A gene expression signature for insulin resistance

Insulin resistance is a heterogeneous disorder caused by a range of genetic and environmental factors, and we hypothesize that its aetiology varies considerably between individuals. This heterogeneity provides significant challenges to the development of effective therapeutic regimes for long-term management of type 2 diabetes. We describe a novel strategy, using large-scale gene expression profiling, to develop a Gene Expression Signature (GES) that reflects the overall state of insulin resistance in cells and patients. The GES was developed from 3T3-L1 adipocytes that were made ‘insulin resistant’ by treatment with tumour necrosis factor-alpha (TNFα) and then reversed with aspirin and troglitazone (‘re-sensitized’). The GES consisted of five genes whose expression levels best discriminated between the insulin resistant and insulin re-sensitized states. We then used this GES to screen a compound library for agents that affected the GES genes in 3T3- L1 adipocytes in a way that most closely resembled the changes seen when insulin resistance was successfully reversed using aspirin and troglitazone. This screen identified both known and new insulin sensitizing compounds including non-steroidal anti inflammatory agents, β-adrenergic antagonists, beta-lactams and sodium channel blockers. We tested the biological relevance of this GES in participants in the San Antonio Family Heart Study (n = 1,240) and showed that patients with the lowest GES scores were more insulin resistant (according to HOMA_IR and fasting plasma insulin levels, P < 0.001). These findings show that GES technology can be used for both the discovery of insulin sensitizing compounds and the characterization of patients into subtypes of insulin resistance according to GES scores, opening the possibility of developing a personalized medicine approach to type 2 diabetes.

The politics of 'sustainability': a critical discourse analysis of Victorian Government policy discourse, 1999-2006

Since its emergence during the 1980s the idea of sustainability has come to provide the dominant frame within which environmental policy is debated. Thus, for many ‘sustainability’ represents the best way to address the economic, social and environmental effects of the myriad of environmental issues facing human societies, including biodiversity loss, soil erosion, pollution of waterways, ozone depletion and climate change. There are however, widely divergent views advocated as to what sustainability means, which has important implications for how serious environmental issues are understood to be, why they are important, what has caused them, and what needs to be done to address them. Given the diversity of such views, the consequences for policy making, and the likelihood of effective responses being developed, are self evident. Within this context, this thesis investigates the politics of sustainability, focussing particularly on the way in which it is defined, because of the implications this has for the way in which environmental issues are understood and addressed. Following a review of various approaches to analysing environmental policy (traditional, mainstream, ecopolitical and discursive), Norman Fairclough’s approach to discourse analysis (Critical Discourse Analysis) was identified as having particular merit. Fairclough’s approach avoids the assumption that policy issues exist independently of the way they are framed and offers a perspective on discourse that links the social theoretical concerns of Foucault with the micro level concerns of linguistics. It also provides a means for taking environmental policy analysis in directions that that have attracted relatively limited attraction, namely the detailed analysis of the ideological effects of language on environmental policy. In this thesis Fairclough’s approach is used to explore how three storylines of sustainability (sustainable development, environmentally sustainable growth and transforming society) and their associated discourses shaped environmental policy making in Victoria, Australia, between 1999 and 2006. In undertaking this analysis, I examined the political and institutional context informing policy making (social practice); the contested process of text production (discourse practice), and; the detailed wording of a policy text (textual analysis). A major policy statement on environmental sustainability released by the Victorian Government in 2005 is subjected to detailed analysis. Based on the analysis undertaken, the substantive finding from this research is that rather than moving beyond neoliberalism, the Victorian Government embraced an approach to sustainability that was informed by neoliberalism and (weak) ecological modernisation, which constructs sustainability in ways that limit its importance and constrain the types of responses that could be advocated. In doing so, it drew heavily on notions of natural assets and ecosystems services as ways to make sense of the environment and why it is important. The Victorian Government also highlighted that environmental issues are caused by the cumulative effects of individual choices, and emphasized the importance of individual choice and behavioural change as central features of sustainability, while restricting opportunities for more transformative ideas to be heard. The broader conclusion arising from this research is that approaches to environmental policy that rely on neoliberal and (weak) ecological modern discourses are flawed, because, in commodifying nature, limiting the nature and magnitude of change required, and placing responsibility onto individuals they offer a constrained understanding of the challenge of sustainability and what needs to be done about it. The overall contribution made by this research is an improved understanding of the discursive nature of the politics of sustainability and the influence of neoliberalism and ecological modernisation, the use of a methodology that has attracted relatively limited attention within environmental policy (despite its widespread use in other areas of policy) and the documentation of a period of significant environmental policy reform in Victoria.

Managing commercially-focused collaborative R&D projects : preliminary findings from an Australian survey

Preliminary findings from a 2005 survey of Cooperative Research Centre (CRC) project leaders are presented. The results provide initial insights into the nature and outcomes of commercially-focused CRC projects. Such projects are modest in size and budget, are focused on producing new technologies, and are seen by the partners to be risky. Project teams tend to have the necessary project management capabilities and effective communication processes. The projects are experienced in positive terms by the partners, and positive collaboration experience is associated with positive project outcomes. The preliminary investigation of an initial sample is the first step in a more detailed analysis aimed at testing a theoretical model explaining the factors determining collaboration experience.

A conceptual framework of corporate and business ethics across organizations

Purpose – The objective of this paper is to introduce and describe a conceptual framework of corporate and business ethics across organizations in terms of ethical structures, ethical processes and ethical performance.

Design/methodology/approach – A framework is outlined and positioned incorporating an ethical frame of reference in the field of organizational chain management.

Findings – A number of areas and sub-areas of corporate and business ethics are framed in the context across organizations.

Research limitations/implications – The introduced framework should be seen as a seed for further development and refinement. It provides opportunities for further research of ethical concerns across organizations.

Practical implications – Organizations may benefit from the findings and insights presented and they may be used to enhance their ability to manage, monitor and evaluate ethical business practices across organizations.

Social implications – Changing societal and market patterns may enforce organizations to address ethical concerns across organizations. A myopic approach restricted to the judicial system may become insufficient and unsatisfactory from the perspective of other stakeholders of the organization.

Originality/value – The framework makes a contribution bringing in ethical concerns across organizations, providing a basis for their ethical values and culture, as well as asymmetric relationships in terms of power and dependence. The authors believe that a true learning organization needs to realise the importance of an extended view of its endeavors of corporate and business ethics in terms of ethical structures, ethical processes and ethical performance across organizations.

A model of cause-related marketing for profit-driven and non-profit organizations

Purpose – The purpose of this paper is to describe a model of cause-related marketing (CRM) for both profit-driven (PD) and non-profit (NP) organizations.
Design/methodology/approach – The model consists of two parallel internal and external organizational processes – one representing the process of a NP organization and the other a PD organization. They are interlinked as the outcome of a CRM-partnership is dependent upon their mutual efforts.
Findings – The authors argue that it is essential to remember that a CRM-partnership is a challenge and risk for both the PD and NP organizations that may harm their reputation and position in the marketplace and/or society. CRM has benefits as well as downsides that should not be underestimated nor neglected.
Research limitations/implications – Will the involvement of the PD or NP organizations in the resultant partnership be perceived as commercialism, altruism or a combination of both, in the marketplace and society? A focus on both processes opens up opportunities for further research.
Practical implications – A contribution is that the CRM-model may be used as a guide for both PD and NP organizations in order to reveal whether a CRM-partnership is appropriate for them with a potential partner or not. It may also indicate whether the motives are based upon commercial reasons or altruistic reasons or a combination of both.
Originality/value – The model enables these organizations to think through the process prior to engaging in CRM.

Teleological business ethics : formative, rationalist and transformative – illustrations and analogies

The strategic, tactical and operational levels of an organization may have different perceptions and convictions on how the organization’s behaviours and practices of business ethics should be managed in the marketplace and the surrounding society. We examine organizations’ behaviours and practices of business ethics in the marketplace and the surrounding society with the aid of complexity sciences. The objective is to describe organizations’ behaviours and practices of business ethics using different teleological approaches. Unethical behaviours and practices may be the outcome of conscious actions, but they may also be subconscious. We will discuss reasons for both possibilities of unethical behaviours and practices by organizations, their managers and employees. An important insight based upon the presented illustrations and analogies is that the different teleological approaches to business ethics in behaviours and practices may be consecutive and simultaneous within an organization. An essential subject for further research is how to deal with the durabilty and variabitlity of behaviours and practices of business ethics of organizations in the marketplace and the surrounding society.