Partial agonists of the [alpha]3[beta]4[ast] neuronal nicotinic acetylcholine receptor reduce ethanol consumption and seeking in rats

Alcohol use disorders (AUDs) impact millions of individuals and there remain few effective treatment strategies. Despite evidence that neuronal nicotinic acetylcholine receptors (nAChRs) have a role in AUDs, it has not been established which subtypes of the nAChR are involved. Recent human genetic association studies have implicated the gene cluster CHRNA3-CHRNA5-CHRNB4 encoding the α3, α5, and β4 subunits of the nAChR in susceptibility to develop nicotine and alcohol dependence; however, their role in ethanol-mediated behaviors is unknown due to the lack of suitable and selective research tools. To determine the role of the α3, and β4 subunits of the nAChR in ethanol self-administration, we developed and characterized high-affinity partial agonists at α3β4 nAChRs, CP-601932, and PF-4575180. Both CP-601932 and PF-4575180 selectively decrease ethanol but not sucrose consumption and operant self-administration following long-term exposure. We show that the functional potencies of CP-601932 and PF-4575180 at α3β4 nAChRs correlate with their unbound rat brain concentrations, suggesting that the effects on ethanol self-administration are mediated via interaction with α3β4 nAChRs. Also varenicline, an approved smoking cessation aid previously shown to decrease ethanol consumption and seeking in rats and mice, reduces ethanol intake at unbound brain concentrations that allow functional interactions with α3β4 nAChRs. Furthermore, the selective α4β2(*) nAChR antagonist, DHβE, did not reduce ethanol intake. Together, these data provide further support for the human genetic association studies, implicating CHRNA3 and CHRNB4 genes in ethanol-mediated behaviors. CP-601932 has been shown to be safe in humans and may represent a potential novel treatment for AUDs.

Varenicline, an alpha-4 beta-2 nicotinic acetylcholine receptor partial agonist, selectively decreases ethanol consumption and seeking

Abstract Alcohol dependence is a disease that impacts millions of individuals worldwide. There has been some progress with pharmacotherapy for alcohol-dependent individuals; however, there remains a critical need for the development of novel and additional therapeutic approaches. Alcohol and nicotine are commonly abused together, and there is evidence that neuronal nicotinic acetylcholine receptors (nAChRs) play a role in both alcohol and nicotine dependence. Varenicline, a partial agonist at the alpha4beta2 nAChRs, reduces nicotine intake and was recently approved as a smoking cessation aid. We have investigated the role of varenicline in the modulation of ethanol consumption and seeking using three different animal models of drinking. We show that acute administration of varenicline, in doses reported to reduce nicotine reward, selectively reduced ethanol but not sucrose seeking using an operant self-administration drinking paradigm and also decreased voluntary ethanol but not water consumption in animals chronically exposed to ethanol for 2 months before varenicline treatment. Furthermore, chronic varenicline administration decreased ethanol consumption, which did not result in a rebound increase in ethanol intake when the varenicline was no longer administered. The data suggest that the alpha4beta2 nAChRs may play a role in ethanol-seeking behaviors in animals chronically exposed to ethanol. The selectivity of varenicline in decreasing ethanol consumption combined with its reported safety profile and mild side effects in humans suggest that varenicline may prove to be a treatment for alcohol dependence.

Engineering sustainable solutions program : critical literacies for engineers portfolio

Purpose While a number of universities in Australia have embraced concepts such as project/problem‐based learning and design of innovative learning environments for engineering education, there has been a lack of national guidance on including sustainability as a “critical literacy” into all engineering streams. This paper was presented at the 2004 International Conference on Engineering Education in Sustainable Development (EESD) in Barcelona, Spain, outlining a current initiative that is seeking to address the “critical literacy” dilemma. Design/methodology/approach The paper presents the positive steps taken by Australia's peak engineering body, the Institution of Engineers Australia (EA), in considering accreditation requirements for university engineering courses and its responsibility to ensure the inclusion of sustainability education material. It then describes a current initiative called the “Engineering Sustainable Solutions Program – Critical Literacies for Engineers Portfolio” (ESSP‐CL), which is being developed by The Natural Edge Project (TNEP) in partnership with EA and Unesco. Findings Content for the module was gathered from around the world, drawing on research from the publication The Natural Advantage of Nations: Business Opportunities, Innovation, and Governance in the Twenty‐first Century. Parts of the first draft of the ESSP‐CL have been trialled at Griffith University, Queensland, Australia with first year environmental engineering students, in May 2004. Further trials are now proceeding with a number of other universities and organisations nationally and internationally. Practical implications It is intended that ESSP‐CL will be a valuable resource to universities, professional development activities or other education facilities nationally and internationally. Originality/value This paper fulfils an identified information/resources need.

Contribution of take-out food consumption to socioeconomic differences in fruit and vegetable intake : a mediation analysis

Lower fruit and vegetable intake among socioeconomically disadvantaged groups has been well documented, and may be a consequence of a higher consumption of take-out foods. This study examined whether, and to what extent, take-out food consumption mediated (explained) the association between socioeconomic position and fruit and vegetable intake. A cross-sectional postal survey was conducted among 1500 randomly selected adults aged 25–64 years in Brisbane, Australia in 2009 (response rate = 63.7%, N = 903). A food frequency questionnaire assessed usual daily servings of fruits and vegetables (0 to 6), overall take-out consumption (times/week) and the consumption of 22 specific take-out items (never to ≥once/day). These specific take-out items were grouped into “less healthy” and “healthy” choices and indices were created for each type of choice (0 to 100). Socioeconomic position was ascertained by education. The analyses were performed using linear regression, and a bootstrap re-sampling approach estimated the statistical significance of the mediated effects. Mean daily serves of fruits and vegetables was 1.89 (SD 1.05) and 2.47 (SD 1.12) respectively. The least educated group were more likely to consume fewer serves of fruit (B= –0.39, p<0.001) and vegetables (B= –0.43, p<0.001) compared with the highest educated. The consumption of “less healthy” take-out food partly explained (mediated) education differences in fruit and vegetable intake; however, no mediating effects were observed for overall and “healthy” take-out consumption. Regular consumption of “less healthy” take-out items may contribute to socioeconomic differences in fruit and vegetable intake, possibly by displacing these foods.

New variational Bayesian approaches for statistical data mining : with applications to profiling and differentiating habitual consumption behaviour of customers in the wireless telecommunication industry

This thesis investigates profiling and differentiating customers through the use of statistical data mining techniques. The business application of our work centres on examining individuals’ seldomly studied yet critical consumption behaviour over an extensive time period within the context of the wireless telecommunication industry; consumption behaviour (as oppose to purchasing behaviour) is behaviour that has been performed so frequently that it become habitual and involves minimal intentions or decision making. Key variables investigated are the activity initialised timestamp and cell tower location as well as the activity type and usage quantity (e.g., voice call with duration in seconds); and the research focuses are on customers’ spatial and temporal usage behaviour. The main methodological emphasis is on the development of clustering models based on Gaussian mixture models (GMMs) which are fitted with the use of the recently developed variational Bayesian (VB) method. VB is an efficient deterministic alternative to the popular but computationally demandingMarkov chainMonte Carlo (MCMC) methods. The standard VBGMMalgorithm is extended by allowing component splitting such that it is robust to initial parameter choices and can automatically and efficiently determine the number of components. The new algorithm we propose allows more effective modelling of individuals’ highly heterogeneous and spiky spatial usage behaviour, or more generally human mobility patterns; the term spiky describes data patterns with large areas of low probability mixed with small areas of high probability. Customers are then characterised and segmented based on the fitted GMM which corresponds to how each of them uses the products/services spatially in their daily lives; this is essentially their likely lifestyle and occupational traits. Other significant research contributions include fitting GMMs using VB to circular data i.e., the temporal usage behaviour, and developing clustering algorithms suitable for high dimensional data based on the use of VB-GMM.

Diversity interventions for a socially sustainable construction industry

Major construction sites in Australia have an above average presence of ethnic minorities. These groups and the interfaces between them require effective management in order to meet the social imperatives of sustainable design and construction. A survey of 1155 workers and 204 managers on Sydney construction sites respectively, found a significant level of normalisation of negative forms of cross cultural interaction. Yet it was also found that anti-racism programs are not currently a management priority and that they generally lack sophisticated community relations aspects. This paper presents the results of a desk-top study of leading global companies within and outside the construction sector which have won international awards and recognition for their cultural diversity strategies. A key insight is that the companies profiled see diversity as a key resource and as an opportunity rather than a risk which is best harnessed through long-term and on-going commitment of senior management. These leading companies also recognise that cultural diversity strategies operate at three levels - in terms of its relationship with its own workforce; its relationship with its clients and; its relationships with the communities in which it operates - and if properly managed it can be a source of competitive advantage.

Challenges facing sustainable housing in Saudi Arabia : a current study showing the level of public awareness

Sustainable housing implementation requires strong support from the public, government and the housing industry. Lack of public awareness and understanding of the language and the meaning of sustainable housing may cause lack of public support. Salama stated that "sustainability or sustainable design is simply a rephrasing of some of the forgotten values of traditional architecture and urbanism"(Salama 2007). This exploratory paper examines public awareness of sustainable housing in Saudi Arabia. In developing countries, like Saudi Arabia, which have been experiencing a rapid rate of urbanisation, sustainable concept intervention is essential due to the scarcity of resources (Reffat 2004a). Sustainable building methods include the full use of the site design, passive solar design, natural light and ventilation. This paper reports on an exploratory survey on understanding the potential of the implementation of sustainable housing in Saudi Arabia. The main problem is that more than half of respondents were not aware of sustainable housing. Thus, one of the recommendations from the survey is to educate the public by using local media to inform people of the benefits of sustainable implementation to both new and existing housing stock.

Developing sustainable housing through building utilities and transport innovation

Sustainability concerns every citizen. Housing affordability and sustainable solutions are being highlighted in research and practice in many parts of the world. This paper discusses the development of a Commuter Energy and Building Utilities System (CEBUS) in sustainable housing projects as a means of bridging the gap between current median house pricing and target affordable house pricing for low income earners. Similar scales of sustainable housing development cannot be achieved through independent application of current best practice methods in ecologically sustainable development strategies or transit oriented development master plans. This paper presents the initial stage of research on first capital and ongoing utilities and transport cost savings available from these sustainable design methods. It also outlines further research and development of a CEBUS Dynamic Simulation Model and Conceptual Framework for the Australian property development and construction industry.

Multiculturalism, education for sustainable development (ESD) and the shifting discursive landscape of social inclusion

Australia has a long and sometimes turbulent relationship with the migrant Other. This paper examines a component of this relationship via the window of contemporary multicultural policy. The paper begins with an analysis of the political and social conditions that enabled a national and bipartisan policy of multiculturalism to emerge as formalised federal policy during the late 1960s and early 1970s. The paper re-problematises the influences that helped shape Australia's articulation of race and ethnicity and argues that multiculturalism, within a post-September 11 environment, can no longer be framed solely within its traditional framework of social justice. The paper positions education for sustainable development (ESD) as an emerging discursive field that provides educators with an alternative road map for critiquing Australia's fluid relationship with the migrant Other. By linking the tenets of multiculturalism with ESD, this paper suggests pre-service teacher educators are presented with a productive, and at the same time politically palatable, means for regaining pedagogical traction for a semi-dormant agenda of social inclusion.