volume ratios and varying pore sizes in PLGA TIPS scaffolds mean that effective in vivo (AV loop) utilization will only be achieved if the foreign body response can be significantly reduced so as to allow successful vascularisation, and hence sustained tissue growth, in pores less than 300 μm. © 2005 Elsevier Ltd. All rights reserved.

Using operations research methodologies to improve operating theatre scheduling

A hospital consists of a number of wards, units and departments that provide a variety of medical services and interact on a day-to-day basis. Nearly every department within a hospital schedules patients for the operating theatre (OT) and most wards receive patients from the OT following post-operative recovery. Because of the interrelationships between units, disruptions and cancellations within the OT can have a flow-on effect to the rest of the hospital. This often results in dissatisfied patients, nurses and doctors, escalating waiting lists, inefficient resource usage and undesirable waiting times. The objective of this study is to use Operational Research methodologies to enhance the performance of the operating theatre by improving elective patient planning using robust scheduling and improving the overall responsiveness to emergency patients by solving the disruption management and rescheduling problem. OT scheduling considers two types of patients: elective and emergency. Elective patients are selected from a waiting list and scheduled in advance based on resource availability and a set of objectives. This type of scheduling is referred to as ‘offline scheduling’. Disruptions to this schedule can occur for various reasons including variations in length of treatment, equipment restrictions or breakdown, unforeseen delays and the arrival of emergency patients, which may compete for resources. Emergency patients consist of acute patients requiring surgical intervention or in-patients whose conditions have deteriorated. These may or may not be urgent and are triaged accordingly. Most hospitals reserve theatres for emergency cases, but when these or other resources are unavailable, disruptions to the elective schedule result, such as delays in surgery start time, elective surgery cancellations or transfers to another institution. Scheduling of emergency patients and the handling of schedule disruptions is an ‘online’ process typically handled by OT staff. This means that decisions are made ‘on the spot’ in a ‘real-time’ environment. There are three key stages to this study: (1) Analyse the performance of the operating theatre department using simulation. Simulation is used as a decision support tool and involves changing system parameters and elective scheduling policies and observing the effect on the system’s performance measures; (2) Improve viability of elective schedules making offline schedules more robust to differences between expected treatment times and actual treatment times, using robust scheduling techniques. This will improve the access to care and the responsiveness to emergency patients; (3) Address the disruption management and rescheduling problem (which incorporates emergency arrivals) using innovative robust reactive scheduling techniques. The robust schedule will form the baseline schedule for the online robust reactive scheduling model.

Has increasing the age for child passengers to wear child restraints improved the extent to which they are used? Results from an Australian focus group and survey study.

Acknowledgement that many children in Australia travel in restraints that do not offer them the best protection has led to recent changes in legislation such that the type of restraint for children under 7 years is now specified. This paper reports the results of two studies (observational; focus group/ survey) carried out in the state of Queensland to evaluate the effectiveness of these changes to the legislation. Observations suggested that almost all of the children estimated as aged 0-12 years were restrained (95%). Analysis of the type of restraint used for target-aged children (0-6 year olds) suggests that the proportion using an age-appropriate restraint has increased by an estimated 7% since enactment of the legislation. However, around 1 in 4 children estimated as aged under 7 years were using restraints too large for good fit. Results from the survey and focus group suggested parents were supportive of the changes in legislation. Non-Indigenous parents agreed that the changes had been necessary, were effective at getting children into the right restraints, were easy to understand as well as making it clear what restraint to use with children. Moreover, they did not see the legislation as too complicated or too hard to comply with. Indigenous parents who participated in a focus group also regarded the legislation as improving children’s safety. However, they identified the cost of restraints as an important barrier to compliance. In summary, the legislation appears to have had a positive effect on compliance levels and on raising parental awareness of the need to restrain children child-specific restraints for longer. However, it would seem that an important minority of parents transition their children into larger restraints too early for optimal protection. Intervention efforts should aim to better inform these parents about appropriate ages for transition, especially from forward facing childseats. This could potentially be through use of other important transitions that occur at the same age, such as starting school. The small proportion of parents who do not restrain their children at all are also an important community sector to target. Finally, obtaining restraints presents a significant barrier to compliance for parents on limited incomes and interventions are needed to address this.