Zoledronic acid preserves bone structure and increases survival but does not limit tumour incidence in a prostate cancer bone metastasis model

Background The bisphosphonate, zoledronic acid (ZOL), can inhibit osteoclasts leading to decreased osteoclastogenesis and osteoclast activity in bone. Here, we used a mixed osteolytic/osteoblastic murine model of bone-metastatic prostate cancer, RM1(BM), to determine how inhibiting osteolysis with ZOL affects the ability of these cells to establish metastases in bone, the integrity of the tumour-bearing bones and the survival of the tumour-bearing mice. Methods The model involves intracardiac injection for arterial dissemination of the RM1(BM) cells in C57BL/6 mice. ZOL treatment was given via subcutaneous injections on days 0, 4, 8 and 12, at 20 and 100 µg/kg doses. Bone integrity was assessed by micro-computed tomography and histology with comparison to untreated mice. The osteoclast and osteoblast activity was determined by measuring serum tartrate-resistant acid phosphatase 5b (TRAP 5b) and osteocalcin, respectively. Mice were euthanased according to predetermined criteria and survival was assessed using Kaplan Meier plots. Findings Micro-CT and histological analysis showed that treatment of mice with ZOL from the day of intracardiac injection of RM1(BM) cells inhibited tumour-induced bone lysis, maintained bone volume and reduced the calcification of tumour-induced endochondral osteoid material. ZOL treatment also led to a decreased serum osteocalcin and TRAP 5b levels. Additionally, treated mice showed increased survival compared to vehicle treated controls. However, ZOL treatment did not inhibit the cells ability to metastasise to bone as the number of bone-metastases was similar in both treated and untreated mice. Conclusions ZOL treatment provided significant benefits for maintaining the integrity of tumour-bearing bones and increased the survival of tumour bearing mice, though it did not prevent establishment of bone-metastases in this model. From the mechanistic view, these observations confirm that tumour-induced bone lysis is not a requirement for establishment of these bone tumours.

Organisational knowledge integration: towards a conceptual framework

This study analyses organisational knowledge integration processes from a multi-level and systemic perspective, with particular reference to the case of Fujitsu. A conceptual framework for knowledge integration is suggested focusing on team-building capability, capturing and utilising individual tacit knowledge, and communication networks for integrating dispersed specialist knowledge required in the development of new products and services. The research highlights that knowledge integration occurring in the innovation process is a result of knowledge exposure, its distribution and embodiment and finally its transfer, which leads to innovation capability and competitive advantage in firm.

Variations on a routine : how selection-adaptation-retention dynamics create variety in organisational routines

The question "what causes variety in organisational routines" is of considerable interest to organisational scholars, and one to which this thesis seeks to answer. To this end an evolutionary theory of change is advanced which holds that the dynamics of selection, adaptation and retention explain the creation of variety in organisational routines. A longitudinal, multi-level, multi-case analysis is undertaken in this thesis, using multiple data collection strategies. In each case, different types of variety were identified, according to a typology, together with how selection, adaptation and retention contribute to variety in a positive or negative sense. Methodologically, the thesis makes a contribution to our understanding of variety, as certain types of variety only become evident when examined by specific types of research design. The research also makes a theoretical contribution by explaining how selection, adaptation and retention individually and collectively contribute to variety in organisational routines. Moreover, showing that routines could be stable, diverse, adaptive and dynamic at the same time; is a significant, and novel, theoretical contribution.

Structuring and restructuring nonprofit associations

In the mid seventies there was a spate of legal claims involving unincorporated not-for-profit associations. These claims highlighted the liability exposure of management committee members and prompted a dramatic increase in the number of associations seeking shelter behind the corporate veil. Corporate structure decisions during this period were primarily motivated by the incentive of limited liability. Twenty years later, the not-for-profit sector is subject to new challenges. The Industry Commission Report into Charitable Organisations in Australia heralds an increasing intrusion of legislative responsibilities and reform in the sector. The traditional sources of funds for not-for-profit organisations are about to radically change with the advent of “competitive tendering” for government funding and the declining benevolence of society. The legal scuffle between Australian Rugby Football League Limited (the “ARL”) and News Limited has also exposed the vulnerability of not-for-profit groups and the many legal and commercial minefields in structural decision-making. The sector is beginning to respond to these pressures by rationalisation and restructure. Corporate structure decisions are now motivated by the need to promote efficiency and resilience. Survival of the fittest. Restructuring is by no means a task for the faint-hearted. A delicate balance between legality and practicality needs to be maintained. The focus of this paper is on the restructuring choices for not-for-profit organisations and groups in Queensland. It answers “how-to” questions and identifies some important restructuring issues.

Spatial inequalities in colorectal and breast cancer survival : premature deaths and associated factors

This study examines the influence of cancer stage, distance to treatment facilities and area disadvantage on breast and colorectal cancer spatial survival inequalities. We also estimate the number of premature deaths after adjusting for cancer stage to quantify the impact of spatial survival inequalities. Population-based descriptive study of residents aged <90 years in Queensland, Australia diagnosed with primary invasive breast (25,202 females) or colorectal (14,690 males, 11,700 females) cancers during 1996-2007. Bayesian hierarchical models explored relative survival inequalities across 478 regions. Cancer stage and disadvantage explained the spatial inequalities in breast cancer survival, however spatial inequalities in colorectal cancer survival persisted after adjustment. Of the 6,019 colorectal cancer deaths within 5 years of diagnosis, 470 (8%) were associated with spatial inequalities in non-diagnostic factors, i.e. factors beyond cancer stage at diagnosis. For breast cancers, of 2,412 deaths, 170 (7%) were related to spatial inequalities in non-diagnostic factors. Quantifying premature deaths can increase incentive for action to reduce these spatial inequalities.

The role of organisational concern for workplace fairness in the choice of a performance mesaurement system

Prior studies linking performance management systems (PMS) and organisational justice have examined how PMS influence procedural fairness. Our investigation differs from these studies. First, it examines fairness as an antecedent (instead of as a consequence) of the choice of PMS. Second, instead of conceptualising organisational fairness as procedural fairness, it relies on the impression management interpretation of organisational fairness. Hence, the study investigates how the need of senior managers to cultivate an impression of being fair is related to the choice of PMS systems and employee outcomes. Based on a sample of 276 employees, the results indicate that the need of senior management to cultivate an impression of being fair is associated with employee performance. They also indicate that a substantial component of these effects is indirect through the choice of comprehensive performance measures (CPM) and employee job satisfaction. These findings highlight the importance of organisational concern for workplace fairness as an antecedent of choice of CPM. From a theoretical perspective, the adoption of the impression management interpretation of organisational fairness contributes by providing new insights into the relationship between fairness and choice of PMS from a perspective that is different from those used in prior management accounting research.

New organisational leadership capabilities : transitional engineer the new designer?

Traditionally, design has been centred within the manufacturing and production areas of companies and or as a styling afterthought. Increasingly, design is viewed as a vital and important strategic business resource (Dell’Era, Marchesi & Verganti, 2010) and consequently companies worldwide look to design to help them innovate, differentiate and compete in the global marketplace. The role of the professional designer is evolving to a point where they are needed to work beyond being a specialist in the manufacturing and aesthetics of an artefact (Wrigley & Bucolo, 2011). This paper challenges the values held by academics and industry regarding the traditional role of designers in business. It investigates the emerging transitional engineering framework and puts forward a proposal for the next generation designer in the future era of design. Questions surrounding how designers will develop these new skills and how the Authors’ new framework of design led innovation can contribute to the future of design will be presented. This research is needed to better equip future designers to have a more central role in business.

Learning how to be responsive to public policy issues affecting SSSI members

Human survival depends on human ingenuity in using resources at hand to sustain human life. The historical record – in wrings and archaeological artefacts – provides evidence of the growth and collapse of political organisations and societies. In the institutions of Western civilisation, some traditions have endured over millennia where the roles of monarchs and public officials have been organised in perpetual succession. These roles were developed as conventions in the British Parliament after 1295 and provided the models of corporate governance in both public and private enterprise that have been continuously refined to the present day. In 2011, the Queensland Parliament legislated to introduce a new and more open system of scrutiny of legislation through a system of portfolio-based parliamentary committees. The committees began to function more actively in July 2012 and have inviting submissions from stakeholders and experts in a structured way to consider the government’s priorities in its legislative programme. The questions now are whether the Surveying and Spatial Sciences can respond expertly to address the terms of reference and meet the timetables of the various parliamentary committees. This paper discusses some of the more important and urgent issues that deserve debate that the profession needs to address in becoming more responsive to matters of public policy.

The relationship between firm survival and innovation : an introduction to the literature

The rapid growth in use of the Internet as a business tool provides a new perspective in the study of the organizational challenges of new technologies. The innovation literature has grown vastly since its establishment in the 1920s, covering a broad range of disciplines (Foxall 1984) and measures a wide variety of variables (Rogers 1995). At first glance, studies that look at the relationship between innovation and firm survival appear contradictory. However, the results appear compatible when additional factors, such as industry type, organizational age, company size or the duration of the study are taken into account.

The governance of inter-organisational decision-making : understanding the impacts of informal networks on formal decision-making regimes in the Brisbane Airport region

Airports and cities inevitably recognise the value that each brings the other; however, the separation in decision-making authority for what to build, where, when and how provides a conundrum for both parties. Airports often want a say in what is developed outside of the airport fence, and cities often want a say in what is developed inside the airport fence. Defining how much of a say airports and cities have in decisions beyond their jurisdictional control is likely to be a topic that continues so long as airports and cities maintain separate formal decision-making processes for what to build, where, when and how. However, the recent Green and White Papers for a new National Aviation Policy have made early inroads to formalising relationships between Australia’s major airports and their host cities. At present, no clear indication (within practice or literature) is evident to the appropriateness of different governance arrangements for decisions to develop in situations that bring together the opposing strategic interests of airports and cities; thus leaving decisions for infrastructure development as complex decision-making spaces that hold airport and city/regional interests at stake. The line of enquiry is motivated by a lack of empirical research on networked decision-making domains outside of the realm of institutional theorists (Agranoff & McGuire, 2001; Provan, Fish & Sydow, 2007). That is, governance literature has remained focused towards abstract conceptualisations of organisation, without focusing on the minutia of how organisation influences action in real-world applications. A recent study by Black (2008) has provided an initial foothold for governance researchers into networked decision-making domains. This study builds upon Black’s (2008) work by aiming to explore and understand the problem space of making decisions subjected to complex jurisdictional and relational interdependencies. That is, the research examines the formal and informal structures, relationships, and forums that operationalise debates and interactions between decision-making actors as they vie for influence over deciding what to build, where, when and how in airport-proximal development projects. The research mobilises a mixture of qualitative and quantitative methods to examine three embedded cases of airport-proximal development from a network governance perspective. Findings from the research provide a new understanding to the ways in which informal actor networks underpin and combine with formal decision-making networks to create new (or realigned) governance spaces that facilitate decision-making during complex phases of development planning. The research is timely, and responds well to Isett, Mergel, LeRoux, Mischen and Rethemeyer’s (2011) recent critique of limitations within current network governance literature, specifically to their noted absence of empirical studies that acknowledge and interrogate the simultaneity of formal and informal network structures within network governance arrangements (Isett et al., 2011, pp. 162-166). The combination of social network analysis (SNA) techniques and thematic enquiry has enabled findings to document and interpret the ways in which decision-making actors organise to overcome complex problems for planning infrastructure. An innovative approach to using association networks has been used to provide insights to the importance of the different ways actors interact with one another, thus providing a simple yet valuable addition to the increasingly popular discipline of SNA. The research also identifies when and how different types of networks (i.e. formal and informal) are able to overcome currently known limitations to network governance (see McGuire & Agranoff, 2011), thus adding depth to the emerging body of network governance literature surrounding limitations to network ways of working (i.e. Rhodes, 1997a; Keast & Brown, 2002; Rethemeyer & Hatmaker, 2008; McGuire & Agranoff, 2011). Contributions are made to practice via the provision of a timely understanding of how horizontal fora between airports and their regions are used, particularly in the context of how they reframe the governance of decision-making for airport-proximal infrastructure development. This new understanding will enable government and industry actors to better understand the structural impacts of governance arrangements before they design or adopt them, particularly for factors such as efficiency of information, oversight, and responsiveness to change.

Psychosocial experience of cancer : surpassing mere survival and recognising the potential for posttraumatic growth as well as distress.

The publication of the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV; American Psychiatric Association, 1994) introduced the notion that a life-threatening illness can be a stressor and catalyst for Posttraumatic Stress Disorder (PTSD). Since then a solid body of research has been established investigating the post-diagnosis experience of cancer. These studies have identified a number of short and long-term life changes resulting from a diagnosis of cancer and associated treatments. In this chapter, we discuss the psychosocial response to the cancer experience and the potential for cancer-related distress. Cancer can represent a life-threatening diagnosis that may be associated with aggressive treatments and result in physical and psychological changes. The potential for future trauma through the lasting effects of the disease and treatment, and the possibility of recurrence, can be a source of continued psychological distress. In addition to the documented adverse repercussions of cancer, we also outline the recent shift that has occurred in the psycho-oncology literature regarding positive life change or posttraumatic growth that is commonly reported after a diagnosis of cancer. Adopting a salutogenic framework acknowledges that the cancer experience is a dynamic psychosocial process with both negative and positive repercussions. Next, we describe the situational and individual factors that are associated with posttraumatic growth and the types of positive life change that are prevalent in this context. Finally, we discuss the implications of this research in a therapeutic context and the directions of future posttraumatic growth research with cancer survivors. This chapter will present both quantitative and qualitative research that indicates the potential for personal growth from adversity rather than just mere survival and return to pre-diagnosis functioning. It is important to emphasise however, that the presence of growth and prevalence of resilience does not negate the extremely distressing nature of a cancer diagnosis for the patient and their families and the suffering that can accompany treatment regimes. Indeed, it will be explained that for growth to occur, the experience must be one that quite literally shatters previously held schemas in order to act as a catalyst for change.